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Background: While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on when and how many of sickness absentees returned to work, became unemployed, or passed away., Methods: We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012-2013 among employees of 11 Japanese private companies (n = 1,209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis., Results: During the 3.5-year period (follow-up rate: 99.9%), 1,014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00-F99) to 95.3% for circulatory diseases (I00-I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00-D48), of which the cumulative incidence of death reached 14.2% by 1.5 years., Conclusion: Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.

Aims: We aimed to investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C) levels and the risk of cardiovascular disease (CVD) and its subtypes., Methods: In this contemporary cohort study, we analyzed the data of 63,814 Japanese employees aged ≥ 30 years, without known CVD in 2012 and who were followed up for up to 8 years. The non-HDL-C level was divided into 5 groups: ＜110, 110-129, 130-149, 150-169, and ≥ 170 mg/dL. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for CVD and its subtypes associated with each non-HDL-C group, considering 130-149 mg/dL as the reference group., Results: During the study period, 271 participants developed CVD, including 78 myocardial infarctions and 193 strokes (102 ischemic strokes, 89 hemorrhagic strokes, and 2 unknowns). A U-shaped association between non-HDL-C and stroke was observed. In the analysis of stroke subtypes, the multivariable-adjusted HR (95% CI) for hemorrhagic stroke was 2.61 (1.19-5.72), 2.02 (0.95-4.29), 2.10 (1.01-4.36), and 1.98 (0.96-4.08), while that for ischemic stroke was 1.54 (0.77-3.07), 0.91 (0.46-1.80), 0.73 (0.38-1.41), and 1.50 (0.87-2.56) in the ＜110, 110-129, 150-169, and ≥ 170 mg/dL groups, respectively. Individuals with elevated non-HDL-C levels had a higher risk of myocardial infarction., Conclusions: High non-HDL-C levels were associated with an increased risk of myocardial infarction. Moreover, high and low non-HDL-C levels were associated with a high risk of stroke and its subtypes among Japanese workers.

Purpose: To develop and validate a risk score assessable in real-time using only retinal thickness-related values measured by spectral domain optical coherence tomography alone for use in population-based glaucoma mass screenings., Methods: A total of 7572 participants (aged 35-74 years) underwent spectral domain optical coherence tomography examination annually between 2016 to 2021 in a population-based setting. We selected 284 glaucoma cases and 284 controls, matched by age and sex, from 11,487 scans in 2016. We conducted multivariable logistic regression with backward stepwise selection of retinal thickness-related variables to develop the diagnostic models. The developed risk scores were applied to all participants in 2018 (9720 eyes), and we randomly selected 723 scans for validation. Additional validation using the Humphrey field analyzer was conducted on 129 eyes in 2020. We assessed the models using sensitivity, specificity, the area under the receiver operating characteristic curve and positive and negative predictive values., Results: The best-predicting model achieved an area under the receiver operating characteristic curve of 0.97 (95% confidence interval, 0.96-0.98) with a sensitivity of 0.93 and specificity of 0.91. The validation dataset showed a positive predictive value of 90.8% for high-risk scorers, corresponding to 6.2% of the population, and negative predictive value of 88.2% for low-risk scorers, corresponding to 85.2%. Sensitivity and specificity for glaucoma diagnosis were 0.85 and 0.91, when we set the risk score cut-off at 90 points out of 100., Conclusions: This risk score could be used as a valid index for glaucoma screening in a population-based setting., Translational Relevance: The score is feasible by installing a simple computer application on an existing spectral domain optical coherence tomography and will help to improve the accuracy and efficiency of glaucoma screening.

Objectives: To investigate the association of diabetes and prediabetes with long-term sickness absence (LTSA) due to mental disorders or specific mental disorders., Methods: A prospective cohort study was conducted using data from the Japan Epidemiology Collaboration on Occupational Health Study. A total of 62,065 workers who received health check-ups in 2011 (nine companies) or 2014 (two companies) and were followed up to March 31, 2020 were included in this study. Diabetes status was defined based on the American Diabetes Association criteria, and diabetes was differentiated into diabetes with/without anti-diabetic treatment for additional analysis. A Cox proportional hazards regression model was used to investigate these associations., Results: During maximum 8-year follow-up period, 1024 participants underwent LTSA due to mental disorders. The adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) of LTSA due to all mental disorders were 1.10 (0.88-1.38) and 1.45 (1.07-1.98) for prediabetes and diabetes, respectively. Diabetic individuals with/without treatment were both at a high risk of LTSA due to mental disorders. For specific mental disorders, diabetes was associated with a higher risk of LTSA due to reaction to severe stress and adjustment disorders (aHR = 3.02, 95% CI = 2.01-4.52) while it was marginally associated with LTSA due to depressive episode (aHR = 1.25, 95% CI = 0.98-1.60). Prediabetes was also associated with LTSA due to reaction to severe stress and adjustment disorders (aHR = 1.41, 95% CI = 1.08-1.84)., Conclusions: The present study suggests the importance of screening diabetes status and providing psychological support for decreasing the risk of LTSA due to mental disorders within working populations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Although previous research has focused on the association between long working hours and several mental health outcomes, little is known about the association in relation to mental health-related sickness absence, which is a measure of productive loss. We aimed to investigate the association between overtime work and the incidence of long-term sickness absence (LTSA) due to mental disorders., Methods: Data came from the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH). A total of 47,422 subjects were followed-up in the period between April 2012 and March 2017. Information on LTSA was obtained via a study-specific registry. Baseline information was obtained at an annual health checkup in 2011; overtime working hours were categorized into <45; 45-79; 80-99; and ≥100 hours/month., Results: During a total follow-up period of 211,443 person-years, 536 people took LTSA due to mental disorders. A Cox proportional hazards model showed that compared to those with less than 45 hours/month of overtime work, those with 45-79 hours/month were at a lower risk of LTSA due to mental health problems (hazard ratio [HR] 0.63; 95% confidence interval [CI], 0.56-0.71) while those with overtime work of ≥100 hours/month had a 2.11 (95% CI, 1.12-3.98) times higher risk of LTSA due to mental health problems., Conclusion: Engaging in excessive overtime work was linked with a higher risk of LTSA due to mental health problems while the lower risk observed among individuals working 45-79 hours/month of overtime work might have been due to a healthy worker effect.

The utility of chest x-ray examination (CXR) in mandatory annual health examinations for occupational health is debatable in Japan. This study aimed to provide basic data to consider future policies for mandatory annual health examinations in the workplace. A nationwide descriptive survey was performed to determine the rate of detection of tuberculosis, lung cancer, and other diseases through CXR in organizations associated with National Federation of Industrial Health Association. The rate of finding on CXR conducted during annual health examinations in FY2016 was evaluated. Data regarding diagnosis based on follow-up examination findings were obtained and compared with the national statistics. In addition, CXR findings were compared with the results of low-dose lung computed tomography performed at the Hitachi Health Care Center. From 121 surveyed institutions, 88 institutions with 8,669,403 workers were included. For all ages, 1.0% of examinees required follow-up examination. Among 4,764,985 workers with diagnosis data, the tuberculosis detection rate was 1.8-5.3 per 100,000 persons. For Lung cancer, 3,688,396 workers were surveyed, and 334 positive cases were detected. The lung cancer detection rate using CXR was 9.1-24.4 per 100,000 persons. From 164 cases with information regarding the clinical stage, 72 (43.9%) had Stage I lung cancer. From 40,045 workers who underwent low-dose computed tomography multiple times, 31 lung cancer cases, all with Stage I disease, were detected (detection rate: 77.4 per 100,000 persons). Our findings suggest that CXR plays a little role in the detection of active tuberculosis. With regard to LC screening, the detection rate of LC by CXR was lower, approximately 50%, than the expected rate (41.0 per 100,000 persons) of LC morbidity based on the age-sex distribution of this study population. However, the role of CXR for LC screening cannot be mentioned based on this result, because assessment of mortality reduction is essential to evaluate the role., Competing Interests: The all authors have declared that no competing interests exist. Y.W., T.N., T.Ho., and T.Ha. are employees of Hitachi Health Care Center. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Physical activity has been linked to a lower risk of chronic kidney disease (CKD); however, evidence on the relationship between domain-specific physical activity and CKD is scarce. This study aimed to examine the risk of CKD in relation to leisure-time, occupational, and commuting physical activities in a large occupational cohort in Japan. Participants were 17,331 workers (20-65 years old) without CKD and were followed-up for a maximum period of 13 years. Incident CKD was defined as an estimated glomerular filtration rate of < 60 mL/min/1.73 m 2 and/or proteinuria determined using the dipstick test. The Cox proportional hazards models were used to examine the associations. During 147,752 person-years of follow-up, 4013 participants developed CKD. Workers who were standing or walking at work and those who were fairly active at work had adjusted hazard ratios of 0.88 (95% confidence interval 0.86-0.96) and 0.89 (95% confidence interval 0.78-1.02), respectively, for developing CKD than sedentary workers. Leisure-time physical activity and walking for commute were not associated with CKD risk. Our findings suggest that occupational, but not leisure-time and commuting physical activities, is associated with a lower CKD risk.

Objective: To examine the association of diabetes and prediabetes with suicide deaths in a Japanese working population., Methods: A nested case-control study was conducted using data from the Japan Epidemiology Collaboration on Occupational Health Study. During 8 years of follow-up, we identified 56 registered cases of suicide death that had information on fasting plasma glucose or glycated hemoglobin A1c at any health check-up during the past 3 years prior to suicide. For each case, we randomly selected five controls matched for age, sex, and worksite. We used the latest health check-up data for analysis. We defined diabetes status based on the American Diabetes Association criteria and used a conditional logistic regression model to investigate the association., Results: Adjusted odds ratios and 95% confidence intervals for suicide death were 0.67 (0.32-1.41) and 3.53 (1.05-11.91) for prediabetes and diabetes, respectively, compared to normoglycemia. Similar results were obtained when diabetes status was exclusively defined by the fasting plasma glucose or glycated hemoglobin A1c level., Conclusion: Diabetes, but not prediabetes, was associated with a higher risk of suicide death, compared with normoglycemia, among a Japanese working population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In occupational settings, smokers may take quitting smoking seriously if they experienced long-term sick leave due to cancer or cardiovascular disease (CVD). However, no study has elucidated the smoking cessation rate after long-term sick leave. We examined the smoking cessation rate after long-term sick leave due to cancer and CVD in Japan. We followed 23 survivors who experienced long-term sick leave due to cancer and 39 survivors who experienced long-term sick leave due to CVD who reported smoking at the last health exam before the leave. Their smoking habits before and after the leave were self-reported. Logistic regression was used to calculate adjusted smoking cessation rates. Smoking cessation rate after long-term sick leave due to cancer was approximately 70% and that due to CVD exceeded 80%. The adjusted smoking cessation rate was 67.6% (95% confidence interval [CI]: 47.0, 88.2) for cancer and 80.7% (95% CI: 67.7, 93.8) for CVD. Smoking cessation rate after a longer duration of sick leave (≥60 d) tended to increase for both CVD and cancer. Although any definite conclusion cannot be drawn, the data suggest that smoking cessation rate after long-term sick leave due to CVD is slightly higher than that for cancer.

Objectives: This study was conducted in order to evaluate the feasibility of a newly developed half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence for T2-weighted MRI of the female pelvis, in which scanning and post-processing filtering techniques were optimized to minimize blurring and the resultant reduction in signal-to-noise ratio (SNR) was compensated by signal averaging of multiple excitations (multi-NEX), and to compare its image quality with that of a conventional turbo spin echo (TSE) sequence., Methods: Fifty females with gynecological disease were prospectively enrolled. They underwent pelvic MRI including sagittal T2-weighted imaging obtained with multi-NEX HASTE (mHASTE) and TSE with acquisition times of 1 m 9 s and 3 m 26 s, respectively. At the prospective reading, mHASTE was reviewed first, and any changes in the image interpretation detected during the subsequent TSE reading were recorded. The SNR and tissue contrast were quantitatively measured. Two radiologists independently assessed tissue conspicuity and overall image quality considering noise, artifacts, and blurring, and visual grading characteristics (VGC) analysis was performed to compare the two sequences., Results: Adding TSE to mHASTE did not change image interpretations in any case. mHASTE produced an equivalent SNR and significantly higher contrast between the myometrium and junctional zone (p < 0.05) compared with TSE. The area under the VGC curve (AUC VGC ) showed that the conspicuity of the uterus, ovaries, and lesions and the overall image quality were significantly higher on mHASTE than on TSE for both readers (AUC VGC , 0.740-0.880; p < 0.01)., Conclusion: mHASTE is a feasible option for T2-weighted MRI of the female pelvis, as it allows faster and higher-quality image acquisition than conventional TSE., Key Points: • High-quality T2-weighted imaging is essential for magnetic resonance imaging of the female pelvis. • A new HASTE sequence was developed, in which a parallel imaging technique, a wide bandwidth, and a post-processing filter were used to minimize blurring, and the resultant reduction in the signal-to-noise ratio was compensated using signal averaging of multiple excitations (multi-NEX). • Multi-NEX HASTE allows fast and high-quality T2-weighted image acquisition.

Background & Aims: Increasing evidence has suggested a protective role of vitamin D on diabetes, but epidemiologic evidence is scarce among Asian populations. Here we prospectively examined the association between serum 25-hydroxyvitamin D 3 (25[OH]D 3 ) and type 2 diabetes (T2D) risk in Japanese individuals., Methods: A nested case-control study was conducted in a biomarker cohort of 4754 employees (baseline age 34-69 years) who had attended in a comprehensive health checkup and donated a blood sample. Diabetes diagnosis was based on plasma glucose, glycated hemoglobin, and self-reporting during the 5-year follow-up. Using density sampling, two controls were randomly matched to each case by sex, age, and date of checkup; 336 cases and 668 controls had serum 25(OH)D 3 data. Association between serum 25[OH]D 3 and the risk of T2D was assessed using conditional logistic regression analysis., Results: Serum 25(OH)D 3 was significantly and inversely associated with T2D risk after adjustment for known risk factors other than BMI (OR [highest vs. lowest serum 25(OH)D 3 quartile] = 0.58, 95% CI = 0.36-0.92; P for trend = 0.03). This association was somewhat attenuated after additional adjustment for BMI (OR = 0.65, 95% CI = 0.40-1.08; P for trend = 0.08). The inverse association was more evident among individuals whose blood samples were taken during the darker season (OR = 0.45; P for trend = 0.01). In the highest quartile of 25(OH)D 3 , progression from prediabetes to T2D was about 37% lower than in the lowest quartile., Conclusions: Higher circulating 25(OH)D 3 was associated with a lower risk of T2D, and this association was stronger among individuals whose blood was taken during the darker season and among those with prediabetes., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The use of Information and Communication Technology devices (ICT) has spread globally; therefore, increasing exposure to these display devices is an important health issue in the workplace. The association between ocular axial length (AL) elongation and ICT use was investigated among 7334 middle-aged Japanese male workers. Detailed ICT use information was obtained using a self-administered questionnaire. The high AL group was defined as the group with AL above the 75th percentile for each 5-year age interval. Logistic analysis showed that the odds ratio (OR) for the high AL group of >8 hours/day, adjusted for potent confounding factors, was significantly elevated relative to <1 hour/day. Notably, there was a strong association in the older groups (OR = 6.60, 95% CI = 3.92-11.12), based on work-related uses: word processing, sending e-mails, preparation of presentation materials, and browsing websites. In addition, among workers with extended ICT use for these work-related purposes, a significant lateral difference was observed in AL. However, these associations were not observed for private use, such as playing games. The results of our prospective cross-sectional study show that increased time spent on work-related ICT uses was associated with AL elongation, particularly in older workers.

Background: Prospective data are sparse for active commuting to work and body weight in Asia. We assessed the association of 5-year changes in commuting mode with body mass index (BMI) and the indicators of abdominal obesity in Japanese working adults., Methods: In this longitudinal study, we studied 29,758 participants (25,808 men and 3950 women) in Japan aged 30 to 64 years at baseline who underwent further health examination 5 years after the baseline examination. Changes in BMI were calculated from objectively measured body height and weight at baseline and follow-up examination. Visceral and subcutaneous fat areas and waist circumference measured by computed tomography scans were used as indicators for abdominal adiposity. Linear regression was applied to estimate the association of changes in commuting mode with the obesity outcomes., Results: Within the 5-year study period, adults who maintained inactive commuting gained weight, and compared with this group, adults who switched to inactive commuting had higher weight gain; conversely, adults who switched to active or public transportation commuting and especially those who maintained active or public transportation commuting experienced less weight gain. Subgroup analysis showed similar tendency across the different transitions of leisure-time exercise or occupational physical activity. For example, among adults who maintained no exercise (n = 16,087), the adjusted mean (95% confidence intervals) of the BMI change over 5 years in kg/m 2 were 0.27 (0.24 to 0.30) for maintained inactive commuting group (reference), 0.34 (0.30 to 0.38) for switching to inactive commuting group (P = 0.046), 0.20 (0.18 to 0.22) for switching to active commuting or public transportation group (P = 0.001), and 0.09 (0.06 to 0.13) for maintained active commuting or public transportation group (P < 0.001). Maintained inactive commuting tended to be associated with larger gain in abdominal adiposity indicators., Conclusion: Switching from inactive commuting mode to more physically active commuting mode and maintaining active commuting can promote body weight control among working adults across different levels of occupational or leisure-time physical activity.

Amino acids have emerged as novel biomarkers for predicting type 2 diabetes (T2D), but the epidemiologic data linking circulating amino acid profiles with T2D are sparse in Asian populations. We conducted a nested case-control study within a cohort of 4,754 nondiabetic Japanese employees who attended a comprehensive health checkup in 2008-2009 and agreed to provide blood samples. During a 5-year follow-up, incident T2D cases were ascertained based on plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case on sex, age, and the date of serum sampling were randomly selected by using density sampling, resulting in 284 cases and 560 controls with amino acid measures. High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Further adjustment for the homeostasis model assessment of insulin resistance attenuated these associations. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms. Insulin resistance may account for or mediate the relationship between these amino acids and risk of incident T2D.

No information exists regarding the effects of working hours on glucose metabolism in adults with pre-diabetes, a high-risk group for developing diabetes. Further, longitudinal patterns in working hours and their effects on glucose metabolism have not been described previously. We investigated the association between changes in overtime working hours over 3 years and the risk for progression to type 2 diabetes among adults with pre-diabetes. We analyzed patterns of overtime working hours from 2008 to 2011 among 18,172 workers in Japan (16,474 men, aged 30 to 64 years) with pre-diabetes in 2011 (baseline) using the sub-cohort data from the Japan Epidemiology Collaboration on Occupational Health Study. Participants were followed up to March 2016. Overtime working hours per month were self-reported annually in 2008-2011 and trajectory patterns were identified using group-based trajectory modeling. Type 2 diabetes was diagnosed by fasting or random plasma glucose test, hemoglobin A1c, and history of diabetes. Multivariable-adjusted hazard ratios of incident diabetes were calculated using Cox regression. We identified 3 distinct trajectories of overtime work: persistently short, long-to-short, and persistently long. During a mean follow-up of 3.5 years, 1613 participants (8.9%) developed diabetes. Compared with persistently short overtime working hours, no material increase in diabetes risk was observed for either long-to-short working hours or persistently long working hours. After adjustment for potential confounders, this association was materially unchanged. The results suggest that among individuals with pre-diabetes, persistently long working hours over 3 years were not associated with an increased risk of developing type 2 diabetes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The effect of smoking on mortality in working-age adults remains unclear. Accordingly, we compared the effects of cigarette smoking and smoking cessation on total and cause-specific mortality in a Japanese working population. Methods and Results: This study included 79,114 Japanese workers aged 20-85 years who participated in the Japan Epidemiology Collaboration on Occupational Health Study. Deaths and causes of death were identified from death certificates, sick leave documents, family confirmation, and other sources. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards regression. During a maximum 6-year follow-up, there were 252 deaths in total. Multivariable-adjusted HRs (95% CIs) for total mortality, cardiovascular disease (CVD) mortality, and tobacco-related cancer mortality were 1.49 (1.10-2.01), 1.79 (0.99-3.24), and 1.80 (1.02-3.19), respectively, in current vs. never smokers. Among current smokers, the risks of total, tobacco-related cancer, and CVD mortality increased with increasing cigarette consumption (P trend <0.05 for all). Compared with never smokers, former smokers who quit <5 and ≥5 years before baseline had HRs (95% CIs) for total mortality of 1.80 (1.00-3.25) and 1.02 (0.57-1.82), respectively., Conclusions: In this cohort of workers, cigarette smoking was associated with increased risk of death from all and specific causes (including CVD and tobacco-related cancer), although these risks diminished 5 years after smoking cessation.

Background and Aims: We aimed to examine the risk of cardiovascular disease (CVD) with persistent prediabetes during the last four years prior to a CVD event in a large occupational cohort in Japan., Methods: We performed a nested case-control study using data from the Japan Epidemiology Collaboration on Occupational Health Study. A total of 197 registered cases of CVD were identified and matched individually with 985 controls according to age, sex, and worksite. Prediabetes was defined as fasting plasma glucose 100-125 mg/dL and/or HbA1c 5.7-6.4%. Persistent prediabetes was defined as having prediabetes at years one and four prior to the onset/index date; persistent normoglycemia was similarly defined. Associations between prediabetes and CVD risk were assessed using conditional logistic regression models., Results: Compared with people with persistent normoglycemia over the four years prior to the onset/index date, the unadjusted odds ratio (95% confidence interval) for CVD was 2.88 (1.56, 5.32) for people with persistent prediabetes. After adjusting for BMI, smoking, hypertension, and dyslipidemia assessed four years before the onset/index date, the association was slightly attenuated to an OR (95% confidence interval) of 2.62 (1.31, 5.25). Prediabetes assessed at single time points was also associated with an elevated risk of CVD, with multivariable-adjusted odds ratio (95% confidence interval) of 1.72 (1.12, 2.64) and 2.13 (1.32, 3.43) for prediabetes at one and four years prior to the onset/index date, respectively., Conclusions: Prediabetes is associated with an increased risk of CVD. Identification and management of prediabetes are important for the prevention of CVD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Oxidative stress leads to many kinds of diseases. Currently, urinary 8-hydroxydeoxyguanosine (8-OHdG) is widely measured as an oxidative stress biomarker. There is a specific advantage if saliva can be used as the sample to measure the oxidative stress biomarker, because saliva is much easier to collect than urine. In this study, we investigated the measurement of 8-hydroxyguanine (8-OHGua) as an oxidative stress marker in saliva, by a column switching HPLC system equipped with an electrochemical detector (HPLC-ECD)., Findings: The 8-OHGua in saliva could be detected as a single peak by HPLC-ECD. The average level of 8-OHGua in saliva was 3.80 ng/mL in ordinary, non-smoking subjects. The salivary 8-OHGua levels of smokers were significantly higher than those of non-smokers., Conclusions: Salivary 8-OHGua may be a useful noninvasive and promising oxidative stress biomarker., Competing Interests: Not applicable.The study was approved by the Ethics Committee of Medical Research, University of Occupational and Environmental Health, Japan.Not applicable.The authors declare that they have no competing interests.

Background: We investigated the risk of cardiovascular disease (CVD) with duration of metabolic syndrome (MetS) for the past 4 years before the CVD event.Methods and Results:We performed a nested case-control study within the Japan Epidemiology Collaboration on Occupational Health Study. A total of 139 registered cases of CVD and 561 self-reported cases of CVD were identified and matched individually on age, sex, and worksite with 695 and 2,803 controls, respectively. MetS was defined by the Joint Interim Statement definition. The odds ratio (95% confidence interval) for registered CVD was 4.7 (2.9, 7.5) for people with persistent MetS (positive for MetS for ≥3 assessments) and 1.9 (1.1, 3.3) for those with intermittent MetS (positive for MetS for 1-2 assessments), compared with people without MetS during the past 4 years before the event/index date (P for trend <0.001). The corresponding odds ratio for self-reported CVD was 2.7 (2.2, 3.5) and 1.8 (1.4, 2.3) (P for trend <0.001). The association with MetS duration was stronger for myocardial infarction than for other CVD subtypes. Similar results were obtained when using the Japanese MetS criteria., Conclusions: The risk of CVD increases with increasing MetS duration. These findings contribute to risk stratification and encourage lifestyle modification for people with MetS to minimize their health risk.

Background: Long-term sick-leave is a major public health problem, but data on its incidence in Japan are scarce. We aimed to present reference data for long-term sick-leave among private sector employees in Japan., Methods: The study population comprised employees of 12 companies that participated in the Japan Epidemiology Collaboration on Occupational Health Study. Details on medically certified sick-leave lasting ≥30 days were collected from each company. Age- and sex-specific incidence rate of sick-leave was calculated for the period of April 2012 to March 2014., Results: A total of 1422 spells in men and 289 in women occurred during 162,989 and 30,645 person-years of observation, respectively. The three leading causes of sick-leave (percentage of total spells) were mental disorders (52%), neoplasms (12%), and injury (8%) for men; and mental disorders (35%), neoplasms (20%), and pregnancy-related disease (14%) for women. Incidence rate of sick-leave due to mental disorders was relatively high among men in their 20s-40s but tended to decrease with age among women. Incidence rate of sick-leave due to neoplasms started to increase after age 50 in men and after age 40 in women, making neoplasms the leading cause of sick-leave after age 50 for women and after age 60 for men and the second leading cause after age 40 for women and after age 50 for men. Pregnancy-related disease was the second leading cause of sick-leave among women aged 20-39 years., Conclusions: These results suggest that mental disorder, neoplasms, and pregnancy-related disease are the major causes of long-term sick-leave among private sector employees in Japan., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: We prospectively examined the association of diabetes risk with the number of metabolic abnormalities, as well as their combinations, according to the presence or absence of impaired fasting glucose (IFG) in a large-scale Japanese working population., Methods: Participants included 55,271 workers at 11 companies who received periodic health check-ups between 2008 and 2013. The metabolic syndrome (MetS) components were defined using the 2009 Joint Interim Statement. IFG was defined as fasting plasma glucose 5.6-6.9 mmol/L. Diabetes newly diagnosed after the baseline examination was defined according to the American Diabetes Association criteria. We calculated the hazard ratios (HRs) for diabetes incidence using the Cox proportional hazards model., Results: During the follow-up period (median 4.95 years), 3183 subjects developed diabetes. In individuals with normal fasting glucose levels, the risk of diabetes increased steadily with the increasing number of MetS components; the multivariable-adjusted HRs for incident diabetes for the number of MetS components were 2.0, 4.3, 7.0, and 10.0 for one, two, three, or four MetS components, respectively, compared with the absence of components. A similar association was observed among individuals with IFG; the corresponding HRs were 17.6, 23.8, 33.9, and 40.7. The combinations that included central obesity appeared to be more strongly associated with diabetes risk than other combinations with the same number of MetS components within the same glucose status., Conclusions: Our findings indicate that risk stratification of individuals by the presence or absence of IFG and the number of MetS components can detect individuals with a high risk of diabetes., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

We prospectively examined diabetes risk in association with a summary measure of degree and duration of weight change. The study participants were 51,777 employees from multiple companies in Japan, who were aged 30-59years, free of diabetes at baseline, and followed up for 7years (2008-2015). Exposure was cumulative body mass index (BMI)-years, which was defined as the area of BMI units above or below baseline BMI during follow-up, and was treated as a time-dependent variable in the Cox proportional hazards regression models. During the 263,539 person-years of follow-up, 3465 participants developed diabetes. The adjusted hazard ratio (HR) of diabetes for a 1-unit increase in cumulative BMI-years was 1.11 (95% confidence interval (CI): 1.09, 1.12). The association was more pronounced among overweight (HR=1.11; 95% CI: 1.08, 1.14) and obese (HR=1.12; 95% CI: 1.08, 1.15) adults compared with normal- and under-weight (HR=1.07; 95% CI: 1.03, 1.11) adults (P for interaction of cumulative BMI-years X baseline BMI-group=0.002). The association of higher cumulative BMI-years with incident diabetes did not substantially differ by metabolic phenotype. The present results emphasize the importance of avoiding additional weight gain over an extended period of time for the prevention of type 2 diabetes, especially among overweight and obese adults, irrespective of metabolic health status., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Data are limited on the sex-specific prevalence of diseases and their risk factors in middle-aged and older workers in Japan. In this cross-sectional study, we investigated the age- and sex-specific prevalence of hypertension, diabetes, dyslipidemia, metabolic syndrome (defined using joint statement criteria), obesity, underweight, abdominal obesity, and smoking among approximately 70,000 to 90,000 Japanese workers (predominantly men) aged 20-69 years in 2014. We also investigated the prevalence of low cardiorespiratory fitness in 2012 and no leisure-time exercise in 2014. In both sexes, the prevalence of lifestyle-related risk factors, including hypertension, diabetes, dyslipidemia, metabolic syndrome, obesity, and abdominal obesity, was increased with aging. In contrast, the prevalence of underweight was decreased with aging. Smoking prevalence exceeded 30% in men regardless of age, whereas the prevalence was around 10% in women of all age groups. Prevalence of no leisure-time exercise exceeded 50% among middle-aged and older workers in both sexes. Among workers aged 50-64 years, less than half of men had low fitness, whereas more than half of women had low fitness. Given the high prevalence of lifestyle-related risk factors among middle-aged and older workers, effective strategies to prevent cardiovascular disease in this age group are needed in Japan.

Data are limited regarding effect of intensity of leisure-time physical activity on metabolic syndrome. Furthermore, no prospective data are available regarding effect of occupational and commuting physical activity on metabolic syndrome. We compared metabolic syndrome risk by intensity level of leisure-time exercise and by occupational and commuting physical activity in Japanese workers. We followed 22,383 participants, aged 30-64 years, without metabolic syndrome until 2014 March (maximum, 5 years of follow-up). Physical activity was self-reported. Metabolic syndrome was defined by the Joint Statement criteria. We used Cox regression models to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of metabolic syndrome. During a mean follow-up of 4.1 years, 5361 workers developed metabolic syndrome. After adjustment for covariates, compared with engaging in no exercise, the HRs (95 % CIs) for <7.5, 7.5 to <16.5, and ≥16.5 metabolic equivalent hours of exercise per week were 0.99 (0.90, 1.08), 0.99 (0.90, 1.10), and 0.95 (0.83, 1.08), respectively, among individuals engaging in moderate-intensity exercise alone; 0.93 (0.75, 1.14), 0.81 (0.64, 1.02), and 0.84 (0.66, 1.06), among individuals engaging in vigorous-intensity exercise alone; and 0.90 (0.70, 1.17), 0.74 (0.62, 0.89), and 0.81 (0.69, 0.96) among individuals engaging in the two intensities. Higher occupational physical activity was weakly but significantly associated with lower risk of metabolic syndrome. Walking to and from work was not associated with metabolic syndrome. Vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise and worksite intervention for physical activity may help prevent metabolic syndrome for Japanese workers.

Background: We sought to establish the optimal waist circumference (WC) cut-off point for predicting diabetes mellitus (DM) and to compare the predictive ability of the metabolic syndrome (MetS) criteria of the Joint Interim Statement (JIS) and the Japanese Committee of the Criteria for MetS (JCCMS) for DM in Japanese., Methods: Participants of the Japan Epidemiology Collaboration on Occupational Health Study, who were aged 20-69 years and free of DM at baseline (n = 54,980), were followed-up for a maximum of 6 years. Time-dependent receiver operating characteristic analysis was used to determine the optimal cut-off points of WC for predicting DM. Time-dependent sensitivity, specificity, and positive and negative predictive values for the prediction of DM were compared between the JIS and JCCMS MetS criteria., Results: During 234,926 person-years of follow-up, 3180 individuals developed DM. Receiver operating characteristic analysis suggested that the most suitable cut-off point of WC for predicting incident DM was 85 cm for men and 80 cm for women. MetS was associated with 3-4 times increased hazard for developing DM in men and 7-9 times in women. Of the MetS criteria tested, the JIS criteria using our proposed WC cut-off points (85 cm for men and 80 cm for women) had the highest sensitivity (54.5 % for men and 43.5 % for women) for predicting DM. The sensitivity and specificity of the JCCMS MetS criteria were ~37.7 and 98.9 %, respectively., Conclusion: Data from the present large cohort of workers suggest that WC cut-offs of 85 cm for men and 80 cm for women may be appropriate for predicting DM for Japanese. The JIS criteria can detect more people who later develop DM than does the JCCMS criteria.

Aims/introduction: Muscle strength training has been suggested to improve glucose metabolism; however, epidemiological evidence regarding strength training's effects on diabetes risk is scarce. We prospectively examined the association between strength training and the risk of type 2 diabetes in Japanese men and women., Materials and Methods: The sample included health checkups on 26,630 Japanese male and female workers aged 30-64 years without diabetes at baseline. Weekly time spent on strength training was elicited using a self-reported questionnaire. Type 2 diabetes was diagnosed based on hemoglobin A1c, fasting glucose, random plasma glucose and self-report in an annual health checkup. Hazard ratio (HR) and its 95% confidence interval (CI) for incident diabetes was estimated using a Cox proportional hazards model., Results: During a mean follow up of 5.2 years with 139,748 person-years, 1,770 individuals developed diabetes. Age- and sex-adjusted HR for diabetes was 0.58 (95% CI 0.42-0.79) in those who engaged in strength training compared with those who engaged in no strength training. After further adjusting for potential confounders, the corresponding HR was 0.66 (95% CI 0.48-0.90). Additional adjustment for body mass index did not materially change the result; the HR was 0.70 (95% CI 0.51-0.96). The association was more pronounced in individuals aged 50 years or older than those aged <50 years, although the difference in the association by age was not significant., Conclusions: These results suggest that engagement in strength training could help to reduce the risk of type 2 diabetes in a Japanese working population.

The production of alkanes in a marine cyanobacterium possessing the α-olefin biosynthesis pathway was achieved by introducing an exogenous alkane biosynthesis pathway. Cyanobacterial hydrocarbons are synthesized via two separate pathways: the acyl-acyl carrier protein (ACP) reductase/aldehyde-deformylating oxygenase (AAR/ADO) pathway for the alkane biosynthesis and the α-olefin synthase (OLS) pathway for the α-olefin biosynthesis. Coexistence of these pathways has not yet been reported. In this study, the marine cyanobacterium Synechococcus sp. NKBG15041c was shown to produce α-olefins similar to those of Synechococcus sp. PCC7002 via the α-olefin biosynthesis pathway. The production of heptadecane in Synechococcus sp. NKBG15041c was achieved by expressing the AAR/ADO pathway genes from Synechococcus elongatus PCC 7942. The production yields of heptadecane in Synechococcus sp. NKBG15041c varied with the expression level of the aar and ado genes. The maximal yield of heptadecane was 4.2 ± 1.2 μg/g of dried cell weight in the transformant carrying a homologous promoter. Our results also suggested that the effective activation of ADO may be more important for the enhancement of alkane production by cyanobacteria.

Objectives: Sense of coherence (SOC) is an individual characteristic related to a positive life orientation, leading to effective coping. Little is known about the relationship between SOC and metabolic syndrome (MetS). This cross-sectional study aimed at testing the hypothesis that workers with a strong SOC have fewer atherosclerotic risk factors, including MetS, and healthier lifestyle behaviors., Material and Methods: One hundred and sixty-seven computer software workers aged 20-64 years underwent a periodical health examination including assessment of body mass index, waist circumference, blood pressure, blood lipid levels, fasting blood sugar (FBS) levels and lifestyle behaviors (walking duration, smoking status, nutrition, alcohol consumption, and sleep duration). During this period, the participants also completed a 29-item questionnaire of SOC and the Brief Job Stress Questionnaire to assess job stressors such as job strain and workplace social support., Results: Our results showed that the participants with a stronger SOC were likely to walk for at least 1 h a day, to eat slowly or at a moderate speed, and to sleep for at least 6 h. Compared with the participants with the weakest SOC, those with the strongest SOC had a significantly lower odds ratio (OR) for being overweight (OR = 0.31; 95% confidence interval (CI): 0.11-0.81), and having higher FBS levels (OR = 0.11; 95% CI: 0.02-0.54), dyslipidemia (OR = 0.29; 95% CI: 0.09-0.84), and MetS (OR = 0.12; 95% CI: 0.02-0.63), even after adjusting for age, gender and job stressors., Conclusions: High SOC is associated with a healthy lifestyle and fewer atherosclerotic risk factors, including MetS.

Background: Waist-to-height ratio (WHtR) has been suggested as a better screening tool than body mass index (BMI) and waist circumference (WC) for assessing cardiometabolic risk. However, most previous studies did not consider age., Methods and Results: Participants were 45,618 men and 8,092 women aged 15-84 years who received periodic health checkups in 9 companies in Japan. Clustering of cardiometabolic risk factors was defined by the existence of 2 or more of high blood pressure, hyperglycemia, and dyslipidemia. In both men and women, unadjusted area under the curve (AUC) of the receiver-operating characteristic curve for WHtR in detecting the clustering of cardiometabolic risk factors was significantly higher than that for either BMI or WC; the AUCs for WHtR, BMI, and WC, respectively, were 0.734, 0.705, and 0.717 in men and 0.782, 0.762, and 0.755 in women. After adjustment for age, however, such differences were not observed; the corresponding values were 0.702, 0.701, and 0.696 in men. In women, the age-adjusted AUC for BMI was slightly higher than for other indices (WHtR, 0.721; BMI, 0.726; WC, 0.707)., Conclusions: The screening performance of WHtR for detecting the clustering cardiometabolic risk factors was not superior to that of BMI.

We report three cases of home palliative chemotherapy with an infuser pump (IP) for continuous infusion of anticancer drugs, which is as effective as being treated at the hospital. Cases are: A 74-year-old man with intraperitoneal metastasis after rectal operation, a 43-year-old woman with pelvis metastasis after a uterus cervical operation and a 70-year-old man with gastric cancer and massive metastases of the liver. Their performance status (PS) ranged from 3-4. All cases underwent continuous infusion of cisplatin 20-30 mg/w with IP and CPT-11:10-40 mg/w in 1 hour. For case 1/2, 5-FU 1,750 mg/w was carried out continuously, and TS-1 80 mg/day/body was administered for case 3. After 4 courses of chemotherapy, all cases indicated effective changes such as decrease of pain, reduction of metastatic tumor size, decrease of tumor bleeding and tumor makers. Their quality of life (QOL) improved. Palliative chemotherapy to improve QOL can be performed at home if used with IP for poor PS patients.