An updated job-exposure matrix for occupational noise: development and validation.

OBJECTIVES: The aim of this study was to create a quantitative job-exposure matrix (JEM) for noise including a large set of measurements for the Swedish workforce, a detailed exposure-level assessment, spanning over an extensive time period from 1970 to 2014. METHODS: The JEM was developed by 2 teams, each with an experienced occupational hygienist and an occupational safety engineer. Each pair assessed the exposure using measurements performed and reported by occupational hygienists, occupational safety engineers, or similar, from 1970 to 2014. The measurements included either the original LAeq(8h) measurements or an LAeq(8h) levels calculated from partial measurements of the working day, provided that the measurement targeted a regular task usually performed during a full workday. The collection of measurement reports was done in 2008 and 2012 by contacting clinics working in the area of occupational health or occupational safety engineers and their submitted reports were added to our own material. Noise exposure assessments were inserted at the appropriate time period for the relevant job family. The final matrix was developed in a consensus procedure and the validity was investigated by comparison of the 2 team's individual results. RESULTS: The noise JEM contains 321 job families with information regarding occupational noise from 1970 to 2014. The time-period label has a 5-yr scale starting in 1970. The estimated average 8 h (TWA) noise level in decibels [dB(A)] for every job family and 5-yr period was coded as 1: <70 dB(A), 2: 70 to 74 dB(A), 3: 75 to 79 dB(A), 4: 80 to 84 dB(A) or 5: 85(+) dB(A). The validation showed no systematic difference in relative position and very high agreement in the ordering of paired ordinal classifications. The JEM has also successfully been applied in several epidemiological studies. CONCLUSIONS: We present a JEM for occupational noise using Swedish data from 1970 to 2014 with a higher degree of sensitivity in assessed noise exposure compared with the previously existing version. Repeated application of the JEM, in epidemiological studies, has shown consistent results and contributed to yielding important findings.

Occupational exposure to particles and biomarkers of cardiovascular disease-during work and after vacation.

OBJECTIVE: Ambient particle matter is a risk factor for cardiovascular disease (CVD). However, little is known about associations between particles in occupational settings and risk of CVD. We investigated associations between occupational dust exposure and biomarkers of CVD, and potential recovery effects after vacation. METHODS: Personal dust exposure measurements (respirable silica, respirable dust < 4 µm, and particles of 0.1-10 µm (PM 0.1-10) were conducted once, and biological sampling were performed twice on non-smoking, male construction workers in Stockholm county, Sweden; during work and immediately after summer vacation. Linear regressions with adjustments for confounders and covariates were performed evaluating associations between occupational dust exposure and biomarkers. Paired t tests were performed evaluating changes before and after vacation. RESULTS: Sixty-five workers participated. Homocysteine concentrations were significantly higher with increasing concentrations (mg/m3) of respirable silica, respirable dust, and PM 0.1-10, and pulse rate with higher levels of respirable dust and dust of PM 0.1-10. Homocysteine levels were also positively correlated to number of years of dust exposure, as were low-density lipoprotein (LDL) levels. A clear recovery effect was present for LDL after vacation, but not for homocysteine. CONCLUSIONS: Occupational dust exposure was associated with some CVD risk markers, even at mean exposure concentrations below the Swedish occupational exposure limits for respirable silica and respirable dust, respectively. Vacation resulted in recovery for some risk markers. However, the change of the homocysteine and LDL levels suggest a long-term effect. Reduction of occupational exposure to dust may decrease the risk of CVD among exposed workers.

Occupational noise exposure and risk of incident stroke: a pooled study of five Scandinavian cohorts.

OBJECTIVES: To investigate the association between occupational noise exposure and stroke incidence in a pooled study of five Scandinavian cohorts (NordSOUND). METHODS: We pooled and harmonised data from five Scandinavian cohorts resulting in 78 389 participants. We obtained job data from national registries or questionnaires and recoded these to match a job-exposure matrix developed in Sweden, which specified the annual average daily noise exposure in five exposure classes (LAeq8h): <70, 70-74, 75-79, 80-84, ≥85 dB(A). We identified residential address history and estimated 1-year average road traffic noise at baseline. Using national patient and mortality registers, we identified 7777 stroke cases with a median follow-up of 20.2 years. Analyses were conducted using Cox proportional hazards models adjusting for individual and area-level potential confounders. RESULTS: Exposure to occupational noise at baseline was not associated with overall stroke in the fully adjusted models. For ischaemic stroke, occupational noise was associated with HRs (95% CI) of 1.08 (0.98 to 1.20), 1.09 (0.97 to 1.24) and 1.06 (0.92 to 1.21) in the 75-79, 80-84 and ≥85 dB(A) exposure groups, compared with <70 dB(A), respectively. In subanalyses using time-varying occupational noise exposure, we observed an indication of higher stroke risk among the most exposed (≥85 dB(A)), particularly when restricting analyses to people exposed to occupational noise within the last year (HR: 1.27; 95% CI: 0.99 to 1.63). CONCLUSIONS: We found no association between occupational noise and risk of overall stroke after adjustment for confounders. However, the non-significantly increased risk of ischaemic stroke warrants further investigation.

The Impact of Occupational Noise Exposure on Hyperacusis: a Longitudinal Population Study of Female Workers in Sweden.

OBJECTIVES: The aim was to assess the risk of hyperacusis in relation to occupational noise exposure among female workers in general, and among women working in preschool specifically. DESIGN: A retrospective longitudinal study was performed. Survey data were collected in 2013 and 2014 from two cohorts: randomly selected women from the population in region Västra Götaland, Sweden, and women selected based on having received a preschool teacher degree from universities in the same region. The final study sample included n = 8328 women born between 1948 and 1989. Occupational noise exposure was objectively assigned to all time periods from the first to the last reported occupation throughout working life, using the Swedish Job-Exposure Matrix (JEM) with three exposure intervals: <75 dB(A), 75 to 85 dB(A), and >85 dB(A). The JEM assigns preschool teachers to the 75 to 85 dB(A) exposure interval. The outcome hyperacusis was assessed by self-report using one question addressing discomfort or pain from everyday sounds. In the main analysis, a hyperacusis event was defined by the reported year of onset, if reported to occur at least a few times each week. Additional sensitivity analyses were performed using more strict definitions: (a) at least several times each week and (b) every day. The risk (hazard ratio, HR) of hyperacusis was analyzed in relation to years of occupational noise exposure, using survival analysis with frailty regression modeling accounting for individual variation in survival times which reflect, for example, noise exposure during years prior to onset. Occupational noise exposure was defined by the occupation held at year of hyperacusis onset, or the occupation held at the survey year if no event occurred. Models were adjusted for confounders including age, education, income, family history of hearing loss, and change of jobs due to noise. RESULTS: In total, n = 1966 hyperacusis events between 1960 and 2014 were analyzed in the main analysis. A significantly increased risk of hyperacusis was found among women working in any occupation assigned to the 75 to 85 dB(A) noise exposure group [HR: 2.6, 95% confidence interval (CI): 2.4-2.9], compared with the reference group <75 dB(A). The risk was tripled among preschool teachers specifically (HR: 3.4, 95% CI: 3.0-3.7), with the crude Kaplan-Meier curve showing a higher rate of onset early in the working life in preschool teachers compared with all the other exposure groups. The risk was increased, but not statistically significant in the main analysis, for the highest exposure group >85 dB(A), where only six hyperacusis events were identified (HR: 1.4, 95% CI: 0.6-3.1). In the sensitivity analysis, where hyperacusis was defined as occurring every day, the HR was significant also in the highest exposure group (HR: 3.8, 95% CI: 1.4-10.3), and generally slightly higher in the other exposure groups compared to the main analysis. CONCLUSIONS: This study indicates increased risk of hyperacusis already below the permissible occupational noise exposure limit in Sweden (85 dB LAeq,8h) among female workers in general, and in particular among preschool teachers. Prospective studies and less wide exposure intervals could confirm causal effects and assess dose-response relationships, respectively, although this study at present suggest a need for risk assessment, improved hearing prevention measures, and noise abatement measures in occupations with noise levels from 75 dB(A). The results could also have implications for management of occupational disability claims.

Occupational exposure to noise in relation to pregnancy-related hypertensive disorders and diabetes.

Objectives Exposure to environmental noise has been associated with an increased risk of cardiovascular diseases and diabetes, but evidence for occupational noise is limited and conflicting, especially related to pregnancy outcomes. This study aimed to evaluate the association of occupational noise exposure with hypertensive disorders of pregnancy (HDP) and gestational diabetes. Methods Our population-based cohort study utilized data on 1 109 516 singletons born to working mothers in Sweden between 1994-2014 from the Medical Birth Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies. Noise exposure came from a job exposure matrix (JEM) in five categories <70, 70-74, 75-80, 80-85, >85 dB(A). Relative risks (RR), adjusted for confounders and other job exposures, were calculated by modified Poisson regressions for the full sample and a subsample of first-time mothers reporting full-time work. Results Exposure to 80-85 dB(A) of noise was associated with an increased risk of all HDP [RR 1.12, 95% confidence interval (CI) 1.05-1.18] and preeclampsia alone (RR 1.14, 95% CI 1.07-1.22) in the full sample. Results were similar for first-pregnancy, full-time workers. Exposure to >85 dB(A) of noise was also associated with an increased risk of gestational diabetes (RR 1.57, 95% CI 1.10-2.24) in the analysis restricted to first-time mothers working full-time. Conclusion In this study, exposure to noise was associated with an increased risk for HDP and gestational diabetes, particularly in first-time mothers who work full-time. Further research is needed to confirm findings and identify the role of hearing protection on this association so prevention policies can be implemented.

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.

Noise exposure and childhood asthma up to adolescence.

OBJECTIVE: Increasing evidence indicates aggravation of immune-mediated diseases due to physiological and psychological stress. Noise is a stressor, however, little is known about its effects on children's respiratory health. This study investigates the association between pre- or postnatal road traffic or occupational noise exposure and asthma as well as related symptoms from infancy to adolescence. METHODS: The study was conducted in the Swedish birth cohort BAMSE, including over 4000 participants followed with repeated questionnaires and clinical tests until 16 years of age. Pre- and postnatal residential road traffic noise was assessed by estimating time-weighted average noise levels at the most exposed façade. Maternal occupational noise exposure during pregnancy was evaluated using a job-exposure-matrix. The associations between noise exposure and asthma-related outcomes were explored using logistic regression and generalised estimating equations. RESULTS: We observed non-significant associations for asthma ever up to 16 years with residential road traffic noise exposure in infancy ≥55 dBLden (adjusted OR = 1.22; 95% CI 0.90-1.65), as well as prenatal occupational noise exposure ≥80 dBLAeq,8h (1.18, 0.85-1.62). In longitudinal analyses, however, no clear associations between pre- or postnatal exposure to residential road traffic noise, or average exposure to noise since birth, were detected in relation to asthma or wheeze until 16 years. CONCLUSION: We did not find a clear overall association between exposure to noise during different time periods and asthma or wheeze up to adolescence.

Traffic noise and other determinants of blood pressure in adolescence.

BACKGROUND: Exposure to traffic noise has been associated with hypertension in adults but the evidence in adolescents is limited. We investigated long-term road traffic noise exposure, maternal occupational noise during pregnancy and other factors in relation to blood pressure and prehypertension at 16 years of age. METHODS: Systolic and diastolic blood pressure were measured in 2597 adolescents from the Swedish BAMSE birth cohort. Levels of road traffic noise were estimated at home addresses during lifetime and for the mother during pregnancy as well as maternal occupational noise exposure during pregnancy. Exposure to NOx from local sources was also assessed. Associations between noise or NOx exposure and blood pressure or prehypertension were analysed using linear and logistic regression. RESULTS: The prevalence of prehypertension was higher among males and in those with overweight, low physical activity or overweight mothers. No strong or consistent associations were observed between pre- or postnatal exposure to road traffic noise and blood pressure at 16 years of age. However, inverse associations were suggested for systolic or diastolic blood pressure and prehypertension, which reached statistical significance among males (OR 0.80 per 10 dB Lden, 95% CI 0.65-0.99) and those with maternal occupational noise exposure ≥ 70 dB LAeq8h (OR 0.60, 95% CI 0.41-0.87). On the other hand, occupational noise exposure during pregnancy tended to increase systolic blood pressure and prehypertension risk in adolescence. No associations were seen for NOx exposure. CONCLUSION: No conclusive associations were observed between pre- or postnatal noise exposure and blood pressure or prehypertension in adolescents.

Airborne and Dermal Exposure to Polycyclic Aromatic Hydrocarbons, Volatile Organic Compounds, and Particles among Firefighters and Police Investigators.

AIMS: The main aim of this study was to assess dermal exposure to polycyclic aromatic hydrocarbons (PAHs) and airway exposure to PAHs, volatile organic compounds (VOCs; benzene and 1,3-butadiene), and particles among firefighters (FFs) and police forensic investigators (PFIs) in Sweden. METHODS: Active (pump with a filter and sorbent tube) and passive (polyurethane foam -cyl and perkin elmer carbopack-tube) personal air sampling and dermal tape stripping (wrist and collar bone) were performed on seven FF team leaders during training fires and nine PFIs investigating the aftermath of live fire events. In addition, passive personal air sampling was performed on eight FF team leaders during live emergency fires. PAHs and VOCs were analysed using high-resolution gas chromatography low-resolution mass spectrometry. The mass concentration of total dust (particles) was determined using standard gravimetric methods. RESULTS: The air samples showed that the exposure to PAHs, benzene, 1,3-butadiene, and particles was below Swedish occupational exposure limits (OELs). Naphthalene was the predominant PAH in all air samples. Benzene and 1,3-butadiene were more abundant in live emergency fires, which caused higher exposures than the other studied situations. Both gaseous- and particle-associated PAHs were present on skin. The wrists seemed to be less well protected than the collarbone area. CONCLUSIONS: FFs and PFIs are exposed to several hazardous compounds during their work. Air exposures varied considerably between working scenarios. The observed exposures were substantially higher than urban background levels but well below Swedish OELs. The measured dermal PAH exposures were comparable to previously reported doses for US FFs but lower than the exposures reported for Swedish chimney sweeps.

Traffic noise exposure in relation to adverse birth outcomes and body mass between birth and adolescence.

BACKGROUND: There is growing evidence that traffic noise exposure is associated with adiposity among adults but data in children are limited. OBJECTIVE: This longitudinal study examined whether pre- and postnatal noise exposure is associated with body mass index (BMI) between birth and adolescence or with adverse birth outcomes. METHODS: The study was conducted using data from the BAMSE birth cohort, which included 4089 children born in Stockholm County, Sweden. Data on BMI from birth to adolescence were collected via questionnaires, clinical examinations and health care records. A national register provided information on birth outcomes. Road traffic noise levels at the most exposed façade were estimated for all residences of the children during follow-up, as well as of their mothers during pregnancy, and time-weighted average exposure was calculated for different time windows. Maternal occupational noise exposure was obtained from a job-exposure-matrix. Logistic- and quantile regression models were used to estimate associations between noise exposure and health outcomes. RESULTS: We found residential road traffic noise exposure to be associated with increases in BMI from school age to adolescence, but not at earlier ages. In the age groups 8-11 years and 12-16 years the BMI increments were 0.11 kg/m2 per 10 dB Lden (95% CI 0.08-0.13) and 0.20 kg/m2 per 10 dB Lden (95% CI 0.17-0.22), respectively. Maternal noise exposure during pregnancy was generally unrelated to adverse birth outcomes and BMI from birth to adolescence in the children, however, traffic noise exposure was associated with a decreased risk of preterm birth CONCLUSION: Residential road traffic noise exposure was associated with BMI increases from school age to adolescence, but not at earlier ages. Maternal occupational noise exposure or exposure from road traffic during pregnancy were not consistently related to birth outcomes or BMI from birth to adolescence.

Longitudinal study of occupational noise exposure and joint effects with job strain and risk for coronary heart disease and stroke in Swedish men.

OBJECTIVES: The aims were to investigate whether occupational noise increased the risk for coronary heart disease (CHD) and stroke and to elucidate interactions with stressful working conditions in a cohort of Swedish men. DESIGN: This is a prospective cohort study on CHD and stroke in Swedish men followed until death, hospital discharge or until 75 years of age, using Swedish national registers on cause of death and hospital discharges. Baseline data on occupation from 1974 to 1977 were used for classification of levels of occupational noise and job demand-control. Cox regression was used to analyse HRs for CHD and stroke. SETTING: Swedish men born in 1915-1925. PRIMARY AND SECONDARY OUTCOME MEASURES: CHD and stroke. PARTICIPANTS: The participants of the study were men from the Primary Prevention Study, a random sample of 10 000 men born in 1915-1925 in Gothenburg. Subjects with CHD or stroke at baseline or were not employed were excluded. The remaining subjects with complete baseline data on occupation, weight, height, hypertension, diabetes, serum cholesterol and smoking constituted the study sample (5753 men). RESULTS: There was an increased risk for CHD in relation to noise levels 75-85 dB(A) and >85 dB(A) compared with <75 dB(A) (HR 1.15, 95% CI 1.01 to 1.31, and HR 1.27, 95% CI 0.99 to 1.63, respectively). Exposure to noise peaks also increased the risk for CHD (HR 1.19, 95% CI 1.03 to 1.38). Among those with high strain (high demands and low control) combined with noise >75 dB(A), the risk for CHD further increased (HR 1.80, 95% CI 1.19 to 2.73). There was no significantly increased risk for stroke in any noise category. CONCLUSIONS: Exposure to occupational noise was associated with an increased risk for CHD and the risk further increased among those with concomitant exposure to high strain. None of the analysed variables were related to increased risk for stroke.

An improved method for determining dermal exposure to polycyclic aromatic hydrocarbons.

Many workers are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), which may cause various health problems, and some PAHs are known or suspected carcinogens. PAH exposure is primarily monitored by air sampling, but contamination may also occur through dermal exposure. PAHs adsorbed to the skin can be sampled by tape-stripping, but subsequent extraction of sampling tapes in organic solvent also releases diverse co-eluting substances that are difficult to remove before analysis of the PAHs by gas chromatography/mass spectrometry (GC/MS). The objective of this study was to optimise a procedure for analytical clean-up after extraction of 32 PAHs from tape-strips, by dialysis in organic solvent using semipermeable membranes. With triplicate subsamples, the developed method yields acceptable precision and repeatability for both the 32 PAHs, across the concentration range 10-160 ng per sample, and for a certified reference material (urban dust). The optimized clean-up procedure and GC/MS methodology was used to assess PAHs on skin from the lower part of the ventral side of the wrist and just below the collar bone of three firefighters and seven controls (office workers). Several gaseous and particle-bound PAHs were detected in all samples, including controls. Thus, the optimized procedure using semipermeable membranes for clean-up of tape-strip extracts can be used to assess the dermal exposure of both occupational and general populations to multiple PAHs. The results also show that both gaseous and particle-bound PAHs, including alkylated species, may be present on skin.

Road traffic noise and determinants of saliva cortisol levels among adolescents.

OBJECTIVES: The understanding of determinants for saliva cortisol levels in adolescents is limited. This study investigated the role of road traffic noise exposure, noise annoyance and various other factors for saliva cortisol levels. METHODS: We collected morning and evening saliva samples from 1751 adolescents from the BAMSE birth cohort based in Stockholm County. Façade noise levels from road traffic were estimated at the residences of the study subjects and repeated questionnaires and medical examinations provided extensive information on various exposures and conditions, including annoyance to noise from different sources. Cortisol was measured using radioimmunoassay. Associations between determinants and saliva cortisol levels were analysed using linear regression. RESULTS: Morning saliva cortisol levels were significantly higher in females than in males (geometric mean 42.4 and 35.0 nmol/l, respectively) as well as in subjects with allergy related diseases. Height and age were related to saliva cortisol levels as well as sampling season. Road traffic noise exposure was not associated with saliva cortisol, however, annoyance to noise tended to increase the levels. Saliva cortisol levels appeared particularly high among those who were highly annoyed and exposed to road traffic noise levels ≥ 55 dB Lden (50.5 nmol/l, p = 0.02). CONCLUSION: Our findings suggest that individual perception of noise may be of importance for saliva cortisol levels. The results also point to the complexity of using saliva cortisol as a marker of noise exposure in adolescents.

Evaluation of polyurethane foam passive air sampler (PUF) as a tool for occupational PAH measurements.

Routine monitoring of workplace exposure to polycyclic aromatic hydrocarbons (PAHs) is performed mainly via active sampling. However, active samplers have several drawbacks and, in some cases, may even be unusable. Polyurethane foam (PUF) as personal passive air samplers constitute good alternatives for PAH monitoring in occupational air (8 h). However, PUFs must be further tested to reliably yield detectable levels of PAHs in short exposure times (1-3 h) and under extreme occupational conditions. Therefore, we compared the personal exposure monitoring performance of a passive PUF sampler with that of an active air sampler and determined the corresponding uptake rates (Rs). These rates were then used to estimate the occupational exposure of firefighters and police forensic specialists to 32 PAHs. The work environments studied were heavily contaminated by PAHs with (for example) benzo(a)pyrene ranging from 0.2 to 56 ng m-3, as measured via active sampling. We show that, even after short exposure times, PUF can reliably accumulate both gaseous and particle-bound PAHs. The Rs-values are almost independent of variables such as the concentration and the wind speed. Therefore, by using the Rs-values (2.0-20 m3 day-1), the air concentrations can be estimated within a factor of two for gaseous PAHs and a factor of 10 for particulate PAHs. With very short sampling times (1 h), our method can serve as a (i) simple and user-friendly semi-quantitative screening tool for estimating and tracking point sources of PAH in micro-environments and (ii) complement to the traditional active pumping methods.

Influence of well-known risk factors for hearing loss in a longitudinal twin study.

OBJECTIVE: The aim was to investigate the influence of environmental exposures on hearing loss in a twin cohort. STUDY SAMPLE: Male twins born 1914-1958, representing an unscreened population, were tested for hearing loss at two occasions, 18 years apart. DESIGN: Clinical audiometry and a questionnaire were performed at both time points in this longitudinal study. Noise and solvent exposure were assessed using occupational work codes and a job exposure matrix. Hearing impairment was investigated using two different pure tone averages: PTA4 (0.5, 1, 2, and 4 kHz) and HPTA4 (3, 4, 6, and 8 kHz). RESULTS: Age affected all outcome measures. Noise exposure between time point one and two affected the threshold shifts of PTA4 and HPTA4 more in participants with a pre-existing hearing loss at time point one. Lifetime occupational noise exposure was a risk factor especially for the low-frequency hearing threshold PTA4. Firearm use was a statistically significant risk factor for all outcome measures. CONCLUSIONS: Pre-existing hearing loss can increase the risk of hearing impairment due to occupational noise exposure. An increased risk for NIHL was also seen in the group with exposures below 85 dB(A), a result that indicates awareness of NIHL should be raised even for those working in environments where sound levels are below 85 dB(A).

A job-exposure matrix for occupational noise: development and validation.

OBJECTIVE: To develop a job-exposure matrix (JEM) for occupational noise in Sweden and to estimate its validity. METHODS: The JEM, developed by a group of experienced occupational hygienists, contains 321 job families with information regarding occupational noise from 1970 to 2004. The occupational noise information derives from measurements collected from different sources. The time period label has a 5-year scale starting in 1970. The estimated average 8h (TWA) noise level in decibel [dB(A)] for every 5-year period was coded either as <75 dB(A), 75-84 dB(A), or ≥85 dB(A) and the risk of peak level exposure assessed. The validity of the JEM is tested, using Svensson's non-parametric methods based on classification consensus, reached by a second group of occupational hygienists. RESULTS/DISCUSSION: Validation results show ~ 80% agreement and no systematic differences, in classification, between the two different groups of occupational hygienists, classifying the occupational noise exposure. However, classification of peak level exposure did show a systematic difference in relative position. The results will give more power to the JEM that it gives a good general estimate for the occupational noise levels in Sweden for different job families during 1970-2004. We, thus, intend to use it in further studies and also make it available to collaborators.

Nitric oxide pathway-related gene alterations in inflammatory bowel disease.

OBJECTIVE: To reveal specific gene activation in nitric oxide (NO)-related inflammation we studied differential gene expression in inflammatory bowel disease (IBD). METHODS: Total RNA was isolated from 20 biopsies of inflamed mucosa from Crohn's disease (CD) and ulcerative colitis (UC) patients each as well as from six controls, labeled with (32)P-dCTP and hybridized to a human NO gene array. Significant genes were analyzed for functional gene interactions and heatmaps generated by hierarchical clustering. A selection of differentially expressed genes was further evaluated with immunohistochemical staining. RESULTS: Significant gene expression differences were found for 19 genes in CD and 23 genes in UC compared to controls, both diseases with high expression of ICAM1 and IL-8. Correlation between microarray expression and corresponding protein expression was significant (r = 0.47, p = 0.002). Clustering analysis together with functional gene interaction analysis revealed clusters of coregulation and coexpression in CD and UC: transcripts involved in angiogenesis, inflammatory response mediated by the transcription factor hypoxia-inducible factor 1, and tissue fibrosis. Also, a fourth cluster with transcripts regulated by the transcription factor Sp1 was found in UC. CONCLUSIONS: Expression analysis in CD and UC revealed disease-specific regulation of NO-related genes, which might be involved in perpetuating inflammatory disease activity in IBD.

Iron-regulatory gene expression during liver regeneration.

BACKGROUND: In rat, the first 18-24 h after partial hepatectomy (PH) are characterized by an acute-phase reaction, after which liver regeneration predominates. Interleukin-6 (IL-6) induces the iron hormone hepcidin, which blocks iron uptake and may compromise iron uptake in the growing liver. The expressions of hepcidin and the iron-regulatory pathway of hepcidin gene expression during the late phase of liver regeneration are unknown. AIM: To characterize the expression pattern of hepcidin and the iron-sensing pathway of hepcidin regulation during liver regeneration. METHODS: Rats were subjected to PH or sham operation. Liver weights, number of S-phase nuclei, and serum levels of iron and IL-6 were determined. Messenger-RNA levels of hepcidin, ferritin, hemojuvelin, transferrin receptor 1 and 2, HFE, divalent metal transporter 1, ferroportin, and ceruloplasmin were determined with qPCR at different time points. Protein levels of STAT3 and SMAD4 were determined with western blot. RESULTS: During the acute-phase response, IL-6 release induced STAT3 protein and hepcidin mRNA, whereas mRNA levels of proteins in the iron-sensing pathway (HFE, hemojuvelin, and transferrin receptor 2) decreased. The mRNA levels of proteins involved in cellular iron uptake were increased and cellular iron export unchanged. During liver regeneration >24 h after PH, gene expressions in the iron-sensing pathway were continuously suppressed and hepcidin mRNA levels declined 3-7 days after surgery. CONCLUSIONS: Hepcidin gene expression peaks during the acute-phase response, but a sustained down-regulation of the iron-sensing pathway of hepcidin regulation gradually reduces hepcidin gene expression until regeneration is complete, thereby promoting iron mobilization to the regenerating liver.

Attenuated liver fibrosis after bile duct ligation and defective hepatic stellate cell activation in neural cell adhesion molecule knockout mice.

AIM: Neural cell adhesion molecule (N-CAM) is expressed by activated hepatic stellate cells (HSC), portal fibroblasts, cholangiocytes and hepatic progenitor cells during liver injury. Its functional role in liver disease and fibrogenesis is unknown. The aim of this study was to investigate the role of N-CAM in liver fibrogenesis. METHODS: To induce fibrosis, N-CAM knockout mice and wild-type controls were subjected to bile duct ligation (BDL) or repeated carbon tetrachloride (CCl(4) ) injections. Fibrosis was quantified by hydroxyproline, immunhistochemistry staining and image analysis. Protein levels were determined with immunoblotting. HSCs were isolated by ultracentrifugation in a Larcoll gradient and thereafter in vitro stimulated with recombinant transforming growth factor (TGF)-ß1. RESULTS: Two weeks after BDL, wild-type mice had developed pronounced liver fibrosis while N-CAM-/- mice had less such alterations. N-CAM-/- mice had less deposition of collagen and fibronectin seen in immunhistochemistry. The protein levels of fibronectin were higher in the liver from the wild type, while laminin were unaltered. CCl(4) -treated N-CAM-/- and wild-type mice showed no significant difference in the extent of liver fibrosis or the expression levels of the above-mentioned genes. HSC isolated from N-CAM-/- mice showed declined levels of smooth muscle actin and desmin after stimulation in vitro with TGF-ß1. CONCLUSIONS: Loss of N-CAM results in decreased hepatic collagen and fibronectin deposition in mice subjected to BDL, but not in animals exposed to repeated CCl(4) injections. HSC isolated from N-CAM null mice show impaired activation in vitro. This indicates a role of N-CAM in cholestatic liver disease and HSC activation.

SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process.

In mammalian cells, active sodium transport and its derived functions (e.g., plasma membrane potential) are dictated by the activity of the Na(+),K(+)-ATPase (NK), whose regulation is essential for maintaining cell volume and composition, as well as other vital cell functions. Here we report the existence of a salt-inducible kinase-1 (SIK1) that associates constitutively with the NK regulatory complex and is responsible for increases in its catalytic activity following small elevations in intracellular sodium concentrations. Increases in intracellular sodium are paralleled by elevations in intracellular calcium through the reversible Na(+)/Ca(2+) exchanger, leading to the activation of SIK1 (Thr-322 phosphorylation) by a calcium calmodulin-dependent kinase. Activation of SIK1 results in the dephosphorylation of the NK alpha-subunit and an increase in its catalytic activity. A protein phosphatase 2A/phosphatase methylesterase-1 (PME-1) complex, which constitutively associates with the NK alpha-subunit, is activated by SIK1 through phosphorylation of PME-1 and its dissociation from the complex. These observations illustrate the existence of a distinct intracellular signaling network, with SIK1 at its core, which is triggered by a monovalent cation (Na(+)) and links sodium permeability to its active transport.