Benefits of group compassion-focused therapy for treatment-resistant depression: A pilot randomized controlled trial.

Major depression is one of the most common mental health problems worldwide. More than one-third of patients suffer from treatment-resistant depression (TRD). In this study, we explored the feasibility of group compassion-focused therapy (CFT) for TRD using a randomized controlled trial with two parallel groups. Eighteen participants were randomly allocated to the intervention group (CFT and usual care) and control group (usual care alone) and a participant in each group withdrew. Participants in the intervention group received a 1.5-h session every week for 12 weeks. The effects of the intervention on the participants' scores were calculated using a linear mixed model. There was a larger reduction in their depressive symptoms and fears of compassion for self and a greater increase in their compassion for self compared to the control group participants. The reliable clinical indices showed that in the CFT (intervention) group, three of nine participants recovered (33%), two improved (22%), two recovered but non-reliably (22%), and the condition of two remained unchanged (22%). These findings indicate adequate feasibility of group CFT for TRD in Japanese clinical settings. Clinical trial registration: [https://clinicaltrials.gov/], identifier [UMIN 000028698].

Study profile: protocol outline and study perspectives of the cohort by the National Institute of Occupational Safety and Health, Japan (JNIOSH cohort).

How work burden affects physical and mental health has already been studied extensively; however, many issues have remained unexamined. In 2017, we commenced a prospective cohort study of workers at companies in Japan, with a follow-up period of 5-10 years, in order to investigate the current situation of overwork-related health outcomes. From 2017 to 2020, a target population of 150,000 workers across 8 companies was identified. Of these, almost 40,000 workers agreed to participate in the baseline survey. Data on working hours, medical check-up measurements, occupational stress levels, and lifestyle habits were collected. The average age of the participants at baseline was 39.2 ± 11.7 years; 73.1% were men, and 87.7% were regular employees. The most common working hours by self-reported was 41-50 hours per week during normal season, and it increased to more than 50 hours during busy season. Furthermore, more than half of the participants reportedly experienced a form of sleep problem, and the percentage of those who experienced nonrestorative sleep was particularly high.

Work e-mail after hours and off-job duration and their association with psychological detachment, actigraphic sleep, and saliva cortisol: A 1-month observational study for information technology employees.

OBJECTIVE: A sufficient duration of time off after work is necessary to ensure workers' health. Better quality of off-job time can also facilitate recovery from fatigue, but its quantitative influence is largely unknown. We aimed to examine how off-job time quality (as measured by the frequency of emailing after work), and off-job duration is associated with psychological detachment, actigraphic sleep, and saliva cortisol using a 1-month observational study. METHODS: The participants were 58 daytime employees working at an information technology company. Sleep actigraphy and saliva cortisol as well as self-reported outcomes were repeatedly measured for 1 month. Two-way (work e-mail frequency × off-job time) multilevel mixed-effects linear regression analyses were performed in both continuous and categorical variables. RESULTS: The frequency of work e-mailing after hours was significantly associated with self-reported outcomes and actigraphic sleep quality, while a significant association was not found in cortisol awakening responses and actigraphic sleep duration. A significantly larger cortisol response after awakening was found in shorter, rather than longer, durations of off-job time. Self-reported detachment, rumination and carry-over fatigue showed significant interactions between work e-mail and off-job time, suggesting that worse outcomes were found in a higher frequency of work e-mail even when employees had longer amounts of off-job time. CONCLUSION: Our findings suggest that ensuring the quality and duration of off-job time is beneficial for recovery from work with sufficient sleep. Specifically, the frequency of e-mailing after work should be minimized to make recovery complete.

Objective and Subjective Working Hours and Their Roles on Workers' Health among Japanese Employees.

Table 3 of the above paper appeared incorrectly in print. Percentage figures on the table were inadvertently listed as negative values. These errors were corrected in online versions of this paper, as shown below.

[Effectiveness of Topical NSAIDs in a Gastric Cancer Patient with Bone Metastasis Pain during Therapy with Opioids and Oral NSAIDs].

Cancer patients often suffer from severe pain related to bone metastasis. We encountered a patient in whom the addition of topical non-steroidal anti-inflammatory drugs (NSAIDs) for persistent pain related to bone metastasis during therapy with opioids and oral NSAIDs reduced pain, improving activities of daily living (ADL). Fentanyl patches, celecoxib, denosumab, and topical NSAIDs (loxoprofen tape, felbinac) were administered to a 72-year-old patient with gastric cancer and pain related to bone metastasis. Pain control was favorable, with a numerical rating scale (NRS) score of 2 and Japanese version Support Team Assessment Schedule (STAS-J) score of 1. Intervention by pharmacists for the use of topical NSAIDs decreased both the NRS and STAS-J scores to zero, improving ADL. The results suggest that topical NSAIDs relieve bone-metastasis-related pain, improving ADL. When bone-metastasis-related pain is localized, the prescription of topical NSAIDs should be considered, and positive intervention by pharmacists regarding their usage should be promoted.

The development of the Japanese version of the compassionate engagement and action scales.

The last few years have seen increasing research on self-report measures of compassion. The Compassionate Engagement and Action Scale (CEAS) is rooted in an evolutionary approach to compassion, which focuses on the competencies of compassion those are engagement with distress or suffering, and taking action to alleviate and prevent it. This study sought to validate the CEAS in a Japanese population using a cross-sectional design. A total of 279 students (82 males, 191 females, 6 unknown) answered self-report questionnaires, including the Japanese version of CEAS. We found single-factor structures for compassion for others scales, compassion from others scales, and compassion for self scales. All scales were found to have acceptable internal consistency, test-retest reliability, content validity, and construct validity. Even though some limitations, these results indicate that the Japanese version of CEAS is an adequately constructed and useful measure to assess compassionate engagement and action toward others, from others, and for the self with Japanese population.

Construct validity and test-retest reliability of the World Mental Health Japan version of the World Health Organization Health and Work Performance Questionnaire Short Version: a preliminary study.

The aim of the study was to investigate test-retest reliability and construct validity of the World Mental Health Japan (WMHJ) version of World Health Organization Health and Performance Questionnaire (WHO-HPQ) short version according the COSMIN standard. We conducted two consecutive surveys of 102 full-time employees recruited through an Internet survey company in Japan, with a two-week interval in 2018. We calculated Pearson's correlation (r) of measures of the WHO-HPQ with other presenteeism scales (Stanford Presenteeism Scale, Work Functioning Impairment Scale, and perceived relative presenteeism), health and psychosocial job conditions. We tested the test-retest reliability (intraclass correlation, ICC) among those who reported no change of job performance during the follow-up. Among 92 (90%) respondents, the absolute presenteeism significantly correlated with WFun and perceived relative presenteeism (r=-0.341 and -0.343, respectively, p=0.001) and psychological distress (r=-0.247, p=0.018). The absolute/relative absenteeism did not significantly correlate with the other covariates. The test-retest reliability over a two-week period was high for the WHO-HPQ absolute presenteeism (ICC, 0.73), while those for absolute/relative absenteeism measures were moderate. The study found an adequate level of test-retest reliability, but limited support for the construct validity of the absolute presenteeism measure of the WMHJ version of the WHO-HPQ. Further research is needed to investigate the construct validity of the WHO-HPQ measures in a larger sample.

Objective and subjective working hours and their roles on workers' health among Japanese employees.

This study investigated the correlation between objective and subjective working hours (OWH and SWH, respectively) and their relation to the workers' health. The study included 6,806 workers of a Japanese company (response rate=86.6%). OWH were collected as the monthly data during fiscal year 2017 from the company record. SWH were self-reported as the weekly data during the past month in November 2017. Both OWH and SWH corresponded to the same period of one month (October 2017). Additionally, the data for the annual health checkup in fiscal year 2017 and self-reported mental health in November 2017 were collected. The results indicated that the longer OWH was related to more underestimation of SWH. The analyses of covariance adjusted for the selected variables showed that irrespective of OWH or SWH, significant relationships were found for stress responses but not for body mass index, aspartate and alanine aminotransferase, fasting blood glucose, hemoglobin A1c, high-density lipoprotein cholesterol, or triglyceride. However, significant relationships with only OWH were noted for systolic and diastolic blood pressure, low-density lipoprotein cholesterol, gamma-glutamyl transpeptidase, and positive work-related state of mind. The present findings show that SWH should be used carefully when assessing the health effects of long working hours.

Hair and fingernail cortisol and the onset of acute coronary syndrome in the middle-aged and elderly men.

Cortisol levels in hair and fingernail samples could represent hormone levels that have accumulated over the past weeks and months. In this study, by using retrospective indexes, the associations between cortisol and the onset of acute coronary syndrome (ACS) were investigated among middle-aged and elderly men. We measured hair/fingernail cortisol levels in 73 ACS patients and 93 healthy controls; hair and fingernail samples for ACS patients were collected within a few weeks after the onset of ACS. The results indicated the patients exhibited significantly higher cortisol levels in their hair and fingernails compared with the healthy controls. In multivariate logistic regression analyses, adjusting for the traditional cardiovascular risk factors for ACS, high levels of hair or fingernail cortisol were associated with two- to three-fold increased risk of ACS, compared with low levels. We demonstrated that cortisol exposure over a relatively long period, assessed by hair and fingernail samples, was associated with the onset of ACS.

Day-to-day variations in daily rest periods between working days and recovery from fatigue among information technology workers: One-month observational study using a fatigue app.

BACKGROUND: The European Union's Working Time Directive stipulates recovery periods as "Eleven consecutive hour daily rest periods (DRPs) between working days." In Japan, adopting this regulation has been discussed. OBJECTIVE: To examine the association between weekday DRPs and recovery from fatigue by conducting a one-month observational study using a fatigue monitoring application (fatigue app) on a smart tablet. METHODS: Fifty-five daytime employees working at an information technology company participated in this study. Visual analogue scales (VAS) regarding fatigue, psychological detachment from work, a psychomotor vigilance task (PVT), and sleep-wake logs were repeatedly measured using a fatigue app that we developed for this study. Sleep was measured by a wrist actigraph. RESULTS: The average and SD of weekday DRPs was 13.1 ± 2.3 h. However, 54.5% of employees experienced less than the minimum 11-hour DRP at least once a month. Sleep duration was significantly changed with weekday DRPs, though no significant difference was found in sleep efficiency. Linear mixed effects models showed that sleep duration increased by approximately 15 minutes for each hour of weekday DRPs (ß = 0.24, 95% CI; 0.17, 0.32, p <.001). VAS-measured fatigue and psychological detachment from work significantly improved as DRPs increased (ß = -3.4, 95% CI; -4.7, -2.1, p <.001; ß = 2.6, 95% CI; 1.2, 4.0, p <.001, respectively). However, PVT performance did not significantly change with weekday DRPs. CONCLUSIONS: Ensuring weekday DRPs plays an essential role in protecting the opportunities to sleep, with better recovery from fatigue and stress among information technology workers.

DNA damage response induced by Etoposide promotes steroidogenesis via GADD45A in cultured adrenal cells.

Glucocorticoid production is regulated by adrenocorticotropic hormone (ACTH) via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway in the adrenal cortex, but the changes in steroidogenesis associated with aging are unknown. In this study, we show that cell-autonomous steroidogenesis is induced by non-ACTH- mediated genotoxic stress in human adrenocortical H295R cells. Low-dose etoposide (EP) was used to induce DNA damage as a genotoxic stress, leading to cellular senescence. We found that steroidogenesis was promoted in cells stained with γH2AX, a marker of DNA damaged cells. Among stress-associated and p53-inducible genes, the expression of GADD45A and steroidogenesis-related genes was significantly upregulated. Immunofluorescence analysis revealed that GADD45A accumulated in the nuclei. Metabolite assay using cultured media showed that EP-treated cells were induced to produce and secrete considerable amounts of glucocorticoid. Knockdown of GADD45A using small interfering RNA markedly inhibited the EP-induced upregulation of steroidogenesis-related gene expression, and glucocorticoid production. A p38MAPK inhibitor, but not a PKA inhibitor, suppressed EP-stimulated steroidogenesis. These results suggest that DNA damage itself promotes steroidogenesis via one or more unprecedented non-ACTH-mediated pathway. Specifically, GADD45A plays a crucial role in the steroidogenic processes triggered by EP-stimulated genotoxic stress. Our study sheds new light on an alternate mechanism of steroidogenesis in the adrenal cortex.

Coordination-Mediated Synthesis of Purification-Free Bivalent 99mTc-Labeled Probes for in Vivo Imaging of Saturable System.

In the synthesis of technetium-99m (99mTc) labeled target-specific ligands, the presence of a large excess of unlabeled ligands over 99mTc in the injectate hinders target accumulation of 99mTc-labeled ligands by competing for target molecules. To circumvent the problem, we recently developed a concept of the metal coordination-mediated multivalency, and proved the concept with a 99mTc-labeled trivalent compound [99mTc(CO)3(CN-RGD)3]+. In this study, D-penicillamine (Pen) was selected as a chelating molecule and a cyclic RGDfK peptide was conjugated to Pen via a hexanoic linkage (Pen-Ahx-c(RGDfK)). 99mTc complexation reaction, and the stability, integrin αvß3 binding affinity, and biodistribution of the 99mTc-labeled probe were investigated to evaluate the applicability of the concept to bivalent probes. 99mTc-[Pen-Ahx-c(RGDfK)]2 was obtained over 95% radiochemical yields under low Pen-Ahx-c(RGDfK) concentration (50 µM). 99mTc-[Pen-Ahx-c(RGDfK)]2 showed approximately 10-times higher integrin αvß3 binding affinity than the monovalent compounds, Pen-Ahx-c(RGDfK) and c(RGDyV). In biodistribution studies, the tumor accumulation of 99mTc-[Pen-Ahx-c(RGDfK)]2 was decreased to 77% and 43% of HPLC-purified (Pen-Ahx-c(RGDfK)-free) 99mTc-[Pen-Ahx-c(RGDfK)]2 by the presence of 5 nmol of unlabeled Pen-Ahx-c(RGDfK) and Re-[Pen-Ahx-c(RGDfK)]2, respectively. 99mTc-[Pen-Ahx-c(RGDfK)]2 provided tumor image without removing unlabeled ligand, while a 99mTc-labeled monovalent probe prepared from a monovalent ligand could not. These findings indicate the availability of the design concept to prepare 99mTc-labeled bivalent probes with a variety of 99mTc core and other metallic radionuclides of clinical relevance.

Examination of validity of a conditioned odor aversion (COA) procedure using low-dose of organic solvent as an applied procedure of the conditioned taste aversion.

Smell of very low dose of chemical might evoke subjective physical symptoms in human by some process of learning named the aversion conditioning. But few scientific evidences of the hypothesis have been reported so far. Validity of conditioned odor aversion (COA) using low-doses of organic solvent as odor conditioned stimulus (CS) was examined. In conditioning phase, water-deprived male Sprague-Dawley rats were presented low, medium or high dose solution for 30 min followed by 0.3 M Lithium Chloride (LiCl) solution or saline injection. The xylene solution and drink water were simultaneously provided on the next day as two-bottle test. Consumption of medium dose of xylene solution was significantly decreased in LiCl injection group as compared with saline group. There was no difference between LiCl and saline injected animals in low group. Animals in high dose did not access to xylene even on the conditioning. These results indicate that animals showed high sensitivity for discrimination against concentration of xylene and that the medium dose of xylene functioned as the CS. We concluded that the COA used in the present study may be one of useful procedures to investigate olfaction of animal.

The development of fears of compassion scale Japanese version.

OBJECTIVES: Cultivation of compassion is a useful way to treat mental problems, but some individuals show resistance. Fears of compassion can be an obstacle for clinicians when providing psychotherapy, and for clients when engaging in interpersonal relationships. Despite its importance, a Japanese version of fears of compassion scales (for others, from others, and for self) has not yet been developed. This study developed a Japanese version of the Fears of Compassion Scales and tested its reliability and validity. DESIGN: This study used a cross-sectional design, and a self-report procedure for collecting data. METHODS: A total of 485 students (121 males and 364 females) answered self-report questionnaires, including the draft Fears of Compassion Scales-Japanese version. RESULTS: There were distinctive factor structures for fear of compassion from others, and for self. The fear of compassion from others scale consisted of concern about compassion from others and avoidance of compassion from others. All scales had good internal consistency, test-retest reliability, face validity, and construct validity. Discrimination and difficulty were also calculated. CONCLUSIONS: These results indicate that the Fears of Compassion Scales-Japanese version is a well-constructed and useful measure to assess fears of compassion and the existence of cultural differences in fears of compassion.

Psychosocial correlates of cortisol levels in fingernails among middle-aged workers.

It was recently suggested that cortisol levels in fingernails reflect cumulative hormone exposure over a relatively long period. This exploratory study cross-sectionally investigated the relationships between fingernail cortisol level and psychosocial stress in a sample of middle-aged workers (94 men and 29 women). The participants were asked to grow their fingernails for ∼2 weeks and then provide fingernail samples from every digit by using nail clippers. Further, they completed questionnaires for assessment of exposure to psychosocial stress in the past (stressful life events in the workplace in the previous year; e.g. change to a different line of work) and in the present (job stress and perceived stress). Results of a regression analysis adjusting for the effects of demographic variables showed that experience of stressful life events, but not job stress and perceived stress, was associated with elevated fingernail cortisol level. These findings indicate the potential of fingernail samples to retrospectively reflect individual differences in cortisol levels related to past psychosocial stress.

Impact of Daily Rest Period on Resting Blood Pressure and Fatigue: A One-Month Observational Study of Daytime Employees.

OBJECTIVE: We aimed to examine the effects of the daily rest period (DRP) on resting blood pressure (BP) and fatigue and determine the optimal DRP for daytime workers. METHODS: Fifty-four daytime employees participated in a 1-month observational study. BP was measured thrice at the workplace. Employees underwent a pre- and post-survey to determine the usual DRP and assess subjective health outcomes. To determine the optimal DRP, DRP criteria were set as 11, 12, 13, and 14 hours. RESULTS: Workers with a shorter DRP had high diastolic BP and fatigue. Diastolic BP was higher in the short group than in the long group for the 14-hour DRP criteria alone. CONCLUSIONS: Shorter DRP was associated with high diastolic BP. We recommend a longer DRP (≥14 hours) for improving workers' cardiovascular health.

Cross-sectional associations between daily rest periods during weekdays and psychological distress, non-restorative sleep, fatigue, and work performance among information technology workers.

A daily rest period (DRP; rest taken from daily work during a 24 h period), is essential to work recovery. This study examined DRPs' distribution and association with health outcomes among information technology workers recruited from an internet panel (N=1,811). Participants completed a web questionnaire examining psychological distress as a primary outcome, along with non-restorative sleep, fatigue (stress reaction), and work performance. Logistic regression analysis showed elevated psychological distress when DRP was <12 h (OR: 2.54; 95% CI: 1.47-4.42) and <11 h (OR: 2.48, 95% CI: 1.17-5.26), although the 95% CI included 1 after adjusting for age, sex, and working and commuting hours. After the above adjustment, similar associations were found with non-restorative sleep and fatigue, but not work performance, when DRP was <12 h. These findings constitute the first analysis of a dose-response relationship between DRP and subjective health outcomes among white-collar workers.

Effects of web-based stress and depression literacy intervention on improving work engagement among workers with low work engagement: An analysis of secondary outcome of a randomized controlled trial.

OBJECTIVE: The purpose of this randomized, controlled trial was to examine the effects of a psychoeducational information website on improving work engagement among individual workers with low work engagement, where work engagement was measured as a secondary outcome. METHODS: Participants were recruited from registered members of a web survey site in Japan. Participants who fulfilled the eligibility criteria were randomly allocated to intervention or control groups. Immediately after the baseline survey, the intervention group was invited to study a psychoeducational website called the "UTSMed," which provided general mental health literacy and cognitive behavioral skills. Work engagement was assessed by using the Utrecht Work Engagement Scale at baseline, 1-, and 4-month follow-ups for both intervention and control groups. An exploratory analysis was conducted for a subgroup with low (lower than the median scores) work engagement scores at baseline. RESULTS: A total of 1,236 workers completed the baseline survey. In the low work engagement subgroup, a total of 313 and 300 participants were allocated to an intervention and control group, respectively. In the high work engagement subgroup, 305 and 318 participants were allocated to an intervention and control group, respectively. The program showed a significant effect on work engagement (t = 1.98, P = 0.048) at the 4-month follow-up in the low work engagement subgroup, with a small effect size (d = 0.17). CONCLUSION: A web-based psychoeducation resource of mental health literacy and cognitive behavioral skills may be effective for improving work engagement among individual workers with low work engagement.

Effects of web-based stress and depression literacy intervention on improving symptoms and knowledge of depression among workers: A randomized controlled trial.

BACKGROUND: The present randomized controlled trial aimed to examine whether a newly developed psychoeducational information website on stress and depression was effective in improving depressive symptoms at one- and four-month follow-ups among workers in Japan. METHODS: Participants were recruited from registered members of a web survey site in Japan. Participants who fulfilled the eligibility criteria were randomly allocated to intervention or control groups. Immediately after the baseline survey, the intervention group was invited to access a psychoeducational website named the "UTSMed" within 4 months after the baseline survey. Depressive symptoms (Beck Depression Inventory II; BDI-II) were assessed as a primary outcome, at baseline, and one- and four-month follow-ups for both intervention and control groups. The analyses were conducted separately by the three subgroups (high-risk, moderate-risk, and low-risk). RESULTS: A total of 1236 workers completed the baseline survey. Participants were randomly allocated to an intervention or control group (N=618 for each), with the subgroups of high-risk (7-8%), moderate-risk (47%) and low-risk (45-46%) in each group. A significant intervention effect on improving depressive symptoms (t=-2.35, P =0.02, d=-0.57) was observed at 1-month follow-up only in the high-risk subgroup. LIMITATIONS: The present study did not use a stratified permuted-block randomization. CONCLUSIONS: A web-based psychoeducation approach may not be effective enough in improving depressive symptoms in a general population of workers, while it may be effective for workers who had recently sought help for mental health.

The Mechanism of False in Vitro Elevation of Uric Acid Level in Mouse Blood.

Thirty minutes incubation at room temperature elevates the uric acid (UA) level of mouse blood in a test tube, and has previously been reported as "false in vitro elevation of the uric acid level." However the UA level of human blood does not elevate using the same incubation. We clarified the mechanism of the false in vitro UA elevation using mice with highly active hypoxanthine phosphoribosyl transferase (Hprt) of B6-ChrXC(MSM), a consomic mouse strain with the chromosome portion of Mus musculus morocinus in the Hprt gene site, or mice with a targeted deletion of the urate oxidase gene (Uox) (Uox-knockout (KO)). The plasma levels of UA, hypoxanthine, and xanthine, determined by HPLC, were compared with those of C57BL/6J laboratory mice used as controls. The uric acid level of Uox-KO mice was approximately 10 times higher than that of control, did not elevated after incubation in the test tube. With allopurinol, the hypoxanthine levels of B6-ChrXC(MSM) and Uox-KO were significantly lower than that of controls. Without allopurinol, the UA and xanthine levels of B6-ChrXC(MSM) were significantly lower than those of C57BL/6J controls. Even with allopurinol, the UA and xanthine levels were still significantly lower than that of controls. In conclusion, "false in vitro elevation of uric acid level" seems to be caused by low levels of erythrocyte HPRT activity and the low plasma uric acid level of laboratory mice.