Historical exposure to metals in contaminated areas and its impact on cardio- and cerebrovascular health.

Environmental pollution is of global concern. In Southeast Sweden, historical glass production has contaminated communities with toxic metals. Long-term residency in these communities and high consumption of local foods may constitute a risk for cardiovascular disease (CVD) or stroke. The current study investigates if residency in these contaminated sites and long-term consumption of local foods is associated with self-reported CVD and stroke. In addition, the body burden of the toxic metals arsenic, cadmium, and lead, as well as inflammatory protein markers, were studied for association with CVD and stroke. From an existing questionnaire cohort and biomonitoring sub cohort (n = 2290/882) of people living in the contaminated areas, self-reported CVD cases (n = 366/166) and stroke cases (n = 78/25) were identified. Individuals were grouped based on their residency within a 2 km radius of glassworks with historical high, moderate, or low air-borne lead emissions. Body burden of arsenic, cadmium, and lead was analyzed using ICP-MS. Inflammatory markers were investigated using electrochemiluminescence. Long-term residency near glassworks with historically high levels of lead emissions, and high consumption of local foods, were associated with CVD. The risk was increasing for each year of residency in high emission areas. Increased body burden of arsenic in blood, and lead in urine, were associated with stroke. Five and two inflammatory markers, respectively, were elevated in CVD and stroke cases after adjusting for confounders. An increased risk for CVD was found in areas with historically high emissions of lead but possibly also other toxic metals. Interestingly, there was an indication of a dose-response relationship with increasing risk for CVD per year of residency time. Inhalation and consumption of local food may constitute major pathways for this association. The study shows that long-term exposure to toxic metals in these contaminated areas is associated with CVD and that there is a need to limit exposure in the general population.

Favourable HDL composition in endurance athletes is not associated with changes in HDL in vitro antioxidant and endothelial anti-inflammatory function.

Given the failure of high-density lipoprotein (HDL) raising therapies to reduce cardiovascular disease risk, attention has turned towards HDL composition and vascular protective functions. In individuals with insulin resistance, exercise interventions recover HDL function. However, the effect of exercise on HDL in otherwise healthy individuals is unknown. This cross-sectional study aimed to measure HDL composition and antioxidant / endothelial anti-inflammatory function in insulin sensitive endurance athlete and healthy control men. HDL was isolated using density gradient ultracentrifugation. HDL composition was measured using microplate assays for apolipoprotein A-I, total cholesterol content and apolipoprotein M. HDL protein composition was measured using nano-liquid chromatography tandem mass spectrometry. HDL subclass distribution was measured by native gel electrophoresis. HDL in vitro antioxidant function was measured by paraoxonase-1 activity assay and anti-inflammatory function assessed in endothelial cells.  Compared to controls, endurance athlete HDL had higher apolipoprotein A-1 (1.65 ± 0.62 mg/mL vs 1.21 ± 0.34 mg/mL, p = 0.028) and higher total cholesterol content (1.54 ± 0.33 mmol/L vs 2.09 ± 0.44 mmol/L, p < 0.001).  Proteomics revealed higher apolipoprotein A-II, A-IV and D and transthyretin in endurance athlete HDL versus controls. There was no difference observed in in vitro HDL antioxidant or anti-inflammatory functions between controls and endurance athletes. Despite a more favourable composition, endurance athlete HDL did not have higher in vitro antioxidant or anti-inflammatory function. It is possible that HDL has a ceiling of function, i.e. that healthy HDL function cannot be enhanced by endurance exercise.

Long-term ambient air pollution exposure and renal function and biomarkers of renal disease.

BACKGROUND: Despite accumulating evidence of an association between air pollution and renal disease, studies on the association between long-term exposure to air pollution and renal function are still contradictory. This study aimed to investigate this association in a large population with relatively low exposure and with improved estimation of renal function as well as renal injury biomarkers. METHODS: We performed a cross-sectional analysis in the middle-aged general population participating in the Swedish CardioPulmonary bioImaging Study (SCAPIS; n = 30 154). Individual 10-year exposure to total and locally emitted fine particulate matter (PM2.5), inhalable particulate matter (PM10), and nitrogen oxides (NOx) were modelled using high-resolution dispersion models. Linear regression models were used to estimate associations between exposures and estimated glomerular filtration rate (eGFR, combined creatinine and cystatin C) and serum levels of renal injury biomarkers (KIM-1, MCP-1, IL-6, IL-18, MMP-2, MMP-7, MMP-9, FGF-23, and uric acid), with consideration of potential confounders. RESULTS: Median long-term PM2.5 exposure was 6.2 µg/m3. Almost all participants had a normal renal function and median eGFR was 99.2 mL/min/1.73 m2. PM2.5 exposure was associated with 1.3% (95% CI 0.6, 2.0) higher eGFR per 2.03 µg/m3 (interquartile range, IQR). PM2.5 exposure was also associated with elevated serum matrix metalloproteinase 2 (MMP-2) concentration, with 7.2% (95% CI 1.9, 12.8) higher MMP-2 per 2.03 µg/m3. There was a tendency towards an association between PM10 and higher levels of uric acid, but no associations were found with the other biomarkers. Associations with other air pollutants were null or inconsistent. CONCLUSION: In this large general population sample at low exposure levels, we found a surprising association between PM2.5 exposure and a higher renal filtration. It seems unlikely that particle function would improve renal function. However, increased filtration is an early sign of renal injury and may be related to the relatively healthy population at comparatively low exposure levels. Furthermore, PM2.5 exposure was associated with higher serum concentrations of MMP-2, an early indicator of renal and cardiovascular pathology.

Long-term ambient air pollution and coronary atherosclerosis: Results from the Swedish SCAPIS study.

BACKGROUND AND AIMS: Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis. METHODS: We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n = 30 154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5 µm (PM2.5), <10 µm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders. RESULTS: Median 10-year average PM2.5 exposure was 6.2 µg/m3 (range 3.5-13.4 µg/m3). 51 % of participants were women and 51 % were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95 % CI 1.13, 1.58, per 2.05 µg/m3). Associations with significant stenoses were inconsistent. CONCLUSIONS: In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.

Hexavalent chromium still a concern in Sweden - Evidence from a cross-sectional study within the SafeChrom project.

OBJECTIVES: Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown. METHODS: This cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance. RESULTS: The exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 µg/m3 (95% confidence interval: 0.11-0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 µg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 µg/L, 5th-95th percentile 0.10-3.20) and RBC concentrations (0.73 µg/L, 0.51-2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 µg/L, 0.06-0.56 and RBC 0.53 µg/L, 0.42-0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today. CONCLUSIONS: Our study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.

Airway contraction and cytokine release in isolated rat lungs induced by wear particles from the road and tire interface and road vehicle brakes.

The dominant road traffic particle sources are wear particles from the road and tire interface, and from vehicle brake pads. The aim of this work was to investigate the effect of road and brake wear particles on pulmonary function and biomarkers in isolated perfused rat lungs. Particles were sampled from the studded tire wear of three road pavements containing different rock materials in a road simulator; and from the wear of two brake pad materials using a pin-on-disk machine. Isolated rat lungs inhaled the coarse and fine fractions of the sampled particles resulting in an estimated total particle lung dose of 50 µg. The tidal volume (TV) was measured during the particle exposure and the following 50 min. Perfusate and BALF were analyzed for the cytokines TNF, CXCL1 and CCL3. The TV of lungs exposed to rock materials was significantly reduced after 25 min of exposure compared to the controls, for quartzite already after 4 min. The particles of the heavy-duty brake pads had no effect on the TV. Brake particles resulted in a significant elevation of CXCL1 in the perfusate. Brake particles showed significant elevations of all three measured cytokines, and quartzite showed a significant elevation of TNF in BALF. The study shows that the toxic effect on lungs exposed to airborne particles can be investigated using measurements of tidal volume. Furthermore, the study shows that the choice of rock material in road pavements has the potential to affect the toxicity of road wear PM10.

Occupational exposure and health surveys at metal additive manufacturing facilities.

Introduction: Additive manufacturing is a novel state-of-the art technology with significant economic and practical advantages, including the ability to produce complex structures on demand while reducing the need of stocking materials and products. Additive manufacturing is a technology that is here to stay; however, new technologies bring new challenges, not only technical but also from an occupational health and safety perspective. Herein, leading Swedish companies using metal additive manufacturing were studied with the aim of investigating occupational exposure and the utility of chosen exposure- and clinical markers as predictors of potential exposure-related health risks. Methods: Exposure levels were investigated by analysis of airborne dust and metals, alongside particle counting instruments measuring airborne particles in the range of 10 nm-10 µm to identify dusty work tasks. Health examinations were performed on a total of 48 additive manufacturing workers and 39 controls. All participants completed a questionnaire, underwent spirometry, and blood and urine sampling. A subset underwent further lung function tests. Results: Exposure to inhalable dust and metals were low, but particle counting instruments identified specific work tasks with high particle emissions. Examined health parameters were well within reference values on a group level. However, statistical analysis implied an impact on workers kidney function and possible airway inflammation. Conclusion: The methodology was successful for investigating exposure-related health risks in additive manufacturing. However, most participants have been working <5 years. Therefore, long-term studies are needed before we can conclusively accept or reject the observed effects on health.

Health hazards of particles in additive manufacturing: a cross-disciplinary study on reactivity, toxicity and occupational exposure to two nickel-based alloys.

The increasing use of additive manufacturing (AM) techniques (e.g., 3D-printing) offers many advantages but at the same time presents some challenges. One concern is the possible exposure and health risk related to metal containing particles of different sizes. Using the nickel-based alloys Hastelloy X (HX) and Inconel 939 (IN939) as a case, the aim of this cross-disciplinary study was to increase the understanding on possible health hazards and exposure. This was done by performing in-depth characterization of virgin, reused and condensate powders, testing in vitro toxicity (cytotoxicity, genotoxicity, oxidative stress), and measuring occupational airborne exposure. The results showed limited metal release from both HX and IN939, and slightly different surface composition of reused compared to virgin powders. No or small effects on the cultured lung cells were observed when tested up to 100 µg/mL. Particle background levels in the printing facilities were generally low, but high transient peaks were observed in relation to sieving. Furthermore, during post processing with grinding, high levels of nanoparticles (> 100,000 particles/cm3) were noted. Urine metal levels in AM operators did not exceed biomonitoring action limits. Future studies should focus on understanding the toxicity of the nanoparticles formed during printing and post-processing.

Temporal risk assessment - 20th century Pb emissions to air and exposure via inhalation in the Swedish glass district.

The objective of the present study was to assess historical emissions of Pb to air around a number of glassworks sites in southeastern Sweden, and the possible implications for human exposure. To do so, a four-step method was applied. First, emissions of Pb to air around 10 glassworks were modelled for the 20th century. Second, an assessment of the resulting exposure was made for a number of scenarios. Third, the number of people potentially exposed at different times was estimated, and fourth, measurements of "current" Pb concentrations in PM10 material from four sites were conducted in 2019. The results show that the highest emissions, and exposures, occurred from 1970 to1980. It coincides with the time period when the highest number of people resided in the villages. At this time, the average Pb concentration in air around the six largest factories was about 2.4 µg Pb/m3, i.e. 16 times the present US national ambient air quality standard (NAAQS) of 0.15 µg Pb/m3. By year 2000 the modelled average concentration had dropped to 0.05 µg Pb/m3, a level that is normal for urban regions today. The PM10 measurements from 2019 indicate a further decline, now with a mean value of about 0.02 µg Pb/m3. Over the entire study period, inhalation hazard quotients (HQs) exceeded the dietary HQ by many orders of magnitude, indicating that inhalation has been the most prevalent exposure pathway in the past. At present, both pathways are judged to be associated with low exposures. Even if only roughly approximated, a picture of the historical exposure can increase our understanding of the connection between exposure and disease, and can be valuable when risks are to be communicated to residents near contaminated areas.

Effect of N-3 Polyunsaturated Fatty Acids on Lipid Composition in Familial Hypercholesterolemia: A Randomized Crossover Trial.

Individuals with familial hypercholesterolemia (FH) have an increased risk of cardiovascular disease. Treatment is mainly low-density lipoprotein cholesterol (LDL-C) reduction. How omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements affect lipoproteins in FH subjects is unknown. We hypothesized that a high-dose n-3 PUFA supplement would reduce atherogenic lipoproteins and influence the high-density lipoprotein cholesterol (HDL-C) function. We performed a randomized, double-blinded crossover study with 34 genetically verified FH individuals (18−75 years, clinically stable, statin treatment > 12 months). Treatment was 4 g n-3 PUFAs (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid daily) or four capsules of olive oil for three months in a crossover design with a washout period of three months. The defined outcomes were changes in triglycerides, lipoproteins, lipoprotein subfractions, apolipoproteins, and HDL-C function. After treatment with n-3 PUFAs, total cholesterol, LDL-C, and triglycerides were reduced compared to placebo (p ≤ 0.01 for all). Total HDL-C levels were unchanged, but the subfraction of large HDL-C was higher (p ≤ 0.0001) after n-3 PUFAs than after placebo, and intermediate HDL-C and small HDL-C were reduced after n-3 PUFAs compared to placebo (p = 0.02 and p ≤ 0.001, respectively). No changes were found in apolipoproteins and HDL-C function. N-3 PUFAs supplements reduced atherogenic lipoproteins in FH subjects, leaving HDL-C function unaffected.

Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles - an interdisciplinary approach.

Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle-protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both 'danger signals', verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations.

Metal exposure from additive manufacturing and its effect on the nasal lavage fluid proteome - a pilot study.

The use of metal additive manufacturing (AM) is steadily increasing and is an emerging concern regarding occupational exposure. In this study, non-invasive sampled nasal lavage fluid (NLF) from the upper airways was collected from metal AM operators at the beginning and end of a workweek during two consecutive years with preventive interventions in the occupational setting in-between (n = 5 year 1, n = 9 year 2). During year one, NLF was also collected from welders (n = 6) from the same company to get a comparison with a traditional manufacturing technique with known exposure and health risks. The samples were investigated using untargeted proteomics, as well as using multi-immunoassay to analyze a panel of 71 inflammatory protein markers. NLF in AM operators from year 1 showed decreased levels of Immunoglobulin J and WAP four-disulfide core domain protein 2 and increased levels of Golgi membrane protein 1, Uteroglobin and Protein S100-A6 at the end of the workweek. At year two, after preventive interventions, there were no significant differences at the end of the workweek. In welders, Annexin A1 and Protein S100-A6 were increased at the end of the workweek. The analysis of 71 inflammatory biomarkers showed no significant differences between the beginning and the end of workweek year 1 in AM operators. We identified several proteins of interest in the AM operators that could serve as possible markers for exposure in future studies with a larger cohort for validation.

Sphingolipids in HDL - Potential markers for adaptation to pregnancy?

Plasma high density lipoprotein (HDL) exhibits many functions that render it an effective endothelial protective agent and may underlie its potential role in protecting the maternal vascular endothelium during pregnancy. In non-pregnant individuals, the HDL lipidome is altered in metabolic disease compared to healthy individuals and is linked to reduced cholesterol efflux, an effect that can be reversed by lifestyle management. Specific sphingolipids such as sphingosine-1-phosphate (S1P) have been shown to mediate the vaso-dilatory effects of plasma HDL via interaction with the endothelial nitric oxide synthase pathway. This review describes the relationship between plasma HDL and vascular function during healthy pregnancy and details how this is lost in pre-eclampsia, a disorder of pregnancy associated with widespread endothelial dysfunction. Evidence of a role for HDL sphingolipids, in particular S1P and ceramide, in cardiovascular disease and in healthy pregnancy and pre-eclampsia is discussed. Available data suggest that HDL-S1P and HDL-ceramide can mediate vascular protection in healthy pregnancy but not in preeclampsia. HDL sphingolipids thus are of potential importance in the healthy maternal adaptation to pregnancy.

Metal additive manufacturing and possible clinical markers for the monitoring of exposure-related health effects.

Additive manufacturing (AM) includes a series of techniques used to create products, in several different materials, such as metal, polymer or ceramics, with digital models. The main advantage of AM is that it allows the creation of complex structures, but AM promises several additional advantages including the possibility to manufacture on demand or replacing smaller worn parts by directly building on an existing piece. Therefore, the interest for and establishment of AM is rapidly expanding, which is positive, however it is important to be aware that new techniques may also result in new challenges regarding health and safety issues. Metals in blood and possible clinical effects due to metal exposure were investigated in AM operators at one of the first serial producing AM facilities in the world during two consecutive years with implementation of preventive measures in-between. As comparison, welders and office workers as control group were investigated. Health investigations comprised of surveys, lung function tests, antioxidant activity and vascular inflammation as well as renal- and hepatic function analysis. AM operators had significantly reduced nickel levels in blood (10.8 vs 6.2 nmol/L) as well as improved lung function (80 vs 92% of predicted) from year 1 to year 2. This is in line with previously published results displaying reduced exposure. Blood cobalt and nickel levels correlated with previously reported urinary levels, while blood chromium did not. Multivariate modelling showed that blood cobalt, antioxidant/inflammatory marker serum amyloid A1/serum paraoxonase/arylesterase 1 activity and the hepatic markers aspartate transaminase, alanine transaminase, and alkaline phosphatase were higher in AM operators compared to controls. The study show that the selected clinical analyses could function as a complement to metal analyses in biological fluids when investigating exposure-related health effects in AM operators. However, validation in larger cohorts is necessary before more definite conclusions could be drawn.

High-density lipoprotein's vascular protective functions in metabolic and cardiovascular disease - could extracellular vesicles be at play?

High-density lipoprotein (HDL) is a circulating complex of lipids and proteins known primarily for its role in reverse cholesterol transport and consequent protection from atheroma. In spite of this, therapies aimed at increasing HDL concentration do not reduce the risk of cardiovascular disease (CVD), and as such focus has shifted towards other HDL functions protective of vascular health - including vasodilatory, anti-inflammatory, antioxidant and anti-thrombotic actions. It has been demonstrated that in disease states such as CVD and conditions of insulin resistance such as Type 2 diabetes mellitus (T2DM), HDL function is impaired owing to changes in the abundance and function of HDL-associated lipids and proteins, resulting in reduced vascular protection. However, the gold standard density ultracentrifugation technique used in the isolation of HDL also co-isolates extracellular vesicles (EVs). EVs are ubiquitous cell-derived particles with lipid bilayers that carry a number of lipids, proteins and DNA/RNA/miRNAs involved in cell-to-cell communication. EVs transfer their bioactive load through interaction with cell surface receptors, membrane fusion and endocytic pathways, and have been implicated in both cardiovascular and metabolic diseases - both as protective and pathogenic mediators. Given that studies using density ultracentrifugation to isolate HDL also co-isolate EVs, biological effects attributed to HDL may be confounded by EVs. We hypothesise that some of HDL's vascular protective functions in cardiovascular and metabolic disease may be mediated by EVs. Elucidating the contribution of EVs to HDL functions will provide better understanding of vascular protection and function in conditions of insulin resistance and potentially provide novel therapeutic targets for such diseases.

Proteomic Analysis of the Cerebrospinal Fluid in Patients With Essential Tremor Before and After Deep Brain Stimulation Surgery: A Pilot Study.

OBJECTIVE: Electrical neuromodulation by deep brain stimulation (DBS) is a well-established method for treatment of severe essential tremor (ET). The mechanism behind the tremor relieving effect remains largely unknown. Our aim of this study was to evaluate alterations in proteomics pre- and post-DBS in patients diagnosed with severe ET. MATERIALS AND METHODS: Ten right-handed ET patients were included in this study. Cerebrospinal fluid (CSF) was obtained by lumbar puncture preoperatively (N = 10) and six months postoperatively (N = 7). The samples were analyzed by high sensitive liquid chromatography tandem mass spectrometry. RESULTS: Twenty-two proteins were statistically significantly altered in the CSF of ET patients before and after DBS treatment. Downregulated proteins were involved in regulatory processes of protein activation, complement activation, humoral immune response as well as acute inflammatory response. The upregulated proteins were involved in pathways for cell secretion, adhesion as well as response to axon injury. CONCLUSIONS: DBS in ET patients effects the neurochemical environment in the CSF. These findings further elucidate the mechanisms of DBS and may lead to new biomarkers for evaluating the effect of DBS treatment.

Exosomes in specific fractions of the boar ejaculate contain CD44: A marker for epididymosomes?

Seminal plasma (SP) is a complex fluid containing proteins, peptides, enzymes, hormones as well as extracellular vesicles (EVs). The SP interacts with spermatozoa and the inner cell lining of the female genital tract, adsorbing proteins and exosomes that modulate sperm functions and female immune responsiveness. In the present study, boar sperm-free SP was studied using flow cytometry (FC) after membrane tetraspanins (CD9, CD63 and CD81) and membrane receptor CD44 marking of non-enriched (whole SP) or gradient fractions enriched through two-step discontinuous KBr-density-gradient ultracentrifugation, in whole ejaculate or in selected ejaculate fractions. The results, evaluated by transmission electron microscopy, confirmed the presence of exosomes in all fractions of the pig SP. Noteworthy, these pig SP-exosomes were CD44-bearing when analysed by FC, with bands detected by western blotting (WB) at the expected 85 kD size. The two-step discontinuous KBr-density-gradient ultracentrifugation enriched the population of exosomes in two specific gradient fractions, indicating exosomes (either prostasomes or epididymosomes) could be separated from low-density lipoprotein (LDL) but they co-sediment with the high-density lipoprotein (HDL)-bearing fraction. The findings pave for the selective isolation of exosomes in functional studies of their function when interacting with spermatozoa, the oocyte and/or the female genitalia, including hyaluronan-CD44 interplay.

Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glassworks area.

BACKGROUND: Production of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer. OBJECTIVE: The aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors. METHODS: The study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979-2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer. RESULTS: Despite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms. CONCLUSIONS: The associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

Modified lipoproteins in periodontitis: a link to cardiovascular disease?

There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of α-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. α-1 antitrypsin and α-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).

Biomonitoring of Metal Exposure During Additive Manufacturing (3D Printing).

BACKGROUND: Additive manufacturing (AM) is a rapidly expanding new technology involving challenges to occupational health. Here, metal exposure in an AM facility with large-scale metallic component production was investigated during two consecutive years with preventive actions in between. METHODS: Gravimetric analyzes measured airborne particle concentrations, and filters were analyzed for metal content. In addition, concentrations of airborne particles <300 nm were investigated. Particles from recycled powder were characterized. Biomonitoring of urine and dermal contamination among AM operators, office personnel, and welders was performed. RESULTS: Total and inhalable dust levels were almost all below occupational exposure limits, but inductively coupled plasma mass spectrometry showed that AM operators had a significant increase in cobalt exposure compared with welders. Airborne particle concentrations (<300 nm) showed transient peaks in the AM facility but were lower than those of the welding facility. Particle characterization of recycled powder showed fragmentation and condensates enriched in volatile metals. Biomonitoring showed a nonsignificant increase in the level of metals in urine in AM operators. Dermal cobalt and a trend for increasing urine metals during Workweek Year 1, but not in Year 2, indicated reduced exposure after preventive actions. CONCLUSION: Gravimetric analyses showed low total and inhalable dust exposure in AM operators. However, transient emission of smaller particles constitutes exposure risks. Preventive actions implemented by the company reduced the workers' metal exposure despite unchanged emissions of particles, indicating a need for careful design and regulation of the AM environments. It also emphasizes the need for relevant exposure markers and biomonitoring of health risks.