Publications by authors named "Vicki Maltby"

Introduction: Newcastle, Australia, has been serially studied for MS epidemiology since 1961, showing consistently increasing prevalence estimates and incidence rates, including to our 2011 study.

Objectives: To assess the 2011-2021 epidemiology of MS in Newcastle and to compare with previous measures.

Methods: Demographic and clinical data were extracted from medical records of MS cases residing in Newcastle, as identified by public and private clinicians.

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  • - Cladribine (Mavenclad®) is an oral treatment for relapsing remitting multiple sclerosis (RRMS), but its effects on the immune system were previously unclear.
  • - A Phase IV study with 41 RRMS patients showed that cladribine significantly reduced the count of certain monocytes and altered levels of cytokines, notably increasing CCL2 at week 1 post-treatment.
  • - The study found that cladribine also affects the P2X7 receptor's activity, highlighting a new action mechanism that suggests further research into its potential use against other forms of MS and neurodegenerative diseases.
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Background: Many diets promoted specifically for multiple sclerosis have been suggested to improve disease activity. Dairy and gluten are two components for which the recommendations vary between these diets. Existing research into the association between these dietary components and disease activity has been conflicting.

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Background: Cognitive impairment is a hallmark of multiple sclerosis (MS) but is usually an under-recorded symptom of disease progression. Identifying the predictive signatures of cognitive decline in people with MS (pwMS) over time is important to ensure effective preventative treatment strategies. Structural and functional brain characteristics as measured by various magnetic resonance (MR) methods have been correlated with variation in cognitive function in MS, but typically these studies are limited to a single MR modality and/or are cross-sectional designs.

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Background And Purpose: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a relapsing demyelinating condition. There are several cross-sectional studies showing evidence of brain atrophy in people with MOGAD (pwMOGAD), but longitudinal brain volumetric assessment is still an unmet need. Current recommendations do not include monitoring with MRI and assume distinct attacks.

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  • Epigenetic mechanisms, like DNA methylation (DNAm), affect how DNA is expressed without altering the sequence and are linked to diseases, including multiple sclerosis (MS).
  • This study analyzed DNA methylation profiles in a large group of people with MS and found significant differences compared to healthy controls that are independent of known genetic risk factors.
  • The findings highlight that these methylation differences mainly occur in immune cells such as B cells and monocytes, shedding light on specific biological pathways involved in the disease.
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Background And Objectives: In multiple sclerosis (MS), accelerated aging of the immune system (immunosenescence) may be associated with disease onset or drive progression. DNA methylation (DNAm) is an epigenetic factor that varies among lymphocyte subtypes, and cell-specific DNAm is associated with MS. DNAm varies across the life span and can be used to accurately estimate biological age acceleration, which has been linked to a range of morbidities.

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Multiple sclerosis (MS) is an autoimmune, demyelinating disease with the highest incidence in women of childbearing age. The effect of pregnancy on disease activity and progression is a primary concern for women with MS and their clinical teams. It is well established that inflammatory disease activity is naturally suppressed during pregnancy, followed by an increase postpartum.

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Introduction: Multiple Sclerosis (MS) has a complex pathophysiology that involves genetic and environmental factors. DNA methylation (DNAm) is one epigenetic mechanism that can reversibly modulate gene expression. Cell specific DNAm changes have been associated with MS, and some MS therapies such as dimethyl fumarate can influence DNAm.

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Background: Pregnancy in women with multiple sclerosis (wwMS) is associated with a reduction of long-term disability progression. The mechanism that drives this effect is unknown, but converging evidence suggests a role for epigenetic mechanisms altering immune and/or central nervous system function. In this study, we aimed to identify whole blood and immune cell-specific DNA methylation patterns associated with parity in relapse-onset MS.

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Background: Cladribine is a useful therapeutic option in RRMS with moderate to high disease activity. Its oral formulation and tolerability make it a useful alternative to infusion therapies. Cladribine is known to deplete CD19 B lymphocytes, but its effect on immunoglobulin subsets is unclear.

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Article Synopsis
  • The study investigates how DNA methylation patterns are associated with the severity of relapse-onset multiple sclerosis (RMS), indicating potential genetic and environmental interactions that affect disease outcomes.
  • Researchers analyzed blood samples from 235 female patients with either mild or severe RMS, identifying 1,472 differentially methylated positions (DMPs) that correlated with disease severity.
  • The results showed that machine learning models using methylation data could classify disease severity more accurately (AUC = 0.91) compared to models using clinical data (AUC = 0.74), suggesting that DNA methylation could serve as a predictive biomarker for RMS.
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  • Cognitive impairment in multiple sclerosis (MS) affects not just health but also the economic burden associated with the disease, impacting employment and quality of life.
  • A study utilized various methods to gauge healthcare costs and quality of life, finding that cognitive performance metrics like memory and writing speed were negatively correlated with care costs.
  • These cognitive deficits are shown to be independently linked to the economic burden of MS, suggesting a need for routine monitoring in patient care.
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Background: Cladribine tablets (marketed as Mavenclad) are a new oral therapy, which has recently been listed on the pharmaceutical benefits scheme in Australia for the treatment of relapsing multiple sclerosis (MS). The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS for up to 4 years in 75% of patients (based on annualized relapse rate). However, the reinitiation of therapy after year 4 has not been studied.

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  • The study investigates DNA methylation profiles in CD4 T cells of progressive multiple sclerosis (MS) patients, aiming to understand the pathology of the disease.
  • It identifies three differentially methylated regions (DMRs) in genes HTR2A, SLC17A9, and HDAC4 that are consistent across two study cohorts, with HTR2A showing significant methylation differences independent of genetic variations.
  • The findings suggest that HTR2A's differential methylation could serve as a potential biomarker for progressive MS, distinguishing it from relapsing-remitting MS (RRMS), as no expression changes were detected in the DMRs.
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Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS).

Objective: To investigate the association of pregnancy with time to CIS onset.

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Background: Multiple sclerosis is a neurodegenerative, autoimmune disease of the central nervous system. Both peripheral blood and central nervous system facets play a role in the pathophysiology. Extracellular vesicles are small membrane-bound vesicles that are released by most cells in response to stress, activation, or pathology.

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Background: Multiple sclerosis is a demyelinating autoimmune disease, for which there is no blood-borne biomarker. Erythrocytes may provide a source of such biomarkers as they contain microRNAs. MicroRNAs regulate protein translation through complementary binding to messenger RNA.

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  • Cognitive impairment is prevalent in multiple sclerosis (MS) and often not effectively monitored by standard assessments; tools like the Audio Recorded Cognitive Screen (ARCS) and Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) can help in clinical settings.
  • A study analyzed the sensitivity of ARCS and BICAMS by assessing MS patients and healthy controls, revealing that ARCS had strong predictive ability for cognitive impairment and better identified higher levels of impairment compared to BICAMS.
  • Although both tests are similarly sensitive for cognitive dysfunction, memory assessments from either are the strongest indicators of employment status, with BICAMS being slightly more effective for predicting work productivity.
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  • Multiple Sclerosis (MS) is a complex disease that involves both inflammation and neurodegeneration in the central nervous system, primarily driven by immune cells like T and B cells.
  • This study focused on examining DNA methylation changes in CD19 B-cells to identify potential genetic factors that may increase MS risk.
  • Significant findings included a notable hypermethylated region at the lymphotoxin alpha (LTA) gene and smaller regions at other MS-related genes, indicating that B-cell DNA methylation could play a role in MS and may lead to new treatment strategies targeting these changes.
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  • DNA methylation is an epigenetic modification influenced by the environment that affects gene expression and is linked to diseases, including multiple sclerosis (MS).
  • In a study comparing T cells from women with relapsing remitting MS to healthy controls, researchers identified differentially methylated regions at several gene loci, specifically noting significant changes in the SLFN12 gene.
  • Corresponding gene expression analysis showed decreased expression of specific genes (HLA-DRB1, NINJ2, SLFN12) in the blood of MS patients, highlighting SLFN12 as a promising target for future research due to its role in T cell activation and response to treatment.
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Background: Dimethyl fumarate is an oral treatment for multiple sclerosis, whose mechanism of action is not fully understood.

Objective: To investigate the effects of dimethyl fumarate on DNA methylation in the CD4 T cells of multiple sclerosis patients.

Methods: We performed Illumina EPIC arrays to investigate the DNA methylation profiles of CD4 T cells derived from multiple sclerosis patients before and after dimethyl fumarate treatment.

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Background: There is a paucity of knowledge concerning erythrocytes in the aetiology of Multiple Sclerosis (MS) despite their potential to contribute to disease through impaired antioxidant capacity and altered haemorheological features. Several studies have identified an abundance of erythrocyte miRNAs and variable profiles associated with disease states, such as sickle cell disease and malaria. The aim of this study was to compare the erythrocyte miRNA profile of relapsing-remitting MS (RRMS) patients to healthy sex- and age-matched controls.

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DNA methylation is a dynamic epigenetic mechanism. Researchers aiming to assess archived DNA samples are expressing concern about the effect of technical factors on methylation, as this may confound results. We reviewed recent reports examining this issue in blood samples and concluded that variation in collection, storage, and processing of blood DNA confers negligible effects on both global methylation and methylation status of specific genes.

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