Publications by authors named "Eva Andersson"

201 Publications

Proteome-scale mapping of binding sites in the unstructured regions of the human proteome.

Mol Syst Biol 2022 Jan;18(1):e10584

Department of Chemistry - BMC, Uppsala University, Uppsala, Sweden.

Specific protein-protein interactions are central to all processes that underlie cell physiology. Numerous studies have together identified hundreds of thousands of human protein-protein interactions. However, many interactions remain to be discovered, and low affinity, conditional, and cell type-specific interactions are likely to be disproportionately underrepresented. Here, we describe an optimized proteomic peptide-phage display library that tiles all disordered regions of the human proteome and allows the screening of ~ 1,000,000 overlapping peptides in a single binding assay. We define guidelines for processing, filtering, and ranking the results and provide PepTools, a toolkit to annotate the identified hits. We uncovered >2,000 interaction pairs for 35 known short linear motif (SLiM)-binding domains and confirmed the quality of the produced data by complementary biophysical or cell-based assays. Finally, we show how the amino acid resolution-binding site information can be used to pinpoint functionally important disease mutations and phosphorylation events in intrinsically disordered regions of the proteome. The optimized human disorderome library paired with PepTools represents a powerful pipeline for unbiased proteome-wide discovery of SLiM-based interactions.
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http://dx.doi.org/10.15252/msb.202110584DOI Listing
January 2022

Associations between long-term exposure to low-level air pollution and risk of chronic kidney disease-findings from the Malmö Diet and Cancer cohort.

Environ Int 2022 Jan 15;160:107085. Epub 2022 Jan 15.

Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: Associations between air pollution and chronic kidney disease (CKD) have been reported, but studies at low exposure levels and relevant exposure time windows are still warranted. This study investigated clinical CKD at low air pollution levels in the Swedish Malmö Diet and Cancer Cohort in different exposure time windows.

Methods: This study included 30,396 individuals, aged 45-74 at enrollment 1991-1996. Individual annual average residential outdoor PM, PM, nitrogen oxides (NO), and black carbon (BC) were assigned using dispersion models from enrollment to 2016. Diagnoses of incident CKD were retrieved from national registries. Cox proportional hazards models were used to obtain hazard ratios (HRs) for CKD in relation to three time-dependent exposure time windows: exposure at concurrent year (lag 0), mean exposure in the 1-5 or 6-10 preceding years (lag 1-5 and lag 6-10), and baseline exposure.

Results: During the study period, the average annual residential exposures were 16 μg/m for PM, 11 μg/m for PM, 26 μg/m for NO, and 0.97 μg/m for BC. For lag 1-5 and lag 6-10 exposure, significantly elevated HRs for incident CKD were found for total PM:1.13 (95% CI: 1.01-1.26) and 1.22 (1.06-1.41); NO: 1.19 (1.07-1.33) and 1.13 (1.02-1.25) and BC: 1.12 (1.03-1.22) and 1.11 (1.02-1.21) per interquartile range increase in exposure. For total PM the positive associations of 1.12 (0.97-1.31) and 1.16 (0.98-1.36) were not significant. For baseline or lag 0 exposure there were significant associations only for NO and BC, not for PM.

Conclusion: Residential exposure to outdoor air pollution was associated with increased risk of incident CKD at relatively low exposure levels. Average long-term exposure was more clearly associated with CKD than current exposure or exposure at recruitment. Our findings imply that the health effects of low-level air pollution on CKD are considerable.
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http://dx.doi.org/10.1016/j.envint.2022.107085DOI Listing
January 2022

Cancer incidence in a cohort of Swedish merchant seafarers between 1985 and 2011.

Int Arch Occup Environ Health 2022 Jan 8. Epub 2022 Jan 8.

Occupational and Environmental Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.

Purpose: Lung cancer, mesothelioma and several lifestyle-associated cancer forms have been reported more common in merchant seafarers. However, few studies reflect recent occupational settings and women seafarers are usually too scarce for meaningful analyses. We conducted a study on cancer incidence between 1985 and 2011 in a Swedish cohort consisting of male and female seafarers.

Methods: All seafarers in the Swedish Seafarers' Register with at least one sea service between 1985 and 2011 and a cumulated sea service time of ≥ 30 days (N = 75,745; 64% men, 36% women; 1,245,691 person-years) were linked to the Swedish Cancer Register and followed-up until 31 December 2011. Standardized incidence ratios (SIR) were calculated with the general population as reference.

Results: There were 4159 cancer cases in total, with 3221 among men and 938 among women. Male seafarers had an increased risk of total cancer (SIR 1.05; 95% CI 1.01-1.09), lung cancer (SIR 1.51; 95% CI 1.35-1.67) and urinary bladder cancer (SIR 1.17; 95% CI 1.02-1.33). Several lifestyle-associated cancer forms were more common in men. Previous work on tankers was associated with leukaemia (SIR 1.41; 95% CI 1.00-1.86). The risk of cancer decreased with a start as a male seafarer after 1985, with a significant trend for total cancer (P < 0.001), lung cancer (P = 0.001) and, for tanker seafarers, leukaemia (P = 0.045). Women seafarers had an increased risk of lung cancer (SIR 1.54; 95% CI 1.23-1.87) but the risk of total cancer was not increased (SIR 0.83; 95% CI 0.78-0.89).

Conclusions: In this cohort of merchant Swedish seafarers 1985-2011, the risk of total cancer was increased in men but not in women compared to the general population. Lung cancer was increased in both genders. The risk of cancer seems to decrease over the last decades, but better exposure assessments to occupational carcinogens and longer observation times are needed.
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http://dx.doi.org/10.1007/s00420-021-01828-2DOI Listing
January 2022

Psychosocial job conditions and biomarkers of cardiovascular disease: A cross-sectional study in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

Scand J Public Health 2022 Jan 6:14034948211064097. Epub 2022 Jan 6.

Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden.

Aims: The aim of this study was to investigate associations between psychosocial work exposure and the presence of biological and imaging biomarkers of cardiovascular disease.

Methods: This cross-sectional study was conducted in a sub-cohort of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Psychosocial exposure was evaluated with the job demand-control model, and analysed according to the standard categorization: high strain, active, passive and low strain (reference). Biomarkers (blood pressure, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, coronary artery calcification (CAC) and metabolic syndrome) were measured, or derived through measurements, from clinical examinations. Gender-specific prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated with regression models and adjusted for age, education, smoking, physical activity, general life stress and body mass index (BMI).

Results: The analyses included 3882 participants (52.5% women). High strain (high demands-low control) was linked to increased PR for low HDL cholesterol in women, adjusted for all covariates (PR 1.76; 95% CI 1.25-2.48). High strain was also related to moderately increased PR for metabolic syndrome in men, after adjustments for all covariates except BMI (PR 1.25; 95% CI 1.02-1.52). In addition, passive work (low demands-low control) was associated with diastolic hypertension in women (fully adjusted: PR 1.29; 95% CI 1.05-1.59). All relationships between psychosocial factors and LDL cholesterol or CAC (both genders), or hypertension (men), were non-significant.

Conclusions:
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http://dx.doi.org/10.1177/14034948211064097DOI Listing
January 2022

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities.

Nat Commun 2021 11 19;12(1):6761. Epub 2021 Nov 19.

Department of Chemistry - BMC, Uppsala University, Box 576, Husargatan 3, 751 23, Uppsala, Sweden.

Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
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http://dx.doi.org/10.1038/s41467-021-26498-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605023PMC
November 2021

Cancer incidence in a Swedish cohort with high exposure to perfluoroalkyl substances in drinking water.

Environ Res 2022 Mar 15;204(Pt C):112217. Epub 2021 Oct 15.

School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30, Gothenburg, Sweden; Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, 413 46, Gothenburg, Sweden.

Background: The use of firefighting foams at a military airport resulted in high levels of perfluorinated substances (PFAS) in the drinking water distributed to one-third of households in the Swedish municipality of Ronneby between the mid-1980s and the end of 2013.

Method: The Ronneby Register Cohort, a large cohort comprising all individuals (N = 60,507) who ever lived in the Ronneby municipality during the period of drinking water contamination, was linked to the Swedish Cancer Register 1985-2016. Individual exposure was classified based on comprehensive data on yearly residential address and water distribution. External analysis explored standardized cancer incidence ratios (SIR) for residents never, or ever, residing in the contaminated water district, compared with those residing in other towns in the same county as reference population. Cox models provided hazard ratios (HR) for different exposure groups within the cohort.

Results: 5,702 individuals with cancer were identified. SIR for overall cancer was 1.04 for men (95%CI 0.96-1.12) and 0.89 for women (95%CI 0.82-0.96) who ever lived in the contaminated drinking water area. Kidney cancer, which was reported with increased risk in C8 study, showed somewhat elevated HR in this study (HR 1.27; 95%CI 0.85-1.89). The HR was modestly elevated for bladder cancer (HR 1.32; 95%CI 1.01-1.72), and reduced for prostate cancer (HR 0.83; 95%CI 0.71-0.98). In subjects who ever lived in the contaminated water area during 2005-2013, when exposure was estimated to be highest, higher risks for kidney cancer (HR 1.84; 95%CI 1.00-3.37) but lower for prostate cancer (HR 0.76; 95%CI 0.59-0.98) were observed.

Conclusion: Analysis of this large cohort exposed to high levels of PFAS, dominated by PFHxS and PFOS, revealed no evidence for an overall increased risk of cancer. A moderately increased risk of kidney cancer was observed, in accordance with previous findings after PFAS exposure dominated by PFOA.
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http://dx.doi.org/10.1016/j.envres.2021.112217DOI Listing
March 2022

Long-Term Exposure to Transportation Noise and Risk of Incident Stroke: A Pooled Study of Nine Scandinavian Cohorts.

Environ Health Perspect 2021 Oct 4;129(10):107002. Epub 2021 Oct 4.

Department of Health Security, Finnish Institute for Health and Welfare, Kuopio, Finland.

Background: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse.

Objective: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population.

Methods: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through linkage to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle confounders, and air pollution.

Results: During follow-up (), 11,056 stroke cases were identified. Road traffic noise () was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for individual- and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of () and ]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40-50 vs. ) (; 95% CI: 0.99, 1.27), but not with higher exposure (, ; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke.

Discussion: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise. https://doi.org/10.1289/EHP8949.
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http://dx.doi.org/10.1289/EHP8949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489401PMC
October 2021

Long-term exposure to particulate air pollution and black carbon in relation to natural and cause-specific mortality: a multicohort study in Sweden.

BMJ Open 2021 09 8;11(9):e046040. Epub 2021 Sep 8.

Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umea University, Umeå, Sweden.

Objectives: To estimate concentration-response relationships for particulate matter (PM) and black carbon (BC) in relation to mortality in cohorts from three Swedish cities with comparatively low pollutant levels.

Setting: Cohorts from Gothenburg, Stockholm and Umeå, Sweden.

Design: High-resolution dispersion models were used to estimate annual mean concentrations of PM with aerodynamic diameter ≤10 µm (PM10) and ≤2.5 µm (PM2.5), and BC, at individual addresses during each year of follow-up, 1990-2011. Moving averages were calculated for the time windows 1-5 years (lag1-5) and 6-10 years (lag6-10) preceding the outcome. Cause-specific mortality data were obtained from the national cause of death registry. Cohort-specific HRs were estimated using Cox regression models and then meta-analysed including a random effect of cohort.

Participants: During the study period, 7 340 cases of natural mortality, 2 755 cases of cardiovascular disease (CVD) mortality and 817 cases of respiratory and lung cancer mortality were observed among in total 68 679 individuals and 689 813 person-years of follow-up.

Results: Both PM10 (range: 6.3-41.9 µg/m) and BC (range: 0.2-6.8 µg/m) were associated with natural mortality showing 17% (95% CI 6% to 31%) and 9% (95% CI 0% to 18%) increased risks per 10 µg/m and 1 µg/m of lag1-5 exposure, respectively. For PM2.5 (range: 4.0-22.4 µg/m), the estimated increase was 13% per 5 µg/m, but less precise (95% CI -9% to 40%). Estimates for CVD mortality appeared higher for both PM10 and PM2.5. No association was observed with respiratory mortality.

Conclusion: The results support an effect of long-term air pollution on natural mortality and mortality in CVD with high relative risks also at low exposure levels. These findings are relevant for future decisions concerning air quality policies.
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http://dx.doi.org/10.1136/bmjopen-2020-046040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438896PMC
September 2021

Dust Exposures in Swedish Soft Tissue Paper Mills.

Ann Work Expo Health 2022 Jan;66(1):14-26

Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objectives: Paper dust has previously been linked to adverse health effects. However, a comprehensive dataset of paper dust exposures does not appear to have been published previously. Our study was intended to address this need by describing a large dataset of measurements made in Swedish soft tissue paper mills.

Methods: We compiled personal and area total dust exposure measurements collected from a range of operations by our research staff at four soft tissue paper mills in Sweden. We also compiled measurements made by the occupational health staff at each mill and the Swedish Work Environment Authority. We analyzed these measurements to describe patterns and trends in exposures and used mixed-effects regression models to identify measurement characteristics that predicted exposure levels.

Results: We compiled 1578 measurements from 1971 to 2009, of which 1026 (65%) were personal samples. Statistically significant differences were found between measurements made by research, mill, and Swedish Work Environment Authority staff, as well as between personal and area measurements. The measurement data suggest that, beginning in the 1980s, exposures declined at three of the four mills, but that overexposures were still common at the end of the period. Papermaking and converting operations had the highest observed dust exposures. One mill had significantly lower exposures than the others. Type of measurement (personal versus area) and source of measurement (research staff, company, or regulatory agency) were not significant predictors of measured total dust exposure after controlling for mill, operation, and time.

Conclusions: Our analysis of measured paper dust exposures may be useful for historical and contemporary exposure assessment in our own and other epidemiological studies. We have identified specific characteristics (i.e. papermaking operations and mill) and time trends that are important data features to consider, and documented continuing overexposure situations. Our results highlight the ongoing need for application of exposure controls to reduce paper dust exposures in the soft tissue paper industry.
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http://dx.doi.org/10.1093/annweh/wxab063DOI Listing
January 2022

Perfluoroalkyl substances (PFAS) in drinking water and risk for polycystic ovarian syndrome, uterine leiomyoma, and endometriosis: A Swedish cohort study.

Environ Int 2021 12 12;157:106819. Epub 2021 Aug 12.

Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: Perfluorinated substances (PFAS) are chemicals with endocrine disruptive properties that may interfere with the female reproductive system. However, few studies have explored the association between benign gynecological diseases and high PFAS exposure.

Objectives: The aim of this study was to investigate the possible associations between PFAS exposure and subsequent diagnosis of polycystic ovarian syndrome (PCOS), uterine leiomyoma (fibroids), and endometriosis in a cohort exposed to PFAS through drinking water.

Material And Methods: In 2013, high levels (with sum of PFAS above 10,000 ng/L), dominated by perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), were found in the drinking water from one of the two waterworks in Ronneby, Sweden. The contamination came from firefighting foams used at a nearby airfield. Females of all ages (n = 29,106) who had ever resided in the municipality between 1985 and 2013 formed a cohort. Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential address data; 27% of the females had ever lived at an address with PFAS-contaminated water. Gynecological health outcomes were retrieved from the Swedish National Patient Register. The Cox proportional hazards model was used to estimate the association between exposure and each diagnosis.

Results: There were in all 161 cases of PCOS, 1,122 cases of uterine leiomyoma, and 373 cases of endometriosis. In women aged 20-50 years (n = 18,503), those with the highest estimated PFAS exposure had increased hazard ratios (HR) for PCOS (HR = 2.18; 95% confidence interval (CI) 1.43, 3.34) and uterine leiomyoma (HR = 1.28; 95% CI 0.95, 1.74). No increased HR for endometriosis was found (HR = 0.74; 95% CI 0.42, 1.29).

Conclusions: Exposure to high levels of PFAS in drinking water was associated with increased risk of PCOS and possibly uterine leiomyoma, but not endometriosis. The findings for PCOS are consistent with prior studies reporting positive associations between PCOS and PFAS exposure at background levels.
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http://dx.doi.org/10.1016/j.envint.2021.106819DOI Listing
December 2021

Is Cadmium a Risk Factor for Breast Cancer - Results from a Nested Case-Control Study Using Data from the Malmö Diet and Cancer Study.

Cancer Epidemiol Biomarkers Prev 2021 09 8;30(9):1744-1752. Epub 2021 Jul 8.

Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels.

Methods: All breast cancers in the Malmö Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991-1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression.

Results: Mean BCd was 0.51 μg/L among 1,274 cases and 0.46 among 2,572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05-1.36] per μg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05-1.73)] for BCd more than 1.20 μg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 μg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found.

Conclusions: The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models.

Impact: This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0181DOI Listing
September 2021

Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults.

Environ Health Perspect 2021 06 23;129(6):67007. Epub 2021 Jun 23.

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined.

Objectives: Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study.

Methods: Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history.

Results: The median B-Cd concentration was . The prevalence of positive coronary artery calcium () was 41% and the prevalence of was 13%. Relative to the lowest quartile (Q) of B-Cd (), the highest quartile (median ) was associated with a small but significant increase in (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for (17 cases in Q4).

Discussion: Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.
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http://dx.doi.org/10.1289/EHP8523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221368PMC
June 2021

Psychosocial job exposure and risk of coronary artery calcification.

PLoS One 2021 25;16(5):e0252192. Epub 2021 May 25.

Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Purpose: The aim was to examine potential associations between psychosocial job exposures, evaluated with the Job Demand-Control-model, and presence of coronary artery calcium.

Methods: We performed a cross-sectional study using the Swedish CArdioPulmonary bioImage Study,(SCAPIS)pilot study. Coronary artery calcium was assessed through computed tomography of the coronary arteries and with coronary artery scoring, CACS. Main outcome was CACS ≥100 compared to CACS 0. Job demand and control was analysed according to the standard categorization of the two variables into: high strain, active, passive and low strain (reference). Associations between these variables and CACS were calculated with prevalence ratios (PR) using Cox regression with robust variance, 95% confidence intervals (CI) and adjusted for age, smoking, education, socioeconomic area and metabolic syndrome.

Results: In total 777 participants were used in our analyses, for which 20% of the men and 5% of the women had CACS ≥100, respectively. The PR of having CACS ≥100 was non-significantly elevated for men in high strain jobs 1.54 (95% CI 0.88-2.69) and in active jobs 1.67 (95% CI 0.92-3.06), adjusted for covariates. For women there was no association between exposure to high strain and having CACS ≥100 PR 1.02 (95% CI 0.24-4.31). Among women reporting passive job, the PR was non-significantly elevated, 2.40 (95% CI 0.83-6.92), adjusted for covariates.

Conclusion: The statistical power of the study was limited, but our results suggests the possibility that exposure to a high strain or an active job situation may increase the risk of CACS in men, while in women, it may rather be exposure to passive job.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252192PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148350PMC
October 2021

Loss of Increases Germ Cell Apoptosis but Is Still Compatible With Sperm Production in Atlantic Salmon ().

Front Cell Dev Biol 2021 16;9:657192. Epub 2021 Apr 16.

Institute of Marine Research, Research Group Reproduction and Developmental Biology, Bergen, Norway.

Entering meiosis strictly depends on () gene function in mammals. This gene is missing in a number of fish species, including medaka and zebrafish, but is present in the majority of fishes, including Atlantic salmon. Here, we have examined the effects of removing on male fertility in Atlantic salmon. As in mammals, expression was restricted to germ cells in the testis, transcript levels increased during the start of puberty, and decreased when blocking the production of retinoic acid. We targeted the salmon gene with two gRNAs one of these were highly effective and produced numerous mutations in , which led to a loss of wild-type (WT) expression in F0 salmon testis. In maturing crispants, the spermatogenetic tubuli were partially disorganized and displayed a sevenfold increase in germ cell apoptosis, in particular among type B spermatogonia and spermatocytes. The production of spermatogenic cysts, on the other hand, increased in maturing crispants. Gene expression analysis revealed unchanged () or reduced levels () of transcripts associated with undifferentiated spermatogonia. Decreased expression was recorded for some genes expressed in differentiating spermatogonia including and or in spermatocytes, such as . Different from -deficient mammals, a large number of germ cells completed spermatogenesis, sperm was produced and fertilization rates were similar in WT and crispant males. While loss of increased germ cell apoptosis during salmon spermatogenesis, crispants compensated this cell loss by an elevated production of spermatogenic cysts, and were able to produce functional sperm. It appears that also in a fish species with a gene in the genome, the critical relevance this gene has attained for mammalian spermatogenesis is not yet given, although detrimental effects of the loss of were clearly visible during maturation.
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http://dx.doi.org/10.3389/fcell.2021.657192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087537PMC
April 2021

Occupational risk factors for airway obstruction in a population-based study in Northern Europe.

Am J Ind Med 2021 07 16;64(7):576-584. Epub 2021 Apr 16.

Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, University of Göteborg, Göteborg, Sweden.

Background: Airway obstruction is a key feature of asthma and chronic obstructive pulmonary diseases (COPD). Smoking habits and workplace exposures to vapors, gas, dusts, and fumes (VGDF) could cause or exacerbate airway obstruction. The aim of this study is to evaluate the risk of airway obstruction due to smoking and workplace exposure, and their interaction, in a large population-based study.

Methods: In this cross-sectional study, a sample (n = 6153) of the Swedish population aged between 24 and 76 years underwent a questionnaire, clinical examination, blood test, and spirometry to gather information on airway obstruction classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria or American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria, risk factors, and confounders. Occupational exposures to VGDF were rated according to a specific job-exposure matrix. Adjusted logistic regression models were used to evaluate risk factors for airway obstruction in smokers and nonsmokers.

Results: In total, 9.8% had airway obstruction by GOLD criteria and 10.3% by ATS/ERS. Smokers with a high likelihood of exposure to VGDF had a higher risk of airway obstruction than those not exposed (odds ratio [OR]: 1.74, 95% confidence interval [CI]: 1.15-2.65 by GOLD; OR: 1.58, 95% CI: 1.06-2.37 by ATS/ERS) especially those >50 years of age. In smokers highly exposed to VGDF, risk estimates were higher than in the whole population, and the interaction between high exposure to VGDF and smoking further increased the risk of airway obstruction.

Conclusions: This study suggests a possible role for interaction between cigarette smoking and VGDF exposure on the risk of airway obstruction.
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http://dx.doi.org/10.1002/ajim.23250DOI Listing
July 2021

Cadmium, total mercury, and lead in blood and associations with diet, sociodemographic factors, and smoking in Swedish adolescents.

Environ Res 2021 06 8;197:110991. Epub 2021 Mar 8.

Department of Risk and Benefit Assessment, Swedish Food Agency, Uppsala, Sweden. Electronic address:

Background: Despite their vulnerability to the toxic effects of certain metals, biomonitoring data on adolescents are limited. In the present study, we assessed blood concentrations of toxic metals (cadmium [Cd], total mercury [Hg], and lead [Pb] in a national representative sample of Swedish adolescents. We also examined the associations of Cd, total Hg and Pb with habitual intakes of major energy-providing food groups and other possible determinants such as age, sex, household education, Nordic or non-Nordic origin, and smoking.

Methods: We analysed blood concentrations of Cd, total Hg, and Pb in a sample of 1099 adolescents from the Riksmaten Adolescents 2016-17 study in three age groups (mean age of 12, 15, and 18 years) using inductively coupled plasma mass spectrometry. The participants completed web-based questionnaires on food consumption frequency, sociodemographic factors and health status. Dietary data from two web-based 24-h dietary recalls were used to estimate the habitual intake of 10 major food groups.

Results: Almost all participants had detectable concentrations of Cd, total Hg, and Pb in whole blood. The median blood concentrations were 0.12 μg/L for Cd, 0.72 μg/L for total Hg, and 7.1 μg/L for Pb. Higher blood concentrations of Cd were observed in girls than in boys, whereas concentrations of total Hg and Pb were higher in boys. We observed an inverse association between Cd and meat intake. Total Hg concentrations were positively associated with intakes of fish, eggs, meat, and vegetables, and Pb concentrations were inversely associated with intakes of dairy products. Furthermore, smokers had higher concentrations of Cd and Pb.

Conclusions: We found that fish was a potentially important source of exposure to total Hg in Swedish adolescents. No other food group was identified to have a strong impact on the blood levels of Cd, total Hg and Pb. Thirteen per cent of the adolescents had blood Pb concentrations above 12 μg/L, the reference point used in the risk assessment of Pb by the European Food Safety Authority (EFSA).
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http://dx.doi.org/10.1016/j.envres.2021.110991DOI Listing
June 2021

Mapping the transition state for a binding reaction between ancient intrinsically disordered proteins.

J Biol Chem 2020 12;295(51):17698-17712

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Electronic address:

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.
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http://dx.doi.org/10.1074/jbc.RA120.015645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762952PMC
December 2020

Serum perfluoroalkyl substances in residents following long-term drinking water contamination from firefighting foam in Ronneby, Sweden.

Environ Int 2021 02 23;147:106333. Epub 2020 Dec 23.

School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:

Background: In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport.

Objectives: To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined.

Methods: Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants.

Results: The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005-2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (r > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60.

Discussion: The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure.
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http://dx.doi.org/10.1016/j.envint.2020.106333DOI Listing
February 2021

Associations between perfluoroalkyl substances and thyroid hormones after high exposure through drinking water.

Environ Res 2021 03 29;194:110647. Epub 2020 Dec 29.

School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: The reported associations for several per- and polyfluoroalkyl substance (PFAS) with thyroid hormones are inconsistent in epidemiological studies. The purpose of the current study was to investigate the possible association of thyroid hormones in relation to serum levels of perfluorohexane sulfonate, perfluorooctane sulfonate and perfluorooctanoic acid, in a Swedish general population, highly exposed through contaminated drinking water, and if the associations with PFAS remained in a comparison to a reference group based only on residency in areas with contrasting PFAS levels.

Method: 3297 participants from Ronneby, a municipality with drinking water highly contaminated by PFAS (exposed group), and a reference group (N = 226) from a nearby municipality with non-contaminated drinking water supply were included. Regression analysis was used to investigate the associations between PFAS exposure, assessed as exposure groups (Ronneby and reference groups) and measured serum PFAS levels, and thyroid hormone levels, with adjustments for age, sex and BMI.

Result: No cross-sectional associations were found between PFAS and thyroid hormones in adults and seniors except for a positive association between PFAS and fT4 in males over 50. Higher thyroid hormone levels were found in the preteen children from Ronneby compared to the reference group. In contrast, within Ronneby, there was weak evidence of associations between increased PFAS levels and decreased fT3 in preteen boys, and decreased TSH in teenage males. No such pattern was found in preteen and teenage girls.

Conclusion: The present study found no consistent evidence to support association of PFAS with thyroid hormones.
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http://dx.doi.org/10.1016/j.envres.2020.110647DOI Listing
March 2021

Work-related Symptoms and Asthma among Fish Processing Workers.

J Agromedicine 2022 Jan 22;27(1):98-105. Epub 2020 Oct 22.

Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

After observing several clinical patients with respiratory symptoms, we initiated a questionnaire survey to assess prevalence of and predictors for asthma and work-related symptoms among workers in fish processing plants. A questionnaire with items on work conditions, work-related symptoms, and respiratory symptoms/diseases was sent to 916 fish processing workers, the 1836 licenced fishermen in Sweden, and 1965 controls; of those, 43%, 57%, and 53%, respectively, responded. Risks, hazard ratios (HRs), and prevalence ratios (PRs) were calculated with Cox regression, and 95% confidence intervals (CIs) were computed. The risk of asthma among fish filleting workers was increased during the years working in the fish processing industry when compared to the other fish processing workers and controls (HR 3.6, 95% CI 1.6-8.1, adjusted for atopy, gender, and ever smoking). The filleters had an increased PR for most of the work-related respiratory symptoms investigated. All fish processing workers had a higher PR for flu-like symptoms. Use of a pressure sprayer was identified as a risk for asthma and respiratory symptoms among both fish processing workers and controls. Filleters had changed work tasks because of respiratory symptoms more often (Fisher's exact test, p = 0.02) than other fish processing workers. In conclusion the fish filleters and pressure sprayer users reported more adult asthma and cough with phlegm compared to the other fish processing workers and controls. The use of pressure sprayers must be reduced and machinery should be completely encased to reduce workers' exposure to bioaerosols and its effects on the respiratory tract.
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http://dx.doi.org/10.1080/1059924X.2020.1834481DOI Listing
January 2022

Effect of footwear on intramuscular EMG activity of plantar flexor muscles in walking.

J Electromyogr Kinesiol 2020 Dec 18;55:102474. Epub 2020 Sep 18.

Neuromuscular Research Centre, Faculty of Sport and Health Sciences, University of Jyvaskyla, Finland; Department for Health, Bath University, UK.

One of the purposes of footwear is to assist locomotion, but some footwear types seem to restrict natural foot motion, which may affect the contribution of ankle plantar flexor muscles to propulsion. This study examined the effects of different footwear conditions on the activity of ankle plantar flexors during walking. Ten healthy habitually shod individuals walked overground in shoes, barefoot and in flip-flops while fine-wire electromyography (EMG) activity was recorded from flexor hallucis longus (FHL), soleus (SOL), and medial and lateral gastrocnemius (MG and LG) muscles. EMG signals were peak-normalised and analysed in the stance phase using Statistical Parametric Mapping (SPM). We found highly individual EMG patterns. Although walking with shoes required higher muscle activity for propulsion than walking barefoot or with flip-flops in most participants, this did not result in statistically significant differences in EMG amplitude between footwear conditions in any muscle (p > 0.05). Time to peak activity showed the lowest coefficient of variation in shod walking (3.5, 7.0, 8.0 and 3.4 for FHL, SOL, MG and LG, respectively). Future studies should clarify the sources and consequences of individual EMG responses to different footwear.
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http://dx.doi.org/10.1016/j.jelekin.2020.102474DOI Listing
December 2020

Cardiovascular mortality in a Swedish cohort of female industrial workers exposed to noise and shift work.

Int Arch Occup Environ Health 2021 Feb 6;94(2):285-293. Epub 2020 Sep 6.

Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.

Purpose: The aim was to study mortality due to cardiovascular disease as well as total mortality, among female industrial workers, and the association to occupational noise and shift work.

Methods: Women from cohorts of soft tissue paper mills (N = 3013) and pulp and paper mills (N = 1483) were merged into one cohort. Job exposure matrices were developed and used for classification of shift work and noise exposure. Every year was classified as shift work excluding nights or shift work including nights. Noise was classified into seven 5 dB(A) bins from < 75 to ≥ 100 dB(A). Mortality from cardiovascular diseases and total mortality during 1956-2013 was calculated as a standardized mortality ratio (SMR) with 95% confidence interval (CI) using the female general population as a reference.

Results: Fatal myocardial infarctions (N = 144) were increased in the total cohort, SMR 1.20 (95% CI 1.01-1.41) but not total mortality. The SMR for myocardial infarction for women exposed to noise ≥ 90 dB(A) for > 10 years was 1.41 (95% CI 1.02-1.89) and for those exposed to night shifts > 10 years, 1.33 (95% CI 0.91-1.89). Shift workers without nights ≤ 65 years, with noise exposure ≥ 90 dB(A), had SMR 2.41 (95% CI 1.20-4.31) from myocardial infarction. There was no increased mortality from cerebrovascular disease.

Conclusions: Female paper mill workers had an increased mortality from acute myocardial infarction, especially before retirement age, when exposed to noise ≥ 90 dB(A) and with long-time employment. Exposure to shift work and noise usually occurred concurrently.
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http://dx.doi.org/10.1007/s00420-020-01574-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873009PMC
February 2021

Long-term exposure to air pollution and atherosclerosis in the carotid arteries in the Malmö diet and cancer cohort.

Environ Res 2020 12 23;191:110095. Epub 2020 Aug 23.

Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:

Background: Long-term exposure to air pollution increases the risk of cardiovascular morbidity and mortality, but the mechanisms are not fully known. Current evidence suggests that air pollution exposure contributes to the development of atherosclerosis. There are few studies investigating associations between air pollution and carotid plaques, a well-known precursor of cardiovascular disease.

Methods: A Swedish population-based cohort (aged 45-64 years at recruitment) was randomly selected from the Malmö Diet and Cancer study between 1991 and 1994, of which 6103 participants underwent ultrasound examination of the right carotid artery to determine carotid plaque presence and carotid intima media thickness (CIMT). Participants were assigned individual residential air pollution exposure (source-specific PM, PM, NO, BC) at recruitment from Gaussian dispersion models. Logistic and linear regression models, adjusted for potential confounders and cardiovascular risk factors, were used to investigate associations between air pollutants and prevalence of carotid plaques, and CIMT, respectively.

Results: The prevalence of carotid plaques was 35%. The mean levels of PM and PM at recruitment were 11 and 14 μg/m, most of which was due to long range transport. The exposure contrast within the cohort was relatively low. PM exposure was associated with carotid plaques in a model including age and sex only (OR 1.10 (95% CI 1.01-1.20) per 1 μg/m), but after adjustment for cardiovascular risk factors and socioeconomic status (SES) the association was weak and not significant (OR 1.05 (95% CI 0.96-1.16) per 1 μg/m). The pattern was similar for PM and NO exposure. Associations between air pollutants and plaques were slightly stronger for long-term residents and in younger participants with hypertension. There was no clear linear trend between air pollution exposure and plaque prevalence. Non-significant slightly positive associations were seen between air pollution exposures and CIMT.

Conclusions: In this large, well-controlled cross-sectional study at low exposure levels we found no significant associations between air pollution exposures and subclinical atherosclerosis in the carotid arteries, after adjusting for cardiovascular risk factors and SES. Further epidemiological studies of air pollution and intermediate outcomes are needed to explain the link between air pollution and cardiovascular events.
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http://dx.doi.org/10.1016/j.envres.2020.110095DOI Listing
December 2020

Extended Support Within a Person-Centered Practice After Surgery for Patients With Pituitary Tumors: Protocol for a Quasiexperimental Study.

JMIR Res Protoc 2020 Jul 21;9(7):e17697. Epub 2020 Jul 21.

Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: Patients with pituitary tumors often live with lifelong consequences of their disease. Treatment options include surgery, radiotherapy, and medical therapy. Symptoms associated with the tumor or its treatment affect several areas of life. Patients need to adhere to long-term contact with both specialist and general health care providers due to the disease, complex treatments, and associated morbidity. The first year after pituitary surgery constitutes an important time period, with medical evaluations after surgery and decisions on hormonal substitution. The development and evaluation of extended patient support during this time are limited.

Objective: The aim of this study is to evaluate whether support within a person-centered care practice increases wellbeing for patients with pituitary tumors. Our main hypothesis is that the extended support will result in increased psychological wellbeing compared with the support given within standard of care. Secondary objectives are to evaluate whether the extended support, compared with standard care, will result in (1) better health status, (2) less fatigue, (3) higher satisfaction with care, (4) higher self-efficacy, (5) increased person-centered content in care documentation, and (6) sustained patient safety.

Methods: Within a quasiexperimental design, patients diagnosed with a pituitary tumor planned for neurosurgery are consecutively included in a pretest-posttest study performed at a specialist endocrine clinic. The control group receives standard of care after surgery, and the interventional group receives structured patient support for 1 year after surgery based on person-centeredness covering self-management support, accessibility, and continuity. A total of 90 patients are targeted for each group.

Results: Recruitment into the control group was performed between Q3 2015 and Q4 2017. Recruitment into the intervention group started in Q4 2017 and is ongoing until Q4 2020. The study is conducted according to the Declaration of Helsinki, and the protocol has received approval from a regional ethical review board.

Conclusions: This study entails an extensive intervention constructed in collaboration between clinicians, patients, and researchers that acknowledges accessibility, continuity, and self-management support within person-centeredness. The study has the potential to compare standard care to person-centered practice adapted specifically for patients with pituitary tumors and evaluated with a combination of patient-reported outcomes and patient-reported experience measures. Following the results, the person-centered practice may also become a useful model to further develop and explore person-centered care for patients with other rare, lifelong conditions.

Trial Registration: Researchweb.org. https://www.researchweb.org/is/sverige/project/161671.

International Registered Report Identifier (irrid): DERR1-10.2196/17697.
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http://dx.doi.org/10.2196/17697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404015PMC
July 2020

Hematologic malignancy in tanker crewmembers: A case-referent study among male Swedish seafarers.

Am J Ind Med 2020 08 23;63(8):685-692. Epub 2020 May 23.

Department of Occupational and Environmental Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.

Background: Work on Swedish petroleum tankers before the late 1980s has been associated with an increased risk of hematologic malignancy (HM). Since then, ship modernizations have decreased occupational exposure to gases, including the carcinogen benzene. We explored the risk of HMs in Swedish seafarers who had worked on newer types of tankers.

Methods: A case-referent study in male seafarers from a cohort of all Swedish seafarers was set up by record linkage with the Swedish Cancer Registry using the subjects' personal identification number. For each case (N = 315), five referents were randomly chosen from within the cohort, matched by birth year and three different periods of first sea service (<1985, 1985-1991, and ≥1992). Information on the type of ship and dates of service was retrieved from the Swedish Seafarers' Registry. Odds ratios (OR) were calculated by conditional logistic regression together with 95% confidence intervals (CI).

Results: The OR of HM was 1.07 (95% CI, 0.80-1.42) for work on tankers. In seafarers that had started to work on tankers ≥1985, the OR was 0.85 (95% CI, 0.50-1.43). For those who started to work on tankers before 1985, the OR was 1.17 (95% CI, 0.84-1.21) and 1.32 (95% CI, 0.86-2.03) if the cumulative time on tankers exceeded 5 years of service. In this last group, the OR of multiple myeloma was 5.39 (95% CI, 1.11-26.1).

Conclusion: Although limited by crude exposure contrast and a short follow-up, work on tankers after 1985 was not associated with an increased risk of HM among Swedish seafarers.
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http://dx.doi.org/10.1002/ajim.23122DOI Listing
August 2020

High affinity between CREBBP/p300 and NCOA evolved in vertebrates.

Protein Sci 2020 07 6;29(7):1687-1691. Epub 2020 May 6.

Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.

The interaction between the transcriptional coactivators CREBBP/p300 and NCOA is governed by two intrinsically disordered domains called NCBD and CID, respectively. The CID domain emerged within the NCOA protein in deuterostome animals (including vertebrates) after their split from the protostomes (molluscs, worms, and arthropods). However, it has not been clear at which point a high affinity interaction evolved within the deuterostome clade and whether all present-day deuterostome animals have a high affinity NCBD:CID interaction. We have here expressed and measured affinity for NCBD and CID domains from animal species representing different evolutionary branches of the deuterostome tree. While all vertebrate species have high-affinity NCBD:CID interactions we found that the interaction in the echinoderm purple sea urchin is of similar affinity as that of the proposed ancestral domains. Our findings demonstrate that the high-affinity NCBD:CID interaction likely evolved in the vertebrate branch and question whether the interaction between CREBBP/p300 and NCOA is essential in nonvertebrate deuterostomes. The data provide an example of evolution of transcriptional regulation through protein-domain based inventions.
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http://dx.doi.org/10.1002/pro.3868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314397PMC
July 2020

Road traffic noise, air pollution and cardiovascular events in a Swedish cohort.

Environ Res 2020 06 31;185:109446. Epub 2020 Mar 31.

Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Urbanization and increasing road traffic cause exposure to both noise and air pollution. While the levels of air pollutants such as nitrogen oxides (NO) have decreased in Sweden during the past decades, exposure to traffic noise has increased. The association with cardiovascular morbidity is less well established for noise than for air pollution, and most studies have only studied one of the two highly spatially correlated exposures. The Swedish Primary Prevention Study cohort consists of men aged 47 to 55 when first examined in 1970-1973. The cohort members were linked to the Swedish patient registry through their personal identity number and followed until first cardiovascular event 1970-2011. The address history during the entire study period was used to assign annual modelled residential exposure to road traffic noise and NO. The Cox proportional hazards model with age on the time axis and time-varying exposures were used in the analysis. The results for 6304 men showed a non-significant increased risk of cardiovascular disease for long-term road traffic noise at the home address, after adjusting for air pollution. The hazard ratios were 1.08 (95% CI 0.90-1.28) for cardiovascular mortality, 1.14 (95% CI 0.96-1.36) for ischemic heart disease incidence and 1.07 (95% CI 0.85-1.36) for stroke incidence, for noise above 60 dB, compared to below 50 dB. This study found some support for cardiovascular health effects of long-term exposure to road traffic noise above 60 dB, after having accounted for exposure to air pollution.
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http://dx.doi.org/10.1016/j.envres.2020.109446DOI Listing
June 2020

Correction to: Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): study protocol for a randomized controlled trial.

Trials 2020 Apr 6;21(1):317. Epub 2020 Apr 6.

Faculty of Psychology, University of Bergen, Box 7800, NO-5020, Bergen, Norway.

Following the publication of our article [1], we have become aware of one error in the exclusion criteria, inconsistencies in Figure 1 and Figure 2, and a typo in the reference list.
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http://dx.doi.org/10.1186/s13063-020-04239-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132867PMC
April 2020

Occupational exposure to soft paper dust and mortality.

Occup Environ Med 2020 08 2;77(8):549-554. Epub 2020 Apr 2.

Dept of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

Objectives: Occupational exposure to soft paper dust is associated with impaired lung function. Whether there is an increased risk for asthma or chronic obstructive pulmonary disease (COPD) is unclear.

Methods: We studied 7870 workers from three Swedish soft paper mills, and defined high-exposed workers, as having been exposed to soft paper dust exceeding 5 mg/m for at least 5 years. The remaining workers were classified as 'low exposed'. Person-years at risk were calculated and stratified according to gender, age and calendar-year. The follow-up time was from 1960 to 2013. The expected numbers of deaths were calculated using the Swedish population as reference and standardised mortality ratios (SMRs) with 95% CIs were assessed.

Results: There was an increased mortality due to obstructive lung disease (asthma and COPD), among high-exposed workers, SMR 1.89, 95% CI 1.20 to 2.83, based on 23 observed cases. High-exposed workers had an increased mortality from asthma, SMR 4.13, 95% CI 1.78 to 8.14, based on eight observed cases. The increased asthma mortality was also observed among high-exposed men, SMR 4.38, 95% CI 1.42 to 10.2, based on five observed cases. The asthma mortality among low-exposed workers, both men and women, was not increased. The COPD mortality was not clearly increased among high-exposed workers (SMR 1.52, 95% CI 0.85 to 2.50).

Conclusion: High occupational exposure to soft paper dust increases the mortality due to asthma, and the results suggest that soft paper dust levels in workplaces should be below 5 mg/m.
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http://dx.doi.org/10.1136/oemed-2019-106394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402447PMC
August 2020

Smoking-Induced Risk of Osteoporosis Is Partly Mediated by Cadmium From Tobacco Smoke: The MrOS Sweden Study.

J Bone Miner Res 2020 08 6;35(8):1424-1429. Epub 2020 Apr 6.

Department of Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Cigarette smoking is a risk factor for osteoporosis and bone fracture. Moreover, smoking causes exposure to cadmium, which is a known risk factor for osteoporosis. It is hypothesized that part of smoking-induced osteoporosis may be mediated via cadmium from tobacco smoke. We investigated this hypothesis using mediation analysis in a Swedish cohort of elderly men. This study was performed in 886 elderly men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study. Urinary samples, bone mineral density (BMD), smoking data, and other background information were obtained at baseline in 2002-2004. Urinary cadmium was analyzed in baseline samples and adjusted for creatinine. The cohort was followed until August 2018 for fracture incidence, based on the X-ray register. Mediation analysis was conducted to evaluate the indirect effect (via cadmium) of smoking on both BMD and fractures. Time to first fracture was analyzed using the accelerated failure time (AFT) model and Aalen's additive hazard model. The mean level of urinary cadmium was 0.25 μg/g creatinine. There were significant inverse associations between smoking and total body, total hip, and trochanter BMD. The indirect effects via cadmium were estimated to be 43% of the total effects of smoking for whole-body BMD, and even more for total hip and trochanter BMD. Smoking was also associated with higher risk of all fractures and major osteoporosis fractures. The indirect effects via cadmium were largest in nonvertebral osteoporosis fractures and hip fractures, constituting at least one-half of the total effects, in both the AFT and Aalen's model. The findings in this study provide evidence that cadmium exposure from tobacco smoke plays an important role in smoking-induced osteoporosis © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.4014DOI Listing
August 2020
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