Impact of psychosocial work factors on risk of medically certified sick leave due to common mental disorders: a nationwide prospective cohort study of Norwegian home care workers.

BACKGROUND: The Norwegian home care services experience a high level of sick leave, a large proportion of which is due to common mental disorders. A substantial number of such cases can be attributed to psychosocial factors at work, but more knowledge about occupation-specific risk factors is needed to develop targeted preventive measures to reduce sick leave levels. The aim of this study is to identify the most prominent psychosocial work factors influencing the risk of sick leave spells due to common mental disorders. METHODS: Employees from a random sample of 130 Norwegian home care services (N = 1.819) completed a baseline survey on 15 psychosocial work factors. Participants were subsequently followed up for 26 months using registry data on sick leave. The outcome measure was the number of medically certified sick leave spells due to common mental disorders during follow-up in the Norwegian social insurance database. Incidence risk ratios (IRR) and 95% confidence intervals (CIs) were calculated using negative binomial regression with robust standard errors. RESULTS: Emotional dissonance (IRR 1.30, 95% CI 1.05-1.60) and emotional demands (IRR 1.35, 95% CI 1.14-1.58) were associated with an excess risk of sick leave, while control over work pacing (IRR 0.78, 95% CI 0.62-0.98) was associated with a reduced risk. An estimated 30% (95% CI 8.73-48.82) of sick leave cases were attributable to emotional dissonance and 27% (95% CI 4.80-46.33) were attributable to emotional demands. Control over work pacing was estimated to have prevented 20% (95% CI 1.32-37.78) of the sick leave cases. CONCLUSIONS: This study found that emotional dissonance and emotional demands were robust risk factors for sick leave due to common mental disorders, and that control of work pacing constituted a robust protective factor against sick leave.

Effects of the Labour Inspectorate Authority's regulatory tools on psychosocial and biomechanical work factors in Norwegian home care services: a cluster randomised controlled trial.

OBJECTIVES: This study aimed to determine the effects of the Labour Inspectorate Authority's (LIA's) regulatory tools on psychosocial and biomechanical work factors in the Norwegian municipal home care services. METHODS: A cluster-randomised controlled trial conducted in the home care services with employee questionnaire data on work factors at baseline, and 6 and 12 months after the interventions. In total, 96 eligible municipalities were randomly assigned to either the control group or one of two interventions: (1) labour inspection visits, based on the LIA's standard inspections; and (2) guidance-through-workshops, where the participating services highlighted issues and trained labour inspectors provided guidance based on existing labour laws and regulations. RESULTS: No favourable intervention effect was observed for the inspection intervention. No effects were observed for most of the variables in the guidance intervention, although an effect was observed for the following psychosocial factors: decision control, control over work intensity and empowering leadership. However, after adjusting for multiple testing, none of the observed effects were statistically significant. CONCLUSION: Labour inspections did not affect psychosocial and biomechanical work factors in the home care services. A favourable effect of the guidance intervention on psychosocial work factors was observed. However, this was not evident after adjusting for multiple testing. Further research is needed to elaborate on how labour inspections and other regulatory tools can impact psychosocial and biomechanical work factors. TRIAL REGISTRATION NUMBER: NCT03855163.

Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations.

Telomere shortening can result in cellular senescence and in increased level of genome instability, which are key events in numerous of cancer types. Despite this, few studies have focused on the effect of nanomaterial exposure on telomere length as a possible mechanism involved in nanomaterial-induced carcinogenesis. In this study, effects of exposure to multiwalled carbon nanotubes (MWCNT) on telomere length were investigated in mice exposed by intrapleural injection, as well as in human lung epithelial and mesothelial cell lines. In addition, cell cycle, apoptosis, and regulation of genes involved in DNA damage repair were assessed. Exposure to MWCNT led to severe fibrosis, infiltration of inflammatory cells in pleura, and mesothelial cell hyperplasia. These histological alterations were accompanied by deregulation of genes involved in fibrosis and immune cell recruitment, as well as a significant shortening of telomeres in the pleura and the lung. Assessment of key carcinogenic mechanisms in vitro confirmed that long-term exposure to the long MWCNT led to a prominent telomere shortening in epithelial cells, which coincided with G1-phase arrest and enhanced apoptosis. Altogether, our data show that telomere shortening resulting in cell cycle arrest and apoptosis may be an important mechanism in long MWCNT-induced inflammation and fibrosis.

Adverse social behaviour at the workplace and subsequent physician certified sick leave: a three-wave prospective study of the general working population in Norway.

OBJECTIVES: We aimed to provide an integrated picture of the relationship between different facets of adverse social behaviour (ASB) at the workplace and sick leave. METHODS: Data from a randomly drawn prospective cohort of the general working population. Eligible respondents were interviewed in 2009, 2013 or 2016, and were registered with an employee relationship of at least 50 working days in the national register the year following the survey interviews (n=21 674 observations/13 470 respondents). We investigated the prospective associations of self-reported exposure to ASB, including threats/acts of violence, bullying and sexual harassment, with physician-certified sick leave of 1-16 days (ie, low level of sick leave (LLSL)) and >16 days (ie, high level of sick leave (HLSL)) by means of mixed effects logistic regression. RESULTS: The prevalence of sick leave was 18.4% (n=3986 observations) for LLSL and 16.1% (n=3492 observations) for HLSL. The different facets of ASB were independently associated with higher odds of sick leave, with stronger associations for HLSL than for LLSL. Adjusted for sex, age, education level, occupation, previous sickness absence level, OR (95% CI) for HLSL was 1.97 (1.61 to 2.35) for threats/acts of violence, 1.97 (1.53 to 2.54) for bullying and 1.41 (1.10 to 1.79) for sexual harassment. The population risks of LLSL and HLSL attributable to ASB were 5.27 (95% CI 1.85 to 8.81) and 8.27% (95% CI 4.01 to 12.48), respectively. CONCLUSIONS: Threats/acts of violence, bullying and sexual harassment were all independent predictors of sick leave, with threats/acts of violence appearing as the single most important factor.

Long-Term Exposure to Nanosized TiO2 Triggers Stress Responses and Cell Death Pathways in Pulmonary Epithelial Cells.

There is little in vitro data available on long-term effects of TiO2 exposure. Such data are important for improving the understanding of underlying mechanisms of adverse health effects of TiO2. Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm2) of TiO2 for 13 weeks and effects on cell cycle and cell death mechanisms, i.e., apoptosis and autophagy were determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels and lipid classes were also analyzed at 13 weeks of exposure. We observed that the TiO2 exposure increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was accompanied by an increase in the fraction of late apoptotic/necrotic cells. This corresponded with an induced expression of key apoptotic proteins i.e., BAD and BAX, and an accumulation of several lipid classes involved in cellular stress and apoptosis. These findings were further supported by quantitative proteome profiling data showing an increase in proteins involved in cell stress and genomic maintenance pathways following TiO2 exposure. Altogether, we suggest that cell stress response and cell death pathways may be important molecular events in long-term health effects of TiO2.

Occupational Noise Exposure and Vestibular Schwannoma: A Case-Control Study in Sweden.

It has been suggested that the association between self-reported occupational noise exposure and vestibular schwannoma (VS), found in several studies, represents recall bias. Therefore, we aimed to study the relationship in a large case-control study using occupational noise measurements. We performed a case-control study using data from Sweden for 1,913 VS cases diagnosed in 1961-2009 and 9,566 age- and sex-matched population controls. We defined occupational history by linkage to national censuses from 1960, 1970, 1980, and 1990. We estimated occupational noise exposure for each case and control using a job-exposure matrix. There was no association between occupational noise exposure and VS. Among subjects assessed as ever exposed to occupational noise levels of ≥85 dB (214 cases and 1,142 controls), the odds ratio for VS per 5 years of exposure was 1.02 (95% confidence interval: 0.90, 1.17). Workers with noise levels of ≥85 dB for at least 15 years (5-year latency period), showed no increased risk of VS (odds ratio = 0.98, 95% confidence interval: 0.73, 1.31) compared with those who had never been exposed to noise levels of 75 dB or higher. In summary, our large study does not support an association between occupational noise exposure and VS.

Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis.

OBJECTIVE: To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. METHODS: A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS <1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS <1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. RESULTS: MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40]. CONCLUSION: Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, http://clinicaltrials.gov, NCT01205854.

Bulky DNA adducts, microRNA profiles, and lipid biomarkers in Norwegian tunnel finishing workers occupationally exposed to diesel exhaust.

OBJECTIVES: This study aimed to assess the biological impact of occupational exposure to diesel exhaust (DE) including DE particles (DEP) from heavy-duty diesel-powered equipment in Norwegian tunnel finishing workers (TFW). METHODS: TFW (n=69) and referents (n=69) were investigated for bulky DNA adducts (by 32P-postlabelling) and expression of microRNAs (miRNAs) (by small RNA sequencing) in peripheral blood mononuclear cells (PBMC), as well as circulating free arachidonic acid (AA) and eicosanoid profiles in plasma (by liquid chromatography-tandem mass spectrometry). RESULTS: PBMC from TFW showed significantly higher levels of DNA adducts compared with referents. Levels of DNA adducts were also related to smoking habits. Seventeen miRNAs were significantly deregulated in TFW. Several of these miRNAs are related to carcinogenesis, apoptosis and antioxidant effects. Analysis of putative miRNA-gene targets revealed deregulation of pathways associated with cancer, alterations in lipid molecules, steroid biosynthesis and cell cycle. Plasma profiles showed higher levels of free AA and 15-hydroxyeicosatetraenoic acid, and lower levels of prostaglandin D2 and 9-hydroxyoctadecadienoic acid in TFW compared with referents. CONCLUSION: Occupational exposure to DE/DEP is associated with biological alterations in TFW potentially affecting lung homoeostasis, carcinogenesis, inflammation status and the cardiovascular system. Of particular importance is the finding that tunnel finishing work is associated with an increased level of DNA adducts formation in PBMC.

Pulmonary function and high-resolution computed tomography examinations among offshore drill floor workers.

PURPOSE: The aim of this study was to assess short-term changes in pulmonary function in drill floor workers currently exposed to airborne contaminants generated as a result of drilling offshore. We also aimed to study the prevalence of pulmonary fibrosis using high-resolution computed tomography (HRCT) scans of another group of previously exposed drill floor workers. METHODS: Pulmonary function was measured before and after a 14-day work period in a follow-up study of 65 drill floor workers and 65 referents. Additionally, 57 other drill floor workers exposed to drilling fluids during the 1980s were examined with HRCT of the lungs in a cross-sectional study. RESULTS: The drill floor workers had a statistically significant decline in forced expiratory volume in 1 s (FEV1) across the 14-day work period after adjustment for diurnal variations in pulmonary function (mean 90 mL, range 30-140 mL), while the small decline among the referents (mean 20 mL, range - 30 to 70 mL) was not of statistical significance. Larger declines in FEV1 among drill workers were associated with the fewer number of days of active drilling. There were no signs of pulmonary fibrosis related to oil mist exposure among the other previously exposed drill floor workers. CONCLUSION: After 14 days offshore, a statistically significant decline in FEV1 was observed in the drill floor workers, which may not be related to oil mist exposure. No pulmonary fibrosis related to oil mist exposure was observed.

Lung function in asphalt pavers: a longitudinal study.

PURPOSE: To study longitudinal changes in lung function in asphalt pavers and a reference group of road maintenance workers, and to detect possible signs of lung disease by high-resolution computed tomography (HRCT) scans. METHODS: Seventy-five asphalt pavers and 71 road maintenance workers were followed up with questionnaires and measurements of lung function. Not every worker was tested every year, but most of them had four or more measurement points. The 75 asphalt pavers were also invited to have HRCT scans of the lungs at the end of the follow-up period. RESULTS: Mean annual decline in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) of the asphalt pavers was 58 and 35 ml, respectively. Adjusted for age at baseline, packyears of smoking and BMI, the asphalt pavers had a significant excess annual decline in FVC and FEV1 compared to the references. The screedmen, the most exposed group of the asphalt pavers, showed a significantly larger decline in FVC than the other asphalt pavers (P = 0.029). Fine intralobular fibrosis without evident cysts was identified with HRCT in three subjects (4 %). CONCLUSION: We conclude that our findings may indicate an excess annual decline in FVC and FEV1 related to exposure to asphalt fumes. The screedmen, who carry out their work behind and close to the paving machine, had the largest decline in lung function. The finding of adverse pulmonary effects in asphalt pavers calls for better technological solutions to prevent exposure.

Physical activity initiated by employer induces improvements in a novel set of biomarkers of inflammation: an 8-week follow-up study.

PURPOSE: We investigated the level of pro- and anti-inflammatory biomarkers before and after 8 weeks of unsupervised physical activity (PA) initiated by employer. METHODS: During autumn 2014, background data, blood samples and self-reported exercise level were collected from 76 men and 41 women in a Norwegian road maintenance company. Monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), leptin, adiponectin, p-selectin and CD40 ligand (CD40L) were analyzed. [Formula: see text] was measured in a subgroup of 50 subjects. RESULTS: With reference point of exercise ≤1 time/week, we found that participants who exercised 2-3 times/week had higher [Formula: see text] values (5.6 mL kg-1 min-1; 95% CI [1.3, 9.9]). MCP-1 was lower in those who exercised ≥ 4 times/week (-81.98 pg/ml [-142.9, -21.0]). IL-6 and p-selectin levels were lower in females who exercised ≥4 times/week (-1.04 pg/ml [-2.04, -0.03] and -13.75 ng/ml [-24.03, -3.48]). Leptin was lower in participants who exercised 2-3 times/week (-0.39 µg/ml ln [-0.68, -0.09]) and ≥4 times/week (-0.69 µg/ml ln [-1.10, -0.28]). During follow-up, [Formula: see text] increased (2.9 mL kg-1 min-1 [1.5, 4.3]), while p-selectin and CD40L decreased (-2.33 ng/ml [-3.78, -0.87] and 718.14 ng/ml [-1368, -68]). MCP-1 levels decreased among men (-32.70 pg/ml [-51.21, -14.19]). A joint analysis of all biomarkers (inversed adiponectin) showed that those who exercised ≥4 times/week at baseline had lower total levels of biomarkers and that total biomarker levels decreased during follow-up. CONCLUSIONS: Exercising several times a week was associated with less inflammation compared to exercising once a week or less. During the 8-week follow-up, total levels of biomarkers of inflammation improved.

Thoracic dust exposure is associated with lung function decline in cement production workers.

We hypothesised that exposure to workplace aerosols may lead to lung function impairment among cement production workers.Our study included 4966 workers in 24 cement production plants. Based on 6111 thoracic aerosol samples and information from questionnaires we estimated arithmetic mean exposure levels by plant and job type. Dynamic lung volumes were assessed by repeated spirometry testing during a mean follow-up time of 3.5 years (range 0.7-4.6 years). The outcomes considered were yearly change of dynamic lung volumes divided by the standing height squared or percentage of predicted values. Statistical modelling was performed using mixed model regression. Individual exposure was classified into quintile levels limited at 0.09, 0.89, 1.56, 2.25, 3.36, and 14.6 mg·m(-3), using the lowest quintile as the reference. Employees that worked in administration were included as a second comparison group.Exposure was associated with a reduction in forced expiratory volume in 1 s (FEV1), forced expiratory volume in 6 s and forced vital capacity. For FEV1 % predicted a yearly excess decline of 0.84 percentage points was found in the highest exposure quintile compared with the lowest.Exposure at the higher levels found in this study may lead to a decline in dynamic lung volumes. Exposure reduction is therefore warranted.

Physical activity initiated by employer and its health effects; an eight week follow-up study.

BACKGROUND: While the health benefits of physical activity are well established, little is known about health effects of physical activity programs initiated by employer. METHODS: Background data and level of physical activity were collected by questionnaire among 78 men and 43 women working in road maintenance pre and post an 8-week physical activity motivational program. As a part of the program steps measured by accelerometer were registered online where team and individual performances could be continuously monitored. The physical activity levels were registered as 1) those physical active ≤1 time per week, 2) 2-3 times per week and 3) ≥4 times a week. Maximal oxygen uptake (VO2max), blood pressure, resting heart rate (RHR) and blood samples (glycosylated hemoglobin, lipids and C-reactive protein) were obtained at baseline and after eight weeks. Mixed models were applied to evaluate associations between physical activity and health parameters. RESULTS: With ≤1 time per week as reference, exercising 2-3 times per week at baseline was associated with higher levels of VO2max. During follow-up, VO2max increased with 2.8 mL ∙ kg(-1)∙ min(-1) (95 % CI = 1.4, 4.3). Women had more favorable body mass index (BMI), blood pressure, RHR and lipid profile than men. Total cholesterol, low density lipoprotein (LDL), RHR and diastolic blood pressure (dBP) were lower among participants who exercised 2-3 times per week or ≥4 times a week, compared with those with ≤1 time per week. Half of the participants reported increased daily PA during follow-up, with high intensity PA such as jogging by 8.6 min (SD 14.6) and 8.3 min (SD 18.2), among women and men, respectively. During follow-up dBP increased among men. Further, total cholesterol and LDL were reduced by 0.12 mmol/L and 0.13 mmol/L, respectively (95 % CI = -022, -0.01 and -0.22,-0.04). CONCLUSIONS: Exercise several times a week was associated with lower blood pressure and a favorable lipid status compared to lower weekly activity. During the 8-week follow-up of an employer initiated exercise program VO2max increased, while total cholesterol and LDL were reduced. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13033050 . Registered 21 August 2015.

Airway inflammation and ammonia exposure among female Palestinian hairdressers: a cross-sectional study.

OBJECTIVES: Little is known about the working conditions and airway inflammation in hairdressers in Palestine. We aimed to investigate if hairdressers in Palestine have a higher level of airway inflammation as compared to a control group. We also assessed the hairdressers' physical working conditions and exposure to ammonia gases at the hair salons. Lastly, we investigated the association between ammonia levels and inflammation markers in the airways and the blood. METHODS: Our study participants were 33 non-smoking hairdressers (aged 19-50 years) and 35 non-smoking control subjects (aged 18-49 years). Both groups answered a questionnaire on respiratory symptoms, and performed lung function and exhaled nitric oxide (eNO) tests. Blood and sputum samples were collected from all participants and air concentration levels of ammonia were measured in 13 salons. RESULTS: Hairdressers had a higher level of sputum neutrophil count (absolute numbers/mg sputum (median (25th-75th centiles)) compared to controls, 376 (183-980) and 182 (96-358), respectively. Hairdressers also had significantly elevated eNO and blood C reactive protein (CRP) levels compared to the control subjects, controlled for age and body mass index. Exposure measurements showed that the hairdressers in salons with scarce ventilation were exposed to ammonia concentration, ranging from 3 to 61 mg/m(3). CONCLUSIONS: Compared to unexposed controls, the hairdressers had signs of neutrophilic airway inflammation, higher eNO levels and higher CRP. The hairdressers were exposed to high concentrations of ammonia from hairdressing chemicals and their working conditions were unsatisfactory.

Exposure to thoracic aerosol in a prospective lung function study of cement production workers.

INTRODUCTION: An exposure study was conducted as part of a multi-national longitudinal study of lung function in cement production workers. AIM: To examine exposure to thoracic aerosol among cement production workers during a 4-year follow-up period. METHODS: Personal shift measurements of thoracic aerosol were conducted among the cement production workers within seven job types, 22 plants, and eight European countries (including Turkey) in 2007, 2009, and 2011. The thoracic sub-fraction was chosen as the most relevant aerosol fraction related to obstructive dynamic lung function changes. Production factors, job type, and respirator use were recorded by questionnaire. The exposure data were log-transformed before mixed models analysis and results were presented by geometric mean (GMadj) exposure levels adjusted for plant or job type, worker, and season as random effects. RESULTS: A total of 6111 thoracic aerosol samples were collected from 2534 workers. Repeated measurements were obtained from 1690 of these workers. The GMadj thoracic aerosol levels varied between job types from 0.20 to 1.2mg m(-3). The highest exposure levels were observed for production, cleaning, and maintenance workers (0.79-1.2mg m(-3)) and could reach levels where the risk of lung function loss may be increased. The lowest levels were found for administrative personnel (0.20mg m(-3)) serving tasks in the production areas. Office work was not monitored. GMadj exposure levels between plants ranged from 0.19 to 2.0mg m(-3). The time of year/season contributed significantly to the total variance, but not year of sampling. Production characteristics explained 63% of the variance explained by plant. Workers in plants with the highest number of employees (212-483 per plant) were exposed at a level more than twice as high as those in plants with fewer employees. Other production factors such as cement production, bag filling, and tidiness were significant, but explained less of the exposure variability. These determinants factors can be useful in qualitative exposure assessment and exposure prevention in the cement production industry. Respirator use was minor at exposure levels <0.5mg m(-3) but more common at higher levels. CONCLUSION: Production, cleaning, and maintenance work were the job types with highest exposure to thoracic aerosol in cement production plants. However, plant had an even larger effect on exposure levels than job type. The number of employees was the most important factor explaining differences between plants. Exposure reached levels where the risk of lung function loss may be increased. No significant differences in exposure between sampling campaigns were observed during the 4-year study period.

A twelve-year longitudinal study of neuropsychological function in non-saturation professional divers.

OBJECTIVES: Our main aim was to study the long-term neuropsychological effects of non-saturation diving. Further, we aimed to investigate whether neuropsychological performance was predictive of subsequent diving accidents and diving status. METHODS: In this prospective longitudinal study, we enrolled 50 male diving students (mean age 25.3 years) at a diving school and followed them up six and 12 years later (43 and 37 divers, respectively). At each wave of the study, divers completed a comprehensive neuropsychological test battery and answered questionnaires on cumulative number of dives, incidents of decompression illness (DCI) and professional diver status. RESULTS: At the 12-year follow-up, the divers reported a median number of 455 (range 40-5,604) cumulative dives. Cumulative number of dives was not associated with any adverse neuropsychological effects. However, divers with an incident of DCI performed worse in a memory test (Benton Visual Retention Test) and reported slightly more neuropsychiatric symptoms (Q 16). Diver students who performed well on a blindfolded memory test (tactual performance test) had an increased likelihood of becoming a professional diver 12 years later. CONCLUSIONS: The main findings in the present study support the view that asymptomatic non-saturation divers who have dived under controlled conditions do not have an increased risk of impaired nervous system function, at least not to an extent that can be detected with neuropsychological tests while they still are relatively young. The observed associations between a history of DCI and impaired results in a memory test and reporting of neuropsychiatric symptoms may be due to a nervous system effect caused by DCI. The diver students' ability of problem-solving while they were blindfolded was predictive of their likelihood of becoming a professional diver 12 years later.

Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet.

Tissue- and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement.

Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema.

Aquaporin-4 (AQP4) is a primary influx route for water during brain edema formation. Here, we provide evidence that brain swelling triggers Ca(2+) signaling in astrocytes and that deletion of the Aqp4 gene markedly interferes with these events. Using in vivo two-photon imaging, we show that hypoosmotic stress (20% reduction in osmolarity) initiates astrocytic Ca(2+) spikes and that deletion of Aqp4 reduces these signals. The Ca(2+) signals are partly dependent on activation of P2 purinergic receptors, which was judged from the effects of appropriate antagonists applied to cortical slices. Supporting the involvement of purinergic signaling, osmotic stress was found to induce ATP release from cultured astrocytes in an AQP4-dependent manner. Our results suggest that AQP4 not only serves as an influx route for water but also is critical for initiating downstream signaling events that may affect and potentially exacerbate the pathological outcome in clinical conditions associated with brain edema.

Effects of the Labor Inspection Authority's regulatory tools on physician-certified sick leave and employee health in Norwegian home-care services - a cluster randomized controlled trial.

OBJECTIVE: This study aimed to determine the effects of the Labor Inspection Authority's regulatory tools on physician-certified sick leave and self-reported health outcomes among employees in municipal home-care services in Norway. METHODS: We conducted a cluster-randomized controlled trial in the home-care service sector, and 96 eligible municipalities were randomly assigned to one of three groups: (i) labor inspection visits, based on the Labor Inspection Authority's standard inspections; (ii) guidance-through-workshops, where participants from home-care services met with labor inspectors to receive information and discuss relevant topics; and (iii) the control group. Data on employee self-reported health (N=1669) were collected at baseline and 6 and 12 months after the interventions. Additionally, registry data (N=1202) on diagnosis specific physician-certified sick leave were collected for 18 months after the interventions. RESULTS: We found no statistically significant effects of either intervention on self-reported health outcomes. There was, for both interventions, a pattern of decrease in days and periods of physician-certified sick leave due to musculoskeletal diagnoses and increase in days and periods of physician-certified sick leave due to psychological diagnoses, but these were not statistically significant. CONCLUSION: Labor inspections and guidance-through-workshops had no statistically significant effect on self-reported health and physician-certified sick leave. The results should be interpreted with caution given the low response rate and subsequent attrition, and in the context of the COVID-19 pandemic. Future studies, in various industries, should further elucidate whether regulatory tools influence employee health and sick leave due to musculoskeletal and mental disorders.

Longitudinal lung function decline among workers in a nitrate fertilizer production plant.

BACKGROUND: This study examines the possible effect of exposure to aerosols and gases on lung function in a fertilizer plant in Norway. METHODS: Dynamic lung volumes (FVC and FEV1) of 383 workers were measured in 2007 and 2010. During the follow-up period, most workers performed tasks with low exposure levels of acid aerosols and inorganic gases. The overall median inhalable and thoracic aerosol exposure levels were 1·1 and 0·21 mg/m(3), respectively. A questionnaire on respiratory symptoms was provided. RESULTS: During the follow-up period, there was an adjusted decrease of FEV1 of 18 ml/year (P<0·001). The respiratory symptoms score was low during follow-up. CONCLUSIONS: Work in this fertilizer industry may lead to an excessive lung function decline. We have, however, not been able to find any plausible exposure related explanation for the overall lung function decline.