A5068470805- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Neurological diseases and metabolism
- Dysphagia Assessment and Management
- Prion Diseases and Protein Misfolding
- Extracellular vesicles in disease
- Neurological disorders and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Lipoproteins and Cardiovascular Health
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Functional Brain Connectivity Studies
- Neurology and Historical Studies
- Dementia and Cognitive Impairment Research
- Biochemical Acid Research Studies
- Cancer, Lipids, and Metabolism
- Studies on Chitinases and Chitosanases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Peripheral Neuropathies and Disorders
- Skin and Cellular Biology Research
- Autoimmune Neurological Disorders and Treatments
- Impact of Technology on Adolescents
University of Oxford
2016-2025
Oxford University Hospitals NHS Trust
2022-2025
John Radcliffe Hospital
2015-2024
Cornell University
2016
Kyoto Prefectural University of Medicine
2006
Universitat de Miguel Hernández d'Elx
2006
Associations of major lipids and apolipoproteins with the risk vascular disease have not been reliably quantified.To assess in risk.Individual records were supplied on 302,430 people without initial from 68 long-term prospective studies, mostly Europe North America. During 2.79 million person-years follow-up, there 8857 nonfatal myocardial infarctions, 3928 coronary heart [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic 2536 unclassified strokes.Hazard ratios (HRs), adjusted for several...
Nitrous oxide is increasingly being used as a recreational drug. Prolonged use of nitrous can have disabling neurological sequelae due to functional inactivation vitamin B<sub>12</sub>. We present three cases illustrating the complications using oxide. Two these patients received consequence repeated hospital attendance and third via 'Whippit' canisters in cream dispensers, which are now widely available. developed sensorimotor peripheral neuropathy with demyelinating features no clinical or...
The neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is a heterogeneous clinical syndrome involving multiple molecular pathways. development of biomarkers for use in therapeutic trials priority. We sought to high-throughput proteomic method identify novel individual cerebrospinal fluid (CSF) samples.Liquid chromatography/tandem mass spectrometry with label-free quantification was used CSF proteins using samples from well-characterized longitudinal cohort comprising patients...
As clinical evidence supports a negative impact of dysfunctional energy metabolism on the disease progression in amyotrophic lateral sclerosis, it is vital to understand how metabolic pathways are altered and whether they can be restored slow progression. Possible approaches include increasing or rerouting catabolism alternative fuel sources supplement glycolytic mitochondrial such as glycogen, ketone bodies nucleosides. To analyse basis catabolic defect sclerosis we used novel phenotypic...
Objective To evaluate the classifier performance, clinical and biochemical correlations of cerebrospinal fluid (CSF) levels chitinase proteins Chitotriosidase-1 (CHIT1), Chitinase-3-like protein 1 (CHI3L1) 2 (CHI3L2) in amyotrophic lateral sclerosis (ALS). Methods CSF CHIT1, CHI3L1, CHI3L2, phosphorylated neurofilament heavy chain (pNFH) C-reactive were measured by ELISA a longitudinal cohort patients with ALS (n=82), primary (PLS, n=10), ALS-mimic conditions (n=12), healthy controls (n=25)...
Abstract The routine clinical integration of individualized objective markers disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multicentre, clinic-based, longitudinal cohort was used to systematically appraise leading candidate biofluid biomarkers stratification and potential assessment sclerosis. Incident patients (n = 258), other neurological diseases 80) healthy control...
Abstract Objective biomarkers for the clinically heterogeneous adult-onset neurodegenerative disorder amyotrophic lateral sclerosis are crucial to facilitate assessing emerging therapeutics and improve diagnostic pathway in what is a syndrome. With non-coding RNA transcripts including microRNA, piwi-RNA transfer present human biofluids, we sought identify whether serum could be sclerosis. Serum samples from our Oxford Study Biomarkers motor neurone disease/amyotrophic discovery cohort of...
Extracellular vesicles (EVs) released by neurons and glia reach the cerebrospinal fluid (CSF). Studying proteome of CSF-derived EVs offers a novel perspective on key intracellular processes associated with pathogenesis neurodegenerative disease amyotrophic lateral sclerosis (ALS) potential source from which to develop biomarkers.CSF were extracted using ultrafiltration liquid chromatography ALS patients controls. EV size distribution concentration was measured nanoparticle tracking analysis...
Background Premorbid body mass index, physical activity, diabetes and cardiovascular disease have been associated with an altered risk of developing amyotrophic lateral sclerosis (ALS). There is evidence shared genetic between ALS lipid metabolism. A very large prospective longitudinal population cohort permits the study a range metabolic parameters subsequent diagnosis ALS. Methods The in those enrolled prospectively to UK Biobank (n=502 409) was examined relation baseline levels blood high...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the corticomotorneuronal network responsible for voluntary movement. There are well-established clinical, genetic and pathological overlaps between ALS frontotemporal dementia (FTD), which together constitute 'TDP-43 proteinopathies'. An ever-expanding list genes in mutation leads to typical have implicated abnormalities RNA processing, protein homoeostasis axonal transport. How these apparently distinct...
Abstract Objective To evaluate the CSF levels of chitinase proteins during presymptomatic and early symptomatic phases amyotrophic lateral sclerosis (ALS). Methods samples were obtained from 16 controls, 55 individuals at‐risk for ALS (including 18 carrying a mutation in C9ORF72 , 33 SOD1 ), 12 patients, 7 phenoconverters (individuals diagnosed with follow‐up). At‐risk enrolled through Pre‐fALS study, which includes an ALS‐associated gene without disease manifestations at initial assessment....
TDP-43 pathology is a key feature of amyotrophic lateral sclerosis (ALS), but the mechanisms linking to altered cellular function and neurodegeneration remain unclear. We have recently described mouse model in which human wild-type or mutant are expressed at low levels where stress granule formation robust phenotype TDP-43M337V/− expressing cells. In present study we use this investigate functional connectivity primary motor neurons under resting conditions response oxidative stress. The...
Key messages Raised blood levels of neurofilament light chain are found in a range conditions associated with neurological injuryUse is highly dependent on the clinical context, low independent diagnostic specificity and limited sensitivity to slowly progressive neuropathologyIn multiple sclerosis amyotrophic lateral sclerosis, measurement could have an role categorising evaluating therapeutic response for drug developmentFor primary dementias, measuring might prognostic value as part wider...
Cerebrospinal fluid (CSF) extracellular vesicles (EVs) show promise as a source of neurological disease biomarkers, although their precise origin is poorly understood. Current extraction techniques produce disappointing yield and purity. This study describes the application ultrafiltration LC (UFLC) to CSF-EVs, compared with ultracentrifugation (UC), explores CSF-EV origin. EVs are extracted from human CSF by UC UFLC characterized using nanoparticle tracking analysis, electron microscopy,...
Abstract Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the motor system marked by significant phenotypic heterogeneity. Motor symptoms in limbs consistently emerge focally and asymmetrically and, whilst variable, pattern regional progression related to balance clinical upper lower neuron signs, versus limb onset hand dominance some extent. The neurobiological mechanisms pathological correlates for this lateralised non-random are uncertain. Cerebral neuroimaging...
This article presents the findings of a 6-month service evaluation following addition computed tomography (CT) abdomen scan to gastrostomy placement pathway for patients with motor neurone disease (MND). Background: several had failed percutaneous endoscopic (PEG) placements. A CT was introduced identify if it would be possible place PEG or another such as radiologically inserted (RIG). Aims: To assess cost-effectiveness adding and evaluate improving patient experience. Method: Data from 1...
Abstract A biomarker specific for the diagnosis of amyotrophic lateral sclerosis must be sensitive across a spectrum clinical heterogeneity. Neurofilament light chain levels in correlate with rate disability progression. Previous attempts to establish diagnostic role neurofilament have been limited comparison healthy individuals or controls alternative diagnoses unlikely confused real-world practice. In tertiary referral clinic, at first visit, serum was taken measurement after prospectively...