A5103028523- Inflammatory Bowel Disease
- Biosimilars and Bioanalytical Methods
- Microscopic Colitis
- Pharmaceutical studies and practices
- RNA and protein synthesis mechanisms
- Health Systems, Economic Evaluations, Quality of Life
- Immunodeficiency and Autoimmune Disorders
- Biotin and Related Studies
- Adolescent and Pediatric Healthcare
- Genetic Syndromes and Imprinting
- Electrochemical sensors and biosensors
- Endoplasmic Reticulum Stress and Disease
- Genomics and Phylogenetic Studies
- Parathyroid Disorders and Treatments
- Fungal and yeast genetics research
- Enzyme function and inhibition
- Pharmaceutical Economics and Policy
- Congenital gastrointestinal and neural anomalies
- RNA modifications and cancer
- Colorectal Cancer Treatments and Studies
- RNA Research and Splicing
- Genomics and Rare Diseases
- Eosinophilic Esophagitis
- Chronic Lymphocytic Leukemia Research
- Biochemical Analysis and Sensing Techniques
University of Southampton
2021-2025
University Hospital Southampton NHS Foundation Trust
2019-2025
Southern District Health Board
2017
University of Washington
2009-2017
Human Genome Sciences (United States)
2014
Mayo Clinic in Florida
2010-2011
Mayo Clinic
2011
WinnMed
2011
University of Nevada, Reno
2007
Geisinger Health System
2004-2006
Patient access to their electronic health care record (EHR) and Web-based communication between patients providers can potentially improve the quality of care, but little is known about patients' attitudes toward this combined access. The objective our study was evaluate values perceptions regarding with primary in context record.We conducted an online survey 4,282 members Geisinger Health System who are registered users application (MyChart) that allows communicate electronically view...
It is believed that depending on the thermodynamic stability of 5′-strand and 3′-strand in stem-loop structure a precursor microRNA (pre-miRNA), cells preferentially select less stable one (called miRNA or guide strand) destroy other miRNA* passenger strand). However, our expression profiling analyses revealed both strands could be co-accumulated as pairs some tissues while being subjected to strand selection tissues. Our target prediction validation assays demonstrated pair equal numbers...
Interpreting variants of uncertain significance (VUS) is a central challenge in medical genetics. One approach to experimentally measure the functional consequences VUS, but date this has been post hoc and low throughput. Here we use massively parallel assays effects nearly 2000 missense substitutions RING domain BRCA1 on its E3 ubiquitin ligase activity binding BARD1 domain. From resulting scores, generate model predict capacities full-length support homology-directed DNA repair, essential...
The RNA recognition motif (RRM) is the most common RNA-binding domain in eukaryotes. Differences RRM sequences dictate, part, both and protein-binding specificities affinities. We used a deep mutational scanning approach to study sequence-function relationship of RRM2 Saccharomyces cerevisiae poly(A)-binding protein (Pab1). By scoring activity more than 100,000 unique Pab1 variants, including 1246 with single amino acid substitutions, we delineated constraints on each residue. Clustering...
Sequence variation in tRNA genes influences the structure, modification, and stability of tRNA; affects translation fidelity; impacts activity numerous isodecoders metazoans; leads to human diseases. To comprehensively define effects sequence on function, we developed a high-throughput vivo screen quantify model tRNA, nonsense suppressor SUP4oc Saccharomyces cerevisiae. Using highly sensitive fluorescent reporter gene with an ochre mutation, fluorescence-activated cell sorting library mutant...
Biosynthetic pathways of phosphatidylcholine and triglyceride were studied in proliferating hepatic endoplasmic reticulum rats pretreated with phenobarbital.Phosphatidylcholine accounted for the major increment membrane phospholipid.In vitro measurements microsomal enzymes which catalyze biosynthesis revealed a significant increase specific activity enzyme governing synthesis by sequential methylation phosphatidylethanolamine.The phosphorylcholine-glyceride transferase, catalyzes from D-1...
Subcutaneous [SC] vedolizumab presents the opportunity for inflammatory bowel disease [IBD] patients to manage their treatment at home. There are currently no data on process of transitioning established intravenous [IV] SC as part routine clinical care. The aim this programme is evaluate and biochemical outcomes switching a cohort IBD IV SC, 12 weeks following transition.
Gastrointestinal functions decline with ageing leading to impaired quality of life, and increased morbidity mortality. Neurodegeneration is believed underlie ageing-associated dysmotilities but the mechanisms have not been fully elucidated. We used progeric mice deficient in anti-ageing peptide Klotho investigate contribution key cell types gastric musculature changes stomach function underlying mechanisms. expression, enteric neurons, interstitial cells Cajal (ICC), smooth muscle electrical...
Abstract Background Risankizumab is an IL-23 inhibitor which received approval for Crohn’s disease (CD) by the NICE committee in May 2023. Our aim was to evaluate real-world outcomes of risankizumab United Kingdom (UK). Methods We conducted a retrospective, multicentre, cohort study across twenty health boards UK, patients with CD treated between 1st January, 2021 and November 2024. primary outcome treatment persistence at 6 months. secondary endpoints were persistence, steroid-free clinical...
Filgotinib, an oral Janus kinase 1 preferential inhibitor, has been shown to be effective treatment for ulcerative colitis (UC) in pre-registration studies. We aimed describe the population, effectiveness and safety of filgotinib a real-world cohort patients with UC. A retrospective observational evaluation was conducted across nine UK inflammatory bowel disease centres. Baseline demographic clinical data, activity scores, endoscopic indices, biomarkers (C-reactive protein faecal...
Pathways of phosphatidylcholine and triglyceride biosynthesis were studied in hepatic endoplasmic reticulum from castrated noncastrated male rats pretreated with estradiol or testosterone. In vitro measurements microsomal enzymes which catalyze revealed a significant increase the specific activity enzyme governing by sequential methylation phosphatidylethanolamine estradiol-treated castrate animals. The phosphorylcholine-glyceride transferase was decreased treatment both noncastrate...
To understand the effectiveness of ustekinumab in treating Crohn's disease (CD) a UK real-world setting. Retrospective cohort study using prospectively maintained clinical records. Single inflammatory bowel centre. Adult patients with an established diagnosis CD prescribed outside trials at University Hospital Southampton (UHS). Ustekinumab, monoclonal antibody to shared p40 subunit interleukin (IL) 12 and IL-23 as part routine care. Effectiveness measured by improvement physician's global...
Many protein interactions are conserved among organisms despite changes in the amino acid sequences that comprise their contact sites, a property has been used to infer location of these sites from homology. In an inter-species complementation experiment, sequence present homologue is substituted into and tested for its ability support function. Therefore, substitutions inhibit function can identify interaction changed over evolution. However, most differences within family remain unexplored...
Background Gastrointestinal symptoms, particularly constipation, increase with aging, but their underlying mechanisms are poorly understood due to lack of experimental models. Previously we established the progeric klotho mouse as a model aging-associated anorexia and gastric dysmotility. We also detected reduced fecal output in these animals; therefore, aim this study was investigate vivo function cellular make-up small intestinal colonic neuromuscular apparatus. Methods Klotho expression...
Progress in DNA-sequencing technologies has provided a catalogue of millions DNA variants the human population, but characterization functional effects these lagged far behind. For example, sequencing tumor samples is driving an urgent need to classify whether or not mutations seen cancers affect disease progression treatment effectiveness instead are benign. Furthermore, can interact with genetic background and environmental effects. A new approach, termed deep mutational scanning, enabled...
Microorganisms have universally adapted their RNAs and proteins to survive at a broad range of temperatures growth conditions. However, for RNAs, there is little quantitative understanding the effects mutations on function high temperatures. To understand how variant tRNA affected by temperature change, we used nonsense suppressor SUP4 oc yeast Saccharomyces cerevisiae perform high-throughput screen two different This yielded comparative values 9243 single double variants. Surprisingly,...
Antimicrobial resistance is a globally recognised health emergency. Intensive care an area with significant antimicrobial consumption, particularly increased utilisation of broad-spectrum antibacterials, making stewardship programmes essential. We aimed to explore antibacterial partnered pathogen surveillance, over five-year period (2018 2023) in tertiary referral adult general intensive unit (ICU). The mean number admissions was 1645 per annum. A comparison between the ICU populations...
<h3>Objectives</h3> Transition from originator biological medicines to their biosimilar equivalents is now part of routine clinical practice, but there little understanding patient experiences, which influence adherence and overall satisfaction with care. Understanding this will help ensure future switches adequately address patients' concerns expectations leading better outcomes for all stakeholders. <h3>Method</h3> 35 patients participating in a trial including an open-label transition...
Abstract Background and Aim New Zealand (NZ) has one of the highest rates non‐melanoma skin cancers (NMSCs) in world. Thiopurine use inflammatory bowel disease (IBD) patients been shown to increase NMSC risk. This study aimed investigate possible risk thiopurine‐treated IBD NZ despite high background rate. Methods Inflammatory treated with thiopurines healthy controls were recruited across two different latitude centers NZ. Consented participants completed a questionnaire identify additional...