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  1. Article ; Online: E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.

    Jasper, Alice E / Faniyi, Aduragbemi A / Davis, Lauren C / Grudzinska, Frances S / Halston, Robyn / Hazeldine, Jon / Parekh, Dhruv / Sapey, Elizabeth / Thickett, David R / Scott, Aaron

    The Journal of allergy and clinical immunology

    2023  Volume 153, Issue 1, Page(s) 320–329.e8

    Abstract: Background: Electronic cigarette (e-cigarette) use continues to rise despite concerns ... exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and ... nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e ...

    Abstract Background: Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.
    Objective: We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.
    Methods: Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.
    Results: Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.
    Conclusions: The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.
    MeSH term(s) Humans ; Neutrophils ; E-Cigarette Vapor/metabolism ; E-Cigarette Vapor/pharmacology ; Electronic Nicotine Delivery Systems ; Nicotine/adverse effects ; Nicotine/metabolism ; Actins/metabolism ; Pulmonary Disease, Chronic Obstructive/metabolism
    Chemical Substances E-Cigarette Vapor ; Nicotine (6M3C89ZY6R) ; Actins
    Language English
    Publishing date 2023-09-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2023.08.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Predicting the pulmonary effects of long-term e-cigarette use: are the clouds clearing?

    Davis, Lauren C / Sapey, Elizabeth / Thickett, David R / Scott, Aaron

    European respiratory review : an official journal of the European Respiratory Society

    2022  Volume 31, Issue 163

    Abstract: Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever ... of harm seen in cigarette use, and those potentially unique to e-cigarette exposure. Evaluation must also ... account for the vast variation in e-cigarette devices (now including at least five generations of devices ...

    Abstract Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever-growing complexity. Given their increasing use by ex-smokers, smokers and never-smokers, it is important to evaluate evidence of their potential pulmonary effects and predict effects of long-term use, since there has been insufficient time to study a chronic user cohort. It is crucial to evaluate indicators of harm seen in cigarette use, and those potentially unique to e-cigarette exposure. Evaluation must also account for the vast variation in e-cigarette devices (now including at least five generations of devices) and exposure methods used
    MeSH term(s) Electronic Nicotine Delivery Systems ; Humans ; Longitudinal Studies ; Smokers ; Vaping/adverse effects
    Language English
    Publishing date 2022-01-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1077620-5
    ISSN 1600-0617 ; 0905-9180
    ISSN (online) 1600-0617
    ISSN 0905-9180
    DOI 10.1183/16000617.0121-2021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Comment on "E-cigarette use increases susceptibility to bacterial infection by impairment of human neutrophil chemotaxis, phagocytosis, and NET formation".

    Jasper, Alice E / Sapey, Elizabeth / Thickett, David / Scott, Aaron

    American journal of physiology. Cell physiology

    2020  Volume 318, Issue 3, Page(s) C704–C705

    MeSH term(s) Bacterial Infections ; Chemotaxis ; Electronic Nicotine Delivery Systems ; Humans ; Neutrophils ; Phagocytosis
    Language English
    Publishing date 2020-03-05
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00554.2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.

    Scott, Aaron / Lugg, Sebastian T / Aldridge, Kerrie / Lewis, Keir E / Bowden, Allen / Mahida, Rahul Y / Grudzinska, Frances Susanna / Dosanjh, Davinder / Parekh, Dhruv / Foronjy, Robert / Sapey, Elizabeth / Naidu, Babu / Thickett, David R

    Thorax

    2018  Volume 73, Issue 12, Page(s) 1161–1169

    Abstract: Objective: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared ... the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function ... chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is ...

    Abstract Objective: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function.
    Methods: AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed.
    Results: Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function.
    Conclusions: ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.
    MeSH term(s) Acetylcysteine/pharmacology ; Antioxidants/pharmacology ; Apoptosis/drug effects ; Cell Survival/drug effects ; Chemokine CCL2/metabolism ; Complex Mixtures/adverse effects ; Electronic Nicotine Delivery Systems ; Gases/adverse effects ; Humans ; Inflammation/etiology ; Inflammation/metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Macrophages, Alveolar/pathology ; Macrophages, Alveolar/physiology ; Matrix Metalloproteinase 9/metabolism ; Necrosis/etiology ; Nicotine/adverse effects ; Phagocytosis/drug effects ; Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors/pharmacology ; Reactive Oxygen Species/metabolism ; THP-1 Cells ; Tumor Necrosis Factor-alpha/metabolism ; Vaping/adverse effects
    Chemical Substances Antioxidants ; CCL2 protein, human ; CXCL8 protein, human ; Chemokine CCL2 ; Complex Mixtures ; Gases ; Interleukin-6 ; Interleukin-8 ; Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors ; Reactive Oxygen Species ; Tumor Necrosis Factor-alpha ; Nicotine (6M3C89ZY6R) ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Acetylcysteine (WYQ7N0BPYC)
    Language English
    Publishing date 2018-08-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 204353-1
    ISSN 1468-3296 ; 0040-6376
    ISSN (online) 1468-3296
    ISSN 0040-6376
    DOI 10.1136/thoraxjnl-2018-211663
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book ; Online: Bronchial Asthma : Emerging Therapeutic Strategies

    Sapey, Elizabeth

    2012  

    Keywords Dermatology ; Respiratory medicine
    Size 1 electronic resource (272 pages)
    Publisher IntechOpen
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021045701
    ISBN 9789535168430 ; 9535168436
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  6. Article: Neutrophil Modulation in Alpha-1 Antitrypsin Deficiency.

    Sapey, Elizabeth

    Chronic obstructive pulmonary diseases (Miami, Fla.)

    2020  Volume 7, Issue 3, Page(s) 247–259

    Abstract: Neutrophils have been implicated in the pathogenesis of alpha-1 antitrypsin deficiency (AATD) since the first descriptions of the disease. Neutrophil proteinases can cause all lung manifestations of AATD, from small airways destruction, to emphysema, to ... ...

    Abstract Neutrophils have been implicated in the pathogenesis of alpha-1 antitrypsin deficiency (AATD) since the first descriptions of the disease. Neutrophil proteinases can cause all lung manifestations of AATD, from small airways destruction, to emphysema, to chronic bronchitis and airflow obstruction. Initially, it was proposed that neutrophil functions were normal in AATD, responding in an initially physiological manner to a high burden of pulmonary inflammation. More recent studies have shed new light on this, describing changes in neutrophil responses (a modulation of usual cellular functions) in the presence of inflammation or infection which might enhance tissue damage while impeding bacterial clearance, providing some evidence to support there being an AATD neutrophil phenotype. Many facets of neutrophil function in AATD can be explained by the loss of alpha-1 antitrypsin (AAT) in diverse biological processes. If this were the only reason for altered neutrophil functions, one would predict similar disease presentation across affected people. However, this is not the case. Despite similar (low) levels of AAT, lung disease is extremely variable in AATD, with some patients suffering a significant burden of lung disease and some much less, irrespective of smoking habits and, in some cases, despite augmentation therapy. This review will explore how complex neutrophil responses are and how they are altered with age, inflammation and AATD. Further, it will discuss the need to understand more completely which aspects of AATD-associated disease are driven by neutrophils and how patients more susceptible to neutrophil dysfunction could be identified to potentially stratify treatment approaches.
    Language English
    Publishing date 2020-07-22
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2771715-X
    ISSN 2372-952X
    ISSN 2372-952X
    DOI 10.15326/jcopdf.7.3.2019.0164
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Spatial confidence regions for combinations of excursion sets in image analysis.

    Maullin-Sapey, Thomas / Schwartzman, Armin / Nichols, Thomas E

    Journal of the Royal Statistical Society. Series B, Statistical methodology

    2023  Volume 86, Issue 1, Page(s) 177–193

    Abstract: The analysis of excursion sets in imaging data is essential to a wide range of scientific disciplines such as neuroimaging, climatology, and cosmology. Despite growing literature, there is little published concerning the comparison of processes that have ...

    Abstract The analysis of excursion sets in imaging data is essential to a wide range of scientific disciplines such as neuroimaging, climatology, and cosmology. Despite growing literature, there is little published concerning the comparison of processes that have been sampled across the same spatial region but which reflect different study conditions. Given a set of asymptotically Gaussian random fields, each corresponding to a sample acquired for a different study condition, this work aims to provide confidence statements about the intersection, or union, of the excursion sets across all fields. Such spatial regions are of natural interest as they directly correspond to the questions 'Where do
    Language English
    Publishing date 2023-09-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 1490719-7
    ISSN 1467-9868 ; 0035-9246 ; 1369-7412
    ISSN (online) 1467-9868
    ISSN 0035-9246 ; 1369-7412
    DOI 10.1093/jrsssb/qkad104
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Reversing the urgent and emergency care spiral of decline.

    Cooksley, Tim / Holland, Mark / Sapey, Elizabeth

    BMJ (Clinical research ed.)

    2023  Volume 382, Page(s) 1530

    MeSH term(s) Humans ; Emergency Medical Services ; Emergency Service, Hospital ; Emergency Treatment
    Language English
    Publishing date 2023-07-03
    Publishing country England
    Document type Editorial
    ZDB-ID 1362901-3
    ISSN 1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    ISSN (online) 1756-1833
    ISSN 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    DOI 10.1136/bmj.p1530
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Exploring fraity and sarcopenia in older adults admitted to acute medical unit, looking at prevalence, trajectory, and outcomes: A protocol testing the feasibility and acceptability of the TYSON study.

    Kamwa, Vicky / Jackson, Thomas / Hassan-Smith, Zaki / Sapey, Elizabeth

    PloS one

    2023  Volume 18, Issue 11, Page(s) e0293650

    Abstract: ... include the Rockwood clinical frailty and e-frailty index. Sarcopenia assessments include the Bilateral ...

    Abstract Background: Frailty and sarcopenia are common in older people and are associated with adverse outcomes including increased mortality and morbidity. It is unclear whether screening for frailty and sarcopenia would identify specific populations most at risk of poor outcomes during unplanned hospital admissions, which screening tools should be used and what the trajectory of both conditions are over the course of an admission. The TYSON study is an observational cohort study aiming to determine the prevalence, trajectory and outcomes associated with frailty and sarcopenia in different patient cohorts. This protocol tests the feasibility and acceptability of TYSON processes.
    Objectives: To determine in acutely admitted medical patients who are older adults: Primary: The feasibility and acceptability of frailty and sarcopenia assessments; Secondary: (1) Differences in community and hospital frailty assessments, as assessed by the medical team, the patient and elderly care physicians, (2) The dynamic changes in frailty and sarcopenia during a hospital admission, and patient outcomes; Exploratory: Inflammatory and metabolic mediators associated with frailty and sarcopenia.
    Methods: A single centre, prospective observational study including patients aged ≥ 65 years admitted to an acute medical unit. Frailty assessments include the Rockwood clinical frailty and e-frailty index. Sarcopenia assessments include the Bilateral Anterior Thigh Thickness (BATT) measurement. Each participant will be asked to complete 5 visits, at day 0, day 3, day 7, month 3 and month 6. Blood samples will be collected to explore inflammatory and metabolic markers associated with frailty and sarcopenia. The study and protocol have been ethically approved by the Health Research Authority (REC 20/WA/0263).
    Discussion: The study will determine the feasibility and acceptability of frailty and sarcopenia assessments in an acute hospital setting, and inform on the prevalence, trajectory and associated outcomes of frailty and sarcopenia in this group of patients. An inflammatory and metabolic profile will be explored in frailty and sarcopenia.
    MeSH term(s) Aged ; Humans ; Sarcopenia/diagnosis ; Sarcopenia/epidemiology ; Sarcopenia/complications ; Frailty/diagnosis ; Frailty/epidemiology ; Frailty/complications ; Frail Elderly ; Prevalence ; Feasibility Studies ; Geriatric Assessment/methods ; Observational Studies as Topic
    Language English
    Publishing date 2023-11-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0293650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: BLMM: Parallelised computing for big linear mixed models.

    Maullin-Sapey, Thomas / Nichols, Thomas E

    NeuroImage

    2022  Volume 264, Page(s) 119729

    Abstract: ... in our previous work, Maullin-Sapey and Nichols (2021). ...

    Abstract Within neuroimaging large-scale, shared datasets are becoming increasingly commonplace, challenging existing tools both in terms of overall scale and complexity of the study designs. As sample sizes grow, researchers are presented with new opportunities to detect and account for grouping factors and covariance structure present in large experimental designs. In particular, standard linear model methods cannot account for the covariance and grouping structures present in large datasets, and the existing linear mixed models (LMM) tools are neither scalable nor exploit the computational speed-ups afforded by vectorisation of computations over voxels. Further, nearly all existing tools for imaging (fixed or mixed effect) do not account for variability in the patterns of missing data near cortical boundaries and the edge of the brain, and instead omit any voxels with any missing data. Yet in the large-n setting, such a voxel-wise deletion missing data strategy leads to severe shrinkage of the final analysis mask. To counter these issues, we describe the "Big" Linear Mixed Models (BLMM) toolbox, an efficient Python package for large-scale fMRI LMM analyses. BLMM is designed for use on high performance computing clusters and utilizes a Fisher Scoring procedure made possible by derivations for the LMM Fisher information matrix and score vectors derived in our previous work, Maullin-Sapey and Nichols (2021).
    MeSH term(s) Humans ; Linear Models ; Neuroimaging ; Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Sample Size
    Language English
    Publishing date 2022-11-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2022.119729
    Database MEDical Literature Analysis and Retrieval System OnLINE

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