Work-related causes of mental health conditions and interventions for their improvement in workplaces.

Mental health problems and disorders are common among working people and are costly for the affected individuals, employers, and whole of society. This discussion paper provides an overview of the current state of knowledge on the relationship between work and mental health to inform research, policy, and practice. We synthesise available evidence, examining both the role of working conditions in the development of mental disorders, and what can be done to protect and promote mental health in the workplace. We show that exposure to some working conditions is associated with an increased risk of the onset of depressive disorders, the most studied mental disorders. The causality of the association, however, is still debated. Causal inference should be supported by more research with stronger linkage to theory, better exposure assessment, better understanding of biopsychosocial mechanisms, use of innovative analytical methods, a life-course perspective, and better understanding of the role of context, including the role of societal structures in the development of mental disorders. There is growing evidence for the effectiveness of interventions to protect and promote mental health and wellbeing in the workplace; however, there is a disproportionate focus on interventions directed towards individual workers and illnesses, compared with interventions for improving working conditions and enhancing mental health. Moreover, research on work and mental health is mainly done in high-income countries, and often does not address workers in lower socioeconomic positions. Flexible and innovative approaches tailored to local conditions are needed in implementation research on workplace mental health to complement experimental studies. Improvements in translating workplace mental health research to policy and practice, such as through workplace-oriented concrete guidance for interventions, and by national policies and programmes focusing on the people most in need, could capitalise on the growing interest in workplace mental health, possibly yielding important mental health gains in working populations.

Emotional demands at work and risk of disability pension: a nationwide cohort study in Denmark.

INTRODUCTION: Working in emotionally demanding jobs is associated with an increased risk of temporarily leaving the labour market due to long-term sickness absence. We tested whether employees working in emotionally demanding jobs are also at higher risk of permanently leaving the labour market due to disability pension compared with employees working in jobs that are not emotionally demanding. METHODS: We conducted a 10-year cohort study in the workforce in Denmark (n=1 670 825), aged 30-59 years at baseline, by linking job exposure matrices with nationwide registries on social transfer payments and covariates. Using Cox regression, we analysed the risk of disability pension in relation to emotional demands in the full population and sex stratified. Multivariable adjusted models included sex, age, cohabitation, migration background, household disposable income and other work environmental factors (physical workload, influence, possibilities for development and role conflicts). RESULTS: We identified 67 923 new cases of disability pension during 15 649 743 person-years of follow-up (mean follow-up: 9.4 years). We found an increasing risk of disability pension with higher levels of emotional demands, with HRs of 1.20, 1.23 and 1.73 for medium-low, medium-high and high emotional demands, respectively, compared with low emotional demands in the most adjusted model. There was an exposure-response association in women and a tendency towards an exposure-response association in men. DISCUSSION: In this nationwide cohort study, we found an increased risk of permanent exit from the labour market due to disability pension in women and men working in emotionally demanding jobs.

Workplace sexual and gender-based harassment in Denmark: a comparison of the self-labelling and behavioural list method.

AIM: Knowledge about the prevalence of sexual and gender-based harassment is hampered by disagreements about definitions and measurement methods. The two most common measurement methods are the self-labelling (a single question about exposure to sexual harassment) and the behavioural list method (an inventory of sexually harassing behaviours). The aim of this paper was to compare the self-labelling and the behavioural list methods for measuring sexual harassment and assess the association with depressive symptoms. METHODS: The study is based on a convenience sample of 1686 individuals employed in 29 workplaces in Denmark. Survey data were collected from November 2020 until June 2021 and there were 1000 participants with full data on key variables. We used a linear mixed-effects model to examine the relationship between sexual harassment and depressive symptoms. RESULTS: In total, 2.5% self-labelled as being sexually harassed, while 19.0% reported exposure to at least one type of sexual and gender-based harassment using the behavioural list method. Both groups reported higher levels of depressive symptoms compared with non-exposed employees. The most common types of behaviours were: that someone spoke derogatorily about women/men (11.6%); being belittled because of one's gender or sexuality (4.7%); and unwanted comments about one's body, clothes or lifestyle (4.5%). CONCLUSIONS: The behavioural list method yielded a higher prevalence of sexual and gender-based harassment compared with the self-labelling method. Self-labelling and reporting at least one type of sexual and gender-based harassment was associated with depressive symptoms.

Work-related suicide: Evolving understandings of etiology & intervention.

Previously published analyses of suicide case investigations suggest that work or working conditions contribute to 10%-13% of suicide deaths. Yet, the way in which work may increase suicide risk is an underdeveloped area of epidemiologic research. In this Commentary, we propose a definition of work-related suicide from an occupational health and safety perspective, and review the case investigation-based and epidemiologic evidence on work-related causes of suicide. We identified six broad categories of potential work-related causes of suicide, which are: (1) workplace chemical, physical, and psychosocial exposures; (2) exposure to trauma on the job; (3) access to means of suicide through work; (4) exposure to high-stigma work environments; (5) exposure to normative environments promoting extreme orientation to work; and (6) adverse experiences arising from work-related injury or illness. We summarise current evidence in a schema of potential work-related causes that can also be applied in workplace risk assessment and suicide case investigations. There are numerous implications of these findings for policy and practice. Various principle- and evidence-based workplace intervention strategies for suicide prevention exist, some of which have been shown to improve suicide-prevention literacy, reduce stigma, enhance helping behaviours, and in some instances maybe even reduce suicide rates. Prevailing practice in workplace suicide prevention, however, overly emphasises individual- and illness-directed interventions, with little attention directed to addressing the working conditions that may increase suicide risk. We conclude that a stronger emphasis on improving working conditions will be required for workplace suicide prevention to reach its full preventive potential.

Emotional demands and all-cause and diagnosis-specific long-term sickness absence: a prospective cohort study in Sweden.

BACKGROUND: High emotional demands at work require sustained emotional effort and are associated with adverse health outcomes. We tested whether individuals in occupations with high emotional demands, compared with low demands, had a higher future risk of all-cause long-term sickness absence (LTSA). We further explored whether the risk of LTSA associated with high emotional demands differed by LTSA diagnoses. METHODS: We conducted a prospective, nationwide cohort study on the association between emotional demands and LTSA (>30 days) in the workforce in Sweden (n = 3 905 685) during a 7-year follow-up. Using Cox regression, we analyzed sex-stratified risks of all-cause and diagnosis-specific LTSA due to common mental disorders (CMD), musculoskeletal disorders (MSD) and all other diagnoses. Multivariable adjusted models included age, birth country, education, living area, family situation and physical work demands. RESULTS: Working in emotionally demanding occupations was associated with a higher risk of all-cause LTSA in women [hazard ratio (HR) = 1.92, 95% confidence interval (CI): 1.88-1.96] and men (HR = 1.23, 95% CI: 1.21-1.25). In women, the higher risk was similar for LTSA due to CMD, MSD and all other diagnoses (HR of 1.82, 1.92 and 1.93, respectively). In men, risk of LTSA due to CMD was pronounced (HR = 2.01, 95% CI: 1.92-2.11), whereas risk of LTSA due to MSD and all other diagnoses was only slightly elevated (HR of 1.13, both outcomes). CONCLUSIONS: Workers in occupations with high emotional demands had a higher risk of all-cause LTSA. In women, risk of all-cause and diagnosis-specific LTSA were similar. In men, the risk was more pronounced for LTSA due to CMD.

Work stress and loss of years lived without chronic disease: an 18-year follow-up of 1.5 million employees in Denmark.

We aimed to examine the association between exposure to work stress and chronic disease incidence and loss of chronic disease-free life years in the Danish workforce. The study population included 1,592,491 employees, aged 30-59 in 2000 and without prevalent chronic diseases. We assessed work stress as the combination of job strain and effort-reward imbalance using job exposure matrices. We used Cox regressions to estimate risk of incident hospital-diagnoses or death of chronic diseases (i.e., type 2 diabetes, coronary heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease, heart failure, and dementia) during 18 years of follow-up and calculated corresponding chronic disease-free life expectancy from age 30 to age 75. Individuals working in occupations with high prevalence of work stress had a higher risk of incident chronic disease compared to those in occupations with low prevalence of work stress (women: HR 1.04 (95% CI 1.02-1.05), men: HR 1.12 (95% CI 1.11-1.14)). The corresponding loss in chronic disease-free life expectancy was 0.25 (95% CI - 0.10 to 0.60) and 0.84 (95% CI 0.56-1.11) years in women and men, respectively. Additional adjustment for health behaviours attenuated these associations among men. We conclude that men working in high-stress occupations have a small loss of years lived without chronic disease compared to men working in low-stress occupations. This finding appeared to be partially attributable to harmful health behaviours. In women, high work stress indicated a very small and statistically non-significant loss of years lived without chronic disease.

Leadership behaviours and health-related early exit from employment: a prospective cohort study of 55 364 employees.

BACKGROUND: Absence of certain leadership behaviours, such as lack of feedback, recognition and involvement in employee development, has been associated with long-term sickness absence. We tested the hypothesis that absence of eight specific behaviours predicts health-related early exit from employment, and investigated differential effects in subgroups to guide future preventive initiatives. METHODS: Using Cox-proportional hazard modelling, we examined the prospective association between absence of leadership behaviours and health-related early exit from employment in a sample of 55 364 employees during 4.3 years follow-up. Leadership behaviours were measured by employee ratings in national surveys from 2012 to 2016. Exit from employment included disability pension and related measures of health-related early exit, retrieved from a national registry. RESULTS: We identified 510 cases of health-related early exit from employment during follow-up. A high level of absence of leadership behaviours, was associated with an increased risk of exit from employment (hazard ratio: 1.57, 95% CI: 1.31; 1.89). Subgroup analyses showed that the association between absence of leadership behaviours and exit from employment was similar for women and men and across age groups. The association was stronger for employees with high level of education than for employees with medium/low education, and the association was not observed among employees with a prevalent depressive disorder. CONCLUSIONS: Absence of the eight leadership behaviours is a risk factor for health-related early exit from employment in the Danish workforce. More studies are needed to confirm the results.

The ClpX chaperone controls autolytic splitting of Staphylococcus aureus daughter cells, but is bypassed by ß-lactam antibiotics or inhibitors of WTA biosynthesis.

ß-lactam antibiotics interfere with cross-linking of the bacterial cell wall, but the killing mechanism of this important class of antibiotics is not fully understood. Serendipitously we found that sub-lethal doses of ß-lactams rescue growth and prevent spontaneous lysis of Staphylococcus aureus mutants lacking the widely conserved chaperone ClpX, and we reasoned that a better understanding of the clpX phenotypes could provide novel insights into the downstream effects of ß-lactam binding to the PBP targets. Super-resolution imaging revealed that clpX cells display aberrant septum synthesis, and initiate daughter cell separation prior to septum completion at 30°C, but not at 37°C, demonstrating that ClpX becomes critical for coordinating the S. aureus cell cycle as the temperature decreases. FtsZ localization and dynamics were not affected in the absence of ClpX, suggesting that ClpX affects septum formation and autolytic activation downstream of Z-ring formation. Interestingly, oxacillin antagonized the septum progression defects of clpX cells and prevented lysis of prematurely splitting clpX cells. Strikingly, inhibitors of wall teichoic acid (WTA) biosynthesis that work synergistically with ß-lactams to kill MRSA synthesis also rescued growth of the clpX mutant, as did genetic inactivation of the gene encoding the septal autolysin, Sle1. Taken together, our data support a model in which Sle1 causes premature splitting and lysis of clpX daughter cells unless Sle1-dependent lysis is antagonized by ß-lactams or by inhibiting an early step in WTA biosynthesis. The finding that ß-lactams and inhibitors of WTA biosynthesis specifically prevent lysis of a mutant with dysregulated autolytic activity lends support to the idea that PBPs and WTA biosynthesis play an important role in coordinating cell division with autolytic splitting of daughter cells, and that ß-lactams do not kill S. aureus simply by weakening the cell wall.

Musculoskeletal pain as a predictor for depression in the general working population of Denmark.

Aim: This study examines the association between musculoskeletal complaints and subsequent use of antidepressants and/or psychiatric hospital treatment for depressive mood disorders in the Danish labour force. Methods: The study is based on two cohorts. The first cohort is the total labour force in 21 Danish municipalities (n=693,860), where the risk of depression (psychiatric diagnosis or antidepressant treatment) during 2010-2015 was compared between individuals on long-term sickness absence due to musculoskeletal disorders (MSD) and non-sick-listed gainfully employed individuals. The second cohort is a random sample of the Danish labour force (n=9248) who were followed during 2011-2015 to estimate the association between self-rated musculoskeletal pain and depression. All analyses were controlled for age, sex, calendar period and socio-economic status. Results: Compared to non-sick-listed gainfully employed individuals, there was an increased risk of depression in individuals sick-listed with MSD, with rate ratios of 2.39 (99% confidence interval (CI) 2.22-2.58) for individuals with less severe MSD and 4.27 (99% CI 3.98-4.59) for individuals with more severe MSD. There was also an increased risk of depression associated with self-rated pain (yes vs. no), with a rate ratio of 2.17 (99% CI 1.69-2.78). The population attributable fraction of depression from musculoskeletal pain was 0.35 (99% CI 0.24-0.45). Conclusions: The results of the present study indicate that musculoskeletal pain is an important predictor of indicators of depression in the general working population of Denmark.

Can leadership quality buffer the association between emotionally demanding work and risk of long-term sickness absence?

We examined whether the association between emotionally demanding work and risk of register-based long-term sickness absence (LTSA, ≥6 weeks) was buffered by high leadership quality among 25 416 Danish employees during 52-week follow-up. Emotional demands were measured at the job group level, whereas leadership quality was measured by workers rating their closest manager. Emotionally demanding work was associated with a higher risk of LTSA, regardless if leadership quality was high or low, with neither multiplicative nor additive interaction. We conclude that we found no evidence for high leadership quality buffering the effect of emotionally demanding work on risk of LTSA.

Contribution of income and job strain to the association between education and cardiovascular disease in 1.6 million Danish employees.

AIMS: We examined the extent to which associations between education and cardiovascular disease (CVD) morbidity and mortality are attributable to income and work stress. METHODS AND RESULTS: We included all employed Danish residents aged 30-59 years in 2000. Cardiovascular disease morbidity analyses included 1 638 270 individuals, free of cardiometabolic disease (CVD or diabetes). Mortality analyses included 41 944 individuals with cardiometabolic disease. We assessed education and income annually from population registers and work stress, defined as job strain, with a job-exposure matrix. Outcomes were ascertained until 2014 from health registers and risk was estimated using Cox regression. During 10 957 399 (men) and 10 776 516 person-years (women), we identified 51 585 and 24 075 incident CVD cases, respectively. For men with low education, risk of CVD was 1.62 [95% confidence interval (CI) 1.58-1.66] before and 1.46 (95% CI 1.42-1.50) after adjustment for income and job strain (25% reduction). In women, estimates were 1.66 (95% CI 1.61-1.72) and 1.53 (95% CI 1.47-1.58) (21% reduction). Of individuals with cardiometabolic disease, 1736 men (362 234 person-years) and 341 women (179 402 person-years) died from CVD. Education predicted CVD mortality in both sexes. Estimates were reduced with 54% (men) and 33% (women) after adjustment for income and job strain. CONCLUSION: Low education predicted incident CVD in initially healthy individuals and CVD mortality in individuals with prevalent cardiometabolic disease. In men with cardiometabolic disease, income and job strain explained half of the higher CVD mortality in the low education group. In healthy men and in women regardless of cardiometabolic disease, these factors explained 21-33% of the higher CVD morbidity and mortality.

High physical work demands and working life expectancy in Denmark.

OBJECTIVE: In most European countries, political reforms gradually increase the statutory retirement age to counter the economic costs of a growing elderly population. However, working to a high age may be difficult for people with hard physical labour. We aim to study the impact of high physical work demands on working life expectancy (WLE). METHODS: We combined physical work demands assessed by job exposure matrix (JEM) and longitudinal high-quality national registers (outcome) in 1.6 million Danish workers to estimate WLE and years of sickness absence, unemployment and disability pension. The JEM value for physical work demand is a summarised score of eight ergonomic exposures for 317 occupations groups, sex and age. The WLE was estimated using a multistate proportional hazards model in a 4-year follow-up period. RESULTS: Individuals with high physical work demands had a significantly lower WLE, than those with low physical work demands, with largest differences seen among women. At age 30 years, women with high physical work demands can expect 3.1 years less working, 11 months more of sickness absence and 16 months more of unemployment than low-exposed women. For 30-year-old men, the corresponding results were 2.0 years, 12 months and 8 months, respectively. CONCLUSION: Our findings show that high physical work demands are a marked risk factor for a shortened working life and increased years of sickness absence and unemployment. The results are important when selecting high-risk occupations, and expand the knowledge base for informed political decision making concerning statutory retirement age.

Effects of a participatory organisational, core work task focused workplace intervention on employees' primary healthcare consultations: secondary analysis of a cluster RCT.

OBJECTIVES: We aimed to examine whether a participatory organisational workplace intervention focusing on core tasks at work resulted in lower primary healthcare utilisation of employees. METHODS: The cluster randomised controlled trial included 78 preschools, 44 allocated to the intervention group (1745 employees) and 34 allocated to the control group (1267 employees). The intervention aimed to involve employees in improving the psychosocial work environment while focusing on core tasks at work. Using Poisson regression, we tested the rate ratios (RRs) of consultations in the intervention compared with the control group in terms of all consultations in primary healthcare and general practitioner (GP) consultations, respectively, per person-year during 31 months of follow-up. The fully adjusted model included adjustment for sex, age, job group, workplace type and size, and previous primary healthcare utilisation. RESULTS: During the follow-up, intervention group employees had 11.0 consultations/person-year, while control group employees had 11.6 consultations/person-year (RR 0.97, 95% CI 0.92 to 1.01). Employees in the intervention group had 7.5 GP consultations/person-year, while control group employees had 8.2 GP consultations/person-year (RR 0.95, 95% CI 0.90 to 0.99). Post hoc analyses indicated that the effect of the intervention was particularly strong in employees in preschools with a moderate or high level of implementation. CONCLUSIONS: The participatory organisational workplace intervention focusing on core tasks at work among preschool employees had a small, statistically non-significant effect on overall primary healthcare utilisation and a small, statistically significant effect on GP consultations. These results suggest a beneficial effect of the participatory organisational intervention on employees' health. TRIAL REGISTRATION NUMBER: ISRCTN16271504.

Cumulated and most recent job control and risk of disability pension in the Danish Work Life Course Cohort (DaWCo).

BACKGROUND: Previous studies have found low job control to be associated with a higher risk of disability pension (DP). Most studies have measured job control only at one time-point, and there is a lack of knowledge regarding the role of exposure duration. This study examines the prospective association between job control and DP measuring exposure both cumulated throughout work life and most recent. METHODS: We included 712 519 individuals (about 4.5 million person-years) from The Danish Work Life Course Cohort which follows young employees in Denmark from their entry into the labour market. Job control was assessed with a job exposure matrix and DP with register data on public transfer payments. We adjusted for several potential life course confounders, including physical demands at work and parental socioeconomic position and psychiatric and somatic diagnoses. RESULTS: Employees in occupations with low job control had a higher risk of DP. There were effects of both cumulated and most recent job control when mutually adjusted. Fully adjusted hazard ratios (HRs) were 1.14 [95% confidence intervals (CIs) 1.11-1.17] and 1.15 (95% CI 1.02-1.29) for cumulated and most recent job control, respectively. Without mutual adjustment, estimates were 1.15 (95% CI 1.13-1.18) and 1.55 (95% CI 1.39-1.72) for cumulated and most recent low job control, respectively. CONCLUSIONS: Low job control predicts a higher risk of DP, even after adjustment for physical demands at work. The results indicate both gradual and short-term effects of low job control on DP risk.

Psychosocial working conditions and depressive disorder: disentangling effects of job control from socioeconomic status using a life-course approach.

PURPOSE: Job control, the combination of skill discretion and decision authority, is considered a central component of the psychosocial working environment. This longitudinal study examines the relation between job control and risk of incident depressive disorder using a life-course approach. METHODS: We analyze data from The Danish Work Life Course Cohort study, including all Danish individuals aged 15-30 who entered the Danish labor market during 1995-2009 and were free from depressive disorder at entry (955,573 individuals). We measured job control using a job exposure matrix. Depressive disorders were measured using information from nationwide registers of psychiatric in- and outpatient admissions. Using Cox regression models we estimated the prospective association between job control and risk of incident depressive disorders. Analyses accounted for a range of potential confounders prior to workforce entry including socioeconomic status in adolescence and parental psychiatric and somatic diagnoses prior to labor market entry, together with potential confounders in adulthood including income, education, and demographics. RESULTS: Lower levels of past year job control were associated with a higher risk of depressive disorder after adjustment for all covariates (HR = 1.27, 95% CI 1.16-1.38). Results stratified by gender showed associations for both men (HR = 1.38, 95% CI 1.19-1.61) and women (HR = 1.19, 95% CI 1.08-1.32). CONCLUSIONS: Our findings suggest that the level of job control at work affects the risk of clinically diagnosed depressive disorder, and that this association is not due to confounding by socioeconomic status.

Effort-reward imbalance at work and weight changes in a nationwide cohort of workers in Denmark.

OBJECTIVE: To investigate the relation between effort-reward imbalance (ERI) at work and subsequent weight changes. METHODS: We included participants from a population-based cohort of workers in Denmark (mean age = 47 years, 54% women) with two (n = 9005) or three repeated measurements (n = 5710). We investigated the association between (a) ERI (ie, the mismatch between high efforts spent and low rewards received at work) at baseline and weight changes after a 2-year follow-up (defined as ≥5% increase or decrease in body mass index (BMI) vs stable), and (b) onset and remission of ERI and subsequent changes in BMI. Using multinomial logistic regression we calculated risk ratios (RR) and 95% confidence intervals (CI), adjusted for sex, age, education, cohabitation, migration background, and follow-up time. RESULTS: After 2 years, 15% had an increase and 13% a decrease in BMI. Exposure to ERI at baseline yielded RRs of 1.09 (95% CI: 0.95-1.25) and 1.04 (95% CI: 0.90-1.20) for the increase and decrease in BMI, respectively. There were no differences between sex and baseline BMI in stratified analyses. The onset of ERI yielded RRs of 1.04 (95% CI: 0.82-1.31) and 1.15 (95% CI: 0.84-1.57) for subsequent increase and decrease in BMI. The RRs for the remission of ERI and subsequent increase and decrease in BMI were 0.92 (95% CI: 0.71-1.20) and 0.78 (95% CI: 0.53-1.13), respectively. Of the ERI components, high rewards were associated with a lower risk of BMI increase. CONCLUSION: ERI was not a risk factor for weight changes. Future studies may investigate whether this result is generalizable to other occupational cohorts and settings.

Workplace bullying and workplace violence as risk factors for cardiovascular disease: a multi-cohort study.

AIMS: To assess the associations between bullying and violence at work and cardiovascular disease (CVD). METHODS AND RESULTS: Participants were 79 201 working men and women, aged 18-65 years and free of CVD and were sourced from three cohort studies from Sweden and Denmark. Exposure to workplace bullying and violence was measured at baseline using self-reports. Participants were linked to nationwide health and death registers to ascertain incident CVD, including coronary heart disease and cerebrovascular disease. Study-specific results were estimated by marginal structural Cox regression and were combined using fixed-effect meta-analysis. Nine percent reported being bullied at work and 13% recorded exposure to workplace violence during the past year. We recorded 3229 incident CVD cases with a mean follow-up of 12.4 years (765 in the first 4 years). After adjustment for age, sex, country of birth, marital status, and educational level, being bullied at work vs. not was associated with a hazard ratio (HR) of 1.59 [95% confidence interval (CI) 1.28-1.98] for CVD. Experiencing workplace violence vs. not was associated with a HR of 1.25 (95% CI 1.12-1.40) for CVD. The population attributable risk was 5.0% for workplace bullying and 3.1% for workplace violence. The excess risk remained similar in analyses with different follow-up lengths, cardiovascular risk stratifications, and after additional adjustments. Dose-response relations were observed for both workplace bullying and violence (Ptrend < 0.001). There was only negligible heterogeneity in study-specific estimates. CONCLUSION: Bullying and violence are common at workplaces and those exposed to these stressors are at higher risk of CVD.

The Sle1 Cell Wall Amidase Is Essential for ß-Lactam Resistance in Community-Acquired Methicillin-Resistant Staphylococcus aureus USA300.

Most clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) strains have become resistant to ß-lactams antibiotics through horizontal acquisition of the mecA gene encoding PBP2a, a peptidoglycan transpeptidase with low affinity for ß-lactams. The level of resistance conferred by mecA is, however, strain dependent, and the mechanisms underlying this phenomenon remain poorly understood. We show here that ß-lactam resistance correlates to expression of the Sle1 cell wall amidase in the fast-spreading and highly virulent community-acquired MRSA USA300 clone. Sle1 is a substrate of the ClpXP protease, and while the high Sle1 levels in cells lacking ClpXP activity confer ß-lactam hyper-resistance, USA300 cells lacking Sle1 are as susceptible to ß-lactams as cells lacking mecA This finding prompted us to assess the cellular roles of Sle1 in more detail, and we demonstrate that high Sle1 levels accelerate the onset of daughter cells splitting and decrease cell size. Vice versa, oxacillin decreases the Sle1 level and imposes a cell separation defect that is antagonized by high Sle1 levels, suggesting that high Sle1 levels increase tolerance to oxacillin by promoting cell separation. In contrast, increased oxacillin sensitivity of sle1 cells appears linked to a synthetic lethal effect on septum synthesis. In conclusion, this study demonstrates that Sle1 is a key factor in resistance to ß-lactam antibiotics in the JE2 USA300 model strain and that PBP2a is required for the expression of Sle1 in JE2 cells exposed to oxacillin.

Perceived and content-related emotional demands at work and risk of long-term sickness absence in the Danish workforce: a cohort study of 26 410 Danish employees.

OBJECTIVES: This study aimed to examine whether high emotional demands at work predict long-term sickness absence (LTSA) in the Danish workforce and whether associations differ by perceived and content-related emotional demands. METHODS: We included 26 410 individuals from the Work Environment and Health in Denmark Study, a nationwide sample of the Danish workforce. Emotional demands at work were measured with two items: one assessing perceived emotional demands (asking how often respondents were emotionally affected by work) and one assessing content-related emotional demands (frequency of contact with individuals in difficult situations). LTSA was register based and defined as spells of ≥6 weeks. Respondents with LTSA during 2 years before baseline were excluded. Follow-up was 52 weeks. Using Cox regression, we estimated risk of LTSA per one-unit increase in emotional demands rated on a five-point scale. RESULTS: During 22 466 person-years, we identified 1002 LTSA cases. Both perceived (HR 1.20, 95% CI 1.12 to 1.28) and content-related emotional demands (HR 1.07, 95% CI 1.01 to 1.13) predicted risk of LTSA after adjustment for confounders. Further adjustment for baseline depressive symptoms substantially attenuated associations for perceived (HR 1.08, 95% CI 1.01 to 1.16) but not content-related emotional demands (HR 1.05, 95% CI 1.00 to 1.11). Individuals working in occupations with above-average values of both exposures had an increased risk of LTSA (HR 1.32, 95% CI 1.14 to 1.52) compared with individuals in all other job groups. CONCLUSIONS: Perceived and content-related emotional demands at work predicted LTSA, also after adjustment for baseline depressive symptoms, supporting the interpretation that high emotional demands may be hazardous to employee's health.

Multicohort study of change in job strain, poor mental health and incident cardiometabolic disease.

OBJECTIVES: Several recent large-scale studies have indicated a prospective association between job strain and coronary heart disease, stroke and diabetes. Job strain is also associated with poorer mental health, a risk factor for cardiometabolic disease. This study investigates the prospective relationships between change in job strain, poor mental health and cardiometabolic disease, and whether poor mental health is a potential mediator of the relationship between job strain and cardiometabolic disease. METHODS: We used data from five cohort studies from Australia, Finland, Sweden and UK, including 47 757 men and women. Data on job strain across two measurements 1-5 years apart (time 1 (T1)-time 2 (T2)) were used to define increase or decrease in job strain. Poor mental health (symptoms in the top 25% of the distribution of the scales) at T2 was considered a potential mediator in relation to incident cardiometabolic disease, including cardiovascular disease and diabetes, following T2 for a mean of 5-18 years. RESULTS: An increase in job strain was associated with poor mental health (HR 1.56, 95% CI 1.38 to 1.76), and a decrease in job strain was associated with lower risk in women (HR 0.70, 95% CI 0.60-0.84). However, no clear association was observed between poor mental health and incident cardiometabolic disease (HR 1.08, 95% CI 0.96-1.23), nor between increase (HR 1.01, 95% CI 0.90-1.14) and decrease (HR 1.08, 95% CI 0.96-1.22) in job strain and cardiometabolic disease. CONCLUSIONS: The results did not support that change in job strain is a risk factor for cardiometabolic disease and yielded no support for poor mental health as a mediator.