Bioaerosol Exposures and Respiratory Diseases in Cannabis Workers.

PURPOSE OF REVIEW: This review investigates occupational inhalation hazards associated with biologically derived airborne particles (bioaerosols) generated in indoor cannabis cultivation and manufacturing facilities. RECENT FINDINGS: Indoor cannabis production is growing across the US as are recent reports of respiratory diseases among cannabis workers, including occupational asthma morbidity and mortality. More information is needed to understand how bioaerosol exposure in cannabis facilities impacts worker health and occupational disease risk. Preliminary studies demonstrate a significant fraction of airborne particles in cannabis facilities are comprised of fungal spores, bacteria, and plant material, which may also contain hazardous microbial metabolites and allergens. These bioaerosols may pose pathogenic, allergenic, toxigenic, and pro-inflammatory risks to workers. The absence of multi-level, holistic bioaerosol research in cannabis work environments necessitates further characterization of the potential respiratory hazards and effective risk prevention methods to safeguard occupational health as the cannabis industry continues to expand across the US and beyond.

Multi-dimensional evaluation of cardiotoxicity in mice following respiratory exposure to polystyrene nanoplastics.

BACKGROUND: Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. RESULTS: Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. CONCLUSION: The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity.

Air pollution and body burden of persistent organic pollutants at an electronic waste recycling area of China.

This paper reviews the concentrations of persistent organic pollutants (POPs) in atmosphere of an electronic waste (e-waste) recycling town, Guiyu, in Southeast China, focusing on polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). We assess the evidence for the association between air pollution and human body burden, to provide an indication of the severity of respiratory exposure. Compared with standards and available existing data for other areas, it clearly shows that four typical POPs, derived from recycling processes, lead to serious atmospheric pollution and heavy body burden. From published data, the estimated respiratory exposure doses of Guiyu adults and children, varied between 2.48-10.37 and 3.25-13.6 ng kg-1 body weight (bw) day-1 for PBDEs, 2.31-7.6 and 4.09-13.58 pg World Health Organization-Toxic Equivalent Quantity (WHO-TEQ) kg-1 bw day-1 for PCDD/Fs, 5.57 and 20.52 ng kg-1 bw day-1 for PCBs, and 8.59-50.01 and 31.64-184.14 ng kg-1 bw day-1 for PAHs, respectively. These results show that air pollution is more harmful to children. Furthermore, except for PBDEs, the hazard quotient (HQ) of the other three pollutants was rated more than 1 by respiratory exposure only, and all of them are at risk of carcinogenesis. So we speculate these pollutants enter the body mainly through air inhalation, making respiratory exposure may be more important than dietary exposure in the Guiyu e-waste recycling area. Effective management policies and remediation techniques are urgently needed to prevent the deterioration of ambient air quality in the e-waste recycling area.

Respiratory assessment of refractory ceramic fibers in a heating technician population.

Refractory ceramic fibers (RCF) have been extensively used for insulation in condensing boilers. The aim of this study was to evaluate the respiratory exposure to these fibers among maintenance heating technicians. We first created a working group (Carsat Brittany and Finistère Occupational Health Services) and carried out a sampling strategy. Atmospheric measurements were done during work tasks, and filters were analyzed by phase contrast microscopy (PCM) and scanning electron microscopy (SEM) in French approved laboratories. Four companies were included for a total of 15 days of work. During those 15 workdays, 12 SEM and 21 PCM samples were taken and analyzed. The phase contrast microscopy and SEM average results were 0.04 and 0.004 fibers/cm3, respectively. In conclusion, the study confirms heating technician RCF respiratory exposure during maintenance work for both condensation gas boilers and atmospheric boilers. Collective and individual prevention measures should be implemented along with appropriate medical follow-up.

A method for evaluating aerosol leakage through the interface between protective suits and full-face respirators.

Military personnel and first responders use a range of personal equipment including protective suits, gloves, boots, and respirators to prevent exposure of their skin and airways to hazardous chemical, biological, radiological, and/or nuclear substances. Although each individual item of personal protective equipment is well tested against existing standards, it is also necessary to consider the performance of the interfaces between items in terms of prevention from exposure, and the protection system as a whole. This article presents an aerosol challenge method for assessing the performance of the interface between a respirator and the hood of a protective suit. The interface is formed between the sealing strip of the hood and the surface of the respirator's outer sealing area and is affected by how well the sealing strip can cover and adapt to the sealing area. The method evaluates the leakage of particles of different sizes into the hood via the interface by particle counting at sampling points around the respirator's perimeter. Three different respirators were tested together with a single hood having a tight-fitting seal. The method variation between measurements was low but increased appreciably when the protective ensemble was re-dressed between measurements. This demonstrates the difficulty of achieving a reliable and reproducible seal between respirator and hood under normal conditions. Different leakage patterns were observed for the three respirators and were linked to some specific design features, namely the respirator's sealing area at the chin and its width at cheek level. Induced leak experiments showed that to detect substantial particle leakage, channels at the hood-respirator interface must be quite large. The method outlined herein provides a straightforward way of evaluating hood-respirator interfaces and could be useful in the further development of personal protective equipment.

Assessment of exposure to pesticides during mixing/loading and spraying of tomatoes in the open field.

Some evidence of exposure-response of metolachlor and pendimethalin for lung cancer and an association of metribuzin with risk of glioma have been reported. The primary objectives in this study were to evaluate exposure and occupational risk during mixing/loading of pesticides and during their application to tomatoes cultivated in open fields. Sixteen farmers were sampled. Respiratory exposure was estimated by personal air sampling using fiberglass filters in a IOM device. Dermal exposure was assessed using skin pads and hand washing. Absorbed doses were estimated assuming 100% lung retention, and 50% or 10% skin absorption for metribuzin, and pendimethalin and metolachlor, respectively. The three pesticides were quantified by gas chromatography tandem mass spectrometry in all matrices. Metolachlor was used as a tracer of contamination of clothes and tractors unrelated to the exposure monitored. Respiratory exposure to metribuzin, used in granular form, was on average more than one order of magnitude higher than exposure to pendimethalin, used in the form of microencapsulated liquid. The actual doses were 0.067-8.08 µg/kg bw, 0.420-12.6 µg/kg bw, and 0.003-0.877 µg/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. Dermal exposure was about 88% of the actual dose for metribuzin and more than 95%, for pendimethalin and metolachlor. For risk assessment, the total absorbed doses (sum of respiratory and skin absorbed doses) were compared with the AOEL for each compound. The actual and absorbed doses of the three pesticides were always lower than the acceptable operator exposure level (AOEL), which are reported to be 234 µg/kg bw, 20 µg/kg bw, and 150 µg/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. In any case, personal protective equipment and spraying devices should be chosen with care to minimize exposure.

[Air Microbial Contamination and Risk of Respiratory Exposure of Workers in Chicken Farms].

Animal farms are important sources of microbial contamination in the air environment. However, there are few reports on the time-regularity characteristics of airborne microbial contamination in farms. In the context of this situation, a study was conducted for more than 80 weeks using 16S rRNA gene amplicon sequencing to characterize the bacterial distribution and respiratory exposure in the farm air and fecal environment, respectively, taking a layer farm as an example. The results showed that 16S rRNA concentrations in air and manure samples ranged from 6.08×105-4.90×106 copies·m-3 and 4.27×108-1.15×1010 copies·g-1, respectively. The mean values of airborne bacterial concentrations were significantly higher in winter than in summer, whereas the biodiversity showed the opposite trend. The dominant bacterial phylum in both air and manure in the layer farm was Firmicutes. During the investigated time, the top three dominant genera in the air were relatively stable, in the order of Lactobacillus, Bacteroides, and Faecalibacterium, whereas the dominant genera in feces fluctuated with the increase in breeding time. The correlation between the community structure of bacteria and pathogenic bacteria in both air and manure was not significant, but the concentrations of both target microorganisms in different media were significantly correlated. The bioaerosolization index of bacteria in manure showed an increasing trend with increasing breeding time, whereas the opposite trend was observed for pathogenic bacteria. In this case, [Ruminococcus]_torques_group, Bacteroides, and Faecalibacterium were the top three pathogenic genera that were the most prone to aerosolization. There were seasonal differences in bacterial respiratory exposures of chicken farm workers, with mean intake values of 2.54×107 copies·d-1 and 2.87×105 copies·d-1 for bacteria and pathogenic bacteria, respectively. The results of this study will provide a scientific basis for systematically assessing the contamination characteristics and potential health risks of airborne microorganisms on farms and for developing corresponding industry standards for occupational exposure and prevention and control measures.

Competitive-like binding between carbon black and CTNNB1 to ΔNp63 interpreting the abnormal respiratory epithelial repair after injury.

Airway epithelium is extraordinary vulnerable to damage owning to continuous environment exposure. Subsequent repair is therefore essential to restore the homeostasis of respiratory system. Disruptions in respiratory epithelial repair caused by nanoparticles exposure have been linked to various human diseases, yet implications in repair process remain incompletely elucidated. This study aims to elucidate the key stage in epithelial repair disturbed by carbon black (CB) nanoparticles, highlighting the pivotal role of ΔNp63 in mediating the epithelium repair. A competitive-like binding between CB and beta-catenin 1 (CTNNB1) to ΔNp63 is proposed to elaborate the underlying toxicity mechanism. Specifically, CB exhibits a remarkable inhibitory effect on cell proliferation, leading to aberrant airway epithelial repair, as validated in air-liquid culture. ΔNp63 drives efficient epithelial proliferation during CB exposure, and CTNNB1 was identified as a target of ΔNp63 by bioinformatics analysis. Further molecular dynamics simulation reveals that oxygen-containing functional groups on CB disrupt the native interaction of CTNNB1 with ΔNp63 through competitive-like binding pattern. This process modulates CTNNB1 expression, ultimately restraining proliferation during respiratory epithelial repair. Overall, the current study elucidates that the diminished interaction between CTNNB1 and ΔNp63 impedes respiratory epithelial repair in response to CB exposure, thereby enriching the public health risk assessment on CB-related respiratory diseases.

Face Mask: As a Source or Protector of Human Exposure to Microplastics and Phthalate Plasticizers?

Wearing masks has become the norm during the Coronavirus disease pandemic. Masks can reportedly interface with air pollutants and release microplastics and plastic additives such as phthalates. In this study, an experimental device was set up to simulate the impact of five kinds of masks (activated-carbon, N95, surgical, cotton, and fashion masks) on the risk of humans inhaling microplastics and phthalates during wearing. The residual concentrations of seven major phthalates ranged from 296 to 72,049 ng/g (median: 1242 ng/g), with the lowest and the highest concentrations detected in surgical (median: 367 ng/g) and fashion masks (median: 37,386 ng/g), respectively. During the whole inhalation simulation process, fragmented and 20-100 µm microplastics accounted for the largest, with a rapid release during the first six hours. After one day's wearing, that of 6 h, while wearing different masks, 25-135 and 65-298 microplastics were inhaled indoors and outdoors, respectively. The total estimated daily intake of phthalates with indoor and outdoor conditions by inhalation and skin exposure ranged from 1.2 to 13 and 0.43 to 14 ng/kg bw/d, respectively. Overall, surgical masks yield a protective effect, while cotton and fashion masks increase human exposure to microplastics and phthalates both indoors and outdoors compared to no mask wearing. This study observed possible risks from common facemasks and provided suggestions to consumers for selecting suitable masks to reduce exposure risks from microplastics and phthalate acid.

Particulate matter exposure in construction sites is associated with health effects in workers.

Background: Exposure to suspended particulate matters (PMs) at high concentrations, mainly observed in the construction workplace, is found to be a risk factor for major health outcomes. The present study was conducted to investigate the degree of exposure to suspended PMs in different stages of construction of the buildings and the health risk associated with the exposure in Lar, Fars, Iran. Methods: In this cross-sectional study, two construction sites were selected in Lar. Cancer and non-cancer health risks of exposure to PM2.5 and PM10 were assessed using the US Environmental Protection Agency method in three-dimensions: inhalation, digestion, and dermal absorption. The hazard quotient (HQ) and total cancer risk (TCR) were considered as parameters for risk analysis. Results: The highest level of non-cancer risk for workers in the concentrations of PM2.5 and PM10 particles in the drilling process were determined to be 2.97 × 10-1 and 8.52 × 10-2, respectively. In the cancer risk analysis, PM10 concentrations were estimated to be at the highest level (1.7 × 10-7) in the drilling process and the lowest level (4.29 × 10-8) in the facilities process. For suspended PM2.5, it was an unacceptable risk level in all processes, except for the implementation of facilities. Conclusion: These results show that the construction industry, especially in developing countries such as Iran, needs better management to maintain the health of construction workers.

Long-term cadmium exposure induces chronic obstructive pulmonary disease-like lung lesions in a mouse model.

Accumulating evidences demonstrate that long-term exposure to atmospheric fine particles and air pollutants elevates the risk of chronic obstructive pulmonary disease (COPD). Cadmium (Cd) is one of the important toxic substances in atmospheric fine particles and air pollutants. In this study, we aimed to establish a mouse model to evaluate whether respiratory Cd exposure induces COPD-like lung injury. Adult male C57BL/6 mice were exposed to CdCl2 (10 mg/L, 4 h per day) by inhaling aerosol for either 10 weeks (short-term) or 6 months (long-term). The mean serum Cd concentration was 6.26 µg/L in Cd-exposed mice. Lung weight and coefficient were elevated in long-term Cd-exposed mice. Pathological scores and alveolar destructive indices were increased in long-term Cd-exposed mouse lungs. Mean linear intercept and airway wall thickness were accordingly elevated in Cd-exposed mice. Inflammatory cell infiltration was obvious and inflammatory cytokines, including TNF-α, IL-1ß, IL-6, IL-8, IL-10 and TGF-ß, were up-regulated in Cd-exposed mouse lungs. α-SMA, N-cadherin and vimentin, epithelial-mesenchymal transition markers, and extracellular matrix collagen deposition around small airway, determined by Masson's trichrome staining, were shown in Cd-exposed mouse lungs. COPD-characteristic lung function decline was observed in long-term Cd-exposed mice. These outcomes show that long-term respiratory exposure to Cd induces COPD-like lung lesions for the first time.

Emissions and Exposures Associated with the Use of an Inconel Powder during Directed Energy Deposition Additive Manufacturing.

Additive manufacturing (AM) has been linked to potential exposure-related health risks, however, there is a paucity of sufficient research. This study aimed to supply information regarding emissions and exposure during directed energy deposition (DED) AM using inconel 718, with the main constituents being nickel, chromium, and cobalt. By using standardized occupational hygiene methods, the measurement strategy consisted of a combined approach, including powder characterization, particle emission monitoring, and personal exposure monitoring of AM operators. Powder characterization of virgin and used powder indicated no significant difference in particle size, shape, or elemental composition. Particle number emissions ranged between 102 and 105 p/cm3 for submicron particles (<1 µm in size). There was no significant difference in the particle emission rate between the three phases of AM or the two types of DED machines (p > 0.05). The particle emission rate for submicron particles peaked at 2.8 × 109 p/min. Metals of concern to human health were detected during the AM process but were considerably lower than the relevant exposure limits. This study confirms particle emissions, predominantly in the submicron range, above the background concentration during DED AM and, although insignificant in terms of potential health effects, AM operators are exposed to detectable concentrations of the metal constituents of inconel.

[Distribution, Respiratory Exposure, and Traceability of Atmospheric Microplastics in Yichang City].

As an emerging environmental pollutant, microplastics have attracted much attention, but the sources and health hazards of atmospheric microplastics (AMPs) remain unclear. In order to explore the distribution characteristics, assess the risk of human respiratory exposure, and analyze the sources of AMPs in different functional areas of Yichang City, AMPs samples from 16 observation points were collected and analyzed, and the HYSPLIT model was used. The results showed that the main shapes of AMPs in Yichang City were fiber, fragment, and film, and six colors were observed including transparent, red, black, green, yellow, and purple. The smallest size was 10.42 µm, and the largest was 4761.42 µm. The deposition flux of AMPs was (4400±474) n·(m2·d)-1. The types of APMs were polyester fiber (PET), acrylonitrile-butadiene-styrene copolymer (ABS), polyamide (PA), rubber (Rubber), polyethylene (PE), cellulose acetate (CA), and polyacrylonitrile (PAN). The order of the subsidence flux in each functional area was as follows:urban residential area>agricultural production area>landfill>chemical industrial park>town residential area. The human respiratory exposure risk assessment models showed that the daily intake of AMPs (EDI) for adults and children in urban residential areas was higher than in town residential areas. The atmospheric backward trajectory simulation showed that the AMPs in the districts and counties of Yichang City mainly came from the surrounding areas via short-distance transportation. This study provided basic data support for the research on AMPs in the middle reaches of the Yangtze River and was of great significance for the traceability and health risk research of AMPs pollution.

A comparison of passive and active dust sampling methods for measuring airborne methicillin-resistant Staphylococcus aureus in pig farms.

Methicillin-resistant strains of Staphylococcus aureus (MRSA) are resistant to most ß-lactam antibiotics. Pigs are an important reservoir of livestock-associated MRSA (LA-MRSA), which is genetically distinct from both hospital and community-acquired MRSA. Occupational exposure to pigs on farms can lead to LA-MRSA carriage by workers. There is a growing body of research on MRSA found in the farm environment, the airborne route of transmission, and its implication on human health. This study aims to directly compare two sampling methods used to measure airborne MRSA in the farm environment; passive dust sampling with electrostatic dust fall collectors (EDCs), and active inhalable dust sampling using stationary air pumps with Gesamtstaubprobenahme (GSP) sampling heads containing Teflon filters. Paired dust samples using EDCs and GSP samplers, totaling 87 samples, were taken from 7 Dutch pig farms, in multiple compartments housing pigs of varying ages. Total nucleic acids of both types of dust samples were extracted and targets indicating MRSA (femA, nuc, mecA) and total bacterial count (16S rRNA) were quantified using quantitative real-time PCRs. MRSA could be measured from all GSP samples and in 94% of the EDCs, additionally MRSA was present on every farm sampled. There was a strong positive relationship between the paired MRSA levels found in EDCs and those measured on filters (Normalized by 16S rRNA; Pearson's correlation coefficient r = 0.94, Not Normalized; Pearson's correlation coefficient r = 0.84). This study suggests that EDCs can be used as an affordable and easily standardized method for quantifying airborne MRSA levels in the pig farm setting.

Evaluating the relationship between the respiratory exposure to the benzene with the primary damages of deoxyribonucleic acid and total antioxidant capacity in one of the oil companies in Iran.

Benzene is a carcinogenic chemical substance which causes the injuries and damages through producing the free radicals in DNA (deoxyribonucleic acid) and the antioxidants are the agents which reduce the impacts of DNA damages by inhibiting the free radicals. This study was conducted aiming at determination of primary damages of DNA and level of plasma oxidative stress markers resulting from the respiratory exposure to the benzene found in petroleum compounds among the workers at loading platforms of a petroleum products distribution center. This study was an analytical (case control) research conducted among the workers in a working shift serving at the loading platforms of petroleum products. The exposure group included the workers with a history of contact with benzene and the control group was composed of the persons with no history of exposure to benzene. To investigate the level of the personnel's exposure to benzene, NIOSH-1501 method was utilized; to analyze the samples taken from the air, GC mass (gas chromatography-mass spectrometry) was applied; and to determine the average of DNA primary damages, comet assay was used. Total antioxidant capacity was determined by a photometric method. Results indicated that tail length (TL), tail density (TD), tail momentum (TM), percentage of tail in the DNA (%DNA), and %TAC in control group were 78.59, 8.35, 1.20, 10.05, and 25.58 and in the exposure group were 59.21, 75.74, 57.74, 3.5, and 16.58, respectively. The previously mentioned results showed a decrease in the TL, %DNA, and %TAC values among the workers already exposed to benzene while an increase in the TD and TM values of the same group compared to the control non-exposed group. In comparing the averages between two studied groups, all study variables had statistically meaningful difference (p < 0.05). More studies are recommended to be conducted on using the methods which identify the special places of breakage and damage in DNA chain due to the exposure to benzene and consequently prevent the complications and consequences.

Hematotoxic Effect of Respiratory Exposure to PHMG-p and Its Integrated Genetic Analysis.

Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in a rat model. Notable abnormalities were found out in the peripheral blood cell count and bone marrow (BM) biopsy, while RNA sequencing of BM tissue revealed markedly altered gene expression. Furthermore, signaling involved in hematopoietic dysfunction was predicted by analyzing candidate genes through Ingenuity Pathway Analysis (IPA) program. Respiratory PHMG-p exposure significantly decreased monocyte and platelet (PLT) counts and total protein, while significantly increasing hemoglobin and hematocrit levels in peripheral blood. Histopathological analysis of the BM revealed a reduced number of megakaryocytes, with no significant differences in spleen and liver weight to body weight. Moreover, PHMG-p exposure significantly activated estrogen receptor signaling and RHOA signaling, and inhibited RHOGDI signaling. In IPA analysis, candidate genes were found to be strongly related to 'hematological system development and function' and 'hematological disease.' Accordingly, our results suggest that PHMG-p could affect hematopoiesis, which participates in monocyte differentiation and PLT production, and may induce hematologic diseases via the respiratory tract.

Size distributions of source-specific risks of atmospheric heavy metals: An advanced method to quantify source contributions to size-segregated respiratory exposure.

Heavy metals in size-segregated particulate matter (PM) were investigated in a Chinese megacity, and an advanced model was developed to quantify source-specific risks focusing on size-segregated respiratory exposure. Incremental lifetime cancer risk (ILCR) and non-cancer risk (hazard quotient: HQ) based on deposition concentrations of heavy metals displayed a peak at 4.7-5.8 µm. The percentage contributions to cancer risk were as follows: industrial emission (IE, 34%) > secondary and transport (ST, 29%) > resuspended dust (RD, 21%) > coal combustion (CC, 11%) > traffic emission (TE, 4%) during spring and summer (SS), and CC (31%) > ST (26%) > IE (21%) > RD (11%) ≈ TE (11%) during autumn and winter (AW). RD (41% of HQ during SS, 28% during AW) and IE (45% of HQ during SS, 35% during AW) dominated non-cancer risk. ILCR and HQ of CC were high at sizes 1.1-2.1 µm and 0.43-0.65 µm; those of RD were high at sizes > 3.3 µm; and those of IE were bimodal at fine (<2.1 µm) and coarse (>2.1 µm) sizes, respectively. Cancer risk was more susceptible to small particles than non-cancer risk, partly because higher ILCR was from CC, but higher HQ was attributed by RD.

Screening for Effects of Inhaled Nanoparticles in Cell Culture Models for Prolonged Exposure.

Respiratory exposure of humans to environmental and therapeutic nanoparticles repeatedly occurs at relatively low concentrations. To identify adverse effects of particle accumulation under realistic conditions, monocultures of Calu-3 and A549 cells and co-cultures of A549 and THP-1 macrophages in the air-liquid interphase culture were exposed repeatedly to 2 µg/cm2 20 nm and 200 nm polystyrene particles with different functionalization. Particle accumulation, transepithelial electrical resistance, dextran (3-70 kDa) uptake and proinflammatory cytokine secretion were determined over 28 days. Calu-3 cells showed constant particle uptake without any change in barrier function and cytokine release. A549 cells preferentially ingested amino- and not-functionalized particles combined with decreased endocytosis. Cytokine release was transiently increased upon exposure to all particles. Carboxyl-functionalized demonstrated higher uptake and higher cytokine release than the other particles in the A549/THP-1 co-cultures. The evaluated respiratory cells and co-cultures ingested different amounts and types of particles and caused small (partly transient) effects. The data suggest that the healthy cells can adapt to low doses of non-cytotoxic particles.

Occupational Exposure and Carriage of Antimicrobial Resistance Genes (tetW, ermB) in Pig Slaughterhouse Workers.

OBJECTIVES: Slaughterhouse staff is occupationally exposed to antimicrobial resistant bacteria. Studies reported high antimicrobial resistance gene (ARG) abundances in slaughter pigs. This cross-sectional study investigated occupational exposure to tetracycline (tetW) and macrolide (ermB) resistance genes and assessed determinants for faecal tetW and ermB carriage among pig slaughterhouse workers. METHODS: During 2015-2016, 483 faecal samples and personal questionnaires were collected from workers in a Dutch pig abattoir, together with 60 pig faecal samples. Human dermal and respiratory exposure was assessed by examining 198 carcass, 326 gloves, and 33 air samples along the line, next to 198 packed pork chops to indicate potential consumer exposure. Samples were analyzed by qPCR (tetW, ermB). A job exposure matrix was created by calculating the percentage of tetW and ermB positive carcasses or gloves for each job position. Multiple linear regression models were used to link exposure to tetW and ermB carriage. RESULTS: Workers are exposed to tetracycline and macrolide resistance genes along the slaughter line. Tetw and ermB gradients were found for carcasses, gloves, and air filters. One packed pork chop contained tetW, ermB was non-detectable. Human faecal tetW and ermB concentrations were lower than in pig faeces. Associations were found between occupational tetW exposure and human faecal tetW carriage, yet, not after model adjustments. Sampling round, nationality, and smoking were determinants for ARG carriage. CONCLUSION: We demonstrated clear environmental tetracycline and macrolide resistance gene exposure gradients along the slaughter line. No robust link was found between ARG exposure and human faecal ARG carriage.

Proteomic analysis reveals procoagulant properties of cigarette smoke-induced extracellular vesicles.

Airway epithelial cells secrete extracellular vesicles (EVs) under basal conditions and when exposed to cigarette smoke extract (CSE). Getting insights into the composition of these EVs will help unravel their functions in homeostasis and smoking-induced pathology. Here, we characterized the proteomic composition of basal and CSE-induced airway epithelial EVs. BEAS-2B cells were left unexposed or exposed to 1% CSE for 24 h, followed by EV isolation using ultrafiltration and size exclusion chromatography. Isolated EVs were labelled with tandem mass tags and their proteomic composition was determined using nano-LC-MS/MS. Tissue factor (TF) activity was determined by a factor Xa generation assay, phosphatidylserine (PS) content by prothrombinase assay and thrombin generation using calibrated automated thrombogram (CAT). Nano-LC-MS/MS identified 585 EV-associated proteins with high confidence. Of these, 201 were differentially expressed in the CSE-EVs according to the moderated t-test, followed by false discovery rate (FDR) adjustment with the FDR threshold set to 0.1. Functional enrichment analysis revealed that 24 proteins of the pathway haemostasis were significantly up-regulated in CSE-EVs, including TF. Increased TF expression on CSE-EVs was confirmed by bead-based flow cytometry and was associated with increased TF activity. CSE-EVs caused faster and more thrombin generation in normal human plasma than control-EVs, which was partly TF-, but also PS-dependent. In conclusion, proteomic analysis allowed us to predict procoagulant properties of CSE-EVs which were confirmed in vitro. Cigarette smoke-induced EVs may contribute to the increased cardiovascular and respiratory risk observed in smokers.