A5007593421- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer, Hypoxia, and Metabolism
- COVID-19 Clinical Research Studies
- Sepsis Diagnosis and Treatment
- Respiratory Support and Mechanisms
- Immune Response and Inflammation
- High Altitude and Hypoxia
- Hemoglobin structure and function
- Metabolism and Genetic Disorders
- Medical Imaging Techniques and Applications
- S100 Proteins and Annexins
- Colorectal Cancer Screening and Detection
- Reliability and Agreement in Measurement
- Inflammasome and immune disorders
- Urban Transport and Accessibility
- Islamic Finance and Communication
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Patient Satisfaction in Healthcare
- Protein Degradation and Inhibitors
- Vitamin C and Antioxidants Research
- Diagnosis and Treatment of Venous Diseases
- CNS Lymphoma Diagnosis and Treatment
- Wound Healing and Treatments
University of Edinburgh
2007-2024
NHS England
2024
Sussex Community NHS Foundation Trust
2024
London Cancer
2024
Centre for Inflammation Research
2017-2023
The Queen's Medical Research Institute
2018-2023
Newcastle upon Tyne Hospitals NHS Foundation Trust
2023
Queen's Medical Centre
2008-2022
Medical Research Council
2017-2019
East and North Hertfordshire NHS Trust
2019
Neutrophils can function and survive in injured infected tissues, where oxygen metabolic substrates are limited. Using radioactive flux assays LC-MS tracing with U-13C glucose, glutamine, pyruvate, we observe that neutrophils require the generation of intracellular glycogen stores by gluconeogenesis glycogenesis for effective survival bacterial killing. These adaptations dynamic, net increases observed following LPS challenge or altitude-induced hypoxia. from patients chronic obstructive...
Rationale: COPD (Chronic Obstructive Pulmonary Disease) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in bioenergetics contribute impaired antioxidant responses pathogenesis has yet be fully delineated. Objectives: Through the study of alveolar (AM) peripheral monocyte-derived (MDM) macrophages, we sought establish if intrinsic defects core metabolic processes drive dysfunction redox imbalance. Methods: AM MDM...
Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, often neglected. In present study, we have shown that ARDS patients were hypoxemic monocytopenic within first 48 h ventilation. Monocytopenia was also observed in mouse models hypoxic lung injury, which hypoxemia drove suppression type I interferon signaling bone marrow....
Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal essential limiting tissue damage. Here, we have identified a critical role the prolyl hydroxylase enzyme Phd2 in maintaining balance between appropriate, predominantly neutrophil-mediated pathogen clearance resolution of response. We demonstrate that myeloid-specific loss resulted an exaggerated inflammatory response Streptococcus pneumonia, with increases...
Infection outcomes are regulated by neutrophil responses to oxygen and nutrient availability.
Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with high mortality that currently in focus given it associated caused by coronavirus disease 2019 (COVID-19). Neutrophils play key role the lung injury characteristic of non-COVID-19 ARDS and there also accumulating evidence neutrophil mediated patients who succumb to infection acute 2 (SARS-CoV-2). Methods: We undertook functional proteomic metabolomic survey circulating populations, comparing COVID-19...
<ns3:p><ns3:bold>Background: </ns3:bold>Acute respiratory distress syndrome (ARDS) is a severe critical condition with high mortality that currently in focus given it associated caused by coronavirus disease 2019 (COVID-19). Neutrophils play key role the lung injury characteristic of non-COVID-19 ARDS and there also accumulating evidence neutrophil mediated patients who succumb to infection acute 2 (SARS-CoV-2).</ns3:p><ns3:p> <ns3:bold>Methods: </ns3:bold>We undertook functional proteomic...
Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression cell surface receptors, signal transduction networks, and metabolic machinery to shape phenotypes response hypoxia. Through tracing labeled amino acids into enzymes, proinflammatory mediators, granule proteins, we...
Acute respiratory distress syndrome is defined by the presence of systemic hypoxia and consequent on disordered neutrophilic inflammation. Local mechanisms limiting duration magnitude this response remain poorly understood.
The prevalence of colorectal cancer is increasing in the elderly. We examined treatment and outcomes our institution patients aged over 85 years with proven adenocarcinoma.One hundred five were identified stratified by received: curative surgery (CS), other treatments (OT) or best supportive care (BSC). Data on demographics, staging, survival was collected analysed.Forty two received CS, 36 OT 27 BSC. While treated groups (CS OT) similar terms age (p=0.35) staging (p=0.16), BSC significantly...
Neutrophilic inflammation is central to disease pathogenesis, for example, in chronic obstructive pulmonary disease, yet the mechanisms that retain neutrophils within tissues remain poorly understood. With emerging evidence axon guidance factors can regulate myeloid recruitment and expression of a class 3 semaphorin, SEMA3F, we investigated role SEMA3F inflammatory cell retention inflamed tissues. We observed upregulate response proinflammatory mediators following neutrophil lung. In both...
Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Va (FVa). Using whole blood RNAseq scRNAseq of peripheral mononuclear cells, we find that FV mRNA expressed leukocytes, identify neutrophils, monocytes, T regulatory cells as sources increased hospitalized patients with COVID-19. Proteomic analysis confirms circulating neutrophils severe COVID-19, immunofluorescence microscopy identifies lung-infiltrating leukocytes COVID-19 lung...
Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised be more diverse malleable than was previously appreciated. Hypoxic signalling pathways known regulate important behaviours and, as such, potential targets for regulating responses.
Background The NHS Jewish BRCA Testing Programme is offering germline BRCA1 and BRCA2 genetic testing to people with ≥1 grandparent. Who have an increased likelihood of having Ashkenazi (AJ) founder pathogenic variant (gPV) compared the general population. offered via a self-referral, home-based saliva sampling pathway, supported by counsellor telephone helpline. A first-of-its-kind in United Kingdom (UK) for population testing, outside research. Methods We reviewed data from 5389 who...
Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose with/without rituximab (R) iNHL were included. Demographics, lymphoma treatment details, grade 3 5 adverse events (AEs)...
To develop and test a set of measures quality care in the process sepsis management, to determine inter-rater reliability case-note review assessment these assess our current standard care. Five one outcome were identified from literature previous experience. Failure modes effects analysis was used by multidisciplinary team validate prioritize them terms associated risk. Forty sets case notes reviewed two independent teams determined using observed percentage agreement kappa statistic. We...
Summary Understanding the mechanisms by which infection with SARS-CoV-2 leads to acute respiratory distress syndrome (ARDS) is of significant clinical interest given mortality associated severe and critical coronavirus induced disease 2019 (COVID-19). Neutrophils play a key role in lung injury characteristic non-COVID-19 ARDS, but relative paucity these cells observed at post-mortem tissue patients who succumb SARS-CoV-2. With emerging evidence dysregulated innate immune response COVID-19,...
Journeys to work form a significant proportion of all car journeys and employer transport plans have been advocated as way manage the needs workers in order contain level trips and, therefore, emissions other negative effects. A questionnaire survey focus group interviews were used evaluate success an plan implemented by University Sheffield September 1997. The policy was associated with marginal (7%) reduction use promoted limited increase travel diversity. An objection principle paying...
Assessment of pressure ulcer (PU) risk is important in clinical practice and the need to document it patient's record paramount. Despite national international guidelines highlighting PU risk, nursing documentation remains variable. The first article this series discussed evidence base underpinning development for PUs, alongside creation bundle approach prevention. second presented results a audit exploring compliance against prevention (aSSKINg framework) an adult community setting South...
"Foetal fibronectin and cervical length measurement following Arabin pessary insertion in a high-risk twin pregnancy: A case report." Journal of Obstetrics Gynaecology, 37(1), pp. 103–104