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This follow-up study was conducted over 30 years in a cadmium-polluted area of Japan. Urinary cadmium (U-Cd) concentration decreased by nearly half from 1986 to 2008 in men and women. However, it increased from 2008 to 2014 and maintained similar levels in 2016. Because renal atrophy may induce an increase in U-Cd, kidney volumes were determined using magnetic resonance imaging (MRI) scans in 2018. Based on the MRI results, we divided the participants into two groups, namely the normal group (n = 6, three men and three women) and the lesion group (n = 6, three men and three women). The level of urinary N-acetyl-β-d-glucosaminidase/creatinine (U-NAG/Cr) in the lesion group was significantly higher than in the normal group. The level of serum alkaline phosphatase (Al-P) was positively associated with U-Cd. Age and renal cortex volumes showed significantly negative associations. However, U-Cd and renal cortex and kidney volumes showed no significant associations. These results suggest that U-NAG and serum Al-P were sensitive biomarkers to reflect renal tubular dysfunction and bone damage caused by cadmium poisoning. Individuals chronically exposed to Cd should be observed carefully, due to the increased effect of aging on renal cortex volumes.

OBJECTIVES We investigated the support environments in companies in Ishikawa prefecture that aim to maintain a balance between work and treatment of their employees' diseases. The relationships between these strategies, company size, and type of industry were examined. METHODS In 2016, as a part of a survey, questionnaires were sent to 1,491 companies with ≥ 50 employees. Of the 688 companies who responded (response rate, 46.1%), 624 companies who provided complete main survey data were included in the final analysis. The questionnaire acquired responses on systems for arranging working hours and sick leave, the role of occupational health physicians, and the outcomes of support that was offered over the last 3 years. The targeted diseases were mental health problems, such as depression, and physical diseases. Responses were compared according to the size of the company and type of industry. RESULTS A total of 409 companies (65.5%) reported their experiences of helping employees maintain a balance between treatment and work over the last 3 years. Employees with depression received the most support. In 36.7% of the companies, some employees had retired due to their disease over the last 3 years, with the highest proportion in medical care and welfare businesses. Further, 66% of the companies had a support system to help employees with diseases, and the proportion of companies with flexible working hours and sick leave increased with the number of employees. The proportion of companies with shorter working hours and hourly paid leave was lower in the manufacturing industry and transportation/traffic business. The proportion of companies in which an occupational health physician interviewed employees who took sick leave and returned to work was 22%. CONCLUSIONS Almost 70% of the companies reported supporting workers during their disease treatment. There were some differences in arranging these support systems between companies of varying sizes and type of industry. The enablement of companies to support workers with diseases so that they keep working and receive treatment requires consideration of company characteristics.

Dementia that occurs before age 65 years is defined as young-onset dementia (YOD). YOD develops during the prime of a person's working life and has a major impact on not only work but life in general. Therefore, Japan is promoting measures to support work and social participation, taking into account the characteristics of people living with YOD. Given the rarity of YOD, few studies have examined the difficulties faced by people living with YOD during this life stage or the kinds of support they require. We believe that studying these difficulties and support requirements will contribute to prolonging the careers of people living with YOD and to providing them support during social, emotional and economic crises. This qualitative study aims to clarify the experiences of working-age Japanese people living with YOD to examine, from their perspective, possibilities for employment support. For this study, people living with YOD who were currently working were recruited by snowball sampling. This study was conducted in Japan between September 2018 and February 2019. A semi-structured interview was conducted, and the contents were transcribed and analysed using Colaizzi's qualitative methodology. Four categories were derived: (a) crisis from continuing to work, (b) seeking support, (c) overcoming challenges to work and (d) reaffirming a sense of purpose by resuming work and social participation. Participants were able to continue working and socialising by letting others know about their illness and seeking support. In the process of reaffirming a sense of purpose by resuming work and social participation, participants continued working or transitioned to socially active lives after leaving their job thanks to the support of work colleagues and medical and healthcare/welfare professionals who understand YOD. The results indicate a need for awareness raising in the workplace to promote understanding of such professional support and its significance.

The relationship between urinary β2 -microglobulin (β2 -MG) and the risk of all-cause mortality and cause-specific mortality in a cadmium (Cd)-polluted area was investigated in 3139 inhabitants (1404 men and 1735 women) of the Kakehashi River basin in Japan at 35-year follow-up. The subjects had been participants in the 1981-1982 health impact survey that assessed Cd-induced renal dysfunction, as measured by the urinary β2 -MG concentration. Hazard ratios were calculated to assess the risk of all-cause and cause-specific mortality according to the urinary β2 -MG concentrations. Risk ratios (RRs) were assessed using the Fine and Gray regression model to account for competing risks of cause-specific mortality. The mortality rate was significantly higher in participants with urinary β2 -MG concentrations >1000 μg/g creatinine (Cr) for men and >300 μg/g Cr for women. In the proportional hazard model, higher urinary β2 -MG concentrations were associated with higher risks of circulatory disease, digestive system diseases, and kidney and urinary tract diseases in men and women, and with senility for women. However, when competing risk was accounted for, the RRs were significantly higher only for kidney and urinary tract diseases in men and women (RR for each increment of 1000 μg/g Cr [95% confidence interval]: 1.02 [1.00-1.04] for men, and 1.01 [1.00-1.02] for women). The long-term prognosis of participants with renal tubular dysfunction was poor, most likely due to kidney and renal tract diseases.

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd (U-Cd) on cancer mortality in the general Japanese population. A 19-year cohort study was conducted in 1107 men and 1697 women who lived in three Cd non-polluted areas in Japan. Mortality risk ratio and 95% confidence interval (95%CI) for continuous U–Cd were estimated for all malignant neoplasms and specific cancers using a Fine and Gray competing risks regression model. The all-cause, including cancer and non-cancer mortality rates per 1000 person-years were 29.8 and 13.9 in men and women, respectively. By using Fine and Gray's method, continuous U–Cd adjusted for creatinine (+1 μg/g cre) was significantly related to mortalities for all malignant neoplasms (risk ratio = 1.06, 95%CI: 1.02–1.11) and pancreas (risk ratio = 1.13, 95%CI: 1.03–1.24) in women. In the present study, U–Cd was significantly associated with increased cancer mortality in the general Japanese population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan.

Early onset periodontitis is rarely seen in infants, though often leads to an acute and serious clinical course when encountered in such patients. Autoimmune neutropenia presents systemic and dental symptoms, as depressed resistance to bacterial infection is caused by a disorder that reduces the number of neutrophils. This disease can result in not only gingival inflammation but also destruction of periodontal tissues, such as attachment loss, alveolar bone absorption, and early tooth loss in primary as well as mixed dentition. Here, we report treatment of a child with marginal periodontitis from the age of 3 years–7 years 9 months. No systemic manifestations were noted until 3 years of age, thus the patient had never received a detailed examination or medication related to the disease. Following examinations at our department, we referred the patient to a pediatrician at our university hospital for possible systemic disease, who made a diagnosis of autoimmune neutropenia. Although administration of antibiotics and professional dental care were continued, neutrophil count was not increased and progressive periodontal destruction was observed. Extraction of teeth with poor prognosis was performed and a prosthetic strategy for the missing teeth developed. It is important to recognize that periodontitis along with autoimmune neutropenia can appear in infants, even though the incidence is quite low. Early detection and early treatment of this disease is necessary for delaying progression of periodontitis and optimal occlusal induction of permanent teeth.

We evaluated the association between urinary cadmium concentration (uCd, μg/g Cr) and risk of cause-specific mortality according to urinary β2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and β2-MG were evaluated in a survey in 1981–1982, where those participants were followed-up over 35 years later. Among the participants with a urinary β2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥10.0 compared with

Primary health care for mental health in workers should apply to actualities of workers’ stress coping and stress response. We conducted an assessment by cross-sectional study concerning stress coping, job stress, and stress response among IT employees in Japan. Subjects were 75 healthy new employees (males). We used the 54-item Maslach Burnout Inventory-General Survey (MBI-GS, domains: exhaustion, cynicism, professional efficacy), the Job Content Questionnaire (JCQ, domains: demand, control, social support), the General Coping Questionnaire (GCQ, domains: emotion expression, emotional support seeking, cognitive reinterpretation, problem solving).

Objective This study investigated associations between three indices of obesity-the body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR)-and the incidence of chronic kidney disease (CKD). Methods The employees of a company in Japan (1,725 men, 1,186 women; aged 35-55 years) had BMI, WC, and WHtR measured in health examinations. The incidence of CKD was determined at annual medical examinations over a six-year period. The hazard ratios for CKD were calculated using proportional hazard models, and the χ2 statistic was used to compare the strengths of the associations. Results The mean BMI (kg/m2), WC (cm), and WHtR were 23.6, 84.3, and 0.49 for men and 22.3, 79.7, and 0.50 for women, respectively. The incidence of CKD (/1,000 person-years) was 18.1 for men and 8.4 for women. In men, positive linear associations were observed between the BMI, WC, and WHtR and the risk of CKD, even after adjusting for the presence of metabolic abnormalities (p for trend

Aims/Introduction This cohort study assessed the risk for bodyweight gain and development of glucose intolerance based on the frequency of consumption of balanced meals including grain, fish or meat and vegetables. Materials and Methods The participants (8,573 men, 3,327 women) were employees of a company in Japan. A self‐administered questionnaire was used to evaluate the frequency of balanced meal consumption. Bodyweight changes and the incidence of glucose intolerance (glycated hemoglobin >6.0%) during the 3‐year follow‐up period were determined through annual health examinations. Results The mean bodyweight change over a period of 3 years was 0.78 kg for men and 0.84 kg for women. A lower frequency of balanced meals was associated with a higher bodyweight gain for men (P for trend = 0.004), but not for women. During the study, 464 men and 115 women developed glucose intolerance. Overall, the frequency of balanced meals was not associated with the risk of glucose intolerance in either sex. However, the interaction between the frequency of balanced meals and degree of obesity had a significant effect on the incidence of glucose intolerance in men (P = 0.005), with less frequent consumption of balanced meals being associated with a higher risk for glucose intolerance among men with a BMI ≥25.0 kg/m2 (P for trend = 0.007). Conclusions A higher frequency of balanced meals, including grain, fish or meat and vegetable dishes – important components of healthy Japanese food – was associated with a lower risk of glucose intolerance in obese men, but not in non‐obese men and women., We evaluated the risk for development of glucose intolerance based on the frequency of consumption of balanced meals including grain, fish and meat, and vegetable dishes. A lower frequency of balanced meals was associated with a higher risk of glucose intolerance in obese men.

The objective of this study was to assess the effect of environmental cadmium exposure according to urinary cadmium concentration (U-Cd) on noncancer mortality in a general Japanese population. We conducted a longitudinal study for 19 years in 2804 inhabitants (1107 men and 1697 women) in some cadmium nonpolluted regions in Japan. The participants were classified into quartiles based on U-Cd (μg/g cre) adjusted for urinary creatinine. Hazard ratio (HR) and 95% confidence interval (95% CI) for continuous U-Cd or the quartiles of U-Cd were calculated for noncancer mortality. By applying a Fine and Gray competing risk model, continuous U-Cd (+1 μg/g cre) showed significant HR for cardiocerebrovascular diseases (HR 1.05, 95% CI: 1.00-1.11), cerebrovascular diseases (HR 1.08, 95% CI: 1.01-1.16), and cerebral infarction (HR 1.11, 95% CI: 1.04-1.20) in men. However, notable significant HR for continuous and quartered U-Cd were not observed in women. In this study, U-Cd was associated with increased cardiocerebrovascular mortality in a general Japanese population, suggesting that environmental cadmium exposure is detrimental to the life prognosis in cadmium nonpolluted regions in Japan.

Odontomas are generally encountered in permanent dentition and rarely seen in primary dentition. These lesions are regarded as essentially benign, though they often cause disturbances in eruption of the associated tooth. We present clinical findings and management of 3 cases of odontomas that occurred in primary dentition, including a 3-year-old girl referred for examination of an unerupted left upper primary canine, a 6-year-old boy with an unerupted left lower second primary molar, and a 5-year-old girl who was presented with an unerupted right upper second primary molar. In all cases, periapical and panoramic radiography revealed a radio-opaque mass surrounded by a narrow radiolucent space located above the crown of the unerupted tooth. Each was diagnosed as a compound odontoma interfering with eruption of a primary tooth and surgical removal was performed under general anesthesia for all patients, with the final diagnosis based on histological findings. Following surgery, the primary canine in Case 1 spontaneously erupted, while a space maintenance appliance was applied in Case 2 and 3. It is important to recognize that an odontoma can appear in primary dentition, though the incidence is quite low. Early detection and removal of an odontoma associated with an impacted primary tooth is necessary for optimal dentition.

SummaryObjective This study investigated the relationship between frequency of skipping breakfast and annual changes in body mass index (BMI) and waist circumference (WC). Methods The participants were 4,430 factory employees. BMI and WC were measured repeatedly at annual medical examinations over a 5-year period. The association between frequency of skipping breakfast at the baseline examination and annual changes in anthropometric indices was evaluated using the generalized estimating equation method. Results The mean (standard deviation) BMI was 23.3 (3.0) kg m−2 for men and 21.9 (3.6) kg m−2 for women; and the mean WC was 82.6 (8.7) cm for men and 77.8 (9.8) cm for women. During the follow-up period, mean BMI increased by 0.2 kg m−2 for men and women, and mean WC increased by 1.1 cm for men and 1.0 cm for women. The annual change in the BMI of men who skipped breakfast four to six times per week was 0.061 kg m−2 higher, and that of those who skipped breakfast seven times per week was 0.046 kg m−2 higher, compared with those who did not skip breakfast. Annual changes in the WC of male participants who skipped breakfast seven times per week was 0.248 cm higher than that of those who did not skip breakfast. Skipping breakfast was not associated with changes in BMI or WC in women. Conclusions Skipping breakfast was closely associated with annual changes in BMI and WC among men, and eating breakfast more than four times per week may prevent the excessive body weight gain associated with skipping breakfast.

Objectives The increasing number of working elderly people has enhanced the importance of workplace health promotion activities. We investigated the association between the health status of workers approximately 60 years of age and the risk of all‐cause mortality after compulsory retirement in Japan. Methods The 2026 participants (1299 males and 727 females) had retired from a metal‐products factory at ≥60 years of age. Baseline health examinations were conducted at 60 years of age and included questions about medical history and lifestyle factors; the participants also underwent a physical examination. The participants were followed up annually by mail for an average of 7.4 years. The association between health status at age 60 years and the risk of all‐cause mortality was assessed by Cox proportional hazards regression analysis. Results During the study, 71 deaths were reported. The age‐ and sex‐adjusted hazard ratio (HR [95% confidence interval]) for all‐cause mortality was higher for males (HR, 3.41 [1.73‐6.69]) compared with females, participants with a low body mass index (

Objectives: The present cohort study investigated the relationship between serum ferritin levels and indices of insulin resistance and β-cell dysfunction in a normoglycemic population without iron overload disorders. Methods: The study participants included 575 normoglycemic Japanese men aged 35–57 years with serum ferritin levels of 400 μg/L or less. Insulin resistance and β-cell dysfunction were estimated at baseline and after 3 years by the homeostasis model assessments of insulin resistance and β-cell function (HOMA-IR and HOMA-β, respectively). To compare the subsequent changes in HOMA-IR and HOMA-β over a 3-year follow-up period among 3 groups based on tertiles of baseline serum ferritin levels (4.9–87.1, 87.2–140.5, and 140.6–396.8 μg/L), the geometric mean HOMA-IR and HOMA-β values at year 3 were calculated for each group using analysis of covariance, incorporating the respective log-transformed parameters at baseline in addition to age, body mass index and major confounding factors. Results: The multivariate-adjusted geometric mean HOMA-IR at year 3 was significantly higher in those in the highest and middle serum ferritin tertiles (1.24 and 1.22, respectively), compared with the lowest tertile (1.07) (p=0.009). When the total study participants were stratified by median body mass index (22.72 kg/m2), similar positive relationships were observed between serum ferritin levels and HOMA-IR for both obese and non-obese participants. However, the adjusted geometric mean HOMA-β at year 3 was similar among the 3 serum ferritin groups. Conclusions: Elevated serum ferritin levels predicted a subsequent increase in HOMA-IR in normoglycemic Japanese men without iron overload disorders.

Background We previously reported that perinatal dioxin exposure increased autistic traits in children living in dioxin-contaminated areas of Vietnam. In the present study, we investigated the impact of dioxin exposure on children’s eating behavior, which is often altered in those with developmental disorders. Methods A total of 185 mother-and-child pairs previously enrolled in a birth cohort in dioxin-contaminated areas participated in this survey, conducted when the children reached 3 years of age. Perinatal dioxin exposure levels in the children were estimated using dioxin levels in maternal breast milk after birth. Mothers were interviewed using the Children’s Eating Behaviour Questionnaire (CEBQ). A multiple linear regression model was used to analyze the association between dioxin exposure and CEBQ scores, after controlling for covariates such as location, parity, maternal age, maternal education, maternal body mass index, family income, children’s gestational age at delivery, and children’s age at the time of the survey. A general linear model was used to analyze the effects of sex and dioxin exposure on CEBQ scores. Results There was no significant association between most dioxin congeners or toxic equivalencies of polychlorinated dibenzo-p-dioxins/furans (TEQ-PCDDs/Fs) and CEBQ scores in boys, although significant associations between some eating behavior sub-scores and 1,2,3,4,6,7,8,9-octachlorodibenzofuran were observed. In girls, there was a significant inverse association between levels of TEQ-PCDFs and enjoyment of food scores and between levels of TEQ-PCDFs and TEQ-PCDDs/Fs and desire to drink scores. Two pentachlorodibenzofuran congeners and 1,2,3,6,7,8-hexachlorodibenzofuran were associated with a decreased enjoyment of food score, and seven PCDF congeners were associated with a decreased desire to drink score. The adjusted mean enjoyment of food score was significantly lower in children of both sexes exposed to high levels of TEQ-PCDFs. There was, however, a significant interaction between sex and TEQ-PCDF exposure in their effect on desire to drink scores, especially in girls. Conclusions Perinatal exposure to dioxin can influence eating behavior in children and particularly in girls. A longer follow-up study would be required to assess whether emotional development that affects eating styles and behaviors is related to dioxin exposure. Electronic supplementary material The online version of this article (10.1186/s12887-018-1171-2) contains supplementary material, which is available to authorized users.

Background Exposure to cadmium (Cd) via food is supposed to affect life prognosis of inhabitants of Cd-polluted area in Japan. However, there have been few reports demonstrating a significant relationship between the amount of Cd intake and mortality. We aimed to investigate the relationship between mortality and individual lifetime Cd intake (LCd) in inhabitants of the polluted Jinzu River basin, Toyama, Japan. Methods We conducted a 26-year follow-up survey in 2407 inhabitants (1208 men and 1199 women) who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The calculation of LCd in each inhabitant was based on the formula of Nogawa (Nogawa et al., 1989): (mean Cd concentration in rice of the present hamlet × 333.5 g/day + 34 μg/day) × 365 days/year × number of years of residence in the present hamlet + 50 μg/day × 365 days/year × number of years living in Cd non-polluted regions. In this formula, 333.5 g/day is the 1970 average daily intake of rice in this area, 34 µg/day is the Cd intake from foods other than rice in this area, and 50 μg/day is the average intake of Cd in non-polluted areas in Japan. Mortality risk ratios of LCd for all and specific causes were estimated after adjustments for age at baseline, smoking status, and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. Results The mortality risk ratios of LCd (+ 1 g) for all causes in women were significantly dose-dependently increased (risk ratio: 1.08). Relative risk of LCd for kidney and urinal tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly higher in women. Conclusions The present study documents that individual LCd dose-dependently decreased life prognosis over long-term observation in women. LCd was significantly related to the increased mortality for renal disease and toxic effect of Cd in women. The result provides clear evidence that life prognosis was adversely affected by Cd-exposure, especially in women.

The present cohort study assessed the risk among Japanese men for developing type 2 diabetes, based on the percentage of energy intake from carbohydrates and degree of obesity. Participants and Methods: The participants were 2,006 male factory employees, and the macronutrient intake of each patient was measured using a self-administered diet history questionnaire. The incidence of diabetes was determined in annual blood examinations over a 10-year period. Results: During the study, 232 participants developed diabetes. The crude incidence rates (/1,000 person-years) for different levels of carbohydrate intake as a percentage of calories consumed (65.0% of energy intake) were 16.5, 14.4, 12.7 and 17.6. Overall, carbohydrate intake was not associated with the risk of diabetes. However, there was significant interaction between carbohydrate intake and degree of obesity on the incidence of diabetes (P for interaction = 0.024). Higher carbohydrate intake was associated with elevated risk for diabetes among participants with a body mass index ≥25.0 kg/m2 (P for trend = 0.034). For obese participants, the multivariate-adjusted hazard ratio for those with carbohydrate intakes >65% energy was 2.01 (95% confidence interval 1.08-3.71), which was significantly higher than that of participants with carbohydrate intakes 50.0-57.4% energy. Conclusions: Higher carbohydrate intake was associated with higher risk of diabetes in obese participants, but not in non-obese participants. Obese participants with carbohydrate intakes >65% energy should reduce their intakes to levels within the desirable carbohydrate energy proportion for Japanese (50-65% energy) to prevent development of type 2 diabetes. © 2016 Asian Association for the Study of Diabetes and John Wiley & Sons Australia, Ltd.

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all-cause mortality in the Japanese general population. A 19-year cohort study was conducted in 1067 men and 1590 women aged 50 years or older who lived in three cadmium non-polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U-Cd (µg g−1 cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U-Cd or the quartiles of U-Cd were estimated for all-cause mortality using a proportional hazards regression.The all-cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U-Cd (+1 µg g−1 cre) was significantly related to the all-cause mortality in men (HR 1.05, 95% CI: 1.02–1.09) and women (HR 1.04, 95% CI: 1.01–1.07). Furthermore in men, the third (1.96–3.22 µg g−1 cre) and fourth quartile (≥3.23 µg g−1 cre) of U-Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03–1.77, fourth: HR 1.64, 95% CI: 1.26–2.14) for all-cause mortality compared with the first quartile (

The aim of this study was to investigate the relationship between mortality and rice cadmium (Cd) concentration in inhabitants of a polluted area in Japan. The target subjects were inhabitants of the Jinzu River basin who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The mean rice Cd concentration in each hamlet was used as an index of the Cd exposure. We conducted a 26 year follow-up survey in 3281 inhabitants (1544 men and 1737 women) whose data regarding the rice Cd concentration were available. Mortality risk ratios for all and specific causes were estimated after adjustments for age at baseline, smoking status and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. The mortality risk ratios of rice Cd concentration (+0.1 ppm) for all causes in women were significantly increased (risk ratio: 1.04). Furthermore, the relative risks of rice Cd concentration for kidney and urinary tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly increased in both sexes. These findings indicated that increased rice Cd concentration decreased the prognosis for life over a long-term observation in women. This result provides important information for determining the worldwide standard for allowable rice Cd concentration.

Aims To examine the relation of insulin resistant status determined by homeostasis model assessment of insulin resistance (HOMA-IR) with the risk of incident hyperuricemia. Methods The study participants included 2071 Japanese men without hyperuricemia and diabetes, aged 35–54 years. The participants had undergone annual heath examinations for 6 years to compare incident hyperuricemia (serum uric acid >416.4 μmol/L (7.0 mg/dL) and/or taking medication for hyperuricemia) in four groups based on quartiles of baseline HOMA-IR. Results During follow-up there were 331 incident cases of hyperuricemia. The hazard ratios for hyperuricemia, compared with HOMA-IR ≤0.66, were 1.42 (95% confidence interval 1.02–1.98) for HOMA-IR 0.67–0.98, 1.20 (0.86–1.68) for HOMA-IR 0.99–1.49 and 1.44 (1.04–1.98) for HOMA-IR ≥1.50 after adjustment for baseline serum uric acid, creatinine, hypercholesterolemia and hypertension status, age, alcohol intake, and smoking and exercise habits. The hazard ratio associated with an increase of one standard deviation in lnHOMA-IR (1.85 as one geometric standard deviation of HOMA-IR) was 1.14 (1.03–1.28) ( p for trend = 0.02). Conclusions Increased HOMA-IR independently predicted the subsequent development of hyperuricemia. Insulin resistance itself or compensatory hyperinsulinemia may contribute to the development of hyperuricemia.

We investigated the relation between overall sleep status based on the modified Pittsburgh Sleep Quality Index (PSQI) global score and subsequent changes in serum high-sensitivity C-reactive protein (hsCRP) in a population of Japanese factory workers, who were predominantly female. A total of 991 Japanese with inflammation classified as low cardiovascular risk (baseline hsCRP 1.0 mg L(-1) ) were grouped according to the presence or absence of unfavourable sleep, defined as a modified PSQI global score 5.5 points. The subsequent changes in hsCRP after 3 years were then compared in the two groups. Analysis of covariance incorporating log-transformed baseline hsCRP, age, sex, lifestyle and physical and biochemical profiles was used to compare the geometric means of hsCRP at year 3 in each sleep status group. A logistic regression model incorporating the same variables was used to calculate the odds ratios for development of inflammation with a medium-to-high cardiovascular risk (hsCRP at year 3 ≥ 1.0 mg L(-1) ) comparing the presence or absence of unfavourable sleep habits. The multivariate-adjusted geometric mean of hsCRP at year 3 was significantly higher in subjects with unfavourable sleep habits compared with those with a normal pattern (0.275 versus 0.242 mg L(-1) ). The multivariate-adjusted odds ratio for developing increased and potentially pathogenic levels of inflammation due to unfavourable sleep was 2.08 (95% confidence interval = 1.29-3.35). There was a significant linear trend for the development of increased inflammation across the modified PSQI global scores (P = 0.04). Unfavourable sleep is associated with activation of low-grade systemic inflammation.

The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and mortality. A 19-year cohort study was conducted in 900 men and 1313 women in 1993 or 1994 who lived in two cadmium non-polluted areas in Japan. Hazard ratio (HR) and 95% confidence interval (95% CI) of urinary β2-microglobulin (β2-MG) and N-acetyl-β-glucosaminidase (NAG) for mortality were calculated using a proportional hazard regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. Simultaneously, the dose-effect relationship between renal tubular markers and urinary cadmium at baseline was evaluated using multiple regression analyses. In men, HR was significant for β2-MG (HR corresponding to an increase of 100 μg/g cre: 1.02) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.05). In women, a significant HR was observed for β2-MG (HR corresponding to an increase of 100 μg/g cre: 1.01) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.02). Dose-effect relationships were significant for urinary cadmium and all renal tubular markers in men and women. The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium non-polluted areas in Japan.

Aims: The aim of this study was to investigate age-related differences in the relationship between work-related factors and heavy drinking. METHODS: This study in 3398 male workers at a factory in Japan examined data on heavy drinking, defined as an alcohol consumption >40 g/day, and work-related factors including occupation, shift work, and job stress evaluated using the Japanese version of the Karasek's Job Content Questionnaire (JCQ). In the present cross-sectional study, alcohol consumption was assessed using a self-administered diet history questionnaire (DHQ). RESULTS: The prevalence of heavy drinkers in the study population was 15.5% and rose with increasing age. An increase in the odds ratio (OR) for heavy drinking was observed consistently in blue-collar workers compared with white-collar workers in all age groups. In subjects aged 20-29 years, shift work had also increased the OR for heavy drinking. In subjects aged 40-49 years, the two groups with a lower decision latitude had an increased OR compared with the highest group. The adjusted OR for individuals who received the lowest level of social support in the workplace was increased significantly compared with the highest group (4.22 [95%CI, 1.07-16.62]). On the other hand, social support showed a positive association with heavy drinking in subjects aged 40-49 and 50-59 yr. Job demand was not related to heavy drinking in any of the age groups. CONCLUSION: Our findings suggest that occupation and work schedule are related to alcohol use more apparently in a younger age group and that psychosocial factors are related to enhancement or prevention of alcohol use. Language: en

Objective This cross-sectional study investigated the associations between the serum thyroid-stimulating hormone (TSH) concentration and indices of obesity in middle-aged Japanese men and women. Methods The participants were 2,037 employees (1,044 men and 993 women; age, 36-55 yr) of a metal products factory in Japan. Clinical examinations were conducted in 2009. We obtained a medical history and anthropometric measurements (body weight, body mass index [BMI] and waist circumference) and measured the serum TSH concentrations. The anthropometric indices were compared across serum TSH quartiles. The associations were evaluated separately according to the smoking status in men. Results The mean body weight (kg), BMI (kg/m(2)) and waist circumference (cm) were 69.2, 23.7 and 83.2 in men and 55.3, 22.3 and 74.3 in women, respectively. Men with a higher TSH concentration had higher body weight and BMI values (p for trend=0.016 and 0.019, respectively), and these significant associations were observed even after adjusting for age, smoking status and other potential confounders. The TSH level was not associated with waist circumference. We found a significant interaction between the TSH level and the smoking status on body weight (p for interaction=0.013) and a significant association between the TSH level and body weight in nonsmokers, but not in current smokers. No significant associations were observed between the TSH level and the anthropometric indices in women. Conclusion Significant positive associations between the serum TSH concentration, body weight and BMI were detected in men only, and an interaction with the smoking status was observed for this association.

Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established.Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6 mg/kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events.This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed.Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.

Aims: To investigate the effects of shift work on increased alcohol intake associated with poor sleep quality. Methods: This cross-sectional survey evaluated the correlation between work schedule, poor sleep quality and heavy drinking among 909 factory workers aged 35-54 years in Japan. Subjects included 530 day workers, 72 shift workers who did not work at night and 290 shift workers who engaged in night work. Heavy drinking was defined as a mean volume of alcohol consumption exceeding 60 g/day. Results: Compared with other workers, night-shift workers who suffered poor sleep quality exhibited the highest frequency of heavy drinking (17.6%). Multiple logistic regression analysis demonstrated that compared with day workers with good sleep, night-shift workers who experienced poor sleep had more than twice the odds of heavy alcohol consumption (odds ratio 2.17 [95% confidence interval (CI), 1.20-3.93]). Shift workers who did not work at night and day workers with poor sleep were not at increased odds of heavy drinking. Conclusion: Shift workers who engage in night work may try to modify their health behavior to cope with sleep problems. Such modification may be a risk factor for heavy drinking. Language: en

Objective: This cohort study investigated the association between eating speed and the incidence of type 2 diabetes in middle-aged Japanese men. Materials/Methods: Participants were 2,050 male employees of a metal products factory in Japan. We measured self-reported categorical eating speed. The incidence of diabetes was determined in annual medical examinations over a 7-year period. The association between eating speed and the incidence of diabetes adjusted for multiple variables (age, family history of diabetes, smoking, alcohol drinking, habitual exercise, and presence of hypertension and hyperlipidemia) was evaluated using Cox proportional hazards models. Results: The prevalence of obesity (BMI ≥ 25 kg/m 2) across the categories of eating speed (slow, medium, and fast) was 14.6, 23.3, and 34.8%, respectively, and a faster eating speed was associated with a higher prevalence of obesity. During the study, 177 participants developed diabetes. Crude incidence rates (/1,000 person-years) across the three categories of eating speed were 9.9, 15.6, and 17.3, respectively. Multivariate-adjusted hazard ratios (95% CI) across the categories were 1.00 (reference), 1.68 (0.93-3.02), and 1.97 (1.10-3.55), respectively, and eating speed was associated with the risk of diabetes (p for trend = 0.030). After further adjustment for BMI, a significant association was not observed. Conclusions: Eating speed was associated with the incidence of diabetes. Since these associations were not significant after adjusting for BMI, eating speed may act via its effect on body weight. Eating speed is a controllable risk factor, and eating slowly could be an acceptable lifestyle intervention for the prevention of diabetes mellitus. © 2012 Elsevier Inc. All rights reserved.

Background: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. Conclusion: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

We investigated the incidence and clinical characteristics of diabetic medication-induced severe hypoglycemia (DMISH) in an emergency department (ED) from 2005 to 2013. The observation was performed in two separate periods (1 July 2005–31 October 2006 and 1 July 2012–31 October 2013) in the ED of Asahikawa Red Cross Hospital. The number of DMISH cases (48 during 2005–2006, and 47 during 2012–2013) and their proportions of all emergency visits (0.77 % during 2005–2006, and 0.79 % during 2012–2013) were almost identical for the two periods. Patients’ mean age (years) was 69.8 during 2005–2006 and 73.8 during 2012–13. Mean HbA1c of the patients was 6.72 % during 2012–2013 and 7.27 % during 2005–2006. Plasma glucose level at ED arrival was significantly higher and hospitalization rate of hypoglycemic patients was significantly lower during 2012–2013 than during 2005–2006. Mean sulfonylurea dose, converted to glimepiride, was 3.0 mg during 2005–2006 and 2.3 mg during 2012–2013. The number of patients living alone increased by 63 %, and those living with younger family members decreased by 50 % during 2012–2013 compared with that during 2005–2006. Although there has been progress in avoiding severe hypoglycemia from 2005 to 2013, the increased number of isolated older diabetic elderly seems to have counteracted clinicians’ efforts. A patient-centered approach that sets individualized glycemic targets and selects treatment that balances efficacy and safety is key to avoiding severe hypoglycemia. Improved social support for diabetic elderly patient is also important.

Objectives Although previous epidemiological studies have investigated the relationship between sleep duration and various cardiovascular events, the results have been inconsistent. Accordingly, we conducted a follow-up survey to investigate the relationship between sleep duration and cardiovascular events among male workers, accounting for occupational factors that might confound the true relationship. Methods A total of 2282 male employees aged 35–54 years based in a factory in Japan were followed for 14 years. The risk of cardiovascular events was compared among 4 groups stratified based on sleep duration at baseline (

Little is known about the relationship between the HOMA of insulin resistance (HOMA-IR) and the risk of cardiovascular events in Asian populations, which have lower levels of HOMA-IR than Western populations. Accordingly, we determined the predictive value of HOMA-IR for cardiovascular risk in a Japanese population that was apparently free of diabetes, addressing whether insulin resistance itself increases cardiovascular risk independently of other relevant metabolic disorders.We followed 2,548 non-diabetic men aged 35 to 59 years for 11 years. The hazard ratios for the incidence of cardiovascular events due to increased HOMA-IR were estimated using a Cox proportional hazards model that was adjusted for potential confounding factors.The multivariate-adjusted hazard ratio for cardiovascular events compared with the first quartile of HOMA-IR (or=0.66) was 1.07 (95% CI 0.44-2.64) for the second (HOMA-IR 0.67-1.01), 1.36 (0.56-3.28) for the third (HOMA-IR 1.02-1.51) and 2.50 (1.02-6.10) for the fourth quartile (HOMA-IRor=1.52). The hazard ratio associated with a one SD (0.61) increment in log-transformed HOMA-IR was 1.51 (1.13-2.02). A similar positive relationship was observed for coronary events and stroke. In addition, the relationship between HOMA-IR and cardiovascular risk was broadly similar in participants with and without hypertension, dyslipidaemia (elevated triacylglycerol and/or reduced HDL-cholesterol), abdominal obesity and current smoking.Increased HOMA-IR predicted subsequent cardiovascular events in non-diabetic Japanese men. The association was independent of traditional cardiovascular risk factors and other relevant metabolic disorders.

金沢大学医薬保健研究域医学系, 金沢医科大学健康増進予防医学（公衆衛生学）, Aims This study investigated the relationship between waist circumference and the subsequent incidence of Type 2 diabetes and the association with insulin resistance and pancreatic B-cell function in relatively lean Japanese individuals. Methods The study participants were 3992 employees (2533 men and 1459 women, aged 35-55 years) of a metal-products factory in Japan. The incidence of diabetes was determined in annual medical examinations during an 8-year follow-up. We calculated age- and sex-adjusted hazard ratios (HRs) according to the sex-specific quintile of waist circumference at baseline. Differences in baseline insulin resistance [homeostatis model assessment (HOMA)-IR] and pancreatic B-cell function (HOMA-B) were compared between participants who developed diabetes and those who did not. Results During the follow-up, 218 participants developed diabetes. Age- and sex-adjusted HRs across the quintiles of waist circumference were 1.78, 1.00 (reference), 1.59, 3.11 and 3.30, respectively (P for trend, < 0.0001). The HR for the lowest quintile was significantly higher than that for the second quintile. Among participants with waist circumference of the lowest quintile, HOMA-B was lower in those who developed diabetes than in those who did not [33.1 (24.1-45.0) vs. 54.3 (37.9-74.6) median (interquartile range), P < 0.0001], but HOMA-IR did not differ between these groups. Conclusions There was a J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes in relatively lean Japanese individuals; lower pancreatic B-cell function may also increase the risk of diabetes in very lean Japanese people. © 2009 Diabetes UK.

Aim The purpose of this study was to examine the relationship between stress coping and burnout in Japanese hospital nurses. Background Findings on effective stress management training are required in order to reduce nurse’s stress and prevent it from becoming chronic. Methods The study included 1291 nurses who completed the General Coping Questionnaire and the Japanese version of the Maslach Burnout Inventory-General Survey. The data were analysed using structural equation modelling. Results In women, a frequent use of cognitive reinterpretation predicted low exhaustion and cynicism and high professional efficacy. In men, a frequent use of problem solving predicted low cynicism and high professional efficacy. Although for women, a frequent use of problem solving predicted high professional efficacy that was similar to men, there was also a concurrent high exhaustion. Conclusion These findings suggested that enhancement of cognitive coping skills for women and problem-solving skills for men could contribute to a reduction of burnout in nurses. Implications for nursing management Our findings suggested that effective intervention strategies in order to prevent hospital nurse’s stress from becoming chronic might be different between men and women. This difference should be taken into account in nursing management.

Objectives: The purpose of this longitudinal study was to investigate the effects of burnout on risk factors for arteriosclerotic disease. Methods: Baseline data were collected from 442 male middle managers working for a manufacturing company in Japan. All participants had a physical health check-up and completed the Japanese Maslach Burnout Inventory-General Survey. We calculated the Japanese-specific cut-off points of the MBI-GS and applied "exhaustion +1" criterion to define subjects as healthy or burnout at baseline. Follow-up measures were collected 4-5 yr later for 383 middle managers. Changes in the subjects' waist circumference, body weight, body mass index (BMI), blood pressure, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, fasting blood sugar, fasting insulin, HOMA-R, and HbA1c over a time period of 4 to 5 yr were compared between the healthy and burnout groups. New cases of large waist circumference, high BMI, metabolic syndrome, hypertension, hypercholesterolemia, high triglycerides, low HDL cholesterol, high LDL cholesterol, and impaired fasting glucose were detected at follow-up. Results: Changes in waist circumference, body weight, and BMI were significantly greater in burned-out managers than in healthy managers. Furthermore, compared to other variables (age and health behaviors such as smoking), burnout was a significant explanatory variable. The odds ratio of the burnout group was 2.80 for hypercholesterolemia with statistical significance after adjusting for age. After adjusting for age, health behaviors, and baseline total cholesterol, the results were similar. Conclusions: Burnout, which results from prolonged exposure to chronic work stress, may be associated with risk factors for arteriosclerotic disease.

Background: Mikulicz’s disease (MD) has been considered as one manifestation of Sjogren’s syndrome (SS). Recently, it has also been considered as an IgG 4 -related disorder. Objective: To determine the differences between IgG 4 -related disorders including MD and SS. Methods: A study was undertaken to investigate patients with MD and IgG 4 -related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG 4 -positive multiorgan lymphoproliferative syndrome (IgG 4 +MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG 4 (>135 mg/dl) and infiltration of IgG 4 + plasma cells in the tissue (IgG 4 +/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG 4 +MOLPS and 31 patients with typical SS were compared. Results: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG 4 +MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG 2 , IgG 4 and IgE levels were significantly increased in IgG 4 +MOLPS. Histological specimens from patients with IgG 4 +MOLPS revealed marked IgG 4 + plasma cell infiltration. Many patients with IgG 4 +MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG 4 + cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG 4 +MOLPS treated with glucocorticoids showed marked clinical improvement. Conclusion: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG 4 +MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG 4 +MOLPS.

The aim of this study was to investigate the effects of shift work on nutrient intakes, including macronutrient intake and micronutrient intake, in a large sample size. The study population included 2,254 male manual workers, 20-59 yr of age, employed in a factory. A self-administered diet history questionnaire was used. The subjects were classified into 3 groups according to their work schedule: (i) fixed day workers; (ii) shift workers without midnight shifts; and (iii) shift workers with midnight shifts. The nutrient intakes of the groups were compared by age group. There was a significant difference in nutrient intakes between subjects aged 20-29 yr and those aged 30 yr and over. Among subjects aged 20-29 yr, the energy density value for saturated fat and the energy adjusted intakes of calcium, potassium, vitamin A, and vitamin B1 were the lowest among shift workers with midnight shifts. Among subjects aged 30 yr and over, the total energy intake was the highest among shift workers with midnight shifts; the difference was significant compared to fixed day workers. Shift workers with midnight shifts had the highest intake of cereals among subjects 30 yr of age and older. In conclusion, there were no significant differences in nutrient intakes between fixed day workers and shift workers without midnight shift. Shift work, particularly midnight shift work, affected nutrient intake. The impact of shift work on nutrient intakes differed by age and the type of shift work.

Background There have been few large-scale nationwide studies investigating both the prognosis and the prognostic factors of idiopathic dilated cardiomyopathy (IDC). A predictive score that can be used in clinical practice has not been established. Methods and Results A nationwide epidemiological study of the prognosis of IDC was conducted in 1999 among randomly selected hospitals in Japan, and 147 departments participated in the present 5-year follow-up survey. The vital status of 1,554 IDC patients was collected in 2004 using medical records and residence-based registers. The crude 5-year survival rate for those diagnosed in 1998 was 78.6%. Cox's regression model selected 5 independent predictors of mortality: male sex, higher age, higher New York Heart Association functional class, higher left ventricular diameter index, and lower left ventricular ejection fraction. A predictive score using these 5 variables effectively predicted prognosis; 5-year survival rates were 90.6% in patients with a score of 4 or less and 49.0% in patients with a score of 9 or 10. Conclusions This nationwide survey revealed the present prognostic status of IDC in Japan and 5 independent predictors of prognosis that can be used in clinical practice as a predictive score. (Circ J 2008; 72: 343 - 348)

Objective: To investigate prognosis and prognostic factors in patients with hypertrophic cardiomyopathy (HCM) in Japan. Design: A nationwide epidemiological study. Setting: Hospitals selected randomly from among all hospitals in Japan. Patients: Clinical and epidemiological information for 2155 patients with HCM were collected in 1999. Main outcome measures: Patients were classified on the basis of baseline prognostic factors. Survival rates up to 5 years were calculated by Cox’s proportional hazard model for 1605 patients. Results: During the follow-up period, 241 deaths were recorded. The crude 5-year survival rate for the entire cohort was 86% (95% CI 84 to 88), and annual mortality ranged from 2.2% to 3.0%. A higher cardiothoracic ratio on chest x ray (HR 1.61; 95% CI 1.26 to 2.05, with 1 SD (6.2%) increase), a lower left ventricular ejection fraction (HR 1.42; 95% CI 1.20 to 1.69, with 1 SD (13%) decrease) and the presence of left bundle branch block (HR 3.14; 95% CI 1.28 to 7.71) were independently associated with a poorer prognosis, whereas the presence of apical hypertrophy at baseline (HR 0.58; 95%CI 0.36 to 0.92) predicted a better chance of survival. Conclusions: The nationwide survey of patients with hypertrophic cardiomyopathy yielded important information on its prognosis and prognostic factors. These observations afford, for the first time, a measure of risk stratification in patients with HCM in Japan.

Objectives The aim of this cohort study was to investigate the effects of shift work on changes in parameters related to metabolic disturbances. Methods The study population included 1529 male blue-collar workers, aged 19–49 years at baseline, working in a sash and zipper factory in Japan. The participants were divided into four groups according to the work schedule at baseline, the end point being workers doing fixed daytime work in both years (day–day), workers who changed from shift work to fixed daytime work (shift–day), workers who changed from fixed daytime work to shift work (day–shift), and workers doing shift work in both years (shift–shift). The changes in body mass index (BMI), blood pressure, serum cholesterol, and glycosylated hemoglobin A1c over a period of 10 years were compared among the groups by work schedule. Results The age-adjusted mean increase in BMI was 1.03 kg/m 2 for the day–shift workers, and it was significantly larger than that of the day–day workers and shift–day workers. The shift–shift workers showed a significantly larger increase in BMI than the day–day workers. These tendencies remained after adjustment for age and all other confounding factors, such as BMI, smoking, drinking, and leisure-time physical activity at baseline. The increase in total cholesterol tended to be higher among the shift–shift workers and the day–shift workers, but there were no significant differences. Blood pressure and hemogrlobin A1c did not differ among the four groups. Conclusions Shift work is considered to be a risk factor for excess weight. However, no significant difference in the biomarkers was found between daytime workers and shift workers.

Objectives: This study was undertaken to examine the association between sickness absence in Japanese employees and job demand/control and occupational class as psychosocial work characteristics. Methods: The study was cross-sectional in design with data collected from 20,464 male and 3,617 female employees, whose mean age was 40.9 years (SD ± 9.1 years) and 36.9 years (SD ± 10.8 years), respectively. The participants were asked to write the total number of sick leaves they had taken during the past year, and a comparison was made between the group with more than 6 days of sickness absence and the group with 0–6 days as a reference group. Job demands, job control, and worksite support from supervisors and colleagues were analyzed by the Job Content Questionnaire, and likewise by the Generic Job Stress Questionnaire of the National Institute for Occupational Safety and Health. Results: Both low job control and low support at the worksite were associated with a high frequency of sickness absence. But there was no clear relationship between job demands and sickness absence. The lowest sickness absence rate was found in male managers and the highest in male and female laborers. Conclusion: This is the first report of a large-scale survey of Japanese employees to show a high frequency of sickness absence associated with increased work stress and a socioeconomically low occupational class.

The influence of cadmium (Cd) body burden on mortality remains controversial. Excess mortality and the dose-response relationship between mortality and urinary cadmium excretion were investigated in this study among environmentally exposed subjects. A 15-year follow-up study was carried out on 3119 inhabitants (1403 men and 1716 women) of the Cd-polluted Kakehashi River basin, whose urinary Cd concentration was examined in a 1981-1982 health impact survey. The mortality risk of high urinary Cd (or = 10 microg/g Cr) subjects after adjustment for age using Cox's proportional hazard model was higher than that of moderate urinary Cd (10 microg/g Cr) subjects in both sexes. When the subjects were divided into five groups according to the amount of urinary Cd (3, 3-5, 5-10, 10-20,or = 20 microg/g Cr), the mortality risk was significantly increased among the subjects with urinary Cdor = 3 microg/g Cr in proportion to the increases in the amount of urinary Cd concentration after adjustment for age, especially in women. Furthermore, special causes of death among high and moderate urinary Cd were investigated, and mortality risk ratio for heart failure, which is a cause of death often diagnosed in cases with a gradual deterioration culminating in death, was significantly increased in both sexes, compared with the moderate urinary Cd subjects. Also, in women the mortality risk for renal diseases in the high urinary Cd subjects was significantly higher than that in the moderate urinary Cd subjects. These results suggest that a causal association between Cd body burden and mortality exists among inhabitants environmentally exposed to Cd but that no special disease may be induced except renal diseases.

We examined the influence of the Q89R variant in low-density lipoprotein receptor-related protein 5 on hypertension in a large Japanese cohort. We used multivariate logistic regression analysis to adjust for the effects of other factors known to influence hypertension such as age, body mass index, blood chemistry and lifestyle. Our cohort consisted of 1444 males and 1161 females selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as systolic blood pressure 140 mmHg and/or diastolic blood pressure 90 mmHg or the use of antihypertensive medication. Because the RR genotype was so rare (three normotensive males and three normotensive females), they were excluded from analyses. Genotype distributions for Q89R in hypertensive females (QR = 14, QQ = 60) were significantly different (p = 0.033) from normotensive females (QR = 113, QQ = 971). In contrast, those in hypertensive males (QR = 26, QQ = 230) and in normotensive males (QR = 145, QQ = 1040) were similar. Allele distributions were not significantly different in either gender. In females, multivariate logistic regression showed that the QR genotype was associated with hypertension with odds ratio of 2.1 compared to the QQ genotype. This study indicates that the Q89R polymorphism is an independent factor for hypertension in Japanese females.

The present study investigated the effects of job stress on cellular immune function, such as NK cell activity and NK cell subsets. The participants were 61 female nurses aged 23-59, who worked in a public psychiatric hospital in Ishikawa, Japan. Each subject completed the Nursing Job Stressor Scale (NJSS) and their NK cell activity and lymphocyte surface antigens (CD16+56+) were evaluated as immune system parameters. The NJSS has seven subscales: conflict with other nursing staff, nursing role conflict, conflict with physicians or autonomy, conflict with death or dying, quantitative work load, qualitative work load and conflict with patients. Factors influencing NK cell activity, and the proportion and cell counts of CD16+56+ lymphocytes were evaluated. Increase in quantitative work load significantly decreased NK cell activity. Conversely, no linear relationship was observed between qualitative work load and immunological variables, with the highest percentage of CD16+56+ lymphocytes observed among participants in the medium work load group. The other five NJSS subscales did not relate to immune parameters. In conclusion, the results suggest that perceived job strains, particularly quantitative work load, decreased NK cell function.

Information has been sparse on the comparison of 4 blood pressure (BP) indexes (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean BP [MBP]) in relation to long-term stroke incidence, especially in middle-aged and older Asian people. A prospective cohort study was performed in 4989 Japanese (1523 men and 3466 women) aged 35 to 79 at baseline with 10 years of follow-up. End points included stroke incidence (total, ischemic, and hemorrhagic). Multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index were determined by Cox proportional hazard analyses; Wald χ 2 tests were used to compare the strength of relationships. Analyses were also done for each of 4 age-gender groups consisting of men and women aged 35 to 64 and 65 to 79 years. During follow-up, 132 participants developed stroke. Adjusted hazard ratios for all strokes were 1.68 for SBP, 1.72 for DBP, and 1.80 for MBP, which were higher than that for PP (1.34). SBP and DBP were related positively to stroke risk after adjustment of each other. PP was not the strongest predictor in any age-gender groups among 4 BP indexes. In men aged 65 to 79 years, SBP showed the strongest relationship to all stoke risk (hazard ratio 1.62) among 4 BP indexes. In women aged 65 to 79 years, hazard ratios for all strokes were 2.48 for MBP, 2.46 for DBP, 2.25 for SBP, and 1.57 for PP. The long-term incident stroke risk of high BP in Asians should be assessed by SBP and DBP together, or by MBP, not by PP.

It has not been fully clarified whether exercise blood pressure (BP) in young adult men and women is useful to predict future BP, especially in Asian people. A long-term prospective study was conducted in graduates of a medical school in Japan; 138 men and 76 women whose mean age was 19.8 and 19.2, respectively, at baseline. A 5-min exercise tolerance test was performed at baseline, and BP immediately after exercise was measured. BP at 50% intensity exercise was also calculated. Multiple regression analysis was carried out to clarify the relationship of exercise BP at baseline to follow-up BP after an average of 12 years. In multivariate-adjusted models, the relationship of systolic blood pressure (SBP) at follow-up was stronger to SBP immediately after exercise (F=7.7, P=0.006) than to resting SBP (F=3.7, P=0.055) in men. The models in men showed that SBP immediately after exercise was a stronger predictor of follow-up SBP than SBP at 50% intensity exercise, and the results were similar for diastolic blood pressure (DBP) in men. For SBP in women, resting SBP was the strongest predictor of follow-up SBP (F=14.3, P

OBJECTIVE To examine the association between hypertension and the C825T polymorphism in the G-protein beta 3 subunit gene in Japanese workers. METHODS This study used logistic regression analysis and multiple regression analyses to investigate whether the C825T polymorphism was associated independently with hypertension or blood pressure when factors such as age, body mass index, blood chemistry and lifestyle were taken into consideration. The target subjects were 1452 male and 1169 female workers selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as a systolic blood pressure > or = 140 mmHg and/or diastolic blood pressure > or = 90 mmHg, or taking antihypertensive medication. The power of the study was estimated as 83% for males and 41% for females based on allelic frequencies in Caucasians. RESULTS Genotype distributions for C825T in hypertensive males (CC = 58, CT = 135, TT = 63) and females (CC = 20, CT = 36, TT = 20) were not significantly different from normotensive males (CC = 300, CT = 614, TT = 282) or females (CC = 274, CT = 602, TT = 217), respectively. Allele distributions were not significantly different in either sex. Multiple logistic regression analysis showed that genotype was not associated significantly with hypertension, whereas there was a significant relationship between hypertension and age, family history of hypertension, body mass index, hematocrit, platelet count, gamma-glutamyl transpeptidase (gamma-GTP) and uric acid. Data analysis using one-way analysis of variance and multiple regression showed that the C825T allele had no significant influence on either systolic, diastolic or mean blood pressure. CONCLUSIONS This study indicates that the C825T polymorphism is not a significant factor for hypertension or blood pressures in Japanese people. Targeting of this polymorphism is therefore unlikely to be beneficial when attempting to prevent hypertension in the general Japanese population.

Background Detailed epidemiological investigations on the relationship of environmental factors, especially occupational and microbiological factors, to the development of idiopathic dilated cardiomyopathy (IDC) are scarce. Methods and Results A multi-hospital case - control study was conducted in 38 hospitals throughout Japan in order to survey IDC cases and age, sex-matched outpatient controls at each hospital. Crude and adjusted odds ratios (ORs) by various environmental factors were calculated in 135 pairs of cases and controls. Univariate analyses revealed significantly increased ORs for lower education, passive smoking in the workplace, cold and/or hot workplace, symptoms of fatigue and history of bacterial infection; in contrast, decreased ORs were associated with a history of rubella and gastroduodenal diseases. Based on multivariate adjusted analyses, lower education (OR 1.96, 95% confidence interval (CI) 1.13-3.40), cold or hot workplace (OR 1.84, 95%CI 1.08-3.12) and history of measles (OR 1.78, 95%CI 1.01-3.08) exhibited a significant positive relationship with IDC risk. History of rubella (OR 0.17, 95%CI 0.06-0.52) and gastroduodenal diseases (OR 0.14, 95%CI 0.07-0.29) were inversely related to the risk. Conclusions Some occupational and microbiological factors appear to relate independently to the development of IDC and further investigation is required to establish their respective mechanisms. (Circ J 2004; 68: 1011 - 1017)

We examined the association of the G-protein beta3 subunit gene (GNB3) C825T polymorphism with overweight in Japanese workers. This cross-sectional study used multivariate analysis to investigate whether a polymorphism in the C825T polymorphism was associated independently with overweight when factors such as age and lifestyle were taken into account. The study in 1453 men and 1172 women involved identifying subjects with the C825T genotype using the polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Overweight was defined as a BMI > or = kg/m(2). Genotype distributions for C825T in overweight men (CC = 80, CT = 162, TT = 80) and women (CC = 52, CT = 91, TT = 40) were not significantly different from normal-weight men (CC = 278, CT = 588, TT = 265) and women (CC = 242, CT = 549, TT = 198). The allele distributions were also not significantly different between either sex. The power of the study was estimated as 98% in men and 81% in women based on the allelic frequencies reported in a previous positive study in Chinese subjects. Multiple logistic regression analysis showed that the genotype was not significantly associated with overweight. In conclusion, this study indicated that the GNB3 C825T polymorphism is not a significant factor for overweight in Japanese people.

Monitoring in Ishikawa Prefecture (mean population; 1,150,000), during the 20-year period from 1981 to 2000, involved monitoring the prevalence of congenital anomalies starting at gestational week 22. The main objectives of the present study were (1) to investigate the trend over the past 20 years in the prevalence of congenital anomalies, and (2) to investigate whether there is area accumulation in congenital anomalies or not. In addition, the prevalence of well-known risk factors such as smoking, drinking and family history among cases with congenital anomalies was analyzed to obtain clues to the background of such anomalies. During the 20 years, more than 200,000 births have been observed. Thirty-three selected congenital anomalies, consisting mainly of external anomalies, were analyzed in this study. The percentage of children born with congenital anomalies did not change markedly between the first and second halves of the monitoring period, remaining at approximately 4.5/1,000 births. There was also no significant change in annual trends in either Ishikawa Prefecture as a whole or in the three regions within Ishikawa. The prevalence of congenital anomalies by type showed a significant decrease in anencephaly and spina bifida. In contrast, Down syndrome and microcephaly increased significantly. The mean maternal age for Down syndrome increased significantly from the first-half period to the second-half period. The percentage of children with polydactyly whose mother smoked were relatively higher than that for the other congenital anomalies.