bluuebunny/crossref_metadata_2025 huggingface dataset:
97 Transferability and Reproducibility of Exposed Air-Liquid Interface co-Culture Lung Models
Authors: Braakhuis Hedwig , Gremmer Eric , Bannuscher Anne , Drasler Barbara , Keshavan Sandeep , Rothen-Rutishauser Barbara , Birk Barbara , Verlohner Andreas , Landsiedel Robert , Meldrum Kirsty , Doak Shareen , Clift Martin , Erdem Johanna Samulin , Foss Oda , Zienolddiny Shan , Serchi Tommaso , Moschini Elisa , Weber Pamina , Burla Sabina , Kumar Pramod , Schmid Otmar , Zwart Edwin , Vermeulen Jolanda , Cassee Flemming , Vandebriel Rob
Published: May 2023

The establishment of reliable and robust in vitro models for hazard assessment, moving away from animal testing, requires evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as monoculture and, to increase the relevance of the model, also as co-culture with macrophages (derived from the THP-1 monocyte cell line or from human blood monocytes). Exposure employed the VITROCELL® Cloud12 system at physiologically relevant doses. Overall, the results of the seven participating laboratories are quite similar. No effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO2) NM-105 exposure on cell viability and barrier integrity were seen in the monoculture and co-culture models. Most laboratories showed that LPS induced cytokine release in the co-culture models, but not the monoculture model. Exposure to DQ12 or TiO2 did not increase cytokine release, probably due to too low deposited doses. Interlaboratory variability indicated acceptable variation for cell viability measurements and relatively high variation for cytokine measurements. Based on the transferability and reproducibility of the model and its air exposure we are confident that, based on detailed SOPs, performing a new round of interlaboratory comparison, and increasing the deposited doses of NMs, these models may be taken further towards a possible OECD guideline.
106 Establishing a Physiologically Relevant in Vitro Airway Model to Assess the Impacts of Environmental Exposures, Like Smoking, on Covid-19 Susceptibility.
Authors: Bowsher Rachel , Goode Emma-Jane , Marczylo Tim , Wright Matthew , Bailey Alexis , Gooch Karen , Marczylo Emma
Published: May 2023

Air-liquid interface (ALI) cultures are commonly used for 3D modelling of the human airways and to examine the effects of direct exposure to airborne toxicants. We explored the suitability of human epithelial cell lines (RPMI 2560, HBEC-3KT, CALU-3 and A549) and primary cells (nasal, bronchiolar and small airways) grown at ALI as a physiologically relevant model to examine whether environmental exposures can increase the susceptibility of the human airways to SARS-COV-2 infection. Cultures were kept at ALI for up to 28 days to allow differentiation. Trans-epithelial electrical resistance (TEER) was measured weekly. Cells were harvested at 0, 7, 14, 21 and 28 days, and transcriptional markers of basal, ciliated and mucus-producing cells together with SARS-COV-2 viral entry genes (ACE2, TMPRSS2 and Furin) and other genes of interest, were assessed by reverse-transcription quantitative PCR. Each cell line yielded differentiated models, with upregulation of markers of ciliated and mucus producing cells from day 7. In contrast to primary cells, immortalised cell lines did not produce cilia but, mucus was produced.  TEER values increased with time, as expected, but values and therefore formation of tight junctions differed between models. Similarly, expression of viral entry genes increased as cells differentiated with marked differences across the different models. This study will be used to select the most appropriate ALI model for investigating the effect of environmental exposures such as smoking and vaping on susceptibility to SARS-COV-2 infection.
121 Cross Government, Industry and Academia Knowledge Sharing Workshops on Opportunities for Advanced Materials (AM) in the UK
Authors: Nasser Fatima , Bard Delphine , Castro Fernando A , Clifford Charles , Evans Gareth , Gee Mark , Heale Frances , Koltsov Denis , Price Alex , Smith Rachel
Published: May 2023

Key decision-making organisations such as the Organization for Economic Cooperation and Development (OECD), the International Organization for Standardization (ISO) and the European Commission (EC) have started to focus on the industrial and economic implications of advanced materials (AMs).  Internationally, there is a strong push for a sustainable and circular economy in which 'safety by design', recyclability and re-use will be high on the agenda.  It is important material scientists, industry, and regulators consider how to work together to support the safe use of AMs. In 2021, DEFRA, HSE Science Division, NPL, UK HSA and BSI held an online workshop with industry experts, materials scientists and regulators to create a UK knowledge sharing community on the safe exploitation of AMs.  This first workshop assessed the level of interest in creating an UK AM knowledge sharing community focussing on the application of safe by design for safer adoption of AMs. The participants concluded that any definition of AM related to a novel material property may be necessary but would make it difficult to use from a practical regulatory perspective. A second event is planned for early 2023 to share views on the benefits and pitfalls of the safe commercialisation of AMs; including the societal benefits that may arise and the potential obstacles to the wider adoption of these new materials.  These events are being attended by organisations developing AMs, those manufacturing and using AMs, and also health and safety experts and regulators. The poster will summarise the outcomes of the two workshops.
124 Risk Assessment and Management of Exposure in a Nanotechnology Industrial Plant: Tools and Exposure Monitorization Following a Tiered Approach
Authors: Laranjeira João , Delgado Erina , Carvalho Fernanda , Matos Cristina , Alberto Rita , Martins Carla , Bianchin Alvise , Pamphilis Marco , Forlin Enrico
Published: May 2023

Nanotechnology as an emerging field has been revolutionizing the materials sector in a broad range of industrial and commercial applications, due to the nanoscale enhanced material properties. In industrial facilities, workers exposure to airborne nanomaterials can occur mainly through inhalation. However once airborne nanomaterials are released, their deposition in surfaces enhances the risk of dermal and eye exposure and to lesser extent even ingestion. On the other hand, if adequate filters, maintenance, and waste programs are not used, the release and emission of industrial indoor airborne nanomaterials can promote contamination of the environmental compartments, and consequently represent an exposure risk for the general population. It is well known that inhaled nanomaterials can cause a variety of pulmonary illnesses.  Several challenges arise when assessing and managing the Health and Safety risks of nanoproducts, due to the limited hazards understanding and knowledge, as well as their exposure potential to humans and the environment, which results in the lack of exposure limit values. As the uncertainties and complexity associated with nanoproducts encompass a broad range of parameters that significantly account for the risk, the implementation of a tiered approach was carried out to screen the potential risks of the workers exposure when handling nanopowders in order to design well supported control measures. This pragmatic and structured strategy was based in the application of sequential nanospecific tools having a life cycle perspective for the nanoproduct under development. An exposure monitorization campaign made in the facility was accomplished using two measurement equipment.
10 Validation of an Aerosol Exposure-Air Liquid Interface (AE-ALI) System to Facilitate Realistic Hazard Identification of Nano-Sized Aerosols
Authors: Buckley Alison , Guo Chang , Laycock Adam , Leonard Martin , Smith Rachel
Published: May 2023

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.
33 The Ultrhas Project: Ultrafine Particles from Transportation – Health Assessment of Sources
Authors: Øvrevik Johan , Rothen-Rutishauser Barbara , Jalava Pasi , Sipopula Olli I , Hänninen Otto , Bucchianico Sebastiano Di , Adam Thomas , Hupfer Andreas , Etzien Uwe , Zimmermann Ralf
Published: May 2023

Current regulations of particulate matter (PM) based on ambient mass concentrations does not encompass source dependent variation in toxicity or the impact of high numbers of ultrafine PM (UFPs) which contribute little to total PM mass. UFPs may pose risks due to their small size and high number/surface area concentrations and propensity to penetrate tissue barriers and reach the circulation and secondary target organs. ULTRHAS (2021-2025) is a project funded under the EU’s Research and Innovation program Horizon 2020 (Grant Agreement No. 955390). The project will specifically address (i) the impact of different transport modes, fuel technologies and wear components, including atmospheric ageing processes, on the physicochemical characteristics of particulate and gaseous emissions; and how these processes and characteristics affects (ii) the biological responses leading to harmful effects in the lung and beyond by applying state-of-the-art emission measurement, exposure and toxicity-testing approaches under highly controlled laboratory conditions. ULTRHAS will (iii) rank the health hazards of different transport mode emissions and (iv) apply an advanced health impact assessment framework incorporating burden of disease methods to quantify baseline and policy scenario impacts for development and prioritization of mitigation measures; and (v) evaluate the future impact and acceptance of new policies on public health, taking into account social aspects. ULTRHAS aims to provide enhanced understanding of health threats posed by nanoparticles from different transport modes; optimize a framework for toxicity and hazard assessment of aerosols; provide guidance for prioritization of mitigation measures for future legislation on air pollutants.
39 Investigation of Workplace Silica Exposures Using Novel Samplers and Methods
Authors: Hall Samantha , Hunwin Graeme , Bard Delphine , Leese Liz , Morton Jackie
Published: May 2023

Scientists from the Health and Safety Executive visited a range of workplaces where there was the potential for exposure to silica. The aim of the visits was to determine potential worker exposures to dust and respirable crystalline silica by static air monitoring and exhaled breath condensate (EBC). To evaluate potential airborne exposures low-cost particle monitors were deployed alongside more established scientific equipment.  On site airborne dust concentrations were measured at different locations using two photometers, an optical particle counter (OPC) and a respirable cyclone. The size distribution was measured in real-time using a low-cost OPC and by offline analysis of a polycarbonate membrane filter housed inside an inhalable sampler using a Coulter Counter III. Pre and post shift samples of EBC were taken from 29 workers, with samples analysed by single particle inductively coupled plasma tandem mass spectrometry to measure Si-containing particles.  The real-time air monitoring data showed sustained increased concentrations or peaks corresponding to specific areas or activities, therefore indicating the tasks and/or locations most likely to contribute to worker exposure. The low-cost instruments were also effective in highlighting site locations and tasks most likely to contribute to worker exposure. An approach combining multiple sampling techniques provided a good characterisation of airborne, silica containing dusts. The EBC results consistently showed increased numbers of silicon containing particles post-shift compared with pre-shift.
42 Elucidating an Association Between Air Pollution and Mental Health
Authors: Christoforou Ella , Mizen Amy , Lyons Jane , Fry Rich , John Ann , Clift Martin
Published: May 2023

Air pollution (AP) is a significant environmental risk to human health. Historically, the impact of AP exposure has focused upon the physical health effects, yet the implications of AP on mental health have received limited attention. Despite this, recent research has highlighted emerging evidence supporting a possible aetiological link. The purpose of this study, therefore, was to investigate the potential consequences of AP upon mental health and well-being. In a PRISMA based systematic review multiple databases were searched from January 2012 to 2022 for peer-reviewed, English-language, human based primary research. Of the 2,224 studies identified in the literature search, 94 met the inclusion criteria. The mental health and wellbeing issues explored were psychosis, anxiety, suicide, mania, overall diagnosed conditions, and self-reported wellbeing symptoms. Depression was omitted due to the volume of attention the condition has received in the literature. Key air pollutants, particulate matter (PM10 and PM2.5), sulphur oxides (SOx), carbon monoxide (CO) and nitrogen oxides (NOx) were investigated. Data revealed a positive association between psychotic disorders and NOx exposure in ten studies with only one contradictory finding. Whereas the other conditions received multiple contradictory findings. To compare these results to real-life situations, currently a pilot study is exploring associations between psychotic disorder diagnoses and AP, specifically NOx, in Wales using the Secure Anonymised Information Linkage (SAIL) database. There is a large body of evidence showing associations between mental health and AP. However, due to research complexities and some contradictory findings more high-quality research is required to elucidate these relationships.
49 Exposure Assessment and Health Surveys at Metal Additive Manufacturing Facilities
Authors: Assenhöj Maria , Almstrand Ann-Charlotte , Ljunggren Stefan A , Ohlin Anna-Carin , Karlsson Helen
Published: May 2023

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.
51 Retained Particle Surface area Drives Inflammation in Rat Lungs Following Acute, Subacute, and Subchronic Inhalation of Nanomaterials
Authors: Cosnier Frédéric , Seidel Carole , Valentino Sarah , Schmid Otmar , Bau Sébastien , Vogel Ulla , Devoy Jérôme , Gaté Laurent
Published: May 2023

The difficulty of nanomaterial (NM) grouping can be simplified if the most toxicologically relevant dose metric is used to assess the toxicological dose-response. Retained surface area could be useful for this purpose. Here, we thoroughly investigated the relationship between acute and chronic inflammation (based on polymorphonuclear neutrophil influx (% PMN) in lung bronchoalveolar lavage) and the retained surface area in the lung. 4-week inhalation studies were performed in rats with three benchmark materials: the TiO2 P25 and the carbon black Printex-90 as poorly soluble particles of low toxicity (PSLT), and the multiwall carbon nanotube (MWCNT) MWNT-7. We compared our results to published data from nearly 30 rigorously selected articles relating to acute (1-week) to subchronic (13-week) inhalation exposure to the classes of NMs considered. Short and long post-exposure recovery times (immediately after exposure up to more than 6 months) allowed us to examine both acute and chronic inflammation. A dose-response relationship across short-term and long-term studies was revealed linking pulmonary retained surface area dose (measured or estimated) and % PMN. This relationship, taking the form of sigmoid curves, is dependent on the class of NM considered and sometimes on the duration of exposure but is independent of the post-exposure time. Based on retained surface area, long and thick MWCNTs (few hundred nm long with an aspect ratio greater than 25) had a higher inflammatory potency with 4 cm²/g lung sufficient to trigger an inflammatory response (at 6% PMN), whereas retained surfaces greater than 150 cm²/g lung were required for PSLT.
52 Use of Exposure Data to Evaluate the Impact of the Boelv on Industry Practices; case Study ASW/RCF.
Authors: Webster Dawn , Robinson Nicola
Published: May 2023

This study assesses the impact of the 0.3f/ml BOELV for aluminosilicate wools/refractory ceramic fibres (ASW/RCF), as implemented in 2020, on exposure levels at industrial sites. Now in its 26th year, CARE/PSP is the European programme collecting representative data for occupational exposure to airborne fibrous dust. With the changing regulatory landscape, CARE participants conducted a review of the data, focusing on evidence of reduced exposure or changed industrial practices since 2017 when the BOELV was first introduced. The data was split pre- and post- 2017 and also compared to alkaline earth silicate wool (AES/LBP) which is not classified and thus not covered by the BOELV, to consider the impact on exposure. An independent third-party statistician extracted the relevant data for this study. There are significant differences in workplace exposure among functional job categories (FJCs), since the introduction of the BOELV there has been a reduction in exposure, greater use of alternative AES/LBP and move to increased use of respiratory protective equipment (RPE) across all FJCs where ASW/RCF is being used. The data review for the period 2017-2021 has demonstrated an overall reduction in fibre exposure at both manufacturers and users’ facilities. The introduction of the BOELV for ASW/RCF has led to a greater awareness of the need to control fibrous dust. An increased uptake in the use of RPE and the use of RPE with higher protection factor is observed. There also appeared to be a move to alternative non-classified HTIW where appropriate.
54 Impact of Carbon Nanoparticle–Triggered Gammaherpesvirus Reactivation on Lung Immunity and Diseases
Authors: Guenther Eva M , Haefner Verena , Han Lianyong , Voss Carola , Yildirim Ali Oender , Adler Heiko , Stoeger Tobias
Published: May 2023

Inhalation of environmental particles and herpesvirus infection are ubiquitous in our society. Herpesviruses persist lifelong in the host in a latent state, which can be exited by stress-induced reactivation with production of lytic virus. Our previous investigations show that pulmonary exposure to carbon nanoparticles (CNP) triggers reactivation of latent murine gammaherpesvirus 68 (MHV-68) in mouse lungs, mainly localizing to CD11b+ infiltrating macrophages and dependent on p38 MAPK signaling. Furthermore, we observed that a two-time repeated CNP administration to latently infected mice resulted in alveolar damage leading to progressive emphysema. However, the underlying adverse mechanisms causing alveolar damage and the corresponding cell communication upon CNP exposure in latently infected lungs is still unclear. To investigate this, we developed a 3D lung organoid culture from primary murine epithelial cells in combination with persistently MHV-68 infected macrophages. This model enables us to detect reactivation and cytokine release upon CNP exposure, and to gain insights into the cellular communication of epithelial cells and macrophages, to understand the mechanisms underlying reactivation-triggered damage. In parallel, adverse effects of this second hit scenario on the alveolar epithelium and subsequent disease development get investigated in vivo. Latently infected mice are exposed to CNP up to 5 times, and virus reactivation and further epithelial damage is analyzed. By uncovering molecular mechanisms underlying the adverse effects and elucidating the communication occurring in vitro and in vivo we want to identify potential targets to prevent exacerbation of lung diseases caused by these two omnipresent factors, herpesvirus infection and ambient particle exposure.
94 Metalsafety – In Vitro, ex Vivo and in Vivo Investigations on Particulate and Nanofibrous Metal Compounds
Authors: Schulz Florian , Sewald Katherina , Hansen Tanja , Honarvar Naveed , Hartwig Andrea , Bitsch Annette
Published: May 2023

Metals and metal compounds are essential in daily life. Besides particulate materials nanofibrous material (nanowires) gain importance in innovative processes like optoelectronics. Toxicological data to assess the hazard is often available only for granular metals while data on nanowires is sparse. The project MetalSafety funded by the German BMBF aims at the development of an in vitro model to allow the grouping of different metal compounds with different bioavailability according to their toxicological hazard.   Ex vivo and in vivo investigations are used to analyse the predictivity of the in vitro results and the underlying mode-of-action and dose-response relationship. Within this contribution the study concept is introduced. Silver and copper, both in particulate and nanofibrous form, are used across all examinations in vitro, ex vivo and in vivo. To allow an interspecies comparison cell lines derived from human and rat lung are used. Exposure to the materials can be investigated either submerse or with air-liquid-interface (ALI) conditions. The correlation between both species can also be examined ex vivo using precision-cut lung slices (PCLS) derived from human and rat lung tissue. Application in vivo by intratracheal instillation in rats is conducted to enable a validation of the in vitro and ex vivo screening models in a best case scenario under physiological conditions. Comparable endpoints in vitro, ex vivo as well as in vivo are measured during the study. This includes cytotoxicity endpoints and cytokine measurements as well as gene expression analyses. The lung tissue is also subjected to a histopathological examination.
113 Development of a Direct Reading Instrument for Oxidative Potential Measurement in Air
Authors: Sauvain Jean-Jacques , Toto Antonio , Montet Estelle , Niquille Adeline , Suarez Guillaume
Published: May 2023

To protect the general population as well as workers, authorities have to identify the most toxic compounds in the particulate aerosol and effectively reduce their concentrations. As the oxidative potential (OP) is suggested to be linked with health effects, it may be more effective to control specific sources of oxidizing particles rather than overall particulate mass. In that case, the use of direct-reading instruments for OP measurement could help to the effective control of noxious air pollutant sources. We present here the development and characterization of a direct-reading instrument based on the acellular ferrous-orange xylenol (FOX) assay, allowing a continuous sensing of ambient oxidizing compounds. The detection principle relies on multiscattering-enhanced absorbance strategy enabling sensitive detection of airborne oxidants (e.g. hydrogen peroxide, hydroxyl radical) with a time resolution of 5 min. Two parallel tasks to improve the reading instrument are underway: 1. A better understanding of the FOX response to the potentially interfering ozone and NOx gases and it relationship with emission sources; 2. Improving the interface for transferring the aerosol in the FOX solution and characterizing the instrument regarding it sensibility, linearity, repeatability and response time.  Continuous determination of OP will enable robust epidemiological studies to evidence potential associations with oxidative stress-related and inflammatory disorders. In the future, mapping the average annual OP – together with current PM10, NOx and O3 – will be an essential chemical dimension of the pollution profile.
134 Hybrid Nanostructures Using Polymers to Reduce the Toxicity of Inorganic Luminescent Nanomaterials and Organic Dyes
Authors: Umezawa Masakazu , Soga Kohei
Published: May 2023

There is a growing research effort to use polymers to encapsulate functional molecules and nanomaterials to control their beneficial effects and toxicity, by minimizing their interactions with biomolecules and organs outside of the target sites. This concept is well known as drug delivery systems using nanoparticles. A good example is the RNA vaccines that encapsulates highly degradable RNA in lipid nanoparticles and delivers RNAs stably to immune cells. Such strategies are expected to be effective in designing nanoscale materials with low toxicity. Here, we investigated a potential of inorganic and organic hybrid nanomaterials (HNMs) for photodynamic therapy (PDT) for lesions in deep tissues, by combining (1) dyes for PDT and (2) upconversion luminescent nanoparticles (UCL-NPs) that activate the dyes under irradiation with the light of near-infrared (NIR), which is in the biological window with high transparency in biological tissues. In this context, we designed an HNM in which a PDT dye, rose Bengal (RB), and UCL-NPs are encapsulated using biodegradable polymer nanoparticles. HNMs significantly reduced the toxicity of RB and protected NPs’ luminescence. By using ultrasmall UCL-NPs (<10 nm) for RB activation, the HNP was designed for UCL-NPs to be excreted via the kidneys. UCL-NPs also emit near-infrared (1550 nm) fluorescence, which enables imaging of deep tissues. Therefore, the PDT-HNM works as a “theranostic” probe to be used for PDT therapy while real-time monitoring the target location. The design of such nanostructures is expected to lead to further biomedical applications of molecular drugs as well as highly functional inorganic nanomaterials.
Best Practices for FACE-Q Aesthetics Research: A Systematic Review of Study Methodology
Authors: Gallo Lucas , Kim Patrick , Yuan Morgan , Gallo Matteo , Thoma Achilles , Voineskos Sophocles H , Cano Stefan J , Pusic Andrea L , Klassen Anne F
Published: May 2023

Background

The FACE-Q Aesthetics module is a validated patient-reported outcome measure (PROM) that evaluates perspectives on facial aesthetic treatments. Improper administration and poor study methodology can compromise the validity and interpretation of this PROM.

Objectives

This systematic review sought to evaluate the administration and scoring of the FACE-Q Aesthetics scales within the literature.

Methods

A search of Ovid Medline, Embase, Cochrane, and Web of Science was performed on December 20, 2022, with the assistance of a health-research librarian (CRD42022383676). Studies that examined facial aesthetic interventions using the FACE-Q Aesthetics module as a primary or secondary outcome measure were included for analysis.

Results

There were 114 studies included. The Face Overall (n = 52, 45.6%), Psychological (n = 45, 39.4%), and Social (n = 43, 37.7%) scales were most frequently reported. Errors in FACE-Q administration were identified in 30 (26.3%) studies. The most common error was the presentation of raw ordinal scores rather than the converted Q score (n = 23). Most studies reported a time horizon for their primary analysis (n = 76, 66.7%); however, only 4 studies provided a rationale for this selection. Sample size calculations for the primary outcome were rarely performed (n = 9, 7.9%).

Conclusions

There continues to be limitations in PROM administration and the quality of articles that report FACE-Q Aesthetic scale data. The authors suggest that future investigators using the FACE-Q refer to the User's Guide regarding administration and scoring of this scale, report a rationale for the study time horizon, and provide an a priori sample size calculation for the primary outcome of interest.
Species divergence despite minimal morphological differentiation and habitat overlap in the Patelloida saccharina (Patellogastropoda: Lottiidae) species complex
Authors: Paran Faith Jessica , Ikeo Kazuho , Asakura Akira , Nakano Tomoyuki
Published: May 2023

We describe the current state of speciation in the species complex of the marine gastropod Patelloida saccharina, using mitochondrial COI, 16S RNA, nuclear histone 3 gene and single-nucleotide polymorphism (SNP) markers from 165 specimens collected from 37 localities across the Japanese archipelago. In total, 28 unique COI haplotypes, 16 16S haplotypes, 11 histone 3 haplotypes and 148 734 SNPs were obtained. Genetic assignments and phylogenetic trees recovered three genetically distinct lineages: P. saccharina saccharina, P. saccharina lanx and an unknown P. sp. from Shionomisaki, Wakayama Prefecture. The divergence between P. saccharina saccharina and P. saccharina lanx was estimated to have occurred around 44 000 years ago—too recent to have accumulated the morphological differences that have confounded taxonomic identification. Continuous gene exchange after an initial split is suggested based on demographic history analyses, which allowed for introgression of the P. saccharina lanx genome and the proliferation of intermediate individuals. Speciation, despite the existence of a contact zone in the Ryukyu Islands, possibly occurred due to the eventual reproductive isolation that followed the initial split with gene flow. Patelloida saccharina saccharina and P. saccharina lanx were strongly supported by our results as two separate species, and a revision of the current taxonomic descriptions based on their phylogeny, demographic history and species distribution is proposed.
O006 Hepatitis A virus cellular receptor 1 (HAVCR1) influences the integrity of blood brain barrier (BBB) of cerebral endothelial cells
Authors: Cao X S , Cong B B , Jiang W G , Martin T A
Published: May 2023

Introduction

Hepatitis A virus cellular receptor 1 (HAVcR1) has been established to play an important role in tight junction (TJ) in cancer cells and in peripheral endothelial cells. Its role in blood brain barrier (BBB) of cerebral endothelium remains unknown. This study aimed to investigate the association and functionality of HAVcR1 in BBB.

Methods

HAVcR1 was knocked down by siRNA in human cerebral microvessel endothelial cell/D3 (hCMEC/D3) cell lines. Changes in tight junction (TJ) behaviour were assessed using electric cell impedance sensing (ECIS), transendothelial resistance (TER), and paracellular permeability (PCP). The expression of HAVcR1 and the binding partners of HAVcR1 protein was assessed using quantitative polymerase chain reaction (qPCR).

Results

The HAVcR1 gene transcript, highly expressed in hCMEC/D3 cells, was successfully knocked down from the cell by anti-HAVcR1 siRNA. HAVcR1 knockdown resulted in an increase in four TJ molecules and a decrease in eight TJ molecules as demonstrated by transcript analysis. HAVcR1 knockdown cells displayed lower electric resistance compared with wild type cells during initial attachment and spreading in hCMEC/D3 cells shown by ECIS. Similarly, TER in HAVcR1 knockdown cells were also reduced. Higher PCP fluorescence signals were detected in HAVcR1 knockdown cell lines compared with wild type.

Conclusion

HAVcR1 regulates paracellular leakage of cerebral endothelial cells and loss of HAVcR1 renders the cells with weaker tight junction by influencing TJ protein expression. HAVcR1 have a function as part of the regulatory apparatus for TJ in BBB.
O011 Investigating the effect of supraphysiological levels of calcium on irreversible electroporation (IRE) of pancreatic cancer cell lines
Authors: Rai Z , Correa R , Khawaja I A , Acedo P , Davidson B R
Published: May 2023

Introduction

Pancreatic cancer remains difficult to treat with a 5-year survival of 2%. Loco-regional therapies are being introduced such as Irreversible Electroporation (IRE); a non-thermal ablative therapy thought to cause cell death by increasing the cell membrane potential resulting in the formation of aqueous pores, leading to cell death. Mitochondrial changes have previously been reported to be a key driver of apoptosis and calcium has been implicated in this process. We aimed to study the influence of calcium in combination with IRE in pancreatic cancer.

Methods

Immortalised pancreatic cancer cell line, PANC-1, and pancreatic cancer patient-derived xenograft cells (PDX 185) were exposed to calcium (Ca2+) and IRE monotherapy and in combination. Cells were trypsinised and electroporated in 4mm cuvettes with a BTX generator (Harvard Apparatus). Cell proliferation and viability were analysed, and depolarised mitochondria were evaluated by TMRE and analysed using flow cytometry.

Results

IRE combined with calcium was more cytotoxic compared to monotherapy with cell proliferation assays demonstrating a statistically significant reduction in proliferation (p<0.0001) across both cell lines. Interestingly, mitochondrial membrane potential analyses demonstrated a depolarising effect only in cells exposed to both calcium and IRE suggesting a mitochondrial mediated effect in cell death in these groups.

Conclusion

Calcium in combination with IRE may act to potentiate cell death through depolarisation of the mitochondrial membrane. Future work will involve understanding the impact of IRE in combination with calcium in 3D models, allowing the evaluation of molecular cell death mechanisms.
O017 Dupuytren's disease (DD): WNT4 knockdown in normal skin fibroblasts leads to ‘DD-like’ changes in the transcriptome
Authors: O’Brien A , Stevenson A , Barrett L , Hortin N , Deng Z , Allahham A , Quondamatteo F , Wood F , Fear M
Published: May 2023

Introduction

Dupuytren's disease (DD), a fibro-proliferative disorder of unknown aetiology, affects the palm and is characterised by progressive fibrosis, thickening of palmar fascia, and excess collagen deposition. Patients present with nodules, causing flexion deformity in ∼50%, resulting in loss of hand function. Excision is the standard treatment for DD, recurrence remains high. A 2015 Cochrane review concluded there is insufficient evidence to show superiority of any procedure used. Genetic and other studies have implicated WNT signalling in Dupuytren's pathology, including WNT4 dysregulation. It is not clear how WNT signalling/WNT4 plays a role in triggering DD.

Methods

Fibroblasts were isolated from the wrists of control healthy adult males and from a family that had inherited DD. Normal skin fibroblasts were treated with WNT4 siRNA and transcriptome of normal skin untreated, normal skin siRNA treated and DD family fibroblasts compared using RNASeq.

Results

Analysis of the transcriptomes from DD patient and normal fibroblasts showed significant differences including in WNT4 expression. Downregulation of WNT4 in normal fibroblasts using siRNA led to ‘DD-like’ changes in the transcriptome.

Conclusion

In people susceptible to DD WNT4 is downregulated even in non-fibrotic fibroblasts. Knockdown of WNT4 in normal fibroblasts led to changes making cells ‘DD-like’, suggesting downregulation of WNT4 could drive DD. Previous studies have shown that WNT4 is downregulated in DD disease in the cord cells. This study shows that WNT4 is downregulated in ‘non-disease’ cells, that downregulating WNT4 in normal skin fibroblasts leads to widespread ‘DD like’ changes in the transcriptome, suggesting WNT4 downregulation is a driver of DD disease.
O018 Determining the relationships between venous reflux patterns, clinical severity, and health-related quality of life
Authors: Wang R , Tan M , Onida S , Davies A H
Published: May 2023

Introduction

Various classification systems have been created to describe the anatomical distribution of venous reflux, including the VEIN-TERM and Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification. It is still unclear whether different reflux patterns correlate with health-related quality of life (HRQoL) and clinical severity.

Methods

Some 507 chronic venous disease patients and 105 asymptomatic controls underwent duplex ultrasound assessment. Patients were stratified according to VEIN-TERM and the CEAP classification systems. The Aberdeen Varicose Vein Questionnaire (AVVQ) score was used to compare HRQoL and the Venous Clinical Severity Score (VCSS) was used to compare clinical severity between groups.

Results

Patients were significantly older than controls (p<0.00001). All VEIN-TERM reflux patterns had significantly greater VCSS than no reflux (p<0.001). Superficial axial and combined axial reflux were associated with significantly greater VCSS than superficial segmental reflux (p<0.001, p=0.042 respectively). All VEIN-TERM reflux types had significantly worse AVVQ scores than no reflux (p<0.03). However, there were no significant differences in AVVQ scores across all VEIN-TERM reflux patterns. Most CEAP reflux patterns had increased VCSS and worse AVVQ scores when compared to no reflux (all p<0.05), except for deep reflux, and deep and perforator reflux only. The deep, superficial and perforator reflux group had significantly higher VCSS (p=0.013) and AVVQ (p<0.001) versus the superficial reflux only group.

Conclusion

When compared to no reflux, both classification systems show associations of any reflux pattern with worse VCSS and AVVQ scores. Combined reflux patterns were associated with the greatest clinical severity and worst HRQoL scores.
O024 Development and validation of a “lab in a box” for remote delivery of core reconstructive surgical skills
Authors: Awad L , Langridge B , Bollen E , Butler P
Published: May 2023

Introduction

Junior doctors and aspiring surgical trainees can have limited surgical exposure and developmental teaching because of rapid rotations, inconsistent rotas, reduced theatre time, and high working pressures. The global pandemic has also initiated a paradigm shift in education, and the methods we use to deliver education. Our aims are to assess the feasibility and validity of a low cost, remote plastic surgical skills course in comparison to the same course delivered face-to-face.

Methods

Our bench-model simulation “Lab in a Box” design was delivered to students remotely and in person. The essential and advanced plastic surgery course included suturing, excision, tendon repair, and local flap design. We undertook a pilot course facilitated by an online platform using a two-device set up. Equipment, including synthetic tendons and skin substitutes, were distributed to each participant. Quantitative evaluation included a global rating assessment and task specific criteria using a 1-5 Likert scale. Results were compared to the face-to-face control group. Qualitative feedback was also collected.

Results

A total of 40 students were recruited. A total cost of less than £30 was achieved. Quantitative feedback demonstrated comparable outcomes in remote training vs face-to-face training. Students reported excellent quality of audio-visual material and equipment, clear feedback, and 100% would recommend this course.

Conclusion

The simulation training course developed provides high-quality, engaging, reproducible and low-cost surgical skills training that can be delivered via distance learning. This model can be used to improve surgical skills training both in the UK and globally in resource poor environments.
O025 Do surgeons’ psychosocial working conditions achieve United Kingdom government standards?
Authors: Houdmont J , Daliya P , Adiamah A , Theophilidou E , Hassard J , Lobo D N
Published: May 2023

Introduction

Burnout is endemic among surgeons in the UK. Identification of contributory work characteristics could inform risk reduction activities. The purpose of this study was to assess the extent to which surgeons’ psychosocial working conditions met aspirational Management Standards delineated by the UK government. A secondary objective was to explore relations between the extent to which the Standards were met and burnout.

Methods

In 2021, trainee surgeons (n = 214) and consultant surgeons (n = 322) completed questionnaire measures of psychosocial working conditions and burnout. Descriptive data were computed for each Standard and hierarchical linear regression was applied to explore relations between the extent to which the Standards were met and burnout.

Results

Trainee surgeons reported significantly poorer psychosocial working conditions than consultant surgeons on the control, peer support, and change Standards. Trainees’ psychosocial working conditions fell below the 10th percentile on four Standards (control, managerial support, role, change) and below the 50th percentile on the remainder (demands, peer support, relationships) when compared to UK workforce norms. Consultant surgeons’ psychosocial working conditions were below the 50th percentile on five of the seven Standards. The Management Standards accounted for 35% of the variance in burnout over and above that accounted for by socio- and occupational-demographic characteristics.

Conclusion

Surgeons’ psychosocial working conditions were poor in comparison to normative data and strongly associated with burnout. These findings suggest that psychosocial risk management activities based on the Management Standards approach would help to reduce stress-related health problems in this population.
O026 The surgical datathon - a high-yield learning model for students: a mixed methods analysis
Authors: The C , China M , Jain R , Joshi S , Pandit A
Published: May 2023

Introduction

Datathons are high-yield research events where cross-disciplinary researchers collaborate to investigate pertinent healthcare problems by analysing multimodal electronic patient data. This paper aims to demonstrate the value of a surgical datathon as a learning model in students using both objective and qualitative assessments.

Methods

Fifteen individuals were recruited for the 24-hour datathon with representation from medicine, psychology, and clinical neurosciences including two postgraduate neurosurgery faculty. All reported interest in learning more academic skills. The aim was to solve a pertinent neurosurgical challenge, namely the prediction of intracranial pressure based on brain MR-imaging, with the goal of completing a full manuscript within 24 hours.

Participants were trained and split into smaller open working groups, supervised allowing real-time specialist feedback. Groups intermittently merged to cross-collaborate. Surveys with mixed-methods analysis explored participant opinions and the value of developing research skills at multiple time points.

Results

Participants’ knowledge were tested showing an increased mean test score post-datathon (69.92%) compared to pre-datathon scores (57.31%). Wilcoxon signed-rank test results demonstrated a significant change for these results (p=0.04, 95% CI -27.21 - -0.04). Likert-scales showed that majority of participants strongly agreed that the datathon accelerated their productivity (58.3%). Data collection was rated particularly useful (100%) despite majority being less than confident in analysing neuro-radiological images (84.6%) pre-datathon. Time pressures were the largest barrier participants faced (47.1%).

Conclusion

A full manuscript was produced and the datathon goal was met with conference acceptance. Surgical datathons represent a pragmatic learning model for students of all backgrounds.
O027 Exploring the educational value of the general surgery handover – an international survey of surgeons and surgical trainees
Authors: Egbe A , Gerogiannis I
Published: May 2023

Introduction

Restrictions in working hours for trainee doctors across the globe have led to an increased number of patient handovers. Little is known about the educational value of handover meetings in general surgery. This international study aims to evaluate surgeon and trainee perceptions regarding the educational value of handover meetings in general surgery, and to identify factors that influence the educational value of handover meetings.

Methods

A 19 item online survey was distributed to surgeons and surgical trainees internationally. The survey questions consisted of demographic information, questions requiring a Likert scale response, and free text responses. Free text responses were analysed using thematic analysis.

Results

There were 79 initial responses to the survey, however there were 44 eligible respondents who completed the full survey. 90.1% of respondents stated that the handover meeting was valuable to them in learning about post-operative complications. 93.2% of respondents stated that the handover meeting was valuable to them in learning about surgical decision making. Key themes included time pressures as a barrier to the educational potential of handover, and the importance of feedback during handover.

Conclusion

This study suggests that there is substantial educational value to the general surgery handover meeting for surgeons across the world. It appears to be particularly useful to surgeons in learning how to make management decisions, learning about post-operative complications, utilising case-based education techniques, and engaging in effective and meaningful feedback around patient management. We recommend that these findings should be used to prioritise education in surgical handover meetings.