A5051285244- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Intracerebral and Subarachnoid Hemorrhage Research
- Bariatric Surgery and Outcomes
- Cardiac, Anesthesia and Surgical Outcomes
- TGF-β signaling in diseases
- Pain Management and Placebo Effect
- Delphi Technique in Research
- Neurological Disease Mechanisms and Treatments
- Esophageal and GI Pathology
- Caveolin-1 and cellular processes
- Helicobacter pylori-related gastroenterology studies
- Folate and B Vitamins Research
- Neurological Disorders and Treatments
- Body Contouring and Surgery
- Mitochondrial Function and Pathology
- Wnt/β-catenin signaling in development and cancer
- Neuroscience and Neuropharmacology Research
- Gastrointestinal disorders and treatments
- Colorectal Cancer Surgical Treatments
- Bone Metabolism and Diseases
- Esophageal Cancer Research and Treatment
- Appendicitis Diagnosis and Management
- Cancer-related gene regulation
- Meta-analysis and systematic reviews
University of Bristol
2011-2025
NIHR Bristol Biomedical Research Centre
2019-2024
University Hospitals Bristol NHS Foundation Trust
2019-2024
University Hospitals Bristol and Weston NHS Foundation Trust
2024
National Institute for Health Research
2020-2023
Royal College of Surgeons of England
2023
Leeds Teaching Hospitals NHS Trust
2022
St James's University Hospital
2022
Medical Research Council
2020
North Bristol NHS Trust
2005-2009
The phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (PKB; also known as Akt) signalling pathway is recognized playing a central role in the survival of diverse cell types. Glycogen synthase kinase-3 (GSK-3) ubiquitously expressed serine/threonine protein that one several substrates PKB. PKB phosphorylates GSK-3 response to insulin and growth factors, which inhibits activity leads modulation multiple regulated cellular processes. We show novel potent selective small-molecule...
Aims: Several observations point to the involvement of angiotensin‐converting enzyme‐1 (ACE‐1) in Alzheimer's disease (AD): ACE‐1 cleaves amyloid‐β peptide (Aβ) vitro , level and activity are reportedly increased AD, variations gene associated with AD. We analysed expression AD control brains, particularly relation Aβ load cerebral amyloid angiopathy (CAA). Methods: was measured frontal cortex from 58 114 cases known CAA severity. The distribution examined immunohistochemically. In five...
The relative amounts of amyloid β‐protein (Aβ) in cerebral blood vessels and parenchyma vary considerably amongst patients with Alzheimer's disease (AD). Although several mechanisms have been proposed to explain this variability, the underlying genetic environmental determinants are still unclear, as functional consequences. Polymorphisms APOE , gene for apolipoprotein E (ApoE), influence risk developing AD deposition Aβ within brain. We examined relationship between genotype extent...
Neprilysin (NEP) degrades amyloid-β (Aβ) and is thought to contribute its clearance from the brain. In Alzheimer disease (AD), downregulation of NEP has been suggested development cerebral amyloid angiopathy (CAA). We examined relationship among NEP, CAA, APOE status in AD elderly control cases. was most abundant tunica media cerebrocortical blood vessels pyramidal neurons. homogenates frontal cortex, protein levels were reduced but not significantly; enzymatic activity significantly AD....
Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP-binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central role in cellular lipid homeostasis. Several single nucleotide polymorphisms (SNPs) spanning ABCA1 been genotyped haplotype-based association analyses performed four independent...
Background Bariatric and metabolic surgery is used as a treatment for patients with severe complex obesity. However, there need to improve outcome selection reporting in bariatric trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported all studies specific condition, may achieve this. Here, we present the development COS BARIAtric Clinical Trials—the BARIACT Study. Methods Findings Outcomes identified from systematic reviews patient interviews informed questionnaire...
The branched chain aminotransferase enzymes (BCAT) serve as nitrogen donors for the production of 30% de novo glutamate synthesis in rat brain. Despite importance this major metabolite and excitatory neurotransmitter, distribution BCAT proteins human brain (hBCAT) remains unreported. We have studied report, first time, that mitochondrial isoform, hBCATm is largely confined to vascular endothelial cells, whereas cytosolic hBCATc restricted neurons. majority hBCATc-labelled neurons were either...
Summary Outcome reporting in bariatric surgery needs a core outcome set ( COS ), an agreed minimum of outcomes reported all studies particular condition. The aim this study was to summarize inform the development . Outcomes randomized controlled trials RCTs ) and large non‐randomized identified by systematic review were listed verbatim categorized into domains, scrutinizing frequency uniformity definitions. Ninety (39 1,088 separate outcomes, grouped nine domains with most n = 920, 85%) only...
A comprehensive evaluation of bariatric surgery is required to inform decision-making. This will include measures benefit and risk. It possible that stakeholders involved with value these outcomes differently, although this has not previously been explored. study aimed investigate compare how professionals patients prioritise surgery.Systematic reviews qualitative interviews created an exhaustive list outcomes. informed the development a 130-item questionnaire, structured in four sections...
The phosphatidylinositol 3‐kinase (PI 3‐kinase)/protein kinase B (PKB; also known as Akt) signalling pathway is recognized playing a central role in the survival of diverse cell types. Glycogen synthase kinase‐3 (GSK‐3) ubiquitously expressed serine/threonine protein that one several substrates PKB. PKB phosphorylates GSK‐3 response to insulin and growth factors, which inhibits activity leads modulation multiple regulated cellular processes. We show novel potent selective small‐molecule...
Cholinesterase inhibitors (ChEIs) are effective symptomatic treatments in dementia with Lewy bodies (DLB), although effects on pathologic mechanisms unknown. In the first human autopsy study examining impact of ChEI treatment brain pathology, we compared treated patients DLB matched untreated for cortical beta-amyloid (Abeta) and tau pathologies. Treated had significantly less parenchymal Abeta deposition, which is relevant to disease management using ChEI.
Transforming growth factor (TGF)-beta is a multifunctional cytokine with anti-inflammatory, reparative and neuroprotective functions. Increased levels of TGFbeta in Alzheimer disease (AD) are associated perivascular deposition extracellular matrix, which may impair clearance beta-amyloid contribute to the development cerebral amyloid angiopathy. signaling transduced by Smad proteins: on receptor activation, Smads 2 3 released from sequestration microtubules, phosphorylated (forming...
Introduction Surgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients oesophageal cancer. Several surgical approaches can be used to remove an tumour. The Ivor Lewis (two-phase procedure) usually in UK. This performed as open oesophagectomy (OO), a laparoscopically assisted (LAO) or totally minimally invasive (TMIO). All three are National Health Service, LAO and OO most common. However, there limited evidence about which approach best terms...
Abstract Purpose Bariatric and metabolic surgery is an effective treatment for severe complex obesity; however, robust long-term data comparing operations lacking. Clinical registries complement clinical trials in contributing to this evidence base. Agreement on standard bariatric needed facilitate comparisons. This study developed a Core Registry Set (CRS) — core include globally. Materials Methods Relevant items were identified from research outcome set, registry dictionary project,...
Abnormalities of cerebral white matter are present in a majority patients with Alzheimer's disease (AD) and probably contribute to motor dysfunction cognitive impairment. The abnormalities usually attributed degenerative vascular amyloid angiopathy (CAA) but the evidence is scanty or inconclusive. In study we examined sections frontal lobe from 125 autopsy‐confirmed cases AD assessed relationship large small vessel disease, CAA, parenchymal Aβ load APOE genotype, several objective measures...
Background: The human branched chain aminotransferases (hBCATm, mitochondrial and hBCATc, cytosolic) are major contributors to brain glutamate production. This excitatory neurotransmitter is thought contribute neurotoxicity in neurodegenerative
Over 90% of patients with Alzheimer's disease (AD) develop cerebral amyloid angiopathy (CAA). Severe dyshoric CAA, in which extends into the surrounding brain parenchyma, may be associated adjacent clustering tau‐immunopositive neurites but relationship CAA to neurofibrillary pathology has not been systematically investigated. In present study this was examined sections frontal, temporal and parietal cortex from 25 AD moderate severe 26 mild or absent CAA. We measured immunolabelling...
Cerebral amyloid angiopathy (CAA) affects over 90% of patients with Alzheimer's disease (AD) and increases the risk cerebral haemorrhage infarction. Caveolae – cholesterol‐enriched plasmalemmal microinvaginations are implicated in production β peptide (Aβ). Caveolin‐1 (CAV‐1) is essential for formation caveolae. Caveolin‐2 (CAV‐2) expressed at plasma membrane only when a stable hetero‐oligomeric complex CAV‐1. CAV‐1 CAV‐2 highly co‐expressed by endothelium smooth muscle. Recent studies...
The aim was to develop and pilot a patient-reported outcome measure (PROM) assess symptoms of parastomal hernia (PSH).
Polymorphisms in the APOE promoter, ACE1 and CYP46 genes have all been reported to be associated with Alzheimer's disease (AD). We studied relationship of these polymorphisms presence AD 86 neuropathologically confirmed cases 58 controls. In addition, we assessed effects on accumulation beta-amyloid (Abeta) cerebral parenchyma vasculature. No association was observed between any AD, parenchymal Abeta load or severity amyloid angiopathy (CAA). Here report that within gene are not risk factors...
Abstract Background Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive interventions, including surgery. In-depth understanding component parts treatment intervention is needed ascertain what should, should not, delivered as part placebo. Assessment risk patients strategies ensure that placebo effectively mimics are also required. To date, no guidance exists This study aimed...