Smoking Is Associated with Shortened Airway Cilia

BACKGROUND:Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6-7 microm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. METHODOLOGY/PRINCIPAL FINDINGS:Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05). In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers. CONCLUSIONS/SIGNIFICANCE:Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease

Determination of a suitable low-dose abdominopelvic CT protocol using model-based iterative reconstruction through cadaveric study.

Introduction: Cadaveric studies provide a means of safely assessing new technologies and optimizing scanning prior to clinical validation. Reducing radiation exposure in a clinical setting can entail incremental dose reductions to avoid missing important clinical findings. The use of cadavers allows assessment of the impact of more substantial dose reductions on image quality. Our aim was to identify a suitable low‐dose abdominopelvic CT protocol for subsequent clinical validation. Methods: Five human cadavers were scanned at one conventional dose and three low‐dose settings. All scans were reconstructed using three different reconstruction algorithms: filtered back projection (FBP), hybrid iterative reconstruction (60% FBP and 40% adaptive statistical iterative reconstruction (ASIR40)), and model‐based iterative reconstruction (MBIR). Two readers rated the image quality both quantitatively and qualitatively. Results: Model‐based iterative reconstruction images had significantly better objective image noise and higher qualitative scores compared with both FBP and ASIR40 images at all dose levels. The greatest absolute noise reduction, between MBIR and FBP, of 34.3 HU (equating to a 68% reduction) was at the lowest dose level. MBIR reduced image noise and improved image quality even in CT images acquired with a mean radiation dose reduction of 62% compared with conventional dose studies reconstructed with ASIR40, with lower levels of objective image noise, superior diagnostic acceptability and contrast resolution, and comparable subjective image noise and streak artefact scores. Conclusion: This cadaveric study demonstrates that MBIR reduces image noise and improves image quality in abdominopelvic CT images acquired with dose reductions of up to 62%

Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells

Microneedles are promising devices for transdermal delivery and diagnostic applications, due to their minimally invasive and painless nature of application. However, so far, applications are limited to small scale research projects. Material selection and production for larger projects remain a challenge. In vitro testing using human cell culture could bridge the gap between cost effective screening of suitable materials and concerns for safety and ethics. In this study, materials were tested for effects on viability and morphology of human endothelial cells and keratinocytes. In addition, materials were assessed for their potential to influence cellular differentiation and barrier formation. Elution-based testing of inflammatory markers revealed no negative effects in all applied tests, whereas the assessment of differentiation markers on cells in direct contact with the material showed differences and allowed the selection of candidate materials for future medical device applications. This study illustrates that elution-based biocompatibility testing can paint an incomplete picture. Advanced staining techniques and cell types specific for the application of the medical device improve material selection to reduce and replace animal testing at an early stage in the development process. © 2018 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 505–512, 2019

Piezoelectric inkjet coating of injection moulded, reservoir-tipped microneedle arrays for transdermal delivery

Coated microneedles have significant potential for use in transdermal delivery applications. In this paper, we describe the fabrication of microneedle master templates using microstereolithography techniques and subsequently use a commercial injection moulding process to replicate these microneedles in biocompatible cyclic olefin polymer (COP) materials. Notably, the 475 μm-tall needle designs feature a shallow pit or reservoir at the tip, thereby providing both a target and holder for incoming droplets that are deposited using a piezoelectric inkjet printer. Using this design, no tilting or rotation of the needle array is required during the filling process. In the preliminary tests reported here, the reservoir is filled with a FITC-labelled dye that acts as a model drug, and ex vivo skin tests are used to verify skin penetration, the transfer of this model drug to the skin and to measure the reliability of the needles themselves. To our knowledge, this is the first time that such an inkjet-filled, reservoir-tipped microneedle has been demonstrated

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Modulators of 14-3-3 Protein-Protein Interactions

Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein-protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as 'undruggable' targets, the last two decades have seen an increasing number of successful examples of PPI modulators resulting in a growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This Perspective focuses on the hub protein 14-3-3, which has several hundred identified protein interaction partners and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide-mimetics and natural products

Assessing radiological images of human cadavers: Is there an effect of different embalming solutions?

The aim of this study is to investigate the impact of different embalming solutions including formalin, Genelyn, Thiel and Imperial College London- Soft Preserving solutions on the quality of radiological images taken from cadavers embalmed with the above mentioned techniques. Two cadavers per embalming technique were imaged pre and post-embalming using three different imaging modalities including ultrasound, plain radiography and computed tomography (CT). Imaging criteria and a qualitative grading system for each imaging modality were adapted from the European Guidelines on Quality Criteria for Computed Tomography, the European Guidelines on Quality Criteria for Diagnostic Radiographic Images, and according to the AIUM Practice Guideline for the performance of ultrasound. Qualitative analysis was performed independently by three readers on a Picture Archiving and Communication System (PACS). The readers were blinded to both the embalmment status and the embalming agent used to preclude bias. On comparison of images pre and post-embalming, brain CT images showed a significant deterioration in image quality post-embalming, while there was no significant change in chest and abdomen/pelvic images and some improvement was observed in Genelyn embalmed cadavers. No changes were observed when using ultrasound to image the spleen and aorta, while a significant improvement in image quality was observed when examining the kidney in all embalmed cadavers with a small improvement when imaging the liver. No significant difference was observed on plain radiography post-embalming, while a minor deterioration was observed mainly in the chest area. Different embalming techniques had varying effects on image quality, in human cadavers, with the range of imaging modalities investigated in this study. Thus, no ideal embalming solution was identified, which would improve the quality of images on all imaging modalities. Further research is required to compare the quality of radiological images at different stages of decomposition taking into consideration antemortal pathologies with a larger number of donors

Radiographers' knowledge, attitudes and expectations of artificial intelligence in medical imaging

Introduction: Artificial intelligence (AI) is increasingly utilised in medical imaging systems and processes, and radiographers must embrace this advancement. This study aimed to investigate perceptions, knowledge, and expectations towards integrating AI into medical imaging amongst a sample of radiographers and determine the current state of AI education within the community. Methods: A cross-sectional online quantitative study targeting radiographers based in Europe was conducted over ten weeks. Captured data included demographical information, participants’ perceptions and understanding of AI, expectations of AI and AI-related educational backgrounds. Both descriptive and inferential statistical techniques were used to analyse the obtained data. Results: A total of 96 valid responses were collected. Of these, 64% correctly identified the true definition of AI from a range of options, but fewer (37%) fully understood the difference between AI, machine learning and deep learning. The majority of participants (83%) agreed they were excited about the advancement of AI, though a level of apprehensiveness remained amongst 29%. A severe lack of education on AI was noted, with only 8% of participants having received AI teachings in their pre-registration qualification. Conclusion: Overall positive attitudes towards AI implementation were observed. The slight apprehension may stem from the lack of technical understanding of AI technologies and AI training within the community. Greater educational programs focusing on AI principles are required to help increase European radiography workforce engagement and involvement in AI technologies. Implications for practice: This study offers insight into the current perspectives of European based radiographers on AI in radiography to help facilitate the embracement of AI technology and convey the need for AI-focused education within the profession

Evaluation of acute and convalescent antibody concentration against pneumococcal capsular polysaccharides for the diagnosis of pneumococcal infection in children with community-acquired pneumonia

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections

An evaluation of information online on artificial intelligence in medical imaging

Background: Opinions seem somewhat divided when considering the effect of artificial intelligence (AI) on medical imaging. The aim of this study was to characterise viewpoints presented online relating to the impact of AI on the field of radiology and to assess who is engaging in this discourse. Methods: Two search methods were used to identify online information relating to AI and radiology. Firstly, 34 terms were searched using Google and the first two pages of results for each term were evaluated. Secondly, a Rich Search Site (RSS) feed evaluated incidental information over 3 weeks. Webpages were evaluated and categorized as having a positive, negative, balanced, or neutral viewpoint based on study criteria. Results: Of the 680 webpages identified using the Google search engine, 248 were deemed relevant and accessible. 43.2% had a positive viewpoint, 38.3% a balanced viewpoint, 15.3% a neutral viewpoint, and 3.2% a negative viewpoint. Peer-reviewed journals represented the most common webpage source (48%), followed by media (29%), commercial sources (12%), and educational sources (8%). Commercial webpages had the highest proportion of positive viewpoints (66%). Radiologists were identified as the most common author group (38.9%). The RSS feed identified 177 posts of which were relevant and accessible. 86% of posts were of media origin expressing positive viewpoints (64%). Conclusion: The overall opinion of the impact of AI on radiology presented online is a positive one. Consistency across a range of sources and author groups exists. Radiologists were significant contributors to this online discussion and the results may impact future recruitment