Yoshihiko Nakagi

A Novel Role of the NRF2 Transcription Factor in the Regulation of Arsenite-Mediated Keratin 16 Gene Expression in Human Keratinocytes

Background Inorganic sodium arsenite (iAs) is a ubiquitous environmental contaminant and is associated with an increased risk of skin hyperkeratosis and cancer. Objectives We investigated the molecular mechanisms underlying the regulation of the keratin 16 (K16) gene by iAs in the human keratinocyte cell line HaCaT. Methods We performed reverse transcriptase polymerase chain reaction, luciferase assays, Western blots, and electrophoretic mobility shift assays to determine the transcriptional regulation of the K16 gene by iAs. We used gene overexpression approaches to elucidate the nuclear factor erythroid-derived 2 related factor 2 (NRF2) involved in the K16 induction. Results iAs induced the mRNA and protein expression of K16. We also found that the expression of K16 was transcriptionally induced by iAs through activator protein-1–like sites and an antioxidant response element (ARE) in its gene promoter region. Treatment with iAs also enhanced the production and translocation of the NRF2 transcription factor, an ARE-binding protein, into the nucleus without modification of its mRNA expression. In addition, iAs elongated the half-life of the NRF2 protein. When overexpressed in HaCaT cells, NRF2 was also directly involved in not only the up-regulation of the detoxification gene thioredoxin but also K16 gene expression. Conclusions Our data clearly indicate that the K16 gene is a novel target of NRF2. Furthermore, our findings also suggest that NRF2 has opposing roles in the cell—in the activation of detoxification pathways and in promoting the development of skin disorders.

Relation of dampness to sick building syndrome in Japanese public apartment houses

ObjectivesThe effect of dampness on sick building syndrome (SBS) symptoms has not been fully investigated in Japan. The purpose of this study is to elucidate the possible effects of dampness on SBS symptoms among residents in Japanese public apartment houses.MethodsA questionnaire was used to investigate the degree of dampness in public apartment houses in Asahikawa, Japan, and its effect on SBS symptoms, involving 480 residents in 64 buildings. Dampness indicators were as follows: condensation on the windowpanes, condensation on the walls and/or closets, visible mold in the bathrooms, visible mold on the walls, window frames, and/or closet, moldy odor, slow drying of the wet towels in bathrooms, water leakage, and bad drainage in bathrooms. ResultsAll dampness indicators except for visible mold in bathrooms had significantly higher odds ratios (ORs) for all or any SBS symptoms after adjustment. The dampness index, the number of positive dampness indicators, was significantly related to all SBS symptoms after adjustment.ConclusionsThere are serious problems relating to dampness in Japanese public housing, which affects the health of residents. There is a need to educate the residents about the relationship between dampness and SBS, and building problems should be rectified.

Dampness, food habits, and sick building syndrome symptoms in elementary school pupils

ObjectivesWe investigated dampness/mold in schools and dwellings, and food habits and subjective symptoms in elementary school pupils, in order to clarify the effect of dampness and food habits on subjective symptoms in elementary school pupils.MethodsQuestionnaires were used to investigate dampness in classrooms and dwellings in Hokkaido, Japan, and its effect on subjective symptoms in 1,077 pupils in 8 elementary schools. We used a dampness index for both the home and classroom; the index was the sum of the presence of four dampness indicators: (1) visible mold, (2) moldy odor, (3) water leakage, and (4) condensation on windowpanes. The questionnaire also contained queries about food habits, as follows: the frequency of eating breakfast, whether the energy provided by the school lunch was sufficient, and whether eating too many snacks and/or sweets were consumed. Adjusted logistic regression was used to determine whether dampness and food habits were related to the subjective symptoms.ResultsIn fully adjusted models, the home dampness index was significantly related to cough, general symptoms, and having at least one symptom; the classroom dampness index was significantly related to nasal symptoms. In addition, usually not eating breakfast was significantly related to eye symptoms, and too many snacks and/or sweets was significantly related to eye, nasal, and general symptoms.ConclusionsBoth home and classroom dampness can affect pupils’ health. Home dampness, in particular, was significantly related to cough and general symptoms, and classroom dampness was significantly related to nasal symptoms. Furthermore, favorable food habits have a positive effect on pupils’ subjective symptoms.

Job stress and burnout among urban and rural hospital physicians in Japan

OBJECTIVE To elucidate the differences in job stress and burnout status of Japanese hospital physicians between large cities, small cities, and towns and villages. DESIGN Cross-sectional study. SETTING Postal self-administered questionnaires were distributed to 2937 alumni of Asahikawa Medical University. PARTICIPANTS Four hundred and twenty-two hospital physicians. MAIN OUTCOME MEASURES The Brief Job Stress Questionnaire was used to evaluate job demand, job control and social support. The Japanese version of the Maslach Burnout Inventory-General Survey (MBI-GS) was used to evaluate burnout. An analysis of covariance was conducted on the mean scores on the Brief Job Stress Questionnaire and the MBI-GS scales after adjusting for sex, age and specialties. RESULTS In adjusted analyses, the job demand score was significantly different among physicians in the three areas. In Bonferroni post-hoc tests, scores in large cities was significantly higher than those in small cities and towns and villages. The job control score showed a significant difference and a marginally significant trend, with large cities associated with lower job control. There were significant differences in support from supervisors and that from family/friends, and scores in large cities was significantly higher than those in small cities in the post-hoc test. There was a significant effect on the exhaustion scale of the MBI-GS, with large cities associated with higher exhaustion, and scores in large cities was significantly higher than those in small cities. CONCLUSIONS Urban hospital physicians had more job demand, less job control and exhaustion caused by burnout, and rural hospital physicians had less social support.

Prevalence of Burnout among Public Health Nurses in Charge of Mental Health Services and Emergency Care Systems in Japan

ObjectivesThe Community Health Act came into effect in 1997 in Japan. This act altered the work system for public health nurses (PHNs) in public health centers (PHCs) nationwide from region-specific to service-specific work. Such major changes to working environment in the new system seem to be exposing PHNs to various types of stress. The present study examined whether prevalence of burnout is higher among PHNs in charge of mental health services (psychiatric PHNs) than among PHNs in charge of other services (non-psychiatric PHNs), and whether attributes of emergency mental health care systems in communities are associated with increased prevalence of burnout.MethodsA questionnaire including the Pines burnout scale for measuring burnout was mailed to 525 psychiatric PHNs and 525 non-psychiatric PHNs. The 785 respondents included in the final analysis comprised 396 psychiatric PHNs and 389 non-psychiatric PHNs.ResultsPrevalence of burnout was significantly higher for psychiatric PHNs (59.2%) than for non-psychiatric PHNs (51.5%). When prevalence of burnout in each group was analyzed in relation to question responses regarding emergency service and patient referral systems, prevalence of burnout for psychiatric PHNs displayed significant correlations to frequency of cases requiring overtime emergency services, difficulties referring patients, and a feeling of “restriction”.ConclusionsPrevalence of burnout is high among psychiatric PHNs, and inadequate emergency mental health service systems contribute to burnout among these nurses. Countermeasures for preventing such burnout should be taken as soon as possible.

Effects of work burden, job strain and support on depressive symptoms and burnout among Japanese physicians

ObjectivesDays off, on call, night duty, working hours and job stress can affect physicians’ mental health, and support from supervisors and co-workers may have a buffering effect. This study elucidates whether job strain and job factors affect physicians’ mental health, and whether support from supervisors and co-workers has a protective effect on their mental health.Material and MethodsThe subjects included 494 physicians. The Brief Job Stress Questionnaire (BJSQ) was used to evaluate job demand, job control and support. High job strain was defined as a combination of high job demand and low job control. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The Maslach Burnout Inventory-General Survey was used to evaluate burnout. Possible confounder adjusted logistic regression analyses were performed to obtain odds ratios for depressive symptoms and burnout.ResultsAs per the analysis, high job strain had significantly higher odds ratios, and support from co-workers had significant protective odds ratios for depressive symptoms. High job strain and having only 2–4 days off per month (compared to > 8 days off per month) had significantly higher odds ratios, and support from co-workers had significant protective odds ratios for burnout.ConclusionsHigh job strain was related to depressive symptoms and burnout, and support from co-workers had a buffering effect on depressive symptoms and burnout. An inadequate number of days off was related to burnout. Assessment of job strain may be a good tool to measure physicians’ mental health, and a sufficient number of days off may be needed to prevent burnout.

Relationships of job demand, job control, and social support on intention to leave and depressive symptoms in Japanese nurses

This study aims to elucidate the relationships among the factors of the demand-control-support model (DCS) on the intention to leave a hospital job and depressive symptoms. Participants included 1,063 nurses. Job demand, job control, and support from supervisors were found to be significantly related to both the intention to leave and depressive symptoms. Based on the odds ratios per 1 SD change in the DCS factors, low support from supervisors was found to be most related to the intention to leave, and low job control was found to be most related to depressive symptoms. In models that did not include “job demand” as an independent variable, 60-h working weeks were found to have a significantly higher odds ratio for depressive symptoms. Support from supervisors is more important in preventing intention to leave and depressive symptoms among nurses than is support from co-workers. Improving job control and avoiding long working hours may be important to prevent depressive symptoms.

Social support and its interrelationships with demand–control model factors on presenteeism and absenteeism in Japanese civil servants

ObjectivesTo elucidate the impact of social support and its interrelations with other demand–control–support (DCS) model factors on presenteeism and absenteeism, and to determine which DCS factors were most influential.MethodsQuestionnaires from 2535 local government employees were analyzed. The Brief Job Stress Questionnaire (BJSQ) was used to assess DCS factors including job demand, job control, and social support from supervisors and coworkers. The Stanford Presenteeism Scale 13-item version (SPS-13) was used to evaluate both absenteeism (absent days) and presenteeism. For the latter, the Work Impairment Score (WIS) and the Work Output Score (WOS) were also used. Possible confounder-adjusted logistic and negative binomial regression analyses were performed to obtain odds ratios (ORs) for WIS and WOS and relative risks (RRs) for absenteeism according to DCS factors.ResultsHigher job control had a significantly protective effect on higher WIS in both males and females and a lower WOS in males. Based on a point estimate of an OR per 1 standard deviation change of each DCS factor, job control had the strongest effect on higher WIS in both males and females and a lower WOS in males. Higher job demand resulted in significantly higher ORs for both male and female WIS, and a lower WOS in females. Support from supervisors had a significantly protective effect on higher WIS in females and a lower WOS in males. Support from coworkers had a significantly protective effect on higher WIS in males. Higher support from coworkers had a significantly protective effect on absenteeism among both males and females, and higher job control had a significantly protective effect in females. The combination of high job strain and low support from supervisors had a significantly worsening effect, except for absenteeism in females. High job strain and low support from coworkers had a significantly worsening effect except for WOS in males.ConclusionsThe results suggest job control was the DCS factor most related to presenteeism. Higher support from supervisors and coworkers had a protective effect on presenteeism, and higher job demand had a worsening effect. Higher support from coworkers had a protective effect on absenteeism among both males and females. Interventions should focus on improving job control as a possible countermeasure to presenteeism, and encouraging support from coworkers as a possible countermeasure to absenteeism.

Comparative study of simple semiquantitative dust mite allergen tests.

ObjectiveTwo simple, commercially available and semiquantitative dust mite allergen tests, namely, the Acarex test® and Mitey Checker®, were compared using 2 and 10 μg of Der 1 allergen per gram of dust, as evaluated by enzyme-linked immunosorbent assay (ELISA), to clarify which method is better suited for practical use.MethodsMite allergen exposure levels of 106 floor, bed and sofa surfaces were evaluated by the Acarex test®, Mitey Checker®, and ELISA. A template of 100 cm×100cm was placed on the same surfaces to identify the examined areas. A dust collection filter was attached to a vacuum cleaner, and the area in the template (1 m2) was vacuumed. Then, to evaluate the other two tests, samples from the two other areas in the template (1 m2) that neighbored each other and did not overlap were vacuumed.ResultsTo predict Der 1 levels of 2 μg/g dust or higher, the sensitivity and specificity of the Acarex test® were 100% and 13.3%, and those, of Mitey Checker® were 91.8% and 71.1%, respectively. To predict Der 1 levels of 10 μg/g dust or higher, the sensitivity and specificity of the Acarex test® were 50.0% and 96.2%, and those of Mitey Checker® were 85.7% and 79.5%, respectively. Compared with Der 1<2.0, 2.0–9.9.≥10.0 (μg/g dust), the percent agreement and kappa of the Acarex test® were 47.2% and 0.234, and those of Mitey Checker® were 70.0% and 0.505, respectively.ConclusionTo evaluate mite allergen exposure level for practical use in Japanese living environments, Mitey Checker® is better than the Acarex test® because of its higher sensitivity and specificity.

Association of premorbid personality with behavioral and psychological symptoms in dementia with Lewy bodies: Comparison with Alzheimer's disease patients

The aim of this study was to elucidate the relation between premorbid personality traits and behavioral and psychological symptoms in dementia (BPSD) in dementia with Lewy bodies (DLB) and Alzheimers disease (AD) patients.