Changes in Challenging Behaviors Accompanying Transition to a New Facility in Individuals with Intellectual Disabilities.

Challenging behavior (CB), the most common example being extreme self-injurious or aggressive/destructive behavior, is often observed as a major behavior issue in individuals with severe intellectual disabilities. This study investigated how CB changed among residents of a facility for people with disabilities before and after it was restructured from a traditional format single room shared by two to three individuals with approximately 20 residents lived together to a format featuring private areas with two rooms per resident and a unitcare system. Twenty-one residents of Care Home A, which was rebuilt in the new care format, were selected. Care staff completed a questionnaire one month before, one month after, and six months after residents moved to the new facility. Scores were compared among each time point. The results revealed significant reductions in residents' aggressive, stereotyped, and targeted behaviors, such as hitting their own head and fecal smearing. The major features of the restructured facility were a living space consisting of two private rooms per resident and a shift to unit care for the entire ward. These new features enabled residents to reduce destructive stimuli and made it easier to understand what to do in each private room.

Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial.

OBJECTIVES: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19). METHODS: In this exploratory multicentre randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6. RESULTS: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; P = 0.022). Serious adverse events were not observed in either group. Phlebitis occurred in ca. 50% of patients treated with nafamostat. CONCLUSIONS: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19.

Factors influencing postpartum depression among Japanese parents: A prospective longitudinal study.

AIM: Postpartum depression (PPD) may have negative effects on the parents and lead to impaired cognitive, socioemotional, and behavioral development in their children. The purpose of this study was to examine factors associated with PPD in parents during the first year after delivery. METHODS: This study used a self-administered questionnaire. Questionnaires were mailed at 5 days, 3 months, 6 months, and 1 year after delivery, respectively. The particpants were 107 pairs of mothers and fathers. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Data on sense of coherence (SOC), Quality Marriage Index, Social Support Scale, Mother-to-Infant Bonding Scale, and sociodemographic variables were collected. Multiple regression analysis was performed to examine the strength of the association between several variables and the EPDS at each survey period for fathers and mothers, respectively. RESULTS: The prevalence of PPD in the first-year postpartum ranged from 12.1%-23.4% to 7.5%-8.4% for fathers and mothers, respectively. SOC had the strongest impact on EPDS scores for both fathers and mothers at all four survey periods. CONCLUSIONS: Our findings suggest that stress coping skills are an important factor affecting PPD throughout the first-year postpartum for both fathers and mothers.

Effect of the Sway Bed on Autonomic Response, Emotional Responses, and Muscle Hardness in Children with Severe Motor and Intellectual Disabilities: A Pilot Study.

This cross-sectional study aimed to examine the effects of being swayed in a sway bed on children with severe motor and intellectual difficulties by examining potential differences in their autonomic and emotional responses, as well as their muscle hardness, and by comparing them with "a control condition without any stimulation". Children's heart rate variability, rectus femoris hardness, and passive hip abduction range of motion (ROM) were measured in two experimental conditions, differentiated by the presence of a 5-min sway stimulus. In each condition, the children's faces were video-recorded and retrospectively rated subjectively by their homeroom teacher concerning the visible expression of eight emotions. Significant intervention-related effects were observed on the heart rate variability and the "Relax" item of the emotional response indicators but not on muscle hardness or hip ROM. Our findings provide evidence that using a motorized sway bed can promote relaxation in children with severe motor and intellectual disabilities by influencing their autonomic response.

Burnout among kindergarten teachers and associated factors.

Burnout among kindergarten teachers is a subject of great concern. Although burnout is reported to be significantly associated with turnover intention and work engagement, few studies have examined factors associated with burnout among these teachers. Therefore, in the present study, we performed a cross-sectional survey of burnout and associated factors among kindergarten teachers. We distributed 3363 questionnaires to all 205 authorized kindergartens and childcare institutions in Nagasaki Prefecture and received 1086 responses (response rate: 32.3%). The participants were limited to full-time female class teachers. After excluding survey forms with incomplete content, we ultimately examined valid responses from 442 participants. The survey examined burnout (Maslach Burnout Inventory, MBI), teacher stress (Nursery Teacher's Stress Scale, NTSS), coping behaviors (Brief Scales for Coping Profile, BSCP), and social support (Social Support Scale, SSS). A multiple regression analysis revealed that all 3 MBI subscales were positively associated with "understanding of how to handle children" on the NTSS and negatively associated with "superiors" on the SSS. "Emotional exhaustion" was significantly associated with "interpersonal relations at work" and "lack of time" on the NTSS, and "avoidance and suppression" on the BSCP. "Depersonalization" was significantly associated with age, "disconnect in working conditions" on the NTSS, and "proactive problem solving" and "venting emotions to others" on the BSCP. "Diminished professional accomplishment" was significantly associated with age, "lack of time" on the NTSS, and "proactive problem solving" and "change in perspective" on the BSCP. These results suggest that support from superiors that enables teachers to better understand children and handle them appropriately is necessary to prevent burnout.

Subjective achievement from psychiatry rotation in the Japanese postgraduate residency system: a longitudinal questionnaire study.

BACKGROUND: Psychiatry rotation has been mandatory in the Japanese postgraduate residency system since 2020. Some psychiatry-related competency items are stipulated as mandatory for residents. The current study aimed to clarify whether psychiatry rotation affected residents' subjective achievement of these competency items. METHODS: This longitudinal study was conducted among postgraduate residents who completed a rotation in the psychiatry department at Nagasaki University Hospital across two academic years (2020-2021). The survey was administered at the start and at the end of the psychiatry rotation. Residents evaluated their subjective understanding and confidence regarding initiating treatment for these competency items using a six-point Likert scale. The average scores for each item were compared between pre-rotation and post-rotation. RESULTS: In total, 99 residents (91.7%) responded to this survey. Residents had significantly higher scores at post-rotation compared with pre-rotation in all psychiatry-related competency items in both subjective understanding and confidence in initiating treatment. Additionally, strong effect sizes were found for many items. CONCLUSION: Residents improved learning about psychiatry-related competency items through psychiatry rotation. This finding suggests that it is reasonable for psychiatry rotation to be mandatory in the current Japanese postgraduate residency system. The importance of psychiatry is likely to increase in both undergraduate and postgraduate medical education in the future. It is necessary to continuously update educational strategies to meet changing social needs over time. As this study was conducted at a single institution, a multi-center study is needed to expand the current findings.

Relationship between Sensitivity Tendency and Psychological Stress Reactivity in Healthy Students.

This study examined the relationship between sensory processing sensitivity and psychological stress reactivity in 69 healthy Japanese university students. The Japanese version of the Highly Sensitive Person Scale and the Japanese version of the Adolescent/Adult Sensory Profile were used for subjective assessment. The Galvanic skin response was measured as an objective measure of stress responses while the participants were completing the Stroop task. The Wilcoxon signed-rank test, the Spearman rank correlation coefficient, and the Mann−Whitney U test were conducted for data analysis. The results demonstrated that there was no significant correlation between the Japanese version of the Highly Sensitive Person Scale and Galvanic skin response. However, there was a marginal trend toward significance between low registration in the Japanese version of the Adolescent/Adult Sensory Profile and Galvanic skin response (rs = 0.231, p < 0.10; rs = 0.219, p < 0.10), suggesting that self-rated sensitivity was not necessarily associated with objective measures. These results indicate that sensory processing sensitivity analyses require the consideration of the traits and characteristics of the participants and multifaceted evaluations using a sensitivity assessment scale other than the Japanese version of the Highly Sensitive Person Scale.

The effectiveness of lamotrigine for persistent depressive disorder: A case report.

AIM: Persistent depressive disorder (PDD) was first introduced in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), which encompasses numerous different conditions, including dysthymia, recurrent major depressive disorder, double depression, and chronic major depression. SSRIs are the first-line drugs for treatment of PDD; however, not all patients respond to SSRI treatment. CASE PRESENTATION: We describe a woman who was diagnosed with PDD. At the age of 38, the patient presented with anxiety, reduced energy, marked tiredness, and sleep disturbances. She was prescribed with three antidepressants (paroxetine, duloxetine, and mirtazapine), which were not effective in relieving her symptoms. She was also prescribed bromazepam, which was also not effective. Subsequently, she was switched to lamotrigine, which resulted in a marked improvement in symptoms. The antidepressants and bromazepam were gradually tapered and discontinued. CONCLUSION: This case demonstrates that lamotrigine may be effective for treating patients with antidepressant resistant PDD and suggests that it may be a promising alternative to combination therapy of antidepressants and benzodiazepines in the treatment of PDD.

Visual attention affects late somatosensory processing in autism spectrum disorder.

PURPOSE: Somatosensory processing problems are often reported in individuals with autism spectrum disorder (ASD), along with an abnormal multimodal integration of visual, tactile or proprioceptive information. However, the effects of visual stimulation and attention on somatosensory processing in ASD remain unknown. This study explores the effects of visual attention on somatosensory processing in ASD. MATERIALS AND METHODS: The neural activity in somatosensory areas and associated regions was investigated by measuring somatosensory evoked potentials (SEPs) elicited by median nerve stimulation, in three different conditions (closed eyes, open eyes and focused attention to a visual task). Nine individuals with ASD and nine typically developing (TD) individuals participated in the study. RESULTS: There were significant interactions between groups (ASD, TD) and conditions (closed eye, open eye, visual task requiring focused attention) for P100-N140 SEP amplitudes evaluated by 2-way analysis of variance. Post hoc analyses revealed that the P100-N140 amplitude with closed eyes recorded larger SEPs in the ASD group than in the TD group at C3' of the international 10-20 system. In the ASD group, the P100-N140 amplitude elicited smaller responses during visual tasks than with closed or open eyes. There were no significant differences in N20-P25 SEP components. CONCLUSIONS: These findings suggest that visual attention affects the later stages of somatosensory processing in individuals with ASD.

Factors associated with kindergarten teachers' willingness to continue working.

ABSTRACT: The turnover rate among kindergarten teachers in advanced countries is extremely high. As such, there is an urgent need to determine the reasons for this turnover and to identify ways to prevent it. The current study investigates the individual and environmental factors that impact kindergarten teachers' willingness to continue working.A total of 600 kindergarten teachers in Japan participated in this study. Participants responded to questionnaires regarding their willingness to continue working, mental health, work engagement, and the availability of social support. Multiple logistic regression analysis was used to analyze participants' data, with willingness to continue working for 5 or more years as the dependent variable. Additionally, Spearman rank correlation was used to examine the correlations between factors associated with willingness to continue working.Factors such as older age, living with a spouse, caring for younger children (up to 2 years old) at work, good mental health, and higher work engagement were significantly associated with teachers' higher willingness to continue working. Factors such as marriage, health and family problems, overtime work, issues with workplace childcare, and education policy, working time/day problems, human relations, and difficulties taking care of children were correlated with teachers' lack of willingness to continue working.The findings of this cross-sectional study suggest that welfare benefits and individual support systems could be key elements to encourage kindergarten teachers to continue working and could lead to their improved job satisfaction and mental health. Balanced work conditions and workers' high agreement with their workplace's overall childcare or educational policies may lead to lower turnover. Some programs - such as relationship counselling - could have a positive impact on teachers' mental health and job satisfaction.

Switching from blonanserin tablets to blonanserin transdermal patches improves tardive dyskinesia: A case report.

Tardive dyskinesia (TD) is a common side effect of antipsychotics, and it remains a persistent and challenging problem. The blonanserin transdermal patch, developed in Japan and launched in September 2019, is the first antipsychotic transdermal treatment. Here, we describe a patient with schizophrenia who exhibited markedly improved orofacial dyskinesia after switching from blonanserin tablets to blonanserin transdermal patches. We speculate that the patch formulation might have led to more stable plasma blonanserin levels, thus reducing the side effects. Specifically, the patch formulation might have contributed to stable plasma levels via the continuous and direct absorption of blonanserin through the skin.

A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models.

Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia.

Genetic and epigenetic analyses of panic disorder in the post-GWAS era.

Panic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.

Genetic and environmental factors of schizophrenia and autism spectrum disorder: insights from twin studies.

Twin studies of psychiatric disorders such as schizophrenia and autism spectrum disorder have employed epidemiological approaches that determine heritability by comparing the concordance rate between monozygotic twins (MZs) and dizygotic twins. The basis for these studies is that MZs share 100% of their genetic information. Recently, biological studies based on molecular methods are now being increasingly applied to examine the differences between MZs discordance for psychiatric disorders to unravel their possible causes. Although recent advances in next-generation sequencing have increased the accuracy of this line of research, there has been greater emphasis placed on epigenetic changes versus DNA sequence changes as the probable cause of discordant psychiatric disorders in MZs. Since the epigenetic status differs in each tissue type, in addition to the DNA from the peripheral blood, studies using DNA from nerve cells induced from postmortem brains or induced pluripotent stem cells are being carried out. Although it was originally thought that epigenetic changes occurred as a result of environmental factors, and thus were not transmittable, it is now known that such changes might possibly be transmitted between generations. Therefore, the potential possible effects of intestinal flora inside the body are currently being investigated as a cause of discordance in MZs. As a result, twin studies of psychiatric disorders are greatly contributing to the elucidation of genetic and environmental factors in the etiology of psychiatric conditions.

Allosteric regulation accompanied by oligomeric state changes of Trypanosoma brucei GMP reductase through cystathionine-ß-synthase domain.

Guanosine 5'-monophosphate reductase (GMPR) is involved in the purine salvage pathway and is conserved throughout evolution. Nonetheless, the GMPR of Trypanosoma brucei (TbGMPR) includes a unique structure known as the cystathionine-ß-synthase (CBS) domain, though the role of this domain is not fully understood. Here, we show that guanine and adenine nucleotides exert positive and negative effects, respectively, on TbGMPR activity by binding allosterically to the CBS domain. The present structural analyses revealed that TbGMPR forms an octamer that shows a transition between relaxed and twisted conformations in the absence and presence of guanine nucleotides, respectively, whereas the TbGMPR octamer dissociates into two tetramers when ATP is available instead of guanine nucleotides. These findings demonstrate that the CBS domain plays a key role in the allosteric regulation of TbGMPR by facilitating the transition of its oligomeric state depending on ligand nucleotide availability.

Nonsense mutation in CFAP43 causes normal-pressure hydrocephalus with ciliary abnormalities.

OBJECTIVE: To identify genes related to normal-pressure hydrocephalus (NPH) in one Japanese family with several members with NPH. METHODS: We performed whole-exome sequencing (WES) on a Japanese family with multiple individuals with NPH and identified a candidate gene. Then we generated knockout mouse using CRISPR/Cas9 to confirm the effect of the candidate gene on the pathogenesis of hydrocephalus. RESULTS: In WES, we identified a loss-of-function variant in CFAP43 that segregated with the disease. CFAP43 encoding cilia- and flagella-associated protein is preferentially expressed in the testis. Recent studies have revealed that mutations in this gene cause male infertility owing to morphologic abnormalities of sperm flagella. We knocked out mouse ortholog Cfap43 using CRISPR/Cas9 technology, resulting in Cfap43-deficient mice that exhibited a hydrocephalus phenotype with morphologic abnormality of motile cilia. CONCLUSION: Our results strongly suggest that CFAP43 is responsible for morphologic or movement abnormalities of cilia in the brain that result in NPH.

Factors associated with preschool workers' willingness to continue working.

In industrialized countries, the turnover rate of preschool workers is extremely high and now represents a social problem. Consequently, it has become important to promote stable early care and educational environments for this population. Several factors related to working environments are known to affect turnover intention; however, the specific factors related to turnover intention among preschool workers have not yet been identified. Considering this, the objective of the present study was to determine factors associated with preschool workers' willingness to continue working.The participants of this study were 1137 preschool workers based in Nagasaki Prefecture, Japan. Multivariate logistic regression analysis was used to analyze the participants' data, with willingness to continue working for 5 years or more set as the dependent variable.Analysis of the results for all subjects clearly showed that male sex, older age, good mental health, high number of social supports, and good work engagement have a positive effect on willingness to continue working. Further, stratifying the participants in terms of age revealed that for preschool workers under 39 years, male sex, good mental health, high number of social supports, and good work engagement act positively in regard to willingness to continue working. Meanwhile, for those over 40 years, it was found that permanent employment and good work engagement act positively in this regard. Thus, work engagement was the only common factor between preschool workers under 39 and over 40.The findings of this cross-sectional study demonstrate that the factors associated with willingness to continue working among preschool workers differ between younger and older professionals. These findings underline the importance of considering age categories when attempting to maximize such professionals' willingness to continue working.

Investigation into the plasma concentration of ω3 polyunsaturated fatty acids in Japanese attention-deficit hyperactivity disorder patients.

Several studies report that patients with attention-deficit hyperactivity disorder (ADHD) have a low plasma concentration of polyunsaturated fatty acids (PUFAs). Since fish intake varies among countries and is high in Japan, those results may not apply to Japanese patients with ADHD. However, there is currently not enough evidence to support this. We compared the plasma PUFAs levels of patients with ADHD with the standard reference levels for healthy subjects, and examined the relationship between those PUFAs levels and the subject's psychological evaluation. The subjects were 24 patients (age < 20 years) previously diagnosed with ADHD (according to the DSM-IV-TR criteria) at the psychiatric department of the Nagasaki University Hospital, between November 2010 and November 2015. The plasma concentrations of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) were measured using gas chromatography. Data pertaining to global assessment of functioning (GAF), clinical global impressions, ADHD Rating Scale-IV, and the drug used for treatment (atomoxetine or methylphenidate) were obtained from the medical records. The plasma concentrations of DHA, EPA, and EPA/AA were significantly lower than the normal reference range, indicating that ADHD patients present an imbalance in PUFAs levels. This trend is similar to ADHD patients in other countries and replacement therapy in Japanese ADHD patients may be useful.