1,149 results match your criteria: "Department of Basic and Clinical Neuroscience[Affiliation]"

Determinants and progression of stigma in amyotrophic lateral sclerosis/motor neuron disease.

Amyotroph Lateral Scler Frontotemporal Degener

January 2025

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.

: Stigma in amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) may be felt or enacted; felt stigma covers feeling devalued by the illness, whereas enacted stigma refers to being treated differently because of it. Stigma in ALS/MND has been shown to increase social withdrawal, worsen quality of life, and reduce use of assistive devices, so we explored prevalence and factors influencing stigma. : Participants in the Trajectories of Outcome in Neurological Conditions-ALS study completed scales measuring stigma, fatigue, spasticity, functioning, mood, worry, self-esteem, and perceived health, as well as demographic information and symptoms like head drop or emotional lability.

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Antibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.

Nat Commun

December 2024

Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, SE1 9RT, UK.

The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection, and the specifics of entry, remain unclear. Using a panel of anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed a detailed assessment of antibody-mediated infection of monocytes/macrophages.

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Test, track, treat using wearable sensors for management of Parkinson's disease: 12‑month prospective observational United Arab Emirates study using Parkinson's Kinetograph (EmPark-PKG Study).

J Neural Transm (Vienna)

December 2024

Department of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 5 Cutcombe Road, London, SE5 9RX, UK.

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by both motor and non-motor symptoms that necessitate ongoing clinical evaluation and medication adjustments. Home-based wearable sensor monitoring offers a detailed and continuous record of patient symptoms, potentially enhancing disease management. The EmPark-PKG study aims to evaluate the effectiveness of the Parkinson's KinetoGraph (PKG), a wearable sensor device, in monitoring and tracking the progression of motor symptoms over 12 months in Emirati and non-Emirati PD patients.

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Early alterations of functional connectivity, regional brain volumes and astrocyte markers in the beta-sitosterol beta-d-glucoside (BSSG) rat model of parkinsonism.

Exp Neurol

December 2024

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Basic and Clinical Neuroscience, King's College London, London, UK. Electronic address:

The β-sitosterol-β-ᴅ-glucoside (BSSG) rat model of experimental parkinsonism develops pathological behaviour and motor changes that progress over time. The purpose of this study was to identify early changes in structure and function of the brain of rats treated with BSSG using both structural and resting-state functional MRI. BSSG and non-BSSG rats were fed five days a week for sixteen weeks, then underwent in vivo MRI scans and an assessment of motor performance 2 and 8 weeks later (18 and week 24 from BSSG).

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An expert consensus statement on biomarkers of ageing for use in intervention studies.

J Gerontol A Biol Sci Med Sci

December 2024

Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, UK.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

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Background: Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.

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Non-motor fluctuations in Parkinson's disease: underdiagnosed, yet important.

J Mov Disord

December 2024

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Non-motor fluctuations (NMF) in Parkinson's disease (PD) significantly affect patients' well-being. Despite being identified over two decades ago, NMF remain largely under-recognized, under-treated, and poorly understood. While they are often temporally associated with motor fluctuations (MF) and can share common risk factors and pathophysiologic mechanisms, NMF and MF are currently considered distinct entities.

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Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant 'local' genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation.

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Subcutaneous electroencephalography monitoring for people with epilepsy and intellectual disability: co-production workshops.

BJPsych Open

December 2024

Cornwall Intellectual Disability Equitable Research (CIDER), Cornwall Partnership NHS Foundation Trust, Bodmin, UK; and Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth, UK.

Background: Nearly 25% of people with intellectual disability (PwID) have epilepsy compared to 1% of the UK general population. PwID are commonly excluded from research, eventually affecting their care. Understanding seizures in PwID is particularly challenging because of reliance on subjective external observation and poor objective validation.

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Article Synopsis
  • Researchers used advanced computational models to explore how different histone marks affect gene expression but found previous approaches missed important factors like cell state and histone function.
  • The study examined seven histone marks in eleven cell types and discovered that no single histone mark consistently predicts gene expression, emphasizing the importance of considering histone function, genomic distance, and cellular context together.
  • The research also included simulations that revealed potential disease-related genetic loci and suggested new ways to leverage deep learning models for further biological discoveries.
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Case Summary: A 16-year-old spayed female domestic shorthair cat with methimazole-treated hyperthyroidism presented with a chronic progressive history of a stiff gait progressing to recumbency. A neurological examination revealed continuous excessive muscle tone with myokymia, which exacerbated with exercise and persisted during general anaesthesia. An electromyographic study revealed myokymic discharges in all tested muscles, as well as complex repetitive discharges, fibrillation potentials and positive sharp waves.

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Morphogen-driven differentiation is precluded by physical confinement in human iPSCs spheroids.

Front Bioeng Biotechnol

November 2024

Centre for Gene Therapy and Regenerative Medicine, King's College London, London, United Kingdom.

Introduction: Cell lineage specification is tightly associated with profound morphological changes in the developing human embryo, particularly during gastrulation. The interplay between mechanical forces and biochemical signals is poorly understood.

Methods: Here, we dissect the effects of biochemical cues and physical confinement on a 3D model based on spheroids formed from human induced pluripotent stem cells (hiPSCs).

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Article Synopsis
  • There is an increasing awareness of the early stages of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to new efforts aimed at prevention, largely driven by the participation of individuals at genetic risk. !* -
  • A recent workshop outlined recommendations for clinical care and lifestyle management tailored to those at elevated risk for ALS and FTD, covering aspects such as genetic testing, early symptom monitoring, and FDA-approved treatments. !* -
  • The guidance document seeks to inform both patients and healthcare providers about best practices and highlights the need for further research to strengthen evidence for future recommendations. !*
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Considerations in the search for epistasis.

Genome Biol

November 2024

Commonwealth Scientific and Industrial Research Organisation, Westmead, Australia.

Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability.

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A revised view of the role of CaMKII in learning and memory.

Nat Neurosci

November 2024

Department of Basic and Clinical Neuroscience, King's College London, London, UK.

The Ca/calmodulin (CaM)-dependent protein kinase II (CaMKII) plays a fundamental role in learning and possibly also in memory. However, current mechanistic models require fundamental revision. CaMKII autophosphorylation at Thr286 (pThr286) does not provide the molecular basis for long-term memory, as long believed.

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Neuromodulation with Transcranial Magnetic Stimulation in Epilepsia Partialis Continua: Scoping review and clinical experience.

Seizure

December 2024

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, United Kingdom; Department of Clinical Neurophysiology, King's College Hospital, London, United Kingdom; Department of Clinical Neurophysiology, Alder Hey Children's Hospital, London, United Kingdom.

Introduction: Epilepsia Partialis Continua (EPC) is a challenging condition in which repetitive transcranial magnetic stimulation (rTMS) can induce a neuromodulation effect of potential diagnostic and therapeutic value.

Methods: A comprehensive literature search was conducted using Pubmed and Web of Science databases to identify cases of EPC who underwent rTMS, including children and adults. Additionally, we present two patients from our centre who underwent rTMS at a low frequency (0.

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The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.

Cell Mol Life Sci

November 2024

Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary.

The complex neuronal architecture and the long distance of synapses from the cell body require precisely orchestrated axonal and dendritic transport processes to support key neuronal functions including synaptic signalling, learning and memory formation. Protein phosphorylation is a major regulator of both intracellular transport and synaptic functions. Some kinases and phosphatases such as cyclin dependent kinase-5 (cdk5)/p35, glycogen synthase kinase-3β (GSK3β) and protein phosphatase-1 (PP1) are strongly involved in these processes.

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From bite to brain: Neuro-immune interactions in food allergy.

Allergy

December 2024

Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK.

Immunoglobulin E (IgE)-mediated food allergies are reported to affect around 3.5% of children and 2.4% of adults, with symptoms varying in range and severity.

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Article Synopsis
  • The study evaluated the effectiveness of various behavioral screening tools for people with ALS, examining their internal consistency and inter-relationships.
  • A total of 84 informants participated, completing both paper and online versions of the screenings, with results showing significant predictive relationships among most tools.
  • Overall, while the tools varied in psychometric qualities, the method of administration (online vs. paper) did not significantly influence total scores.
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: The genetic underpinnings of Parkinson's disease (PD) and parkinsonism have drawn increasing attention in recent years. Mutations in the Factor-Induced Gene 4 ( have been implicated in various neurological disorders, including Charcot-Marie-Tooth disease type 4J (CMT4J), amyotrophic lateral sclerosis (ALS), and Yunis-Varón syndrome. This review aims to explore the association between mutations and parkinsonism, with a specific focus on the rare missense mutation p.

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Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data.

Cell Genom

November 2024

Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK; National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA; RNA Therapeutics Laboratory, National Center for Advancing Translational Sciences (NCATS), NIH, Rockville, MD 20850, USA. Electronic address:

Article Synopsis
  • Repeat expansions in the C9orf72 gene are a leading genetic cause of ALS and frontotemporal dementia, but understanding how this mutation causes neuron death is still unclear, complicating the search for effective therapies.
  • Researchers analyzed data from over 41,000 ALS and healthy samples to identify potential treatments, discovering that acamprosate, a drug used for other conditions, might be repurposed for C9orf72-related diseases.
  • Their findings demonstrated that acamprosate has neuroprotective properties in cell models and works similarly well as the current treatment, riluzole, showing the potential of using genomic data to find new drug applications.
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Article Synopsis
  • Wearable biosensors from the wrist can monitor seizures, but poor signal quality affects reliability, making it crucial to understand how seizures impact data quality during different phases.
  • The study evaluates the signal quality of various biosignals during different seizure types and examines the effects of peri-ictal movements on data accuracy.
  • Findings show that tonic-clonic seizures cause a significant drop in blood volume pulse signal quality and increase accelerometer activity, highlighting the need for improved data assessment methods in seizure monitoring.
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Article Synopsis
  • Traumatic brain injury (TBI) is a major global cause of long-term disability, and while imaging and fluid biomarkers show promise in predicting outcomes and complications soon after injury, assessments for ongoing symptoms in chronic cases remain limited.
  • New consensus criteria for traumatic encephalopathy syndrome, related to conditions like chronic traumatic encephalopathy, have only recently been established but may not apply to everyone experiencing chronic TBI effects.
  • Research on fluid biomarkers in chronic TBI indicates links to inflammation and neurodegeneration, suggesting the need for advanced methods to distinguish TBI from other neurodegenerative diseases, along with identifying future research priorities.
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