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Synchrotron radiation circular dichroism shows that gold and silver nanoparticles modify the secondary structure of lung surfactant protein-B analogue SP-B1–25.

Carbon nanotube (CNT) in vivo inhalation studies are increasingly providing estimates of the quantity of material deposited in the lung, generally estimated using standard formulae and pulmonary deposition models. These models have typically been developed and validated using data from studies using sphere-like particles. Given the importance of particle morphology to pulmonary deposition, the appropriateness of such an approach was explored to identify any potential limitations. Aerosolized CNT particles typically form ‘fiber-like’ and/or ‘broadly spherical’ agglomerates. A review of currently used deposition models indicates that none have been directly validated against results for CNT, however, models for spherical particles have been extensively validated against a wide range of particle sizes and materials and are thus expected to provide reasonable estimates for most ‘broadly spherical’ CNT particles, although experimental confirmation of this would be of benefit, especially given their low density. The validation of fiber deposition models is significantly less extensive and, in general, focused on larger particles, e.g. asbestos. This raises concerns about the accuracy of deposition estimates for ‘fiber-like’ CNT particles and recommendations are made for future research to address this. An appreciation of the uncertainties on CNT deposition estimates is important for their interpretation and thus it is recommended that model sensitivity and uncertainty assessments be undertaken. Issues surrounding the measurement and derivation of model input data are also addressed, including instrument responses and particle density assessment options. Recommendations are also made for aerosol characterization to ‘future-proof’ CNT inhalation studies regarding advances in deposition modeling and toxicological understanding.

To facilitate hazard characterisation for inhaled engineered nanomaterials we have established an aerosol exposure air-liquid-interface (AE-ALI) system, incorporating a Cultex RFSTM cell exposure system. While offering potential benefits in terms of more realistic aerosol exposure mode over traditional submerged in vitro models and being in-line with the principles of the 3Rs, (replace, reduce and refine animal use), detailed system characterisation is required to produce reliable and reproducible results. As such, this work looked to fully characterise our AE-ALI system with a view to optimising cell viability of system controls and deposition quantity, uniformity, and reproducibility for engineered nanomaterials. Using a nano-CeO2 aerosol, the effects of exposure conditions and system parameters (e.g. temperature, electrostatic precipitator voltage and airflow) on deposition efficiency, pattern and reproducibility were investigated using ICP-MS. While results showed that appropriate choice of operating parameters can produce broadly uniform deposition, reproducibility was low, and dose monitoring during exposures is recommended. After initial optimisation of the system for deposition, the effect of exposure duration, well size and flowrate on cellular responses (e.g. cytotoxicity (LDH) and selected gene expression (IL-8, CXCL1, HMOX1, SPP1) of system controls (H2O aerosol) was investigated using human lung alveolar (A549) and primary small airway epithelial cells. Results indicate that even after optimisation for cell health, the system itself is “toxic” to cells in comparison to incubator controls, with increasing effects observed with exposure duration meaning exposure durations must be minimised. Results from this study highlight the need for detailed characterisation of AE-ALI systems prior to use.

Cerium oxide nanoparticles (CeO2NPs) from some diesel fuel additives and other applications have been detected in ambient air. Concerns have been raised over their potential human health impact in situations of inadvertent exposure. Oxidative mechanisms have been suggested as a common feature for pulmonary injury in response to airborne particulate matter, including engineered nanomaterials. To understand in depth how CeO2NPs may influence oxidative stress induced pulmonary inflammation and fibrotic events, we used both in vivo and in vitro bleomycin-induced lung injury models. Male Sprague-Dawley rats were intratracheally instilled with bleomycin or saline (control) followed by nose-only inhalation exposure to nano-sized CeO2NP aerosols (mass concentration 1.8 mg/m3) or water (controls) for 3 hours per day for 4 days per week for one or two weeks. At 3 days post exposure, animals were sacrificed and bronchoalveolar lavage (BAL) fluid, lung histopathology and global mRNA expression analysed. Bleomycin exposure resulted in an increase in total BAL cells, fibrotic staining and significant induction of inflammatory and oxidative stress on mRNA sequencing analysis. Modifications of these responses by one-week exposure to CeO2NPs included attenuation of fibrotic staining and gene expression markers of lung function, inflammation and epithelial-mesenchymal transition (EMT). CeO2NP alone resulted in increased inflammatory responses but did not appear to cause fibrotic changes. Interpretation of these responses at a cellular level was further explored using 3D human small airway epithelium cultures (SmallAirTM) in an aerosol exposure air-liquid-interface system. This also indicated that some bleomycin-induced cellular responses could be attenuated by exposure to CeO2NP aerosols.

Ambient nitrogen dioxide (NO2) and particulate matter (PM) concentrations are often found to be proportional, such that inhalation of one pollutant is expected to be accompanied by the inhalation of the other. Epidemiological evidence consistently demonstrates the health burdens associated with the inhalation of NO2 and PM, though has difficulty deciphering the inhalation hazard of either pollutant individually. Airway models can be exposed to NO2 and PM separately or as a co-exposure in vitro, allowing mechanisms of toxicity to be elucidated. Herein, NCI-H441 cells were exposed to either 780 ng/cm2 Printex 90 carbon black (CB) (a surrogate model of PM) using a VitroCell Cloud12, 5 ppm NO2 (within a modified Coy hypoxic cabinet) or a combination of NO2+CB over 24 hours. Cytotoxicity was not altered by NO2 or CB (trypan blue exclusion assay), however CB, and to a lesser extent CB+NO2 exposure resulted in a non-significant increase in membrane permeability (p>0.05). qPCR revealed no alterations in expression of superoxide dismutase 1 (SOD1) for any exposure condition. Both CB and NO2 exposures resulted in significantly increased IL6 and IL8 release (ELISA) (p

Experimental modelling to identify specific inhalation hazards for nanomaterials has in the main focussed on in vivo approaches. However, these models suffer from uncertainties surrounding species specific differences and cellular targets for biological response. In terms of pulmonary exposure, approaches which combine ‘inhalation-like’ nanoparticulate aerosol deposition with relevant human cell and tissue air-liquid interface cultures are considered an important complement to in vivo work. In this study, we utilized such a model system to build on previous results from in vivo exposures, which highlighted the small airway epithelium as a target for silver nanoparticle (AgNP) deposition. RNA-SEQ was used to characterise alterations in mRNA and miRNA within the lung. Organotypic reconstituted 3D human primary small airway epithelial cell cultures (SmallAir) were exposed to the same spark generated AgNP and at the same dose used in vivo, in an aerosol-exposure air-liquid-interface (AE-ALI) system. Adverse effects were characterised using lactate, LDH release and alterations in mRNA and miRNA. Modest toxicological effects were paralleled by significant regulation in gene expression, reflective mainly of specific inflammatory events. Importantly, there was a level of concordance between gene expression changes observed in vitro and in vivo. We also observed a significant correlation between AgNP and mass equivalent silver ion (Ag(+)) induced transcriptional changes in SmallAir cultures. In addition to key mechanistic information relevant for our understanding of the potential health risks associated with AgNP inhalation exposure, this work further highlights the small airway epithelium as an important target for adverse effects.

Nanoparticles have been incorporated into a range of consumer spray products, providing the potential for inadvertent inhalation by users and bystanders. The levels and characteristics of nanoparticle inhalation exposures arising from the use of such products are important inputs to risk assessments and informing dose regimes for in vitro and in vivo studies investigating hazard potentials. To date, only a small number of studies have been undertaken to explore both the aerosols generated from such products and the metal nanoparticles within them. The objective of the current study was to add to the limited data in this field by investigating a range of nano-containing spray products available within the UK. Six products were selected and the nanoparticles characterised using a combination of techniques, including: inductively coupled plasma mass spectrometry (ICP-MS), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), transmission electron microscopy energy-dispersive X-ray spectroscopy (TEM-EDX) and single particle ICP-MS (spICP-MS). The aerosol produced by these products, when sprayed within a glovebox, was characterised by scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS). A cascade impactor with thirteen stages (NanoMOUDI) was used with one product to generate information on the size specific nanoparticle elemental distribution within the aerosol. The results demonstrated the presence of solid nanoparticles (silver, gold or silica) in each of the products at low concentrations (, Graphical abstract Image 1, Highlights • Nanomaterials (Ag, Au, silica) characterised in 6 consumer spray products. • Multi-method analytical approach allowed characterisation of particles and aerosols. • Large variations in aerosol mass and number concentrations across the products. • Non-uniform distribution of nanoparticles across aerosol particle size distribution.

Studies using Langmuir-Wilhelmy balance (LWB) systems have demonstrated that engineered nanoparticles (NPs) can disrupt the surface tension behaviour of model lung surfactants. However, the majority of such studies used approaches that do not accurately mimic in vivo deposition at the air-liquid interface of inhaled particles – using instead NP suspensions. The present study investigated for the first time the effect of the mode of delivery of NPs to the interface on the compression surface pressure (Π) – mean molecular area (Mma) isotherms of surfactant monolayers, using an LWB. A novel system to deposit a well characterised aerosol of cerium oxide nanoparticles (CeO2NPs) on a dipalmitoylphosphatidylcholine (DPPC) monolayer was developed. The effects of depositing CeO2NPs from an aerosol were compared with two alternative approaches used in the literature: CeO2NPs suspended in chloroform and deposited on a DPPC monolayer and mixtures of CeO2NPs and DPPC in chloroform deposited directly on the subphase. Experiments were undertaken using a physiologically relevant subphase and temperature, 37 °C, with additional experiments at 21 °C. In each case Langmuir-Blodgett films were imaged using scanning electron microscopy and the distribution of cerium mapped using time of flight – secondary ion mass spectrometry. The results clearly demonstrate that mode of delivery has a differential effect on surface tension behaviour and that caution should be exercised in the use of solvent deposition techniques because of effects on NP agglomeration state and the pattern of distribution of NP agglomerates, which may not accurately reflect the behaviour in vivo of inhaled particles. The study findings therefore suggest that aerosol deposition techniques are to be preferred, however, there are issues that need to be investigated further, including the effect of control air exposures, and also a need to explore the effects of cycling and the use of more complete lung surfactant models, before such a recommendation can be confirmed.

Background Concerns have been expressed that inhaled nanoparticles may behave differently to larger particles in terms of lung clearance and translocation, with potential implications for their toxicity. Studies undertaken to investigate this have typically involved limited post-exposure periods. There is a shortage of information on longer-term clearance and translocation patterns and their dependence on particle size, which this study aimed to address. Methods Rats were exposed (

The fifth in our seven-part series on patient narrative explores empathy. We focus on a patient story relevant to all fields of nursing and raise key issues about how health professionals convey empathy to patients.

This series has explored the value of patient narratives in enabling nurses to reflect on how their practice is perceived by, and affects, patients and their families. This article describes how two student learning disability nurses used patient and carer narratives to highlight the effect of a hospital trust's lack of toilet provision for people with physical impairments, using the stories to persuade the trust to develop appropriate facilities.

This series exploring how narratives can be used to reflect on practice has focused on patient narratives. This sixth article uses nurse narratives to explore professional boundaries between patients and nurses. These can be difficult to negotiate and can depend on individual circumstances: what may be appropriate in one situation may be unacceptable in another.

This article is the fourth of a seven-part series that explores how patient narratives help us reflect on patient care. In previous articles we have explored themes related to communication, consent and power. This article explores how we use language to explain treatment in care and how it can be interpreted differently by patients and staff.

Many factors can result in an imbalance of power between patients and nurses. This can have a range of negative effects on patients' experience of care. This third article in a seven-part series on the use of patient narratives to reflect on care focuses on power inequalities and their effects, and suggests points that nurses can use to reflect on their own practice.

This is the second article in a seven-part series demonstrating the value of analysing patient narratives in nursing and nurse education. Part 1 reviewed the evidence regarding the use of narrative and focused on unintended communication. This article draws on a story exploring consent and capacity, and demonstrates the lessons that can be learnt for all fields of nursing. We hope your reflections on the narratives will help to inform your professional practice and provide evidence for revalidation.

There is an increasing emphasis on, and commitment to, using patient narratives in nursing practice and nurse education. Listening to the voices of those receiving our care is just the beginning. The challenge is to use these narratives to improve practice and the patient experience. This seven-part series will present narratives from three fields of nursing: adult, mental health and learning disability. Each article will include opportunities to reflect on the stories presented and consider their implications for practice. Part 1 explores how patient narratives can be used as an evidence base for nursing practice. It uses a patient story to explore the unintended consequences of communication between a nurse and a patient, as well as how the environment in which patients find themselves can relay important messages.

Concerns about the potential health effects of exposure to nanomaterials have led to a growing number of in vivo inhalation toxicity studies using nanoparticle aerosols. Estimates of aerosol deposition within the respiratory tract are important for these studies to enable: (a) the interpretation of the results, in particular, the evaluation of dose–response relationships; (b) comparison with the results of other related studies; and (c) the extrapolation of results from animal models to human. Unfortunately, only a limited number of studies have been undertaken to investigate respiratory tract deposition efficiencies for nano-sized aerosol particles. This is of particular importance as deposition efficiencies are predicted to vary significantly over the nano-size range for some elements of the respiratory tract. In this study, female Wistar-Kyoto rats were exposed in a new design nose-only inhalation exposure system to spark generated radioactive iridium-192 nanoparticle aerosols of four particle sizes chosen to cover the majority of the nano-size range (nominal sizes: 10, 15, 35, and 75 nm). The content of iridium-192 in the lung, head, gastrointestinal tract, and various other organs and tissues was measured. Aerosol deposition efficiencies in the whole respiratory tract and components (head airways, lung, alveolar region, and tracheobronchial region) were estimated and compared with the predictions of the Multiple Path Particle Dosimetry (MPPD) model (v2.11). The experimentally derived deposition efficiencies were broadly consistent with, but typically higher than, model predictions and the results of comparable studies in the literature. Copyright © 2016 American Association for Aerosol Research