The sustained psychological impact of coronavirus disease 2019 pandemic on hospital workers 2 years after the outbreak: a repeated cross-sectional study in Kobe.

BACKGROUND: Healthcare workers who are exposed to coronavirus disease 2019 are psychologically distressed. This study aimed to evaluate the mental health outcomes of hospital workers 2 years after the outbreak of coronavirus disease 2019 and to identify changes in the stress of hospital workers and predicted risk factors. METHODS: This survey was conducted 2 years after the initial evaluation performed under the first emergency declaration of the coronavirus disease 2019 pandemic among hospital workers at the same hospital in an ordinance-designated city in Japan from June to July 2022. Sociodemographic data, 19 stress-related question responses, the Impact of Event Scale-Revised, and the Maslach burnout inventory-general survey were collected. Multiple regression models were used to identify factors associated with each of the mental health outcomes 2 years after the coronavirus disease 2019 outbreak. RESULTS: We received 719 valid responses. Between 2020 and 2022, hospital workers' anxiety about infection decreased, whereas their exhaustion and workload increased. Multiple regression analysis revealed that 2 years after the coronavirus disease 2019 outbreak, nurses and young people were at a higher risk of experiencing stress and burnout due to emotional exhaustion, respectively. CONCLUSIONS: This is the first study to examine the long-term stress of hospital workers measured in Japan. Exhaustion and workload were worsened 2 years into the pandemic. Therefore, health and medical institutions should continuously monitor the physical and psychological health of staff members.

COVID-19 delirium and encephalopathy: Pathophysiology assumed in the first 3 years of the ongoing pandemic.

Background: The coronavirus disease (COVID-19) continues to spread worldwide. It has a high rate of delirium, even in young patients without comorbidities. Infected patients required isolation because of the high infectivity and virulence of COVID-19. The high prevalence of delirium in COVID-19 primarily results from encephalopathy and neuroinflammation caused by acute respiratory distress syndrome (ARDS)-associated cytokine storm. Acute respiratory distress syndrome has been linked to delirium and psychotic symptoms in the subacute phase (4 to 12 weeks), termed post-acute COVID-19 syndrome (PACS), and to brain fog, cognitive dysfunction, and fatigue, termed "long COVID," which persists beyond 12 weeks. However, no review article that mentions "COVID-19 delirium" have never been reported. Basic Procedures: This narrative review summarizes data on delirium associated with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and related neurological symptoms of persistent post-infection illness (PACS or long COVID) after persistence of cognitive dysfunction. Thus, we describe the pathophysiological hypothesis of COVID-19 delirium and its continuation as long COVID. This review also describes the treatment of delirium complicated by COVID-19 pneumonia. Main Findings: SARS-CoV-2 infection is associated with encephalopathy and delirium. An association between COVID-19 infection and Alzheimer's disease has been suggested, and studies are being conducted from multiple facets including genetics, cytology, and postmortem study. Principal Conclusions: This review suggests that COVID-19 has important short and long-term neuropsychiatric effects. Several hypotheses have been proposed that highlight potential neurobiological mechanisms as causal factors, including neuronal-inflammatory pathways by cytokine storm and cellular senescence, and chronic inflammation.

Characteristics of suicidal emergency room patients before and during the COVID-19 pandemic in Japan.

AIM: Owing to the stress caused by the behavioral restrictions and lifestyle changes during the COVID-19 pandemic, suicide rates have increased in Japan, especially among young people. This study aimed to identify the differences in the characteristics of patients hospitalized for suicide attempts in the emergency room, requiring inpatient care before and during the pandemic over 2 years. METHODS: This study was a retrospective analysis. Data were collected from the electronic medical records. A descriptive survey was conducted to examine changes in the pattern of suicide attempts during the COVID-19 outbreak. Two-sample independent t-tests, Chi-square tests, and Fisher's exact test were used for data analysis. RESULTS: Two hundred one patients were included. No significant differences were found in the number of patients hospitalized for suicide attempts, average age, or sex ratio before and during the pandemic periods. Acute drug intoxication and overmedication in patients increased significantly during the pandemic. The self-inflicted means of injury with high fatality rates were similar during the two periods. The rate of physical complications significantly increased during the pandemic, while the proportion of unemployed individuals significantly decreased. CONCLUSIONS: Despite studies predicting an increase in suicides based on past statistics of young people and of women, no significant changes were observed in this survey of the Hanshin-Awaji region, including Kobe. This may have been owing to the effect of suicide prevention measures and mental health measures implemented by the Japanese government after an increase in suicides and after past natural disasters.

Remorse-related suicide attempts among young mothers after COVID-19 infection.

Background: In Japan, there is a tendency to view COVID-19 infection as one's own responsibility, which may result in more feelings of guilt than in other countries. During the COVID-19 pandemic, the curfew imposed by COVID-19 restricted social behavior and increased anxiety and loneliness, which may have increased the risk of suicide among young women, especially mothers who were highly stressed regarding COVID-19 infection in their children. Case Presentation: This is a case report of two Japanese mothers who developed feelings of guilt following infection with COVID-19, leading to suicide attempts. They feared stigma or denial due to the infection, which they were unable to explain to others, leading to a heightened sense of self-blame and suicide attempts. In addition, Japanese women have a heavy burden of housework, despite their dual roles at home and at work; the pandemic's behavioral restrictions led to increased time at home and stress. These women were also more affected by the economic crisis in the early stages of the pandemic than men. Relatedly, neuropsychiatric symptoms that persisted after recovering from COVID-19, such as depression, anxiety, fatigue, and pain, namely postacute COVID-19 syndrome or long COVID, may have precipitated the suicidal ideation in these cases. Moreover, the complication of bipolar disorder by COVID-19 could have led to suicide attempts caused by infection-related neuropsychiatric symptoms and the exacerbation of the bipolar disorder by restrictions imposed during the pandemic. Conclusion: Suicide prevention measures need to be taken more seriously among mothers during or after the COVID-19 pandemic.

Novel Methanobacterium Strain Induces Severe Corrosion by Retrieving Electrons from Fe0 under a Freshwater Environment.

Methanogens capable of accepting electrons from Fe0 cause severe corrosion in anoxic conditions. In previous studies, all iron-corrosive methanogenic isolates were obtained from marine environments. However, the presence of methanogens with corrosion ability using Fe0 as an electron donor and their contribution to corrosion in freshwater systems is unknown. Therefore, to understand the role of methanogens in corrosion under anoxic conditions in a freshwater environment, we investigated the corrosion activities of methanogens in samples collected from groundwater and rivers. We enriched microorganisms that can grow with CO2/NaHCO3 and Fe0 as the sole carbon source and electron donor, respectively, in ground freshwater. Methanobacterium sp. TO1, which induces iron corrosion, was isolated from freshwater. Electrochemical analysis revealed that strain TO1 can uptake electrons from the cathode at lower than -0.61 V vs SHE and has a redox-active component with electrochemical potential different from those of other previously reported methanogens with extracellular electron transfer ability. This study indicated the corrosion risk by methanogens capable of taking up electrons from Fe0 in anoxic freshwater environments and the necessity of understanding the corrosion mechanism to contribute to risk diagnosis.

Psychological impact of the COVID-19 pandemic on hospital workers in Kobe: A cross-sectional survey.

Aim: Many health-care workers exposed to coronavirus disease 2019 (COVID-19) are psychologically distressed. This study aimed to investigate the psychological impact of the COVID-19 pandemic on hospital workers under the emergency declaration in Japan. Methods: This cross-sectional, survey-based study collected sociodemographic data and responses to 19 stress-related questions and the Impact of Event Scale-Revised (IES-R), which measures post-traumatic stress disorder (PTSD) symptoms, from all 3217 staff members at Kobe City Medical Center General Hospital from April 16, 2020 to June 8, 2020. Exploratory factor analysis was applied to the 19 stress-related questions. Multiple regression models were used to evaluate the association of personal characteristics with each score of the four factors and the IES-R. Results: We received 951 valid responses; 640 of these were by females, and 311 were by respondents aged in their 20s. Nurses accounted for the largest percentage of the job category. Women, those aged in their 30s-50s, nurses, and frontline workers had a high risk of experiencing stress. The prevalence of stress (IES-R ≥ 25) was 16.7%. The psychological impact was significantly greater for those aged in their 30s-50s and those who were not medical doctors. Conclusions: This is the first study to examine the stress of hospital workers, as measured by the IES-R, under the emergency declaration in Japan. It showed that women, those aged in their 30s-50s, nurses, and frontline workers have a high risk of experiencing stress. Health and medical institutions should pay particular attention to the physical and psychological health of these staff members.

Association study of gender identity disorder and sex hormone-related genes.

To investigate the biological mechanism of gender identity disorder (GID), five candidate sex hormone-related genes, encoding androgen receptor (AR), estrogen receptors alpha (ERalpha) and beta (ERbeta), aromatase (CYP19), and progesterone receptor (PGR) were analyzed by a case-control association study. Subjects were 242 transsexuals (74 male-to-female patients (MTF) and 168 female-to-male patients (FTM)), and 275 healthy age- and geographical origin-matched controls (106 males and 169 females). The distributions of CAG repeat numbers in exon 1 of AR, TA repeat numbers in the promoter region of ERalpha, CA repeat numbers in intron 5 of ERbeta, TTTA repeat numbers in intron 4 of CYP19, and six polymorphisms (rs2008112, rs508653, V660L, H770H, rs572698 and PROGINS) of PGR were analyzed. No significant difference in allelic or genotypic distribution of any gene examined was found between MTFs and control males or between FTMs and control females. The present findings do not provide any evidence that genetic variants of sex hormone-related genes confer individual susceptibility to MTF or FTM transsexualism.

Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence.

Because methamphetamine (METH) is metabolized by CYP2D6 at the first step of hydroxylation and demethylation, it is possible that functional variants of CYP2D6 alter susceptibility to methamphetamine-induced dependence. We genotyped CYP2D6*1, *4, *5, *10, and *14 for 202 patients with METH dependence and 337 controls in a Japanese population and found a significant association of the CYP2D6 gene with METH dependence (p=0.0299). The patients had fewer *10 and *14 alleles, which are hypofunction alleles, than the controls. CYP2D6 genotypes were divided into three phenotypes: extensive metabolizers, intermediate metabolizers, and poor metabolizers. There was no poor metabolizer among our Japanese subjects, and intermediate metabolizers of CYP2D6 were significantly fewer in methamphetamine-dependent subjects than in controls (p=0.0212), with an odds ratio of 0.62 (95% confidence interval: 0.51-0.76). The present study demonstrated that reduced CYP2D6 activity was a negative risk factor for methamphetamine dependence.

A genetic variant of the serine racemase gene is associated with schizophrenia.

BACKGROUND: Serine racemase (SRR) is a brain-enriched enzyme that converts L-serine to D-serine, which acts as an endogenous ligand of N-methyl D-aspartate (NMDA) receptors. Dysfunction of SRR may reduce the function of NMDA receptors and susceptibility to schizophrenia. METHODS: We genotyped three single-nucleotide polymorphisms (SNPs) of the 5' region of the SRR gene in 525 patients with schizophrenia and 524 healthy controls. Effects of SNPs on the promoter activity and on serum levels of total and D-serine were examined. RESULTS: We found a significant excess of the IVS1a+465C allele of the SRR gene in schizophrenia, especially in the paranoid subtype (p = .0028). A reporter assay showed that the IVS1a+465C allele had 60% lower promoter activity than did the IVS1a+465G allele. CONCLUSIONS: The IVS1a+465C allele of the SRR gene, which reduces expression of the gene, is a risk factor for schizophrenia, especially the paranoid subtype.

Genetic variant of prodynorphin gene is risk factor for methamphetamine dependence.

Previous studies have indicated that genetic factors substantially affect development of substance use disorders, including methamphetamine dependence. Prodynorphin (PDYN) is an opioid peptide precursor that yields dynorphins, endogenous kappa opioid-receptor agonists that play important roles in substance abuse. A physiologically active polymorphism of 1-4 repeats of a 68-bp element in the promoter region of the PDYN gene has been identified. We analyzed this polymorphism of the PDYN gene by a case-control association study in 143 patients with methamphetamine dependence and 209 healthy controls in the Japanese population. A 3- or 4-repeat allele in the PDYN gene promoter was found significantly more frequently in patients with methamphetamine dependence than in controls (chi(2)=9.45, p=0.0021). A 3- or 4-repeat allele in the PDYN gene promoter, which was shown to produce significantly higher transcription activity of the PDYN gene than a 1- or 2-repeat allele, is a genetic risk factor for development of methamphetamine dependence (odds ratio: 1.83, 95% CI=1.24-2.68).

The ZDHHC8 gene did not associate with bipolar disorder or schizophrenia.

The zinc finger and DHHC domain-containing protein 8 (ZDHHC8) gene is located on chromosome 22q11, which several genome scans have provided repeated evidence for a significant linkage with bipolar disorder (BPD) and schizophrenia. A recent study revealed that a single nucleotide polymorphism (SNP), rs175174, which has potential effects on splicing, in intron 4 of the ZDHHC8 gene is associated with susceptibility to patients with schizophrenia in US and South Africa. We examined three SNPs of the ZDHHC8 gene, including rs175174, by case-control association in Japanese patients with BPD (N=172) and controls (N=298) or patients with schizophrenia (N=407) and controls (N=497). No significant association with BPD or schizophrenia was observed. After stratification by subcategories, bipolar I and II of BPD, and paranoid and disorganized types of schizophrenia, no significant association was found, nor was a significant association with either disorder found after dividing by gender. These data suggest that the ZDHHC8 gene may not be associated with susceptibility to BPD or schizophrenia, at least in a Japanese population.

The X-box binding protein 1 (XBP1) gene is not associated with methamphetamine dependence.

Bipolar disorder has known as a high risk factor for substance abuse and dependence such as alcohol and illegal drugs. Recently, Kakiuchi et al. reported that the -116C/G polymorphism in the promoter region of the X-box binding protein 1 (XBP-1) gene, which translates a transcription factor specific for endoplasmic reticulum stress caused by misfolded proteins, was associated with bipolar disorders and schizophrenia in a Japanese population. Abuse of methamphetamine often produces affective disorders such as manic state, depressive state, and psychosis resembling paranoid-type schizophrenia. To clarify a possible involvement of XBP-1 in the etiology of methamphetamine dependence, we examined the genetic association of the -116C/G polymorphism of the XBP-1 gene by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism either with methamphetamine dependence or any clinical phenotype of dependence. Because the polymorphism is located in the promoter region of the XBP-1 gene and affects transcription activity of the gene, it is unlikely that dysfunction of XBP-1 may induces susceptibility to methamphetamine dependence.

The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder.

Several genetic studies have revealed that bipolar disorders are linked with the chromosomal locus of 15q11-q13, where the gamma-aminobutyric acid (GABA) receptor alpha5 subunit gene (GABRA5) locates. GABA is one of the major neurotransmitters that may be involved in the pathogenesis of bipolar disorder. Five polymorphisms in the GABRA5 gene, -754C>T in the promoter region, IVS1-21G>A, IVS2-26T>A, (*)302C>T in 3'-UTR of exon 5, and a CA repeat polymorphism in the 3' flanking region were examined in a Japanese population. IVS1-21G>A exhibited significant differences in the distribution of the genotype and allele frequency in bipolar I disorder patients but not in bipolar II disorder patients, compared with control subjects. The haplotype analysis showed that IVS1-21G>A/IVS2-26A>T was associated with bipolar I disorder, and the IVS1-21A/IVS2-26T haplotype was a negative risk factor for susceptibility to the disorders (odds ratio: 0.57, 95% confidence interval: 0.44-0.73). These results suggest that the GABRA5 gene may confer susceptibility to bipolar I disorder.