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Abstract
Welding fume constitutes a source of particles and dust that effects a large number of individuals at occupational environments throughout the world. Besides being classified as a carcinogen, welding fume has potential inflammatory properties and has been linked to cardiovascular disease. To further increase the knowledge regarding potential health and inflammatory effects, workers at occupational environments with exposure to welding fume were investigated before but also after extensive preventive actions to investigate potential effects that may be pathways for cardiovascular disease. Exposure was assessed by collecting respirable dust through stationary and personal sampling at multiple occasions over the study. Dust was used for metal analysis by ICP-MS. Particle levels were assessed by using three handheld particle-counting instruments, Lighthouse 3016-IAQ (0.3-10 µm), DustTrak 8520 (0.1-10µm) and Philips Aerasense NanoTracer (10-300 nm). A total of approximately 100 individuals were screened at the beginning and end of a workweek at the beginning of the study and again after two years after the companies had introduced a wide range of preventive actions to reduce the exposure of the workforce. Participants had metals measured in both blood and urine, markers used in clinical practice for stress in different tissues were measured, lung function using spirometry was done and a set of 40 different acute inflammatory markers were measured using electrochemiluminiscence. The study adds to the growing knowledge of effects of welding fumes on human health and how preventive actions may affect this.

AbstractParticle exposure has been linked to an increased incidence of cardiovascular disease. Furthermore, particle exposure has been shown to have a chronic inhibitory effect on lung development in young people and may result in increased respiratory problems in adults or children with respiratory-related diseases. In today's urban environments, particle levels are mainly monitored gravimetrically; however, other factors such as particle size, shape and surface reactivity have recently been noted as highly important in relation to possible health outcomes. Here, particles from TEOM monitor filters placed in three different cities were studied. The purpose of the study was to investigate whether there are variations in particle masses, cadmium and lead contents, as well as endotoxin levels between locations and time points over the year and if this can be correlated to the particles ability to induce a pro-inflammatory response in vitro. Results showed that it is possible to detect variations at different locations and at different time points over the year and that cadmium, lead and endotoxin levels did not coincide with the increased total particle masses while endotoxin levels coincided with pro-inflammatory responses in vitro. The present study shows that filter analysis is a useful complement to gravimetric or particle-counting measurements in studies of particle-related health effects and will give useful information regarding future air quality measurements.

Abstract
Additive manufacturing (AM) is the process of building parts from 3D model data by joining materials. AM includes different techniques, such as binder jetting and powder bed fusion which uses metal powder as feedstock. Knowledge regarding exposure-related health risks in metal AM environments is still limited. Herein, we report emission data from 8 different AM companies along with health examinations of 39 controls and 48 additive manufacturing machine users (AMMU).
Exposure assessment of dust and metals was performed through stationary and personal sampling of total and inhalable dust followed by metal analysis by ICP-MS. Two handheld particle-counting instruments, Lighthouse 3016-IAQ (0.3-10 µm) and Philips Aerasense NanoTracer (10-300 nm), were used to identify dusty work tasks and thereby to help prioritize preventive measures. Health examinations consisted of questionnaires, spirometry, blood sampling after a workweek and collection of urine samples before and after a workweek. Clinical markers in urine (α1-microglobulin) and plasma (ASAT, ALAT, ALP, ApoA-1, ApoB, SAA1/PON1), and urinary metal levels were analyzed.
Results: Daily averages of dust and metal exposure were in general low compared to Swedish occupational exposure limits. However, particle counting instruments identified specific work tasks with high exposure risk. Mann Whitney U-test indicated statistical differences between exposed and controls for three clinical markers; ASAT and ApoA-1 in plasma as well as α-1-microglobulin in urine. There were no significant increase in exposure markers Monday to Friday nor between AMMU and controls at a group level. Although high exposure levels were seen in some individuals.

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. ; Funding Agencies|Region Ostergotland ALF [LIO-606891]; AFA insurances [150246]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [2012.0083 CTS, 18:399]; Center in Nano Science and Nano technology at LiTH (CeNano) at Linkoping University

Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects. ; Funding Agencies|Swedish Research Council for Health, Working Life and Welfare [FAS2006-0803]; Swedish Governmental Funding for Clinical Research; Skane County Councils research and development foundation (ALF); FORTE

The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1P297S mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1P297S heterozygotes. Lipoproteins from six SR-B1P297S carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed. Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I. The SR-B1P297S mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1. ; Funding agencies: EUs Sixth Framework Program [037631]; European Union [FP7-603091-2]; CardioVascular Research Initiative [CVON2011-16]; Research Council of South East Sweden [FORSS-3755]; County Council of Ostergotland (C-ALF); Faculty of Health Sciences in Linkoping; Ven