Shiftwork and metabolic dysfunction

Many of the health problems that are more prevalent among shiftworkers are thought to be linked to their heightened susceptibility to metabolic syndrome, i.e., the association of even moderate degrees of visceral obesity, dyslipidemia, abnormal blood pressure, and serum glucose levels in the same individual. Although previous studies have identified associations between shiftwork and metabolic syndrome, there is relatively little evidence to date of how the risk of developing it varies as a function of exposure to shiftwork. The current study seeks to confirm earlier findings of an association between shiftwork exposure and metabolic dysfunction, and to examine the impact of exposure duration, while adjusting for a number of covariates in the analyses. The analyses were based on data from VISAT, a study involving the measurement of physiological, behavioral, and subjective outcomes from 1757 participants, 989 being current or former shiftworkers. The sample comprised employed and retired wage earners, male and female, who were 32, 42, 52, and 62 yrs old. The first analysis sought to confirm previous findings of an association between exposure to shiftwork and the risk of developing metabolic syndrome. It indicated that participants who were or who had previously been shiftworkers (i.e., working schedules that involved rotating shifts; not being able to go to bed before midnight; having to get up before 05:00 h; or being prevented from sleeping during the night) were more likely to exhibit symptoms of metabolic syndrome, after adjusting for age, sex, socioeconomic status, smoking, alcohol intake, perceived stress, and sleep difficulty (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.03-3.08). The results suggest the association between shiftwork and metabolic syndrome cannot be fully accounted for by either higher levels of strain or increased sleep difficulty among shiftworkers, although it remains a possibility that either one or both of these factors may have played a contributing role. The second analysis addressed the issue of duration of exposure to shiftwork. Participants with >10 yrs' experience of working rotating shifts were more likely to exhibit symptoms of metabolic syndrome than participants without exposure to shiftwork, i.e., dayworkers, even after adjusting for age and sex (OR 1.96; 95% CI 1.03-3.75). Thus, the current study confirms the association between shiftwork exposure and metabolic syndrome. It also provides new information regarding the time course of the development of the illness as function of exposure duration, although this was only examined in relation to rotating shiftwork. It is concluded that those responsible for monitoring workers' health should pay particular attention to indices of metabolic dysfunction in workers who have been exposed to shiftwork for >10 yrs.     

Shiftwork and Metabolic Dysfunction

Many of the health problems that are more prevalent among shiftworkers are thought to be linked to their heightened susceptibility to metabolic syndrome, i.e., the association of even moderate degrees of visceral obesity, dyslipidemia, abnormal blood pressure, and serum glucose levels in the same individual. Although previous studies have identified associations between shiftwork and metabolic syndrome, there is relatively little evidence to date of how the risk of developing it varies as a function of exposure to shiftwork. The current study seeks to confirm earlier findings of an association between shiftwork exposure and metabolic dysfunction, and to examine the impact of exposure duration, while adjusting for a number of covariates in the analyses. The analyses were based on data from VISAT, a study involving the measurement of physiological, behavioral, and subjective outcomes from 1757 participants, 989 being current or former shiftworkers. The sample comprised employed and retired wage earners, male and female, who were 32, 42, 52, and 62 yrs old. The first analysis sought to confirm previous findings of an association between exposure to shiftwork and the risk of developing metabolic syndrome. It indicated that participants who were or who had previously been shiftworkers (i.e., working schedules that involved rotating shifts; not being able to go to bed before midnight; having to get up before 05:00?h; or being prevented from sleeping during the night) were more likely to exhibit symptoms of metabolic syndrome, after adjusting for age, sex, socioeconomic status, smoking, alcohol intake, perceived stress, and sleep difficulty (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.03–3.08). The results suggest the association between shiftwork and metabolic syndrome cannot be fully accounted for by either higher levels of strain or increased sleep difficulty among shiftworkers, although it remains a possibility that either one or both of these factors may have played a contributing role. The second analysis addressed the issue of duration of exposure to shiftwork. Participants with >10 yrs' experience of working rotating shifts were more likely to exhibit symptoms of metabolic syndrome than participants without exposure to shiftwork, i.e., dayworkers, even after adjusting for age and sex (OR 1.96; 95% CI 1.03–3.75). Thus, the current study confirms the association between shiftwork exposure and metabolic syndrome. It also provides new information regarding the time course of the development of the illness as function of exposure duration, although this was only examined in relation to rotating shiftwork. It is concluded that those responsible for monitoring workers' health should pay particular attention to indices of metabolic dysfunction in workers who have been exposed to shiftwork for >10 yrs. (Author correspondence: p.t.tucker@swansea.ac.uk)     

Estimation of the benchmark duration of shiftwork associated with weight gain in male Japanese workers

The authors estimated the benchmark durations (BMDs) and their 95% lower confidence limit (BMDL) for the reference duration of shiftwork for weight gain. A 14-yr prospective cohort study was conducted in male workers at a Japanese steel company (n?=?7254) who had received annual health check-ups between 1991 and 2005. The endpoints in the study were either a 5%, 7.5%, or 10% increase in body mass index (BMI) during the period of observation, compared to the BMI at entry. The association between the duration of shiftwork and weight gain was investigated using multivariate pooled logistic regression analyses with stepwise selection of covariates, including age, BMI measured during the study, drinking and smoking habits, and habitual exercise. The BMDL/BMD for shiftwork in subjects aged in their 40s or ≥50 yrs was estimated using benchmark responses (BMRs) of 5% or 10% and parameters for the duration of shiftwork and other covariates. For workers aged in their 40s, the BMDL/BMD for shiftwork with a BMR of 5% was 18.6/23.0 yrs (≥7.5%) and 16.9/19.4 yrs (≥10%). For workers aged ≥50 yrs, the BMDL/BMD with a BMR of 5% was 22.9/28.2 yrs (≥7.5%) and 20.6/23.6 yrs (≥10%). The reference duration of shiftwork that associated with weight gain was shown to be at least 17 yrs in middle-aged workers. Special attention should be paid to prevent weight gain at an earlier stage and not when this increase in weight has become apparent.     

Blood pressure and heart rate variability in workers of 8-hour shifts

This study examined the effects of shiftwork on the cardiovascular system. The blood pressure (BP) and heart rate variability (HRV) of 134 male workers, who worked 8-hour shifts with rapid rotation of shifts at 3-day intervals, were examined for all the three shifts. In addition, the job stress was measured by Karasek's JCQ 49-item questionnaire and the circadian type was assessed by the morningness-eveningness questionnaire. The smoking and alcohol drinking habits, marital status and past medical history were also obtained. The method of analyzing the measured data based on a mixed model was used to illustrate the association between the shiftwork duration and the BP or HRV. The average age of workers was 29 years (between 25-44). Among them, 77.9% were current smokers, 50% showed the passive type of job strain in Karasek's model. The mean shiftwork duration was 5.21 years (range 5.4 months--10 years). In the circadian type, none of them belonged to a definitely morning type or a definitely evening type. In the multivariate analysis adjusted by age, job strain, shift, circadian rhythm and smoking, the blood pressure showed significantly increasing trends according to shiftwork duration in both the systolic and diastolic BP. The heart rate variability also showed a significantly decreasing trend according to the shiftwork duration in both the parasympathetic and sympathetic functions (p < 0.05). These results suggests that there are negative health effects arising from shiftwork on the cardiovascular system.     

ESTIMATION OF THE BENCHMARK DURATION OF SHIFTWORK ASSOCIATED WITH WEIGHT GAIN IN MALE JAPANESE WORKERS

The authors estimated the benchmark durations (BMDs) and their 95% lower confidence limit (BMDL) for the reference duration of shiftwork for weight gain. A 14-yr prospective cohort study was conducted in male workers at a Japanese steel company (n?=?7254) who had received annual health check-ups between 1991 and 2005. The endpoints in the study were either a 5%, 7.5%, or 10% increase in body mass index (BMI) during the period of observation, compared to the BMI at entry. The association between the duration of shiftwork and weight gain was investigated using multivariate pooled logistic regression analyses with stepwise selection of covariates, including age, BMI measured during the study, drinking and smoking habits, and habitual exercise. The BMDL/BMD for shiftwork in subjects aged in their 40s or ≥50 yrs was estimated using benchmark responses (BMRs) of 5% or 10% and parameters for the duration of shiftwork and other covariates. For workers aged in their 40s, the BMDL/BMD for shiftwork with a BMR of 5% was 18.6/23.0 yrs (≥7.5%) and 16.9/19.4 yrs (≥10%). For workers aged ≥50 yrs, the BMDL/BMD with a BMR of 5% was 22.9/28.2 yrs (≥7.5%) and 20.6/23.6 yrs (≥10%). The reference duration of shiftwork that associated with weight gain was shown to be at least 17 yrs in middle-aged workers. Special attention should be paid to prevent weight gain at an earlier stage and not when this increase in weight has become apparent. (Author correspondence: suwa@faculty.chiba-u.jp)     

Association of shiftwork and immune cells among police officers from the Buffalo Cardio-Metabolic Occupational Police Stress study

Shift workers suffer from a constellation of symptoms associated with disruption of circadian rhythms including sleep abnormalities, and abnormal hormone secretion (e.g. melatonin, cortisol). Recent, but limited, evidence suggests that shift workers have elevated levels of circulating white blood cells (WBCs) compared to their day working counterparts. Interestingly, recent reviews highlight the strong linkage between the immune system and circadian rhythms which includes, but is not limited to, circulating cell populations and functions. The elevated levels of these WBCs may be associated with the increased chronic disease risk observed among this group. The purpose of this analysis was to examine the cross-sectional association between long- and short-term (3, 5, 7, and 14 days) shiftwork (SW) and counts of WBCs among officers in the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) cohort. Data collection for this analysis took place among 464 police officers working in Buffalo, New York, USA between 2004 and 2009. Precise SW histories were obtained using electronic payroll records. Officers were assigned a shift type based on the shift (i.e. day, evening, night) that they spent a majority (i.e. ≥50%) of their time from 1994 to the data collection date for long-term SW. The same process was applied to SW over 3, 5, 7, and 14 days prior to data collection. A fasted blood sample collected in the morning of a non-work day was used for characterization of WBCs (total), neutrophils, monocytes, lymphocytes, eosinophils, and basophils. Potential confounding factors included demographic characteristics (e.g. age, sex, race), occupational characteristics (e.g. rank), health behaviors (e.g. smoking, alcohol consumption, diet), anthropometrics, and other biomarkers (e.g. lipids, hemoglobin A1C, leptin). Generalized linear models were used to estimate least square means of the immune cells according to SW categorization for long- and short-term SW histories. Compared to the day shift group, those working long-term night shifts had greater absolute numbers of total WBCs, neutrophils, lymphocytes, and monocytes (all p < 0.05). Those working mainly on the night shift over 7-days had elevated counts of WBCs, lymphocytes, and monocytes (p < 0.05) compared to those mainly working day shifts. Results based on 3-, 5-, and 14-day SW were similar to the 7-day results. This study corroborates other studies with similar findings. However, this analysis provided insights into the effect of both long- and short-term SW on the number of circulating WBCs. SW may lead to disruption of circadian-influenced components of the immune system, which in term, may result in various chronic diseases. These findings, plus previous findings, may provide evidence that SW may lead to immune system dysregulation. Future research is needed to understand whether increases in immune cells among shift workers may be associated with the increased disease risk among this group.     

Role of vascular cell adhesion molecules and leukocyte apoptosis in the lymphopenia and thrombocytopenia of patients with severe acute respiratory syndrome (SARS)

The immunopathogenesis of leukopenia and thrombocytopenia in patients with severe acute respiratory syndrome (SARS) is unclear. In order to explore the leukopenia mechanism, we studied 15 SARS patients who were previously healthy, and 15 age-matched normal controls in a paired design. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble Fas ligand (sFasL) in plasma were measured by ELISA, and intracellular activated caspase-3 fragment in different leukocytes was determined by flow cytometry. Patients with SARS had significantly lower lymphocyte and platelet counts and significantly higher sVCAM-1 and sFasL levels compared to healthy controls. sVCAM-1 levels correlated negatively with total leukocytes and platelet counts, but positively with plasma sFasL levels. Intracellular cleaved caspase-3 expression was also significantly higher in lymphocytes from SARS patients in acute phase than in convalescent stage. Lymphopenia and thrombocytopenia in SARS patients may be caused, in part, by enhanced vascular sequestration associated with increased sVCAM-1 levels. However, lymphopenia may be due to enhanced cell death. Inhibition of cell adhesion and caspase-3 activation could, therefore, have prevented SARS patients from developing thrombocytopenia and lymphopenia.     

Predicting shiftwork-related outcomes: shiftwork locus of control and circadian type

This research discusses the use and viability of the shiftwork locus of control construct alongside circadian type measures as a potential predictor of shiftwork-related outcomes. The shiftwork locus of control (SHLOC) scale, measures of circadian type and shiftwork-related outcome measures were completed by 100 shiftworkers on two occasions separated by seven months. The SHLOC scale measures shiftworkers' generalised beliefs about the levels of personal control they perceive in relation to four major functional domains commonly associated with shiftwork-related disruption. These domains include: sleep, social, health and work problems. The results of multivariate regression analysis showed the SHLOC scale to be predictive of the experience of shiftwork-related sleep and social-life problems while the circadian type measures were predictive of alertness at 7 months. The results suggest that a constellation of personality factors may be an important influence on an individual's tolerance to shiftwork.     

Impact of nightshift work on overweight and abdominal obesity among workers of a poultry processing plant in southern Brazil

The authors examined the associations of shiftwork with overweight and abdominal obesity through a cross-sectional study of 1206 employees 18 to 50 yrs of age who were working on a production line in a poultry processing plant. Night-shift workers (n = 800) were considered exposed, whereas day shiftworkers (n = 406) were considered nonexposed. Overweight was defined as a body mass index ≥ 25 kg/m(2) and abdominal obesity as a waist circumference ≥ 88 cm in women and ≥ 102 cm in men. The mean age of the workers was 30.5 yrs (standard deviation = 8.7 yrs), and 65.2% were women. Nightshift workers compared to dayshift workers showed higher prevalences of overweight (42.2% vs. 34.3%; p=?.020) and abdominal obesity (24.9% vs. 19.5%; p =?.037). After adjusting for sociodemographics, parental overweight status, behavioral characteristics, and sleep characteristics, including hours of sleep, the prevalence ratios for overweight and abdominal obesity were 1.27 (95% confidence interval [ CI]: 1.00-1.61) and 1.45 (95% CI: 1.10-1.92), respectively, for the nightshift workers compared to the dayshift workers. A consistent finding in our study was the independent contribution of night shiftwork to overweight and abdominal obesity among Brazilian workers. Further studies are needed to understand the biological mechanisms involved and the complex behavioral and social adaptations experienced by night-shift workers.     

Shiftwork and Sickness Absence Among Police Officers: The BCOPS Study

Shiftwork, regarded as a significant occupational stressor, has become increasingly prevalent across a wide range of occupations. The adverse health outcomes associated with shiftwork are well documented. Shiftwork is an integral part of law enforcement, a high-stress occupation with elevated risks of chronic disease and mortality. Sickness absence is an important source of productivity loss and may also serve as an indirect measure of workers’ morbidity. Prior studies of shiftwork and sickness absenteeism have yielded varying results and the association has not been examined specifically among police officers. The objective of this study was to compare the incidence rate of sick leave (any, ≥3 consecutive days) among day-, afternoon-, and night-shift workers in a cohort of police officers and also examine the role of lifestyle factors as potential moderators of the association. Participants (N?=?464) from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) study examined between 2004 and 2009 were used. Daily work history records that included the shift schedule, number of hours worked, and occurrence of sick leave were available for up to 15 yrs starting in 1994 to the date of the BCOPS study examination for each officer. Poisson regression analysis for ungrouped data was used to estimate incidence rates (IRs) of sick leave by shift, and comparison of IRs across shifts were made by computing incidence rate ratios (IRRs) and their 95% confidence intervals (CIs). Sick leave occurred at a higher rate on the night shift (4.37 per 10?000 person-hours) compared with either day (1.55 per 10?000 person-hours) or afternoon (1.96 per 10?000 person-hours) shifts. The association between shiftwork and sickness absence depended on body mass index (BMI). For overweight individuals (BMI?≥?25?kg/m²), the covariate-adjusted incidence rate of sick leave (≥1 day) was twice as large for night-shift officers compared with those working on the day (IRR?=?2.29, 95% CI: 1.69–3.10) or afternoon (IRR?=?1.74, 95% CI: 1.29–2.34) shift. The IR of three or more consecutive days of sick leave was 1.7 times larger for those working on night shift (IRR?=?1.65, 95% CI: 1.17–2.31) and 1.5 times larger for those working on afternoon shift (IRR?=?1.50, 95% CI: 1.08–2.08) compared with day shiftworkers. For subjects with normal BMI (<25?kg/m²), the incidence rates of sick leave did not differ significantly across shifts. In conclusion, shiftwork is independently associated with sickness absence, with officers who work the night shift having elevated incidence of sick leave. In addition, overweight officers who work the night shift may be at additional risk for sickness absence.     

Impact of Nightshift Work on Overweight and Abdominal Obesity Among Workers of a Poultry Processing Plant in Southern Brazil

The authors examined the associations of shiftwork with overweight and abdominal obesity through a cross-sectional study of 1206 employees 18 to 50 yrs of age who were working on a production line in a poultry processing plant. Night-shift workers (n?=?800) were considered exposed, whereas day shiftworkers (n?=?406) were considered nonexposed. Overweight was defined as a body mass index ≥25?kg/m² and abdominal obesity as a waist circumference ≥88?cm in women and ≥102?cm in men. The mean age of the workers was 30.5 yrs (standard deviation?=?8.7 yrs), and 65.2% were women. Nightshift workers compared to dayshift workers showed higher prevalences of overweight (42.2% vs. 34.3%; p?=?.020) and abdominal obesity (24.9% vs. 19.5%; p?=?.037). After adjusting for sociodemographics, parental overweight status, behavioral characteristics, and sleep characteristics, including hours of sleep, the prevalence ratios for overweight and abdominal obesity were 1.27 (95% confidence interval [ CI]: 1.00–1.61) and 1.45 (95% CI: 1.10–1.92), respectively, for the nightshift workers compared to the dayshift workers. A consistent finding in our study was the independent contribution of night shiftwork to overweight and abdominal obesity among Brazilian workers. Further studies are needed to understand the biological mechanisms involved and the complex behavioral and social adaptations experienced by night-shift workers. (Author correspondence: mtolinto@gmail.com)     

Effect of shiftwork on systemic markers of inflammation

Shiftwork is associated with an increased risk of cardiovascular diseases, but the possible role of inflammation in this relationship is not well known. We tested the hypothesis that shiftwork would be associated with higher levels of C-reactive protein (CRP) and increased leukocyte count. We analyzed the cross-sectional associations between work arrangements and low-grade inflammation in 1877 airline-company employees separately for men (n?=?1037) and women (n?=?840). The participants were classified into five categories according to their work schedule: day workers who have not worked in shifts (referent group), former shiftworkers, 2-shift workers, 3-shift workers, and in-flight workers. In models adjusted for age and recent infectious diseases, CRP levels were higher among male 3-shift workers (p = .002) and marginally higher in male 2-shift workers (p = .076). In addition, leukocyte count was higher in 2-shift (p = .005) and 3-shift (p = .021) working men. In women, CRP level was higher in 2-shift workers (p = .028), whereas leukocyte count was lower in flight workers (p = .005). Any separate adjustment additionally for smoking, education, alcohol consumption, physical activity, and obesity did not substantially affect the results of 2- and 3-shift work. In the fully adjusted model, only the association between 3-shift work and CRP in men (p = .021) and 2-shift work and leukocyte count in men (p = .020) and leukocyte count in 3-shift-working women (p = .044) were significant. Our results suggest that 2- and 3-shift work is associated with increased systemic inflammation and the relationship is relatively independent of the considered risk factors of cardiovascular disease.     

LIGHT INTENSITY EXPOSURE,SLEEP DURATION,PHYSICAL ACTIVITY,AND BIOMARKERS OF MELATONIN AMONG ROTATING SHIFT NURSES

Long-term, night shiftwork has been identified as a potential carcinogenic risk factor. It is hypothesized that increased light at night exposure during shiftwork reduces melatonin production, which is associated with increased cancer risk. Sleep duration has been hypothesized to influence both melatonin levels and cancer risk, and it has been suggested that sleep duration could be used as a proxy for melatonin production. Finally, physical activity has been shown to reduce cancer risk, and laboratory studies indicate it may influence melatonin levels. A cross-sectional study of light exposure, sleep duration, physical activity, and melatonin levels was conducted among 61 female rotating shift nurses (work schedule: two 12?h days, two 12?h nights, five days off). Light intensity was measured using a light-intensity data logger, and sleep duration and physical activity were self-reported in a study diary and questionnaire. Melatonin concentrations were measured from urine and saliva samples. The characteristics of nurses working day and night shifts were similar. Light intensity was significantly higher during sleep for those working at night (p<?0.0001), while urinary melatonin levels following sleep were significantly higher among those working days (p?=?0.0003). Mean sleep duration for nurses working during the day (8.27?h) was significantly longer than for those working at night (4.78?h, p<?0.0001). An inverse association (p?=?0.002) between light exposure and urinary melatonin levels was observed; however, this was not significant when stratified by shift group. There was no significant correlation between sleep duration and melatonin, and no consistent relationship between physical activity and melatonin. Analysis of salivary melatonin levels indicated that the circadian rhythms of night workers were not altered, meaning peak melatonin production occurred at night. This study indicates that two nights of rotating shift work may not change the timing of melatonin production to the day among those working at night. Additionally, in this study, sleep duration was not correlated with urinary melatonin levels, suggesting it may not be a good proxy for melatonin production. (Author correspondence: anne.grundy@queensu.ca)     

The inseminating bull and plasma pregnancy-associated glycoprotein (PAG) levels were related to peripheral leukocyte counts during the late pregnancy/early postpartum period in high-producing dairy cows

It has been established that the immunologic and endocrine status of the peripartum dairy cow determines the animal's subsequent productive and reproductive performance. Thus, at parturition reduced immune functions of peripheral blood polymorphonuclear cells (PMN) has been observed after a peak in pregnancy-associated glycoproteins (PAGs), and, more recently, the inseminating bull was linked to plasma levels of bovine PAGs in pregnant Holstein-Friesian dairy cows. The present study sought to determine whether changes in leukocyte counts during the peripartum period, indicative of the animal's immune status, could be related to the inseminating bull and to PAG levels. Ninety-six clinically healthy, single pregnant cows in a commercial dairy herd were selected. Four samples were collected before parturition (on gestation Days 220-226, 234-240, 248-254, and 262-268) and two samples after parturition (on Days 14-21, and 28-34 postpartum) to analyze total and differential blood cell counts. Based on GLM analysis procedures of variance for repeated measures, the inseminating bull was found to affect counts of total leukocytes and lymphocytes (P < 0.001; between-subject effects) throughout the peripartum period. In addition, cows with high plasma PAG levels (> 900 ng/ml) on Day 262-268 of gestation had higher numbers of total leukocytes and neutrophils throughout the peripartum (P < 0.001; between-subject effects). Young animals (≤ 1 lactation) had higher total leukocyte and lymphocyte counts than older cows (2 or more lactations) throughout the study period. These results reveal a clear relationship between the inseminating bull or plasma PAG levels and peripheral leukocyte counts during the peripartum period in dairy cows.     

Biomonitoring of occupational exposure to styrene in a plastics lamination plant.

A comprehensive approach to biological monitoring of 44 workers occupationally exposed to styrene in a hand lamination plant was performed by using several end-points: styrene in workplace air, styrene in exhaled air, styrene in blood, DNA strand breaks (SBs) and oxidised bases in mononuclear leukocytes, chromosomal aberrations in lymphocytes, immune parameters and genotyping of polymorphic genes of some xenobiotic-metabolizing enzymes (CYP 1A1, EPHX, GSTM1 and GSTP1). We found a significantly higher number of DNA SBs, measured by a modified comet assay, in mononuclear leukocytes of the styrene-exposed workers compared with results from 19 unexposed controls (P<0.001). A fairly strong correlation was observed between SBs and years of exposure (P<0.001, r=0.545). The styrene-exposed workers also showed a significantly increased frequency of chromosomal aberrations (P<0.0001 for highly exposed group, P<0.004 for medium-exposed group, and P=0.0001 for low-exposed group). The proliferative response of T-lymphocytes stimulated with concanavalin A was significantly suppressed in people exposed to styrene (P<0.05). We recorded a significant increase of the percentage of monocytes in differential white blood cell counts in the exposed group (P<0.05). Using flow cytometry, we found an increased expression of adhesion molecules CD62L, CD18, CD11a, CD11b, CD49d and CD54 in the exposed workers as compared with the control group (P<0.05).     

EPIGENETIC EFFECTS OF SHIFTWORK ON BLOOD DNA METHYLATION

In the present study, the authors investigated the effects of shiftwork exposure on DNA methylation using peripheral blood DNA from subjects working in two chemical plants in Northern Italy. The investigation was designed to evaluate (a) DNA methylation changes in Alu and long interspersed nuclear element-1 (LINE-1) repetitive elements as a surrogate of global methylation and (b) promoter methylation of glucocorticoid receptor (GCR), tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ). One hundred and fifty white male workers (mean?±?SD: 41.0?±?9 yrs of age) were examined: 100 3?×?8 rotating shiftworkers (40.4?±?8.7 yrs of age) and 50 day workers (42.2?±?9.4 yrs of age). The authors used bisulfite-pyrosequencing to estimate repetitive elements and gene-specific methylation. Multiple regression analysis, adjusted for age, body mass index (BMI), and job seniority, did not show any significant association between the five DNA methylation markers and shiftwork. However, job seniority, in all subjects, was significantly associated with Alu (β?=??0.019, p?=?.033) and IFN-γ (β?=??0.224, p?<?.001) methylation, whereas TNF-α methylation was inversely correlated with age (β?=??0.093, p?<?.001). Considering only shiftworkers, multiple regression analysis, adjusted for age, BMI, and job seniority, showed a significant difference between morning and evening types in TNF-α methylation (mean morning type [MT] 11.425 %5mC versus evening type [ET] 12.975 %5mC; β?=?1.33, p?=?.022). No difference was observed between good and poor tolerance to shiftwork. Increasing job seniority (<5, 5–15, >15 yrs) was associated with significantly lower Alu (β?=??0.86, p?=?.006) and IFN-γ methylation (β?=??6.50, p?=?.007) after adjustment for age, BMI, and morningness/eveningness. In addition, GCR significantly increased with length of shiftwork (β?=?3.33, p?=?.05). The data showed alterations in blood DNA methylation in a group of shiftworkers, including changes in Alu repetitive elements methylation and gene-specific methylation of IFN-γ and TNF-α promoters. Further studies are required to determine the role of such alterations in mediating the effects of shiftwork on human health. (Author correspondence: giovanni.costa@unimi.it)     

Gender and sleep in nightworkers: a quantitative analysis of sleep in days off

Differences in sleep patterns between workdays and days off contribute to shiftwork effects on workers' health and well-being. But regardless of shift schedules, female workers face more difficulties in fulfilling their sleep need because of housework. This study analyzes gender differences concerning sleep in days off by comparing sleep patterns in male and female nightworkers, analyzing sleep as related to the presence of children and testing the association of sleep features between workdays and days off. Male (n = 16) and female (n = 30) workers at a plastic plant, working from 10 p.m. to 6 a.m., on weekdays, filled sleep logs for seven consecutive weeks. Male and female samples did not differ in length of night sleep or in total length of sleep. For both samples, sleep length/day in days off increased, but the difference was lager among females. Also important were the relations between sleep in workdays and days off, specially among women. Among female workers, the results indicated that workers with children tended to sleep less in Saturday mornings, suggesting a negative effect of motherhood on sleep not restricted to workdays. The general results indicate that sleep need on the one hand, and social factors on the other determine the actual amount of sleep.     

Unaltered instrumental learning and attenuated body-weight gain in rats during non-rotating simulated shiftwork

Exposure to shiftwork has been associated with multiple health disorders and cognitive impairments in humans. We tested if we could replicate metabolic and cognitive consequences of shiftwork, as reported in humans, in a rat model comparable to 5 wks of non-rotating night shifts. The following hypotheses were addressed: (i) shiftwork enhances body-weight gain, which would indicate metabolic effects; and (ii) shiftwork negatively affects learning of a simple goal-directed behavior, i.e., the association of lever pressing with food reward (instrumental learning), which would indicate cognitive effects. We used a novel method of forced locomotion to model work during the animals' normal resting period. We first show that Wistar rats, indeed, are active throughout a shiftwork protocol. In contrast with previous findings, the shiftwork protocol attenuated the normal weight gain to 76 ± 8 g in 5 wks as compared to 123 ± 15 g in the control group. The discrepancy with previous work may be explained by the concurrent observation that with our shiftwork protocol rats did not adjust their between-work circadian activity pattern. They maintained a normal level of activity during the "off-work" periods. In the control experiment, rats were kept active during the dark period, normally dominated by activity. This demonstrated that forced activity, per se, did not affect body-weight gain (mean ± SEM: 85 ± 11 g over 5 wks as compared to 84 ± 11 g in the control group). Rats were trained on an instrumental learning paradigm during the fifth week of the protocol. All groups showed equivalent increases in lever pressing from the first (3.8 ± .7) to the sixth (21.3 ± 2.4) session, and needed a similar amount of sessions (5.1 ± .3) to reach a learning criterion (≥ 27 out of 30 lever presses). These results suggest that while on prolonged non-rotating shiftwork, not fully reversing the circadian rhythm might actually be beneficial to prevent body-weight gain and cognitive impairments.