Separate optogenetic manipulation of Nerve/glial antigen 2 (NG2) glia and mural cells using the NG2 promoter.

Nerve/glial antigen 2 (NG2) is a protein marker of NG2 glia and mural cells, and NG2 promoter activity is utilized to target these cells. However, the NG2 promoter cannot target NG2 glia and mural cells separately. This has been an obstacle for NG2 glia-specific manipulation. Here, we developed transgenic mice in which either cell type can be targeted using the NG2 promoter. We selected a tetracycline-controllable gene induction system for cell type-specific transgene expression, and generated NG2-tetracycline transactivator (tTA) transgenic lines. We crossed tTA lines with the tetO-ChR2 (channelrhodopsin-2)-EYFP line to characterize tTA-dependent transgene induction. We isolated two unique NG2-tTA mouse lines: one that induced ChR2-EYFP only in mural cells, likely due to the chromosomal position effect of NG2-tTA insertion, and the other that induced it in both cell types. We then applied a Cre-mediated set-subtraction strategy to the latter case and eliminated ChR2-EYFP from mural cells, resulting in NG2 glia-specific transgene induction. We further demonstrated that tTA-dependent ChR2 expression could manipulate cell function. Optogenetic mural cell activation decreased cerebral blood flow, as previously reported, indicating that tTA-mediated ChR2 expression was sufficient to impact cellular function. ChR2-mediated depolarization was observed in NG2 glia in acute hippocampal slices. In addition, ChR2-mediated depolarization of NG2 glia inhibited their proliferation but promoted their differentiation in juvenile mice. Since the tTA-tetO combination is expandable, the mural cell-specific NG2-tTA line and the NG2 glia-specific NG2-tTA line will permit us to conduct observational and manipulation studies to examine in vivo function of these cells separately.

NO-mediated signal transmission in bladder vasculature as a therapeutic target of PDE5 inhibitors. Rodent model studies.

BACKGROUND AND PURPOSE: While the bladder vasculature is considered as a target of PDE5 inhibitors to improve bladder storage dysfunctions, its characteristics are largely unknown. Thus, the functional and morphological properties of arteries/arterioles of the bladder focusing on the NO-mediated signal transmission were explored. EXPERIMENTAL APPROACH: Diameter changes in rat bladder arteries/arterioles were measured using a video-tracking system. Intercellular Ca2+ dynamics in pericytes or smooth muscle cells (SMCs) of suburothelial arterioles were visualised using transgenic mice expressing GCaMP6 under control of the NG2- or parvalbumin-promoter. The perivascular innervation was investigated using fluorescence immunohistochemistry. KEY RESULTS: In rat suburothelial arterioles and vesical arteries, tadalafil (100 nM) attenuated nerve-evoked sympathetic vasoconstrictions. In both vascular segments, tadalafil-induced inhibition of sympathetic vasoconstriction was prevented by N ω-propyl-l-arginine hydrochloride (l-NPA, 1 µM), an nNOS inhibitor or N ω-nitro-l-arginine (l-NA, 100 µM). Both vascular segments were densely innervated with nNOS-positive nitrergic nerves in close apposition to tyrosine hydroxylase-immunoreactive sympathetic nerves. In pericyte-covered pre-capillary arterioles of the mouse bladder where sympathetic nerves were absent, nerve stimulation evoked transient reductions in pericyte Ca2+ levels that were shortened by l-NPA and abolished by l-NA. In SMC-containing arterioles, tadalafil (10 nM) caused a l-NPA-sensitive suppression of sympathetic Ca2+ transients. In mice, nitrergic perivascular nerves were distributed in the arterioles and the pre-capillary arterioles. CONCLUSION AND IMPLICATIONS: Both nitrergic nerve and nerve-evoked endothelial NO release appear to be involved in vasodilatory signal transmission in bladder vasculature. The NO-mediated signal transmission is a potential target for PDE5 inhibitor therapy in bladder dysfunctions.

Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice.

An artificial tool for manipulating local cerebral blood flow (CBF) is necessary for understanding how CBF controls brain function. Here, we generate vascular optogenetic tools whereby smooth muscle cells and endothelial cells express optical actuators in the brain. The illumination of channelrhodopsin-2 (ChR2)-expressing mice induces a local reduction in CBF. Photoactivated adenylyl cyclase (PAC) is an optical protein that increases intracellular cyclic adenosine monophosphate (cAMP), and the illumination of PAC-expressing mice induces a local increase in CBF. We target the ventral striatum, determine the temporal kinetics of CBF change, and optimize the illumination intensity to confine the effects to the ventral striatum. We demonstrate the utility of this vascular optogenetic manipulation in freely and adaptively behaving mice and validate the task- and actuator-dependent behavioral readouts. The development of vascular optogenetic animal models will help accelerate research linking vasculature, circuits, and behavior to health and disease.

Calculation of the benchmark duration of shift work associated with the development of impaired glucose metabolism: a 14-year cohort study on 7104 male workers.

OBJECTIVES: The aim of this study was to calculate the benchmark doses (BMD) and their 95% lower confidence boundary (BMDL) for the threshold number of years of shift work associated with a relative increase in haemoglobin A1c (HbA(1c)), an index of glucose metabolism. METHODS: A 14-year prospective cohort study was conducted in male workers at a Japanese steel company (n=7104) who had received annual health check-ups between 1991 and 2005. The endpoints were either a 10%, 15%, 20%, 25% or 30% increase in HbA(1c) levels during the observation period, compared to HbA(1c) at entry to the study. The associations between years of shift work and increases in HbA(1c) were investigated using pooled logistic regression, adjusted for age, body mass index, mean arterial pressure, total serum cholesterol, creatinine, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, drinking habits, smoking habits and habitual exercise. RESULTS: The BMDL/BMD for years of shift work were calculated using benchmark responses (BMRs) of 5% or 10% and parameters for duration of shift work and other covariates. Assuming a mean age of 53 years in workers aged 50 years or older, the BMDL/BMD for years of shift work with a BMR of 5% were 17.8/23.9 (> or = 15%), 15.7/18.7 (> or = 20%), 18.9/22.7 (> or = 25%) and 25.2/31.7 (> or = 30%). With a BMR of 10%, the respective values were 29.5/39.7 (> or = 15%), 24.3/28.9 (> or = 20%), 27.3/32.7 (> or = 25%) and 34.1/42.9 (> or = 30%). CONCLUSION: These results suggest that special attention should be paid to middle-aged workers whose years of shift work exceeds these threshold times.

Longitudinal evaluation of the effect of smoking initiation on body weight, blood pressure, and blood biochemistry.

OBJECTIVE: To evaluate the effect of smoking initiation on annual changes in body weight, blood pressure, and blood biochemistry. METHODS: This study analyzed the results of annual health examinations from 1991 to 2005 in male Japanese workers. Subjects who started smoking (n=214) initially responded as non-smokers in a self-administered questionnaire (baseline year) and then answered consistently as smokers for 3 subsequent years. Out of 2547 non-smokers, we selected 1589 controls who had data available for at least four successive years. The time course of physiological and laboratory data was analyzed using a linear mixed model. RESULTS: A significant temporal decrease from baseline in body mass index (first year, -0.1 kg/m(2)), diastolic blood pressure (second year, -1.5 mm Hg) and gamma-glutamyl transpeptidase (second year, -3.5 IU/L) was observed for subjects who started smoking. An opposite pattern was observed in non-smokers. On average, those who started smoking had significantly lower body mass index (first year, -0.2 kg/m(2); second year, -0.2 kg/m(2)), systolic blood pressure (second year, -2.1 mm Hg), diastolic blood pressure (second year, -2.0 mm Hg), and gamma-glutamyl transpeptidase (second year, -4.5 IU/L) than non-smokers. CONCLUSION: In this study, smoking initiation did not yield clinically significant long-term benefits with respect to physiological or biochemical outcomes. These results are important because few studies have tracked these types of changes longitudinally from initiation through 3 years of follow-up.

Smoking as an independent risk factor for hypertension: a 14-year longitudinal study in male Japanese workers.

There have been few large longitudinal studies on the relationship between smoking and blood pressure and those results have been inconsistent. The aim of this study was to clarify the influence of smoking on the onset of hypertension. A 14-year longitudinal study was conducted in Japanese male workers at a steel company between 1991 and 2005. We adopted three different endpoints of observation, hypertension [systolic blood pressure (SBP) >or= 140 mmHg and diastolic blood pressure (DBP) >or= 90 mmHg], systolic hypertension (SBP >or= 140 mmHg), and diastolic hypertension (DBP >or= 90 mmHg), with initiation of antihypertensive medication. The cohort for each endpoint (hypertension: n = 5,512, systolic hypertension: n = 5,765, diastolic hypertension: n = 6,063) was selected, excluding the subjects whose blood pressure was higher than above criteria at their first health examination from all 8,251 workers. The strict criteria for hypertension resulted in exclusion of more subjects, yielding smaller cohort for hypertension. The association between smoking and each endpoint was investigated adjusting for age, body mass index, drinking, habitual exercise, job schedule type, hemoglobin A1c, total cholesterol, creatinine, aspartic aminotransferase, gamma-glutamyl transpeptidase, and uric acid by pooled logistic regression analyses. The significant odds ratios (and 95% confidence intervals) of smoking were 1.13 (1.03 to 1.23) for hypertension and 1.15 (1.05 to 1.25) for systolic hypertension. This study revealed that smoking is independently related to the onset of hypertension and systolic hypertension in Japanese male workers. These results provide important information necessary to define the effect of smoking on blood pressure.

Effect of circadian rhythm type on serum lipid levels in shift workers: A 5-year cohort study.

We investigated how differences in circadian rhythm type affect the health of workers engaged in shift work. Employees, who were newly hired in a steel company between 2007 and 2011, received the Morningness-Eveningness Questionnaire (MEQ) survey. The target participants were 153 male shift workers who were not being treated with any antihyperlipidemic drugs and underwent periodic physical examinations including blood tests at least twice. According to the score of the MEQ at the time of joining the company, we classified the subjects into five types. Longitudinal changes in serum lipid level were estimated among the circadian rhythm types adjusted for age, BMI, and other covariates using a linear mixed model. The regression coefficient of total cholesterol level in the "definitely and moderately morning" group was -17.83 (95% confidence interval (CI): -33.42 to -2.23), and in the "intermediate 'group' was -16.84 [95% CI: -30.40 to -3.28], compared to the moderate evening type." The total cholesterol level was higher in the moderately evening type than in any of the other groups. Between the Morningness-Eveningness (ME) type and Low-density lipoprotein (LDL) cholesterol levels, compared with the "moderately evening type" group, the regression coefficient in the "intermediate type" group was -16.08 (95% CI: -28.79 to -3.37), and in the "definitely and moderately morning type" group was -17.50 [95% CI: -32.11 to -2.88]. The "moderately evening type" group had a higher LDL cholesterol level than any of the other groups. Evening-type circadian rhythm type shift workers are more prone to elevated serum lipid levels.

Relationship between shift work and hypercholesterolemia in Japan.

OBJECTIVES: The objective of this study was to clarify the influence of shift work on total cholesterol levels in serum in male Japanese workers. METHODS: Pooled logistic regression analyses were applied in this 14-year cohort study of 5510 male workers in a steel company. In examining how the adjustments influenced the results, the effect of shift work on the onset of hypercholesterolemia (>or=220 mg/dl, 5.7 mmol/l) was calculated by adjusting only for age (step 1), for age and lifestyle factors (drinking habit, smoking habit, habitual exercise) (step 2), for age, body mass index (BMI), and the laboratory data [creatinine, glycosylated hemoglobin A1c (HbA1c), aspartic aminotransferase, gamma-glutamyl transpeptidase (gamma-GTP), uric acid] (step 3), and for age, BMI, lifestyle factors, and the laboratory data (step 4). RESULTS: The odds ratio (OR) for shift work with respect to the onset of hypercholesterolemia was significant in step 4 [OR 1.10, 95% confidence interval (95% CI) 1.00-1.21, P-value 0.048], whereas the corresponding odds ratios in steps 1, 2, and 3 were not significant. In step 4, the other significant covariates were age (OR 1.01, 95% CI 1.00-1.02), BMI (OR 1.07, 95% CI 1.05-1.09), HbA1c (OR 1.07, 95% CI 1.02-1.11), gamma-GTP (OR 1.03, 95% CI 1.02-1.04) and alcohol consumption (OR 0.89, 95% CI 0.81-0.99). CONCLUSIONS: In the present study, shift work was shown to be a potential risk factor for hypercholesterolemia among male Japanese workers. However, no consistent association was found between shift work and hypercholesterolemia in the hierarchical evaluation of the statistical model. The present study could not provide well-established evidence for a relationship between shift work and hypercholesterolemia.

Benchmark duration of work hours for development of fatigue symptoms in Japanese workers with adjustment for job-related stress.

The objective of this study was to calculate benchmark durations and lower 95% confidence limits for benchmark durations of working hours associated with subjective fatigue symptoms by applying the benchmark dose approach while adjusting for job-related stress using multiple logistic regression analyses. A self-administered questionnaire was completed by 3,069 male and 412 female daytime workers (age 18-67 years) in a Japanese steel company. The eight dependent variables in the Cumulative Fatigue Symptoms Index were decreased vitality, general fatigue, physical disorders, irritability, decreased willingness to work, anxiety, depressive feelings, and chronic tiredness. Independent variables were daily working hours, four subscales (job demand, job control, interpersonal relationship, and job suitability) of the Brief Job Stress Questionnaire, and other potential covariates. Using significant parameters for working hours and those for other covariates, the benchmark durations of working hours were calculated for the corresponding Index property. Benchmark response was set at 5% or 10%. Assuming a condition of worst job stress, the benchmark duration/lower 95% confidence limit for benchmark duration of working hours per day with a benchmark response of 5% or 10% were 10.0/9.4 or 11.7/10.7 (irritability) and 9.2/8.9 or 10.4/9.8 (chronic tiredness) in men and 8.9/8.4 or 9.8/8.9 (chronic tiredness) in women. The threshold amounts of working hours for fatigue symptoms under the worst job-related stress were very close to the standard daily working hours in Japan. The results strongly suggest that special attention should be paid to employees whose working hours exceed threshold amounts based on individual levels of job-related stress.

The relation between cumulative fatigue and marital status in Japanese workers.

The authors' aim in this study was to clarify the influence of marital status on mental and physical fatigue symptoms. For 5,582 men and 484 women workers, the authors determined odds ratios of marital status using positive findings of 8 subscales on the Cumulative Fatigue Symptoms Index (CFSI) as dependent variables and other potential covariates as independent variables by logistic regression analysis. In men, the odds ratios for decreased vitality, physical disorders, decreased willingness to work, anxiety, and depressive feelings of CFSI were significantly higher in the unmarried group. In women, the odds ratios on CFSI for decreased vitality and decreased willingness to work were likewise significantly higher. The results verified that unmarried status was more associated with fatigue than was married status and being overworked.

Benchmark dose of working hours in relation to subjective fatigue symptoms in Japanese male workers.

PURPOSE: We used a multiple logistic regression model to calculate benchmark doses (BMDs) and their 95% lower confidence bound (BMDL) of working hours for subjective fatigue symptoms. METHODS: A self-administered questionnaire survey was conducted in 3069 male daytime workers between the ages of 18 and 60 years who worked in a Japanese steel company. Dependent variables were positive findings for eight properties by using the Cumulative Fatigue Symptoms Index (CFSI): decreased vitality, general fatigue, physical disorders, irritability, decreased willingness to work, anxiety, depressive feelings, and chronic tiredness. Independent variables were daily working hours, age, lifestyle factors, working conditions (type of work and number of holidays), marital status, and living arrangements. Using significant parameters for working hours and those for other covariates, BMD/BMDL of working hours was calculated for the corresponding property of the CFSI. Additionally, benchmark response (BMR) was set at 5% or 10%. RESULTS: The BMD/BMDL of working hours per day with a BMR of 5% were 11.8/10.8 (irritability), 11.4/10.2 (anxiety), and 11.2/10.6 (chronic tiredness), and those with a BMR of 10% were 14.2/12.6 (irritability), 14.2/12.1 (anxiety), and 13.1/12.2 (chronic tiredness). CONCLUSIONS: These results strongly suggest that special attention should be given to workers whose working hours exceed these BMD/BMDL values.

Long-term longitudinal study on the relationship between alternating shift work and the onset of diabetes mellitus in male Japanese workers.

OBJECTIVE: This study investigated the effect of alternating shift work (ASW) on the onset of diabetes mellitus in Japanese workers compared with onset in day-shift work (DSW). METHODS: A longitudinal study was carried out on a DSW group (n = 3203) and ASW group (n = 2426) of a steel company who received their annual health checkups over a 10-year period between 1991 and 2001. The association between job schedule type and onset of diabetes mellitus (glycated hemoglobin A1c > or =6.0% or medication) was investigated by multivariate pooled logistic regression analyses. RESULTS: The odds ratio (95% confidence interval) for the development of diabetes mellitus in the ASW group compared with the DSW group was 1.35 (1.05-1.75). CONCLUSIONS: Our study revealed that the ASW is an independent risk factor for the onset of diabetes mellitus.

Benchmark dose of alcohol consumption for development of hyperuricemia in Japanese male workers: An 8-year cohort study.

BACKGROUND: To estimate the benchmark dose (BMD) and their 95% lower confidence limits (BMDL) of alcohol consumption as the reference level for the development of hyperuricemia based on the dose-response relationship. METHODS: An 8-year prospective cohort study was conducted in 8097 male workers at a Japanese steel company who received annual health check-ups between 2002 and 2009. The endpoints for development of hyperuricemia were defined as a uric acid ≥7 mg/dL or taking any anti-hyperuricemic medication. The dose-response relationship of alcohol consumption was investigated using multivariate-pooled logistic regression analyses adjusted for other potential covariates. We estimated the BMD and BMDL of alcohol consumption for the development of hyperuricemia, using the parameters obtained by pooled logistic regression with a benchmark response (BMR) of 5% or 10%. RESULTS: Mean observed years per person was 3.86 years. The incidence rate per 1000 person-years was 61.1. The odds ratio calculated for the development of hyperuricemia was 1.29 [95% confidence interval, (1.22-1.36)] with an increase in alcohol consumption per 1 gou/day (1 gou/day = alcohol 22 g/day). The estimated BMDL/BMD with a BMR of 5% was 2.5/2.8 gou/day (54.5/61.8 g/day) and with a BMR of 10% was 4.0/4.6 gou/day (88.9/100.9 g/day). CONCLUSIONS: The present study showed that alcohol consumption of 2.5 gou/day (=ethanol 55 g/day) caused a distinct increase in the risk of hyperuricemia. Valuable information for preventing alcohol-induced hyperuricemia was obtained by a long-term follow-up study of a large cohort.

A longitudinal study on the relationship between shift work and the progression of hypertension in male Japanese workers.

OBJECTIVE: In this 1991-2001 cohort study of 6495 male workers in a Japanese steel company, we investigated whether shift work affects progression from mild hypertension to severe hypertension. DESIGN: A prospective cohort study. PARTICIPANTS: Participants had mild hypertension at entry into the study with systolic blood pressure of 140-159 mmHg or diastolic blood pressure of 90-99 mmHg or both before treatment. In summary, 2911-2941 workers were included for each endpoint. Pooled logistic regression analysis was performed to adjust for the effect of contributing factors and annual variations. MAIN OUTCOME: Either severe hypertension (systolic blood pressure >or= 160 mmHg and/or diastolic blood pressure >or= 100 mmHg), severe systolic hypertension (systolic blood pressure >or= 160 mmHg) or severe diastolic hypertension (diastolic blood pressure >or= 100 mmHg) was defined as a different endpoint of observation. RESULTS: Job schedule was significantly associated with progression from mild hypertension to severe hypertension and severe diastolic hypertension. The odds ratios of shift workers compared with regular day workers were 1.23 (95% confidence interval: 1.05-1.44) and 1.28 (95% confidence interval: 1.07-1.52) for severe hypertension and severe diastolic hypertension, respectively. Age, body mass index, creatinine, gamma-glutamyl transpeptidase, and glycosylated hemoglobin A1c were also significantly associated with severe hypertension, severe systolic hypertension and severe diastolic hypertension. CONCLUSION: Our study revealed that shift work is a significant and independent risk factor for the progression of hypertension.

Estimation of cumulative cadmium intake causing Itai-itai disease.

This study was undertaken to estimate the amount of cadmium (Cd) exposure needed for the development of Itai-itai disease. The investigated subjects comprised 82 Itai-itai disease patients and 11 persons requiring observation who were admitted in 1977 and 1978 for medical testing. With the period when the Itai-itai disease patients started to perceive leg/back pain defined as the 'mild disease onset', and the period when they experienced the most severe manifestations such as ambulatory disturbance and bone fractures defined as 'severe disease onset'. Relative cumulative person number distribution according to life time cadmium intake (LCD) at mild disease onset, severe disease onset, and time of death was depicted as an sigmoid curve and the establishment of probit regression lines was demonstrated between them. LCD at the time when mild disease onset and severe disease onset were recognized in half of the Itai-itai disease patients was 3.1 and 3.8 g, respectively. Furthermore, LCD at the time when mild disease onset and severe disease onset were recognized in 5% of the Itai-itai disease patients was calculated to be 2.6 and 3.3 g, respectively. The present results clarify that Itai-itai disease, the most severe stage of chronic Cd poisoning, occurs at levels of Cd consumption amounting to approximately three-fold of those currently seen in Japan.

Three-shift system increases job-related stress in Japanese workers.

We assessed the relationship between shift work and job stress. The target subjects were 4,962 male workers (3,078 day workers and 1,884 shift workers) aged 18 to 60 yr who work in a Japanese steel company. We used the "Brief Job Stress Questionnaire", which was developed by a research group organized by the Japanese Ministry of Labour. We evaluated the effect of shift work on job stress using logistic regression analysis including age, lifestyle factors, work conditions, marital status, and living arrangements in the model. Job schedule type was significantly associated with job control, with an odds ratio of 2.22 for shift workers compared to day workers. The logistic regression analysis revealed that the odd ratios for having one or more stressor items in an unfavorable condition were significantly higher for shift workers compared to day workers. Increase in the amount of overtime and decrease in the number of holidays led to a significant deterioration in job stress. Our study reveals that the 3-shift system of employment increases work-related stress, and that job control is low among shift workers. To reduce job stress in this occupational population, a reduction in the amount of overtime and an increase in the number of holidays seem to be useful interventions.

Excretion of urinary cadmium, copper, and zinc in cadmium-exposed and nonexposed subjects, with special reference to urinary excretion of beta2-microglobulin and metallothionein.

The objectives of this study were to examine the association between urinary excretion of cadmium (U-Cd), copper (U-Cu), and zinc (U-Zn) and the severity of two different indicators of renal toxicity (urinary excretion of beta2-microglobulin [U-beta2-MG] and metallothionein [U-MT]) in Cd-exposed subjects compared to controls, and to assess the physiologic mechanisms by which the exposure to environmental Cd affects U-Cd, U-Cu, and U-Zn. The target population included 3508 Cd-exposed and 294 nonexposed participants who received a health survey conducted among the population of the Kakehashi River basin. Increases of U-Cd, U-beta2-MG, and U-MT in the Cd-exposed population were observed relative to excretion of these substances in controls. Regression analysis using a general linear model revealed that the correlations between U-Cd or U-Cu, and U-beta2-MG and between U-Cd, U-Cu or U-Zn, and U-MT were statistically significant in both sexes, but the correlation between U-Zn and U-beta2-MG excretion was significant only in men. These results suggest U-Cd and U-Cu is affected by dysfunction in renal tubular absorption (indicated by U-beta2-MG), whereas not only U-Cd and U-Cu but also U-Zn appear to be a function of renal cellular desquamation (indicated by U-MT).

Dose-response relationship between tobacco or alcohol consumption and the development of diabetes mellitus in Japanese male workers.

BACKGROUND: The aim of this study was to examine the dose-response relationships between tobacco or alcohol consumption and the development of diabetes mellitus. METHODS: An 8-year prospective cohort study was conducted in 8423 male workers who received annual health check-ups between 2002 and 2010 at a Japanese steel company. The endpoints were defined as an HbA(lc)≥6.1% or taking any anti-diabetic medication. The dose-response relationships of tobacco or alcohol consumption were investigated using a proportional hazards regression with time-dependent covariates selected from baseline age, body mass index, mean arterial pressure, total serum cholesterol, aspartate aminotransferase, creatinine and uric acid, shift work or day work, and habitual exercise by stepwise selection method. RESULTS: A positive dose-response relationship between tobacco consumption and the development of diabetes mellitus was observed, with a significantly higher hazard ratio (HR) seen with higher tobacco consumption (11-20 cigarettes/day, HR 1.26 [95% confidence interval (CI), 1.00-1.59], ≥21 cigarettes/day, HR 1.54 [95%CI, 1.20-1.97]). In contrast, we observed a negative dose-response relationship between alcohol consumption and the development of diabetes mellitus, with a significantly lower HR with higher weekly alcohol consumption (7.0-13.9 gou/week [154-307 g/week], HR 0.73 [95% CI, 0.55-0.97], ≥14.0 gou/week [308 g/week], HR 0.75 [95% CI, 0.57-0.98]). CONCLUSIONS: The results indicated that decreasing tobacco consumption will achieve significant prevention of diabetes mellitus. On the other hand, we observed a significant, negative dose-response relationship between alcohol consumption and the development of diabetes mellitus, in contrast to previous studies that reported a positive relationship in the Japanese population.

The influence of being overweight on the relationship between shift work and increased total cholesterol level.

PURPOSE: The aim of this study was to clarify the influence of shift work on serum total cholesterol (T-Cho) levels according to body mass index (BMI) at entry in Japanese male workers. METHODS: A 14-year prospective cohort study was conducted in day workers (n = 4079) and alternating shift workers (n = 2807) who received annual health check-ups between 1991 and 2005 in a Japanese steel company. The association between job schedule and increases in T-Cho was investigated using multivariate pooled logistic regression analyses with age, BMI, lifestyle (smoking habit, drinking habit, habitual exercise), and the results of blood chemistries (creatinine, glycosylated hemoglobin A1c, aspartic aminotransferase, γ-glutamyl transpeptidase, uric acid) serving as covariates in those who were not overweight (BMI < 25 kg/m(2), n = 5082) and overweight (BMI ≥ 25 kg/m(2), n = 1804) at entry, respectively. The endpoints in the study were either a 20%, 25%, 30%, 35%, 40%, or 45% increase in T-Cho during the period of observation compared to T-Cho at entry. RESULTS: In subjects who were not overweight at entry, alternating shift work was associated significantly with five serum T-Cho endpoints (≥20%: odds ratio [OR] = 1.15, 95% confidence interval [CI)] = 1.05, 1.26; ≥25%: OR = 1.17, 95% CI = 1.05, 1.31; ≥35%: OR = 1.24, 95% CI = 1.05, 1.46; ≥40%: OR = 1.30, 95% CI = 1.06, 1.61; ≥45%: OR = 1.31, 95% CI = 1.01, 1.71). However, alternating shift work was not associated with any of the six T-Cho endpoints in subjects who were overweight at entry. CONCLUSIONS: In the present study, shift work was shown to be a potential risk factor for increased T-Cho in non-overweight Japanese male workers. However, we did not obtain a consistent association between shift work and an increase in T-Cho levels in overweight subjects. The results suggest that the effect of shift work on lipid regulation may be influenced by BMI.

Longitudinal effect of smoking cessation on physical and laboratory findings.

BACKGROUND: Detailed information on the expected physiologic changes after smoking cessation is practically useful to encourage people to stop smoking. Furthermore, weight increase after cessation may affect such physiologic changes. PURPOSE: This article aims to evaluate the effect of smoking cessation on annual changes in body weight, blood pressure, and blood biochemistry. METHODS: This study analyzed the results of annual health examinations from 1991 to 2005 in male Japanese workers in 2009. Subjects classified as stopping smoking (n=445) responded initially as smokers in a self-administered questionnaire (baseline year) and then answered consistently as nonsmokers for 3 subsequent years. Of the 2672 smokers identified in the study, 2403 subjects who had data available for at least 4 successive years were selected as controls. The time course of physiologic and laboratory data was analyzed using a linear mixed model. RESULTS: Data adjusted for age, type of job schedule, drinking and physical activity showed that subjects who stopped smoking had significantly greater increases in weight, BMI, systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and uric acid and a greater decrease in hemoglobin in the 3 years following smoking cessation than continuing smokers. Additional adjustment for change in BMI from baseline negated the significant deterioration in systolic and diastolic blood pressure and total cholesterol that occurred following smoking cessation. CONCLUSIONS: Increase in body weight, blood pressure, and blood biochemistry can continue for at least 3 years after smoking cessation. This study also indicated that these increases were related to the weight increase that occurred after smoking cessation.