[Particulate emissions from residential wood combustion : Evaluation under real-life operating conditions and toxicological relevance]. / Partikuläre Emissionen aus Einzelraumfeuerungen für Holzbrennstoffe : Bewertung unter realen Betriebsbedingungen und toxikologische Relevanz.

Due to their high emission of particulate matter, wood fired furnaces have become a focal point of public discussion in Germany. Log-fired single room heaters can be identified as a main contributor to this matter. The particulate matter emitted by outdated as well as modern furnaces directly affects the pollution inside residential areas. This is demonstrated by a test campaign of a fibrous filter system developed by the Technology of Fuels Unit at RWTH Aachen University. The filter system captures the emitted particles and retains them inside a highly porous media. Particles from different households and combustion systems were collected over half a heating season. Afterwards, the chemical composition of the accumulated particulate matter was analysed. Based on the particle composition, the furnace operation can be evaluated and consequently improved. This method can be seen as an integral evaluation of the emitted particles of small scale furnaces under real-life operating conditions.

Histone deacetylase 2 controls p53 and is a critical factor in tumorigenesis.

Histone deacetylase 2 (HDAC2) regulates biological processes by deacetylation of histones and non-histone proteins. HDAC2 is overexpressed in numerous cancer types, suggesting general cancer-relevant functions of HDAC2. In human tumors the TP53 gene encoding p53 is frequently mutated and wild-type p53 is often disarmed. Molecular pathways inactivating wild-type p53 often remain to be defined and understood. Remarkably, current data link HDAC2 to the regulation of the tumor suppressor p53 by deacetylation and to the maintenance of genomic stability. Here, we summarize recent findings on HDAC2 overexpression in solid and hematopoietic cancers with a focus on mechanisms connecting HDAC2 and p53 in vitro and in vivo. In addition, we present an evidence-based model that integrates molecular pathways and feedback loops by which p53 and further transcription factors govern the expression and the ubiquitin-dependent proteasomal degradation of HDAC2 and of p53 itself. Understanding the interactions between p53 and HDAC2 might aid in the development of new therapeutic approaches against cancer.

Human biomonitoring of chromium and nickel from an experimental exposure to manual metal arc welding fumes of low and high alloyed steel.

OBJECTIVES: The uptake and elimination of metals from welding fumes is currently not fully understood. In the Aachen Workplace Simulation Laboratory (AWSL) it is possible to investigate the impact of welding fumes on human subjects under controlled exposure conditions. In this study, the uptake and elimination of chromium or chromium (VI) respectively as well as nickel was studied in subjects after exposure to the emissions of a manual metal arc welding process using low or high alloyed steel. METHODS: In this present study 12 healthy male non-smokers, who never worked as welders before, were exposed for 6h to welding fumes of a manual metal arc welding process. In a three-fold crossover study design, subjects were exposed in randomized order to either clean air, emissions from welding low alloyed steel, and emissions from welding high alloyed steel. Particle mass concentration of the exposure aerosol was 2.5mg m(-3). The content of chromium and nickel in the air was determined by analysing air filter samples on a high emission scenario. Urine analysis for chromium and nickel was performed before and after exposure using methods of human biomonitoring. RESULTS: There were significantly elevated chromium levels after exposure to welding fumes from high alloyed steel compared to urinary chromium levels before exposure to high alloyed welding fumes, as well as compared to the other exposure scenarios. The mean values increased from 0.27 µg l(-1) to 18.62 µg l(-1). The results were in good agreement with already existing correlations between external and internal exposure (German exposure equivalent for carcinogenic working materials EKA). The variability of urinary chromium levels was high. For urinary nickel no significant changes could be detected at all. CONCLUSIONS: Six-hour exposure to 2.5mg m(-3) high alloyed manual metal arc welding fumes lead to elevated urinary chromium levels far higher (7.11-34.16 µg l(-1)) than the German biological exposure reference value (BAR) of 0.6 µg l(-1) directly after exposure. On the other hand mean urinary nickel concentrations slightly increased, but did not exceed background levels due to lower bioavailability. We could underline with our single exposure experiment that a welding work related chromium exposure can be measured immediately after the work shift, while the same is not possible for nickel exposure due to lower nickel bioavailability. The data provide useful information for real occupational welding work places.

Human biomonitoring of aluminium after a single, controlled manual metal arc inert gas welding process of an aluminium-containing worksheet in nonwelders.

PURPOSE: Several existing field studies evaluate aluminium welding works but no thoroughly controlled exposure scenario for welding fume has been described yet. This study provides information about the uptake and elimination of aluminium from welding fumes under controlled conditions. METHODS: In the Aachen Workplace Simulation Laboratory, we are able to generate welding fumes of a defined particle mass concentration. We exposed 12, until then occupationally unexposed participants with aluminium-containing welding fumes of a metal inert gas (MIG) welding process of a total dust mass concentration of 2.5 mg/m(3) for 6 h. Room air filter samples were collected, and the aluminium concentration in air derived. Urine and plasma samples were collected directly before and after the 6-h lasting exposure, as well as after 1 and 7 days. Human biomonitoring methods were used to determine the aluminium content of the samples with high-resolution continuum source atomic absorption spectrometry. RESULTS: Urinary aluminium concentrations showed significant changes after exposure compared to preexposure levels (mean t(1) (0 h) 13.5 µg/L; mean t(2) (6 h) 23.5 µg/L). Plasma results showed the same pattern but pre-post comparison did not reach significance. CONCLUSIONS: We were able to detect a significant increase of the internal aluminium burden of a single MIG aluminium welding process in urine, while plasma failed significance. Biphasic elimination kinetic can be observed. The German BAT of 60 µg/g creatinine was not exceeded, and urinary aluminium returned nearly to baseline concentrations after 7 days.

Number size distribution of fine and ultrafine fume particles from various welding processes.

Studies in the field of environmental epidemiology indicate that for the adverse effect of inhaled particles not only particle mass is crucial but also particle size is. Ultrafine particles with diameters below 100 nm are of special interest since these particles have high surface area to mass ratio and have properties which differ from those of larger particles. In this paper, particle size distributions of various welding and joining techniques were measured close to the welding process using a fast mobility particle sizer (FMPS). It turned out that welding processes with high mass emission rates (manual metal arc welding, metal active gas welding, metal inert gas welding, metal inert gas soldering, and laser welding) show mainly agglomerated particles with diameters above 100 nm and only few particles in the size range below 50 nm (10 to 15%). Welding processes with low mass emission rates (tungsten inert gas welding and resistance spot welding) emit predominantly ultrafine particles with diameters well below 100 nm. This finding can be explained by considerably faster agglomeration processes in welding processes with high mass emission rates. Although mass emission is low for tungsten inert gas welding and resistance spot welding, due to the low particle size of the fume, these processes cannot be labeled as toxicologically irrelevant and should be further investigated.

Experimental exposure of healthy subjects with emissions from a gas metal arc welding process--part II: biomonitoring of chromium and nickel.

OBJECTIVES: The objective of this study was to investigate whether there is a relationship between the external exposure dose of chromium and nickel caused by a metal active gas welding process with a solid high-alloyed steel welding wire and inner exposure of subjects. In order to perform welding fume exposure under controlled and standardized conditions, the investigations were conducted in the "Aachen Workplace Simulation Laboratory". METHODS: To perform biological monitoring of chromium and nickel, blood and urine samples of 12 healthy male non-smokers who never worked as welders were collected before and after a 6-h exposure to ambient air (0 mg/m(3)) and to welding fumes of a metal active gas welding process once with a concentration of the welding fume of 1 mg/m(3) and once with a concentration of 2.5 mg/m(3). RESULTS: Although the internal exposure to chromium and nickel in this study was comparatively low, the subjects showed significantly increased concentrations of these metals in urine after exposure to welding fume compared to the values at baseline. Moreover, the observed increase was significantly dose dependent for both of the substances. CONCLUSION: For the biological monitoring of chromium and nickel in urine of subjects exposed to welding fumes, a dependency on exposure dose was seen under standardized conditions after a single exposure over a period of 6 h. Thus, this study contributes to a better understanding of the relationship between ambient and biological exposures from welding fumes and provides a good basis for evaluating future biological threshold values for these metals in welding occupation.

The British Athletics Muscle Injury Classification grading system as a predictor of return to play following hamstrings injury in professional football players.

OBJECTIVES: Investigate the British Athletics Muscle Injury Classification (BAMIC) grading system as a predictor of return to play (RTP) following primary hamstring strain injury (HSI) and its agreement with the Peetron's classification system in professional footballers. METHODS: A retrospective cohort study of 39 hamstrings strains in a professional English football club were identified. Two musculoskeletal radiologists reviewed historical MRI's and classified them against the BAMIC and Peetron's grading system. Classification, oedema length and cross-sectional area were compared against RTP. RESULTS: Pearson's correlation coefficient demonstrated a weak but statistically significant correlation between BAMIC and RTP (r = 0.32; 95%CI 0.01 to 0.58; p = 0.05). Maximum length of intramuscular oedema demonstrated weak correlations with RTP (r = 0.3; 95%CI -0.02 to 0.56; p = 0.06). Percentage cross sectional demonstrated a weak correlation with RTP (r = 0.02; 95%CI -0.3 to 0.33; p = 0.91). Multiple regression demonstrated that 16% of the variance in RTP was explained by the model. Kappa for the agreement between BAMIC and Peetron's was 0.21 (95%CI 0 to 0.42). CONCLUSIONS: A significant association between the grade of HSI on the BAMIC system and RTP was found. Findings suggest BAMIC could provide valuable prognostic information on the RTP.

Factors Promoting Posttraumatic Growth in Sexual Minority Adults Following Adolescent Bullying Experiences.

The minority stress model posits that stigmatized identities expose sexual minority individuals to chronic stressors that contribute to health disparities, but that individual-level resources may mitigate psychological distress. Sexual minority adolescents experience one such stressor, bullying victimization, at higher rates than heterosexual peers. Whereas negative consequences of sexual identity-based bullying are well documented, potential positive outcomes are not well understood. The present work examined hypothesized pathways to posttraumatic growth (PTG)-positive psychological changes stemming from trauma-in sexual minority adults following adolescent bullying experiences. We predicted that attributing bullying to one's sexual identity, as opposed to other factors (e.g., weight/appearance, personality), would exacerbate perceived bullying severity but, in turn, enhance PTG. We also predicted that outness about sexual identity would enhance social support and, in turn, facilitate PTG. The hypothesized conceptual model was tested in two samples of sexual minority adults who had experienced bullying during adolescence (Sample 1: Community Sample [N = 139]; Sample 2: National Online Sample [N = 298]), using structural equation modeling with Bayesian estimation. Mediation hypotheses were tested using the PROCESS v3.4 macro. Participants reported their adolescent experiences with bullying, attributions for bullying, outness, social support, and PTG as a result of adolescent bullying experiences, in addition to demographics. Supporting the hypothesized model, in both samples, attributions to sexual identity-based bullying directly and indirectly (via bullying severity) predicted greater PTG, and outness predicted greater PTG through proximal impact on social support. This research underscores the importance of supportive responses to individuals who disclose sexual minority identities and of (re)framing attributions about bullying to facilitate growth.

Direct Exposure of Welders to Welding Fumes and Effect of Fume Extraction Systems Under Controlled Conditions.

INTRODUCTION: Welding fume exposure of welders occurs either directly from the welding process and sputters or from the fume background within the workshop. In this study the contribution of fume originating directly from the welding process was assessed. METHODS: Exposure was quantified by measuring the time integral of fume mass concentration using a tapered element oscillating micro balance connected to a welder dummy. RESULTS: Direct fume exposure was highest for welding processes with low fume emission rates and lowest for processes with high fume emission rates. CONCLUSIONS: This finding is supposed to be due to the higher energy input of high emitting processes which stabilizes the thermic column and therefore eliminates fume particles from the welder's breathing zone. Exposure can be minimized by additionally optimizing workshop ventilation.

Discrepancy of particle passage in 101 mask batches during the first year of the Covid-19 pandemic in Germany.

During the first wave of Covid-19 infections in Germany in April 2020, clinics reported a shortage of filtering face masks with aerosol retention> 94% (FFP2 & 3, KN95, N95). Companies all over the world increased their production capacities, but quality control of once-certified materials and masks came up short. To help identify falsely labeled masks and ensure safe protection equipment, we tested 101 different batches of masks in 993 measurements with a self-made setup based on DIN standards. An aerosol generator provided a NaCl test aerosol which was applied to the mask. A laser aerosol spectrometer measured the aerosol concentration in a range from 90 to 500 nm to quantify the masks' retention. Of 101 tested mask batches, only 31 batches kept what their label promised. Especially in the initial phase of the pandemic in Germany, we observed fluctuating mask qualities. Many batches show very high variability in aerosol retention. In addition, by measuring with a laser aerosol spectrometer, we were able to show that not all masks filter small and large particles equally well. In this study we demonstrate how important internal and independent quality controls are, especially in times of need and shortage of personal protection equipment.

Biological effect markers in exhaled breath condensate and biomonitoring in welders: impact of smoking and protection equipment.

PURPOSE: The objective of this study was to investigate the effect of welding as well as the impact of smoking and protection measures on biological effect markers in exhaled breath condensate. Additionally, biomonitoring of chromium, aluminium and nickel in urine was performed to quantify internal exposure. METHODS: Exhaled breath condensate (EBC) and urine samples of 45 male welders and 24 male non-exposed control subjects were collected on Friday pre-shift and after 8 h of work post-shift. In EBC, biological effect markers such as malondialdehyde, nitrite, nitrate, 3-nitrotyrosine, tyrosine, hydroxyproline, proline, H(2)O(2) and pH-value were measured while aluminium, nickel, and chromium were measured in the urine samples. RESULTS: Although internal exposure to aluminium, nickel and chromium in this study was low, welders showed significantly increased concentrations of all these parameters at baseline compared to non-exposed controls. Moreover, welders had higher nitrate concentrations in EBC at baseline and after shift. Nitrate concentration was considerably lower after shift if personal protection equipment was used. H(2)O(2) was increased only when subjects smoked during shift. CONCLUSION: It has been shown that welding-associated long-term and short-term health effects could be detected in a population of welders. The results also showed that using personal protection equipment is of high importance and H(2)O(2) may be an effect marker associated with smoking rather than with welding fumes, while nitrate in EBC seems to be sensitive to welding fume exposure.

Inter-reader variability in chest radiography and HRCT for the early detection of asbestos-related lung and pleural abnormalities in a cohort of 636 asbestos-exposed subjects.

PURPOSE: To compare inter-reader variability of chest X-ray and high resolution computed tomography (HRCT) scans of formerly asbestos-exposed employees over a 4-year period. METHODS: In this longitudinal study, 636 formerly asbestos-exposed persons were annually examined with chest radiographs and HRCT scans. Ten observer pairs classified the radiographs and HRCT scans, using the ILO classification and a custom-made CT classification. Inter-observer variability was calculated using the kappa-coefficient. RESULTS: Despite all expectations, HRCT inter-reader variability according to asbestos-related lung or pleura alterations at an early stage did not turn out to be better than X-ray inter-reader variability. Substantial inter-observer agreement was found for pleural calcifications (kappa(X-ray) = 0.63; kappa(CT) = 0.64). Averaging over kappa led to fair inter-observer agreement of both methods (kappa(X-ray) = 0.36; kappa(CT) = 0.34). CONCLUSIONS: High resolution computed tomography scans are superior to X-rays in detecting lung alterations after asbestos exposure and are supposedly easier to interpret. Nevertheless, inter-observer variability did not differ between the two methods in this study. This was probably due to the only discrete asbestos-related lung or pleura alterations of this cohort and to the unfamiliar CT classification sheet, which was revised on the basis of the presented results.

No Observed Effect Level (NOEL) for Systemic Inflammation by Copper and Zinc in Welding Fumes.

: Copper and zinc containing welding fumes are able to induce systemic inflammation in healthy subjects. In this study the no observed effect levels (NOEL) for welding fumes containing either copper or zinc were assessed.Fifteen healthy male volunteers participated in an exposure. Each subject was exposed to two different concentrations of both, copper and zinc containing welding fumes. Exposure was performed in the Aachen Workplace Simulation Lab.The NOEL was found at metal concentrations between 0.2 and 0.3 mg/m for copper and between 0.8 and 1.2 mg/m for zinc.The NOEL identified in this study was about a factor of 10 higher than the German workplace threshold limit values (TLV). However, TLV in other countries was in the same range or even higher than the NOEL indicating a considerable risk for workers.

Increased Neutrophil Granulocyte and Myeloperoxidase Levels Indicate Acute Inflammation Due to the Exposure of Zinc- and Copper-Containing Welding Fumes.

OBJECTIVE: Recent studies have shown an increase of C-reactive-protein (CRP) after exposure to zinc- and copper-containing welding fumes. The objective of this study was to determine the effects of exposure to zinc- and copper-containing welding fumes on leukocytes, their subtypes, and myeloperoxidase (MPO). METHODS: Serum samples of male volunteers were examined after exposures to welding fumes in two settings: repeated exposure on 4 consecutive days for 6 hours and single exposures for different times (3, 4, 5 hours). RESULTS: Neutrophil granulocyte and MPO levels showed increases 24 hours after single and repeated exposures for 6 hours similar to CRP increases reported in literature. Overall leukocyte levels and levels of monocytes and lymphocytes were not significantly affected. CONCLUSIONS: This study indicates the involvement of neutrophil granulocytes in welding fume fever additional to mediator related effects.

The Effects of Repeated Exposure to Zinc- and Copper-Containing Welding Fumes on Healthy Volunteers.

OBJECTIVE: Recently, the proinflammatory effects of welding fumes containing zinc and copper have been demonstrated. In the present study, it was investigated if the inflammation persists under repeated exposure. METHODS: Fifteen healthy male subjects were exposed to 6 hours of exposure with zinc- and copper-containing welding fumes on 4 consecutive days under controlled conditions. RESULTS: Inflammatory marker serum levels showed significant increases compared with baseline either 6 or 24 hours after the first exposure and stayed elevated for all following exposures. In nasal secret samples only C-reactive protein levels were increased compared with baseline. CONCLUSIONS: The current study demonstrates a persistent increase of systemic inflammatory markers indicating an elevated risk for welders chronically exposed to zinc- and copper-containing welding fumes. Topical inflammation of the upper airways did not occur.

The Effects of Exposure Time on Systemic Inflammation in Subjects With Exposure to Zinc- and Copper-Containing Brazing Fumes.

INTRODUCTION: Inhalation of copper and zinc containing brazing fumes (2.5 mg/m for 6 hours) is able to induce asymptomatic systemic inflammation which is supposed to be connected with an increased risk for cardiovascular disease. In this study it was investigated if inflammation can be prevented by reducing the exposure time. METHODS: A total of 15 healthy male subjects were exposed to such brazing fumes in a crossover design for 3, 4, and 5 hours in randomized order. Before and 24 hours after exposure, blood samples were taken and c-reactive protein (CRP) as marker for an acute phase reaction was measured. RESULTS: Five-hour exposure induced an increase of CRP, whereas the shorter exposure times did not result in a significant inflammatory reaction. CONCLUSIONS: Reducing daily exposure times below 5 hours is able to prevent systemic inflammatory reactions.

The pro-inflammatory stimulus of zinc- and copper-containing welding fumes in whole blood assay via protein tyrosine phosphatase 1B inhibition.

An asymptomatic systemic inflammation after exposure to zinc- and copper-containing welding fumes has been described as mild form of metal fume fever in recent studies. Since chronic systemic inflammation leads to a higher cardiovascular risk, examining the inflammation with the underlying pathomechanism is necessary to estimate and hopefully prevent long-term effects of welding. We established a whole blood assay to investigate the effects of zinc- and copper-containing welding fume particles on the blood immune response. Increased levels of IL-6, IL-8, TNFα and IL-1ß determined after 24 hours of exposure indicated an acute systemic inflammatory reaction. In vitro increases of IL-6 were comparable to in vivo increases of serum IL-6 levels in a study with welding fume exposure of human subjects. Inhibition of PTP1B was identified as one pathway responsible for the effects of zinc- and copper-containing welding fumes and therefore welding fume fever. In conclusion, the whole blood assay is a reliable and feasible method to investigate effects of zinc- and copper-containing welding fumes on the immune system and as a surrogate for systemic inflammation and welding fume fever. Future research can utilize whole blood assays to reduce and partially replace human exposure studies for further investigations of welding fume fever.

The effects of zinc- and copper-containing welding fumes on murine, rat and human precision-cut lung slices.

Recently, the pro-inflammatory effects of metal inert gas brazing welding fumes containing zinc and copper have been demonstrated in humans. Here, murine, rat and human precision cut lung slices (PCLS) were incubated in welding fume containing media with 0.1, 1, 10 and 100 µg/ml for 24 or 48 h. 24 h incubation were determined either by incubation for the total time or for only 6 h followed by a 18 h post-incubation phase. Cytotoxicity, proliferation and DNA repair rates, and cytokine levels were determined. Welding fume particle concentrations of 0.1 and 1 µg/ml showed no toxic effects on PCLS of all three species, while for 10 and 100 µg/ml a concentration-dependent toxicity occurred. Proliferation and DNA repair rates were reduced for all tested concentrations and incubation times. Additionally, the cytokine levels in the supernatants were markedly reduced, while after 6 h of exposure with 18 h of post-incubation time a trend towards increased cytokine levels occurred. PCLS are a reliable and feasible method to assess and offer a prediction of toxic effects of welding fume particles on human lungs. Rat PCLS showed similar responses compared to human PCLS and are suitable for further evaluation of toxic effects exerted by welding fume particles.

Lung deposition of radiolabeled tiotropium in healthy subjects and patients with chronic obstructive pulmonary disease.

Lung deposition of 18 microg tiotropium administered via a dry-powder inhaler was investigated in 5 healthy subjects and patients with mild (n = 4), moderate (n = 6), and severe (n = 5) chronic obstructive pulmonary disease after 14 days of treatment with 18 microg tiotropium. On day 15, subjects inhaled 2 capsules of radiolabeled tiotropium, and lung deposition was assessed using gamma scintigraphy. Repeated plasma and urine collections were performed on days 14 and 15. Mean delivered dose from the dry-powder inhaler was 45.1%. Mean lung deposition relative to the delivered dose was 42% (19%, relative to nominal dose) with low intersubject variability (20%). Mean extrathoracic deposition was 57.5% (25.8%, relative to nominal dose). There were no significant differences in deposition among the subgroups. No significant correlation between individual tiotropium deposition and lung function was observed. These results suggest that all stages of chronic obstructive pulmonary disease may gain full therapeutic benefit from the drug.

Lung deposition of formoterol HFA (Atimos/Forair) in healthy volunteers, asthmatic and COPD patients.

In this study, the influence of lung function on lung deposition of a radioactively labeled Formotoerol HFA MDI (Forair) was investigated. Eighteen subjects were measured: 6 healthy subjects (FEV(1) = 107% pred), 6 patients with Asthma (FEV(1) = 72% pred), and 6 patients with COPD (FEV(1) = 40% pred). The lung deposition of the radioactive-labeled drug was measured with a gamma camera. The lung deposition relative to the emitted dose was 31% for healthy subjects, 34% for asthmatics, and 35% for COPD patients. These data suggest a comparable lung deposition in the different populations. There was no significant correlation between lung function (FEV(1)) and lung deposition. The extrathoracic deposition was around 50%. The finding were that lung deposition of the inhaled Formoterol did not depend on lung function and the relative high values of lung deposition can be explained by the small particle size (0.8 microm) of the HFA-Formoterol-Formulation and the slow inhalation (30 L/min flow) used in this study. It can be concluded, that with this modern HFA drug formulation, the deposition is high, even in obstructed lungs.