Association between discrimination and subsequent psychotic experiences in patients with COVID-19: A cohort study.

Although cross-sectional studies have suggested that discrimination has a negative impact on the mental health of patients with COVID-19, no cohort studies with longitudinal data have established a causal relationship. Therefore, this study aimed to investigate the association between COVID-19-related discrimination and subsequent psychotic experiences in individuals who had contracted the disease. Secondary outcomes were PTSD symptoms, psychological distress, and suicidal ideation. We utilized inverse probability weighting and marginal structural models with robust standard errors to analyze the association, accounting for confounders and loss to follow-up. In a sensitivity analysis, we evaluated the robustness of the estimates to potential unmeasured confounding by analyzing E-values. Of 7760 participants who had contracted COVID-19, 5971 were included after excluding those with missing sociodemographic data. Of these, 1736 (29.1 %) reported experiencing COVID-19-related discrimination. Of the 2559 participants who completed the study, 253 (9.9 %) reported having at least one psychotic experience. Participants who reported experiencing any COVID-19-related discrimination showed a higher risk of subsequent psychotic experiences compared with participants without such discrimination (risk difference 6.6 %, 95 % CI 4.0 %-9.9 %; risk ratio 1.82, 95 % CI 1.42-2.47). A negative impact was also found in suicidal ideation, PTSD symptoms, and psychological distress. E-values demonstrated the robustness of some of the observed associations to unmeasured confounding. The study found that COVID-19-related discrimination was associated with subsequent psychotic experiences and other mental health outcomes in individuals who had contracted the disease. A study focusing on prevention strategies, such as an anti-discrimination campaign, is warranted.

Difference in the risk of discrimination on psychological distress experienced by early wave infected and late wave infected COVID-19 survivors in Japan.

The psychological distress experienced by coronavirus disease of 2019 (COVID-19) survivors after recovery from the illness is amplified by discrimination endured because of their infection status. However, the difference in the risk of facing discrimination and risk of experiencing psychological distress in the early and late waves of the COVID-19 pandemic remain unclear. This study aimed to investigate whether the risk of facing discrimination because of infection status was lower in the early or late waves and whether risk of discrimination on psychological distress was more serious in later, rather than earlier waves. We conducted two online surveys to collect data from survivors divided into two groups. The participants with scores of five or more on the Kessler Psychological Distress Scale were identified as having experienced psychological distress. The participants were identified as having experienced discrimination based on infection status if they had endured being blamed, some type of discrimination, or having themselves or their families maligned. The timing of infection was split into infected during early waves of the pandemic for 2021 participants and infected during later waves of the pandemic for 2022 participants. Modified Poisson regression analyses were performed using experiences of discrimination as criteria and timing of infection as predictors. Modified Poisson regression analyses were further performed using the presence of psychological distress as a criteria and experiences of discrimination and timing of infection as the criteria, in addition to interaction effect of these es. The data of 6010 participants who were infected in early waves and 5344 participants who were infected in later waves were analyzed. The risks of being blamed, some forms of discrimination, and participants and their families being maligned were significantly lower in the group who were infected in later waves than those infected in earlier waves. Experiences of discrimination were highly associated with psychological distress in those infected in later waves than those infected in earlier waves, while only being blamed showed a significant association. Risk of discrimination was found to be lower in those infected in later waves, whereas risk of discrimination on psychological distress was shown to be more serious in those infected in later waves. Therefore, we submit that it is more important to support COVID-19 survivors who face discrimination, than it is to attempt to decrease the current discriminatory climate caused by the COVID-19 pandemic.

Dysregulation of Aldh1a2 underlies motor neuron degeneration in spinal muscular atrophy.

Lower motor neuron degeneration is the pathological hallmark of spinal muscular atrophy (SMA), a hereditary motor neuron disease caused by loss of the SMN1 gene and the resulting deficiency of ubiquitously expressed SMN protein. The molecular mechanisms underlying motor neuron degeneration, however, remain elusive. To clarify the cell-autonomous defect in developmental processes, we here performed transcriptome analyses of isolated embryonic motor neurons of SMA model mice to explore mechanisms of dysregulation of cell-type-specific gene expression. Of 12 identified genes that were differentially expressed between the SMA and control motor neurons, we focused on Aldh1a2, an essential gene for lower motor neuron development. In primary spinal motor neuron cultures, knockdown of Aldh1a2 led to the formation of axonal spheroids and neurodegeneration, reminiscent of the histopathological changes observed in human and animal cellular models. Conversely, Aldh1a2 rescued these pathological features in spinal motor neurons derived from SMA mouse embryos. Our findings suggest that developmental defects due to Aldh1a2 dysregulation enhances lower motor neuron vulnerability in SMA.

Research note reliability and validity of Japanese version of the trauma-informed care provider survey (TIC provider survey).

OBJECTIVE: Robust instruments to evaluate the ability of trauma-informed care among healthcare workers need to be developed, as this would help the implementation of trauma-informed care to prevent re-traumatization of patients. This study aims to assess the reliability and validity of the Japanese version of the Trauma-Informed Care (TIC) Provider Survey. A total of 794 healthcare workers were surveyed using a self-administered questionnaire, including the TIC Provider Survey, and six measures that were considered to be correlated with it. We calculated the Cronbach's alpha coefficient to investigate the internal consistency of each category of the TIC Provider Survey (knowledge, opinions, self-rated competence, practices, and barriers). Spearman's rank correlation coefficients were used to investigate the correlation between each category of the TIC Provider Survey, and other measures of construct validity. RESULTS: Cronbach's alpha coefficients of each category of the TIC Provider Survey were 0.40 (Knowledge), 0.63 (Opinions), 0.92 (Self-rated competence), 0.93 (Practices), and 0.87 (Barriers). The Spearman's rank correlation coefficients were small. We confirmed the reliability of the acceptable levels and examined the validity of modest or unacceptable levels of the Japanese version of the TIC provider survey among Japanese workers in a healthcare setting.

Association of preexisting psychiatric disorders with post-COVID-19 prevalence: a cross-sectional study.

Evidence demonstrating the association of preexisting psychiatric disorders with post-COVID-19 is limited. We aim to investigate the association using larger sample sizes and more extended postinfection periods than previous studies. A total of 6015 (response rate = 77.5%) COVID-19 survivors were surveyed using a self-administered questionnaire from July to September 2021. Poisson regression analysis with robust error variance was performed to estimate post-COVID-19 prevalence ratios (PRs) with or without preexisting psychiatric disorders. Participants with preexisting psychiatric disorders numbered 1067 (17.7%), and with post-COVID-19 were 2149 (35.7%). Post-COVID-19 PR with preexisting psychiatric disorders was 1.09 (95% CI 1.02-1.18, p = 0.013). The interaction between preexisting psychiatric disorders and postinfection periods was significant (p for interaction < 0.001). The subgroup analysis showed that those with preexisting psychiatric disorders might be at greater prolonged risk of post-COVID-19 than those without the disorders. These findings suggested that preexisting psychiatric disorders were associated with an increased post-COVID-19 risk, and post-COVID-19 with preexisting psychiatric disorders might prolong even if time passes.

Relationship between attitudes toward COVID-19 infection, depression and anxiety: a cross-sectional survey in Japan.

BACKGROUND: Although negative attitudes are known to develop with experiences of COVID-19 infection, it remains unclear whether such attitudes contribute to depression and anxiety as sequelae of COVID-19. We aimed to investigate the relationships between attitude towards COVID-19 infection and post-COVID-19 depression and anxiety. METHODS: A cross-sectional survey of COVID-19 recovered patients was conducted from July to September 2021 in Japan. Outcome variables, depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7); scores of 10 and above were identified as having symptoms of depression and anxiety, respectively. Exposure variables were whether participants were experiencing the following attitude strongly: threat to life due to COVID-19 infection, helplessness regarding COVID-19 infection, blaming a third party who did not restrain from going outside, blaming themselves for their COVID-19 infection, worry about spreading the infection to others, and self-stigma (Self-Stigma Scale-Short). Modified Poisson regression analyses were performed to analyze the findings. RESULTS: A total of 6016 responses were included in the analyses. The proportion of depression was 19.88%, and anxiety was 11.47%. The threat of life due to COVID-19 infection, helplessness regarding COVID-19 infection, blaming oneself for their COVID-19 infection, and self-stigma were significantly associated with depression and anxiety after adjusting covariates. Blaming the third party who did not restrain from going outside was associated with anxiety. There was no association between the worry about spreading infection to others and depression or anxiety. CONCLUSION: Negative attitudes, including self-stigma with the experience of COVID-19 infection, were related to depression and anxiety. Further studies confirming whether countermeasures for preventing or decreasing the negative attitude towards COVID-19 infection mitigate these symptoms are needed.

Reliability and Validity of the Japanese Version of the Attitudes Related to Trauma-Informed Care (ARTIC-10) Scale.

BACKGROUND: Trauma-informed care is recommended to avoid the inadvertent retraumatization of patients by health care providers. Psychometric evaluation of trauma-informed care instruments is needed. The Japanese version of the Attitudes Related to Trauma-Informed Care (ARTIC-10) Scale has not yet been psychometrically validated. OBJECTIVE: The study's objective was to examine the reliability and validity of the ARTIC-10. METHODS: This psychometric study of the ARTIC-10 compared with five other scales associated with attitudes related to trauma-informed care used a cross-sectional survey design conducted in November 2020 with a convenience sample of Japanese physicians and nurses recruited from an internet research agency. Participants completed self-administered questionnaires including the (a) ARTIC-10; (b) the Japanese version of the Moral Sensitivity Questionnaire 2018; (c) Patient Health Questionnaire-9; (d) Generalized Anxiety Disorder-7; (e) Stress Underestimation Beliefs; and (f) Negative Acts Questionnaire-Revised. Cronbach's α measured reliability internal consistency, and construct validity was measured by Spearman's rank. RESULTS: A total of 794 physicians and nurses completed the surveys. Cronbach's α value of ARTIC-10 was 0.56. Higher scores of ARTIC-10 were positively and significantly correlated with Moral Sensitivity Questionnaire 2018 and negatively and significantly correlated with other scales (r =-.12 to .30). CONCLUSION: This study found only modest internal consistency and construct validity of the Japanese version of ARTIC-10 in physicians and nurses. Further study is needed to identify factors that affect the reliability and validity of this Japanese scale to improve its psychometric properties.

Differences in the Course of Depression and Anxiety after COVID-19 Infection between Recovered Patients with and without a Psychiatric History: A Cross-Sectional Study.

BACKGROUND: This study aimed to examine the course of depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. METHODS: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. A total of 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. RESULTS: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. CONCLUSIONS: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.

Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology.

While amyloid-ß lies upstream of tau pathology in Alzheimer's disease, key drivers for other tauopathies, including progressive supranuclear palsy (PSP), are largely unknown. Various tau mutations are known to facilitate tau aggregation, but how the nonmutated tau, which most cases with PSP share, increases its propensity to aggregate in neurons and glial cells has remained elusive. Here, we identified genetic variations and protein abundance of filamin-A in the PSP brains without tau mutations. We provided in vivo biochemical evidence that increased filamin-A levels enhance the phosphorylation and insolubility of tau through interacting actin filaments. In addition, reduction of filamin-A corrected aberrant tau levels in the culture cells from PSP cases. Moreover, transgenic mice carrying human filamin-A recapitulated tau pathology in the neurons. Our data highlight that filamin-A promotes tau aggregation, providing a potential mechanism by which filamin-A contributes to PSP pathology.

Temporary employment and suicidal ideation in COVID-19 pandemic in Japan: A cross-sectional nationwide survey.

OBJECTIVES: Association between employment contract (temporary vs. permanent) and suicidal ideation (persistent suicidal ideation [i.e., with onset before COVID-19] or newly developed under COVID-19 pandemic) was examined using a nationally representative cross-sectional study in Japan. METHODS: An Internet survey was conducted from August to September 2020. The participants' inclusion criteria for this study were as follows: (i) 20-65 years old, (ii) employees (excluding self-employed, students, retired, housewives, and unemployed). The associations of suicidal ideation with the employees' factors were analyzed using the multinomial logistic regression model, adjusting for covariates (sex, age, marital status, education, company size, industries, and a history of psychiatric disease). RESULTS: Of total 12 249 participants, 72.4% were permanent and 27.6% were temporary employees. The prevalence was 8.5% for persistent suicidal ideation and 3.2% for newly developed suicidal ideation in the COVID-19 pandemic. Temporary employment was significantly associated with persistent suicidal ideation (adjusted odds ratio [aOR] = 1.36 [95% confidence interval, CI: 1.16-1.59]; P < .001), but not associated with newly developed suicidal ideation (aOR = 1.10 [0.85-1.42]; P = .457) after adjusting the covariates. Sensitivity analysis showed temporary employment was significantly associated with persistent suicidal ideation only in women. Newly developed suicidal ideation was significantly higher among participants of a young age, employees in drinking/eating/hotel business industry, and those having a history of psychiatric disease than among the counterparts. CONCLUSIONS: Working on a temporary employment contract was associated with persistent suicidal ideation under conditions of COVID-19 outbreaks in Japan. However, the result showed no significant difference in newly developed suicidal ideation. Further longitudinal study will be needed to examine the risk of being employed on an unstable occupational contract in the prolonged pandemic.

Association between Work-Related Trauma Exposure and Posttraumatic Stress Symptoms among Child Welfare Workers in Japan: A Cross-Sectional Study.

Child welfare workers often experience work-related traumatic events and may be at risk of post-traumatic stress disorder (PTSD), which can hinder early interventions for child abuse. This study examined the association between each single work-related traumatic event experienced by child welfare workers and the cumulative number of traumatic event types with PTSD symptoms. A checklist of traumatic events was used to investigate work-related traumatic events. The PTSD checklist for DSM-5 (PCL-5) was used to screen for PTSD symptoms. Two multivariate analyses were performed. A total of 140 workers were included in the analyses. In the first multivariate analysis, the event, "Witnessed a parent violently beating, hitting, kicking, or otherwise injuring a child or the other parent during work" (ß = 11.96; 95% CI, 2.11-21.80; p < 0.05) and resilience (ß = -0.60; 95% CI, -0.84 to -0.36; p < 0.01) were significantly associated with PTSD symptoms, as was resilience in the second multivariate analysis (ß = -0.60; 95% CI, -0.84 to -0.36; p < 0.01). The association between the cumulative number of event types and PTSD symptoms was not significant, but it was stronger when the cumulative number was four or more. The findings suggest the importance of reducing child welfare worker exposure to traumatic events.

DNA methylation inhibitor attenuates polyglutamine-induced neurodegeneration by regulating Hes5.

Spinal and bulbar muscular atrophy (SBMA) is a polyglutamine-mediated neuromuscular disease caused by a CAG repeat expansion in the androgen receptor (AR) gene. While transcriptional dysregulation is known to play a critical role in the pathogenesis of SBMA, the underlying molecular pathomechanisms remain unclear. DNA methylation is a fundamental epigenetic modification that silences the transcription of various genes that have a CpG-rich promoter. Here, we showed that DNA methyltransferase 1 (Dnmt1) is highly expressed in the spinal motor neurons of an SBMA mouse model and in patients with SBMA. Both genetic Dnmt1 depletion and treatment with RG108, a DNA methylation inhibitor, ameliorated the viability of SBMA model cells. Furthermore, a continuous intracerebroventricular injection of RG108 mitigated the phenotype of SBMA mice. DNA methylation array analysis identified hairy and enhancer of split 5 (Hes5) as having a CpG island with hyper-methylation in the promoter region, and the Hes5 expression was strongly silenced in SBMA. Moreover, Hes5 over-expression rescued the SBMA cells possibly by inducing Smad2 phosphorylation. Our findings suggest DNA hyper-methylation underlies the neurodegeneration in SBMA.

Highly efficient enzymatic synthesis of 3'-deoxyapionucleic acid (apioNA) having the four natural nucleobases.

The synthesis of the 3'-deoxyapionucleoside 3''-triphosphates (apioNTPs) having the four natural nucleobases and their enzymatic incorporation into a DNA-DNA primer-template have been tried. Therminator DNA polymerase was shown to incorporate these apioNTPs effectively giving 43mer DNA-apioNA chimera.

The present and future situation of "model project for investigation and analysis of medical practice associated deaths" in Osaka, Japan.

To enhance the quality and safety of medical care, the Ministry of Health, Labor and Welfare (MHLW) launched a model project in September 2005 for investigation and analysis of medical practice associated deaths in an attempt to move the existing system in a different direction. The project, initiated in Tokyo, Osaka, Nagoya, and Kobe, has now been implemented in nine prefectures. In the hope that the model project will lead to the nationwide development of medical safety investigating committees, the MHLW has submitted a provisional third plan. Based on our practical experience of the model project in Osaka, we present and discuss practical problems and legal issues involving surgeons' criminal punishment.

Synthesis of 3'-deoxyapionucleoside triphosphates and their incorporation into DNA by DNA polymerase.

Here, we report the synthesis of 3'-deoxyapionucleoside 3''-triphosphates (apioNTPs) and the analysis of their property as substrate of enzymatic polymerization. We established the large scale synthetic route of 3-deoxy-D-apiose from D-galactose, and regio- and stereo-selective glycosylation procedures. Resulting 3'-deoxyapionucleosides were then converted into their 3''-triphosphates. We carried out primer-extension reactions and found that Therminator polymerase, a variant of 9 degrees N DNA polymerase, was an efficient enzyme for incorporation of apioNTPs to synthesize DNA-dependent 3'-deoxy-D-apiose nucleic acids (apioNAs).