Diabetes, Prediabetes, and the Risk of a Composite Outcome of Long-term Sickness Absence and Pre-retirement Death Due to Physical Disorders.

BACKGROUND: Diabetes and prediabetes have been linked with morbidity or mortality from cardiovascular disease, cancer, or other physical disorders among working-age populations, but less is known about outcomes directly related to labor loss (eg, Tlong-term sickness absence [LTSA] or pre-retirement death due to physical disorders).This prospective study aimed to examine the association of diabetes and prediabetes with the risk of a composite outcome of LTSA and pre-retirement death due to physical disorders. The present study also examined the associations of severe outcomes (LTSA or death) due to specific physical disorders or injuries/external causes in relation to diabetes and prediabetes. METHODS: Data were derived from the Japan Epidemiology Collaboration on Occupational Health study. A total of 60,519 workers from 12 companies were followed for 8 years. Diabetes and prediabetes were defined based on the American Diabetes Association criteria. A Cox proportional hazards regression model was used to examine the association between diabetes/prediabetes and severe outcomes due to physical disorders or injuries/external causes. RESULTS: The adjusted hazard ratios of severe outcomes due to all physical disorders were 1.22 (95% confidence interval [CI], 1.02-1.45) and 2.32 (95% CI, 2.04-2.64) for prediabetes and diabetes, respectively. In cause-specific analyses, an increased risk was observed for severe outcomes due to cancers, cardiovascular diseases, diseases of the musculoskeletal system, and injuries/external causes in relation to either or both diabetes and prediabetes. CONCLUSION: Diabetes and prediabetes were associated with an increased risk of severe outcomes due to physical disorders or injuries/external causes among Japanese workers.

Metabolic syndrome and the risk of severe cancer events: a longitudinal study in Japanese workers.

BACKGROUND: Metabolic syndrome (MetS) is associated with cancer risk; however, little is known regarding its relationship with the risk of cancer-related premature death and long-term sick leave (LTSL), which can lead to a substantial loss in working years. The present study aimed to quantify the all-site and site-specific associations between MetS and the risk of severe cancer events (a composite outcome of LTSL and mortality due to cancer) in a large working population in Japan. METHODS: We recruited 70,875 workers (59,950 men and 10,925 women), aged 20-59 years, who attended health check-ups in 2011 (10 companies) and 2014 (2 companies). All workers underwent follow up for severe cancer events until March 31, 2020. MetS was defined in accordance with the Joint Interim Statement. Cox regression models were used to quantify the association between baseline MetS and severe cancer events. RESULTS: During 427,379 person-years of follow-up, 523 participants experienced the outcome consisting of 493 LTSLs of which 124 eventually resulted in death, and 30 deaths without taking LTSL. The adjusted hazard ratios (HR) (95% confidence intervals [CI]) for composite severe events due to all-site, obesity-related, and non-obesity-related cancer among those with vs. without MetS were 1.26 (1.03, 1.55), 1.37 (1.04, 1.82), and 1.15 (0.84, 1.56), respectively. In cancer site-specific analyses, MetS was associated with an increased risk of severe events due to pancreatic cancer (HR, 2.06; 95% CI, 0.99-4.26). When mortality was treated solely as the endpoint, the association was significant for all-site (HR, 1.58; 95% CI, 1.10-2.26), and obesity-related (HR, 1.59; 95% CI, 1.00-2.54) cancer. Additionally, a greater number of MetS components was associated with a greater risk of both severe cancer events and cancer-related mortality (P trend < 0.05). CONCLUSION: Among Japanese workers, MetS was associated with an increased risk of severe cancer events, especially those due to obesity-linked cancer.

Metabolic Syndrome and the Increased Risk of Medically Certified Long-term Sickness Absence: A Prospective Analysis Among Japanese Workers.

BACKGROUND: Metabolic syndrome (MetS) has been associated with various chronic diseases that may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically certified LTSA among Japanese workers. METHODS: We recruited 67,403 workers (57,276 men and 10,127 women), aged 20-59 years from 13 companies in Japan during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and we followed them for LTSA events (≥30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for LTSA associated with MetS and its components. RESULTS: During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41-1.68) among those with MetS compared to those without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76); cardiovascular diseases (3.16); diseases of the musculoskeletal system and connective tissue (2.01); cancers (1.24); obesity-related cancers (1.35); mental, behavioral, and neurodevelopmental disorders (1.28); reaction to severe stress and adjustment disorders (1.46); and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk. CONCLUSION: MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.

Diastereodivergent Intermolecular 1,2-Diamination of Unactivated Alkenes Enabled by Iodine Catalysis.

The stereospecific, substrate (nitrogen source)-controlled intermolecular anti- and syn-1,2-diaminations of unactivated alkenes using the same catalysis (an iodine catalyst) is reported. The combined use of the two potential methods provides access to all of the disastereomeric forms of 1,2-diamines in spite of the availability of E- and Z-alkenes, and the resulting products can be readily converted into free vicinal diamines.

Loss of Working Life Years Due to Mortality, Sickness Absence, or Ill-health Retirement: A Comprehensive Approach to Estimating Disease Burden in the Workplace.

BACKGROUND: While much effort has focused on quantifying disease burden in occupational health, no study has simultaneously assessed disease burden in terms of mortality and morbidity. We aimed to propose a new comprehensive method of quantifying the disease burden in the workplace. METHODS: The data were obtained from the Japan Epidemiology Collaboration on Occupational Health (J-ECOH) Study, a large-scale prospective study of approximately 80,000 workers. We defined disease burden in the workplace as the number of working years lost among the working population during a 6-year period (April 2012 to March 2018). We calculated the disease burden according to consequences of health problems (ie, mortality, sickness absence [SA], and ill-health retirement) and disease category. We also calculated the age-group- (20-39 and 40-59 years old) and sex-specific disease burden. RESULTS: The largest contributors to disease burden in the workplace were mental and behavioural disorders (47.0 person-years lost per 10,000 person-years of working years; ie, per myriad [proportion]), followed by neoplasms (10.8 per myriad) and diseases of the circulatory system (7.1 per myriad). While mental and behavioural disorders made a greater contribution to SA and ill-health retirement compared to mortality, the latter two disorders were the largest contributors to the disease burden in the workplace due to mortality. The number of working years lost was greater among younger versus older female participants, whereas the opposite trend was observed in males. CONCLUSIONS: Our approach is in contrast to those in previous studies that focused exclusively on mortality or morbidity.

Blood pressure classification using the Japanese Society of Hypertension Guidelines for the Management of Hypertension and cardiovascular events among young to middle-aged working adults.

The Japanese Society of Hypertension updated guidelines for hypertension management (JSH2019), changing the blood pressure (BP) classification. However, evidence is sparse regarding the association of the classification with cardiovascular disease (CVD) events among young to middle-aged workers in Japan. We examined this issue using longitudinal data from Japan Epidemiology Collaboration on Occupational Health Study with a prospective cohort design. Participants were 81,876 workers (aged 20-64 years) without taking antihypertensive medication at baseline. BP in 2011 or 2010 was used as exposure. CVD events that occurred from 2012 to 2021 were retrieved from a within-study registry. Cox regression was used to calculate multivariable-adjusted hazard ratios of CVD events. During 0.5 million person-years of follow-up, 334 cardiovascular events, 75 cardiovascular deaths, and 322 all-cause deaths were documented. Compared with normal BP (systolic BP [SBP] < 120 mmHg and diastolic BP [DBP] < 80 mmHg), multivariable-adjusted hazard ratios (95% confidence intervals) of cardiovascular events were 1.98 (1.49-2.65), 2.10 (1.58-2.77), 3.48 (2.33-5.19), 4.12 (2.22-7.64), and 7.81 (3.99-15.30) for high normal BP (SBP120-129 mmHg and DBP < 80 mmHg), elevated BP (SBP130-139 mmHg and/or DBP80-89 mmHg), stage 1 hypertension (SBP140-159 mmHg and DBP90-99 mmHg), stage 2 hypertension (SBP160-179 mmHg and/or DBP100-109 mmHg), and stage 3 hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg), respectively. The highest population attributable fraction was observed in elevated BP (17.8%), followed by stage 1 hypertension (14.1%). The present data suggest that JSH2019 may help identify Japanese workers at a higher cardiovascular risk.

Impact of the COVID-19 pandemic on the incidence of cardiometabolic risk factors among workers: results from the Japan Epidemiology Collaboration on Occupational Health study.

BACKGROUND: The COVID-19 pandemic and associated restrictions on human activities have greatly changed lifestyles, which might have deteriorated the cardiometabolic profile. OBJECTIVE: This study aimed to examine the effect of the COVID-19 pandemic on the incidence of cardiometabolic risk factors among Japanese workers in fiscal years (FY) 2020 and 2021 compared with the prepandemic period. METHOD: This study comprised an average of 71 025 employees in Japan who underwent annual health check-ups for at least two successive years from 2015 to 2021. Annual incidence rates from 2016 to 2021 were assessed for obesity, diabetes, hypertension, dyslipidaemia and metabolic syndrome (MetS). The observed incidence rates in 2020 and 2021 were compared with the predicted incidence based on prepandemic trends (2016 to 2019). RESULTS: Relative to the prepandemic, the incidence of all the outcomes, except for dyslipidaemia, significantly increased in 2020. Between FY 2016 and 2019, the adjusted mean incidence of obesity, diabetes, hypertension, dyslipidaemia and MetS was 5.0%, 1.4%, 5.3%, 17.4% and 7.6%, respectively. In FY 2020, the adjusted incidence (95% CI) of these outcomes increased to 6.02 (5.80 to 6.24), 1.84 (1.73 to 1.96), 6.62 (6.40 to 6.83), 19.31 (18.83 to 19.78) and 8.51 (8.23 to 8.78), which were higher than the predicted incidence of 5.24 (4.99 to 5.49), 1.54 (1.41 to 1.67), 6.02 (5.76 to 6.27), 18.58 (18.00 to 19.16) and 8.05 (7.71 to 8.38) for 2020, respectively. The incidence returned to the prepandemic levels in FY 2021. CONCLUSION: Results showed a worsening of the cardiometabolic profile during the initial year of the pandemic, which was reverted in the second year to the levels before the pandemic.

Diabetes, prediabetes, and long-term sickness absence due to mental disorders: Japan Epidemiology Collaboration on Occupational Health Study.

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.

Non-High-Density Lipoprotein Cholesterol and Risk of Cardiovascular Disease: The Japan Epidemiology Collaboration on Occupational Health Study.

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.

Isomer pattern and elimination of dioxins in workers exposed at a municipal waste incineration plant.

The aim of this study was to clarify patterns of serum concentrations of dioxins in the employees of a waste incineration plant and to estimate elimination rates and half-lives of serum dioxin isomers, and the maximum serum concentrations of dioxin isomers at the time of plant shutdown. Sixteen subjects participating 3 times or more in annual health examinations during an 8-yr period from 2000 to 2007 were recruited for this study. Serum concentrations of dioxins expressed as TEQ/g lipid decreased gradually after plant shutdown with the highest decrease observed in polychlorinated dibenzofurans (PCDFs) followed by polychlorinated deibenzo-p-dioxins (PCDDs) and then coplanar PCBs. The serum toxic equivalency (TEQ) concentrations of PCDF and PCDD congeners in the employees were higher than those in the general population survey by the Ministry of the Environment, Japan, whereas the serum concentrations of coplanar PCBs were similar to those in the general population. The estimated half-lives and elimination rates of PCDDs and PCDFs in the highly exposed workers increased compared with the moderately exposed workers. The estimated geometric mean serum concentrations of PCDDs, PCDFs and total dioxins at the time of plant shutdown were 35, 53 and 107 pg TEQ/g lipid, respectively.

A cross-sectional analysis of dioxins and health effects in municipal and private waste incinerator workers in Japan.

This cross-sectional study was intended to examine health effects of 678 male workers employed during an 8-yr period from 2000 to 2007 at 36 municipal and private waste incineration plants in Japan. Blood samples were obtained for analysis of concentrations of dioxins including coplanar polychlorinated biphenyls (coplanar PCBs) and evaluation of health effects. Health effects including diabetes were surveyed via a physician's interview or clinical data from blood samples. There was a certain difference in serum concentrations of polychlorinated dibenzofurans (PCDFs) between the incinerator workers and Japanese general population, although no differences in the concentrations of total dioxins or polychlorinated dibenzo-p-dioxins (PCDDs) were found between the two groups. A few positive correlations between serum levels of PCDDs and PCDFs and the results of laboratory and physiological tests were found, but coplanar PCBs showed significant relations with 14 parameters of the tests. The background serum levels of PCDDs, PCDFs and total dioxins were significantly associated with the prevalence of diabetes. No essential differences in serum concentrations of total dioxins and in prevalence of diabetes between our subjects and the general population suggested that the incinerator workers were marginally exposed to dioxins in the workplace without any recognizable adverse health effects.

Periodicity of Cytoplasmic Cycle in Nonnucleate Fragments of Sea Urchin and Starfish Eggs*: (cortical tension/sea urchin/starfish/cytoplasmic cycle).

Fertilized eggs of the sea urchin, Hemicentrotus pulcherrimus and the starfish, Asterina pectinifera were separated by manual bisection to obtain pairs of nucleate and non-nucleate fragments. Simultaneous observation on the pair revealed that the cyclic change in the cortical tension in the non-nucleate fragment was definitely prolonged than the cleavage interval of nucleate partner by about 30%. Activated non-nucleate cytoplasmic fragments derived from the unfertilized eggs and colchicine treated whole eggs of H. pulcherrimus still showed the same degree of prolongation.

Absence of Species Specificity of Germinal Vesicle Factor Required for the Cytoplamic Cycle During Meiotic Division: (starfish oocyte/meiotic division/germinal vesicle/cortical tension/cytoplasmic cycle).

Germinal vesicles (GV) of starfish oocytes are known to contain some factor(s) indispensable for inducing cyclic cytoplasmic activity, which may be involved in driving meiotic cell cycle. We have examined species specificity of the factor by injecting enucleated oocytes of the starfish, Asterina pectinifera, with GV contents of either different starfish (Asterias amurensis, Astropecten scoparius) or sea cucumber (Holothuria moebi). The injected oocytes showed cyclic changes in cortical tension after treatment with 1-methyladenine. Thus the nature of the factor appears similar among echinoderms. Growing oocytes of A. pectinifera much smaller (75% in diameter) than fully-grown oocytes did contain the factor to rescue the enucleated oocytes, even though such small oocytes themselves did not respond to 1-methyladenine. This result suggests that the factor begins to accumulate at the earlier stage of oogenesis.

Effects of tooth-conditioning agents on bond strength of a resin-modified glass-ionomer sealant to enamel.

OBJECTIVES: The purpose of this study was to evaluate the effects of tooth-conditioning agents on bond strength of resin-modified glass-ionomer sealant (Fuji III LC) to bovine enamel as well as on dissolution of calcium ions from the bovine enamel surfaces. METHODS: The enamel surfaces of bovine lower incisors were treated with 10 and 20% polyacrylic acid, 12% citric acid and 35% phosphoric acid for 20s. Fuji III LC was applied to the etched enamel surfaces, and the shear bond strength of each specimen was measured using an Instron Universal Testing Instrument. The amounts of calcium ions dissolved from the treated enamel surfaces were also measured using a polarized Zeeman atomic absorptiometer. RESULTS: In specimens pretreated with distilled water, 10% polyacrylic acid, 20% polyacrylic acid, 12% citric acid and 35% phosphoric acid, the mean values of shear bond strength were 5.5, 12.5, 15.2, 15.2 and 15.1MPa, respectively, and the amounts of Ca(2+) dissolved from the enamel surfaces were 5.6, 41.4, 88.5, 131.6 and 588.3 microg/cm(2), respectively. CONCLUSIONS: The adhesion of a resin-modified glass-ionomer sealant to bovine enamel was significantly improved by the use of tooth-conditioning agents. Especially, treatment of an enamel surface with 20% polyacrylic acid results in good shear both strength and relatively small degree of enamel erosion.

A longitudinal study on Raynaud's phenomenon in workers using an impact wrench.

OBJECTIVES: The purpose of this study was to clarify the occurrence of Raynaud's phenomenon among workers using an impact wrench for a long time. METHODS: The subjects were 704 workers regularly using an impact wrench and taking special medical examinations for vibration syndrome from 1981 to 2008. Raynaud's phenomenon was observed in 39 subjects during the observation period. RESULTS: The mean operating years at the occurrence of Raynaud's phenomenon was 25.5 ± 8.3 (standard deviation) yr. The mean total operating time (geometric average) at the occurrence of Raynaud's phenomenon was 11,689 h. By the person-year method, the incidence rate of Raynaud's phenomenon was 6.27 persons per 1,000 person-years. The estimated risk of developing Raynaud's phenomenon did not increase until 12 years after starting to operate an impact wrench but increased exponentially after that. The vibration level of an impact wrench (from 4.9 m/s(2) to 22.6 m/s(2)) exceeded the occupational exposure limit value (4.9 m/s(2)). Various countermeasures, such as introducing automatically apparatus and keeping the working environment warm to protect from cold exposure, were taken at the factory. CONCLUSIONS: These findings showed that the rate of occurrence of Raynaud's phenomenon was not high, although the vibration level of the impact wrench was high. This may result from various countermeasures to prevent the occurrence of Raynaud's phenomenon. A long period of exposure to vibration had the potential to lead to the occurrence of Raynaud's phenomenon even under various countermeasures.

Formation of polar-body-like structures induced in polyspermic starfish oocytes that had been inseminated at the germinal vesicle stage.

Immature starfish oocytes, which are arrested at the first meiotic prophase and contain a large nucleus called the germinal vesicle (GV), are known to accept multiple sperm on insemination. We found that if these polyspermic starfish oocytes are induced to mature, they often form small protrusion(s) adjacent to the first polar body emitted shortly earlier. We refer to these protrusion(s) as 'polar-body-like structures (PLS).' Fluorescent staining of PLS indicated that they were not merely cytoplasmic protrusions, but contained some chromatin. Maturing process of these polyspermic oocytes was examined by immnofluorescent staining, which showed that: (i) numerous sperm asters were observed after the onset of GV breakdown; (ii) before the first polar body (PB1) emission, a complex microtubular structure resembling a multipolar spindle was formed; and (iii) several isolated asters were observed after PB1 emission. These results indicate that PLS formation may be induced by interaction of meiosis-I spindle with paternal centrosomes incorporated at GV stage.

Malformation of immature starfish oocytes by theonellapeptolide Ie, a Tridecapeptide lactone from a marine sponge Petrosia species, through disturbance of cortical F-actin distribution.

Theonellapeptolide Ie (Tp), an oligopeptide lactone isolated from a marine sponge, Petrosia sp., was shown to induce an unprecedented morphological change in the immature oocytes of the starfish Asterina pectinifera. The cortical F-actin was disturbed and assembled to form dots and rings, as evidenced by staining with rhodamine-conjugated phalloidin. The oocyte eventually became malformed. When Tp was added to an immature oocyte which had been pretreated with cytochalasin B or D, inhibitors of actin polymerization, no malformation was observed. When Tp was added to an oocyte which had been induced to mature by 1-methyladenine (1-MeAde), a maturation-inducing substance in starfishes, no morphological changes were observed in the maturing oocytes which reached the first meiotic prometaphase 40 min after the start of 1-MeAde treatment. This is the first description of a chemical that induces aberrant redistribution of F-actin-based cytoskeleton in an animal oocyte which is arrested at the first meiotic prophase.