Identification of distinct immune signatures in inclusion body myositis by peripheral blood immunophenotyping using machine learning models.

Objective: Inclusion body myositis (IBM) is a progressive late-onset muscle disease characterised by preferential weakness of quadriceps femoris and finger flexors, with elusive causes involving immune, degenerative, genetic and age-related factors. Overlapping with normal muscle ageing makes diagnosis and prognosis problematic.

Methods: We characterised peripheral blood leucocytes in 81 IBM patients and 45 healthy controls using flow cytometry.

From data to diagnosis: how machine learning is revolutionizing biomarker discovery in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of muscle disorders including adult and juvenile dermatomyositis, polymyositis, immune-mediated necrotising myopathy and sporadic inclusion body myositis, all of which present with variable symptoms and disease progression. The identification of effective biomarkers for IIMs has been challenging due to the heterogeneity between IIMs and within IIM subgroups, but recent advances in machine learning (ML) techniques have shown promises in identifying novel biomarkers. This paper reviews recent studies on potential biomarkers for IIM and evaluates their clinical utility.

The 'PD Warrior' exercise programme improves motor outcomes and quality of life in patients with early Parkinson disease: results of a pilot study.

Background: 'PD Warrior' (PDW) is a popular exercise programme for Parkinson disease; however, there are no published studies on the outcomes of the programme.

Aims: To investigate short-term functional and quality of life (QoL) outcomes after the PDW 10-week programme in a pilot study of individuals with early Parkinson Disease (PD).

Methods: Twenty individuals with PD (Hoehn & Yahr 1-3) attending a hospital outpatient clinic were recruited into the PDW 10-week programme, comprising a weekly 1-h supervised class complemented by an individualised daily home exercise programme.

High-resolution HLA genotyping in inclusion body myositis refines 8.1 ancestral haplotype association to DRB1*03:01:01 and highlights pathogenic role of arginine-74 of DRβ1 chain.

Objectives: Inclusion body myositis (IBM) is a progressive inflammatory-degenerative muscle disease of older individuals, with some patients producing anti-cytosolic 5'-nucleotidase 1A (NT5C1A, aka cN1A) antibodies. Human Leukocyte Antigens (HLA) is the highest genetic risk factor for developing IBM. In this study, we aimed to further define the contribution of HLA alleles to IBM and the production of anti-cN1A antibodies.

A longitudinal study using B mode ultrasound and power Doppler as monitoring imaging tools in inclusion body myositis.

Objectives: There is growing interest in ultrasound (US) as an outcome measure in IBM. Our study aimed to determine the ability of B mode US and power Doppler (PD) to detect changes in affected muscles over time and if US domains correlate with disease progression.

Methods: Participants attended on four occasions over a median follow-up period of 26 months.

Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults.

Osteoporosis and Alzheimer's disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (Aβ) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into Aβ- (n = 65) and Aβ+ (n = 35) according to their brain Aβ load assessed using Aβ-PET (positron emission tomography) imaging.

The longitudinal study of muscle changes with ultrasound: differential changes in idiopathic inflammatory myopathy subgroups.

Objectives: We investigated shear wave elastography (SWE), B mode US and power Doppler (PDUS) as imaging biomarkers for longitudinal follow-up in idiopathic inflammatory myopathy (IIM), with a particular focus on immune-mediated necrotizing myopathy (IMNM) and DM.

Methods: Participants had serial SWE, PDUS on the deltoid (D) and vastus lateralis (VL) muscles on four occasions at intervals of 3-6 months. Clinical assessments included manual muscle testing, and patient- and physician-reported outcome scales.

Uncovering the significance of expanded CD8 large granular lymphocytes in inclusion body myositis: Insights into T cell phenotype and functional alterations, and disease severity.

Introduction: Inclusion body myositis (IBM) is a progressive inflammatory myopathy characterised by skeletal muscle infiltration and myofibre invasion by CD8 T lymphocytes. In some cases, IBM has been reported to be associated with a systemic lymphoproliferative disorder of CD8 T cells exhibiting a highly differentiated effector phenotype known as T cell Large Granular Lymphocytic Leukemia (T-LGLL).

Methods: We investigated the incidence of a CD8 T-LGL lymphoproliferative disorder in 85 IBM patients and an aged-matched group of 56 Healthy Controls (HC).

Quality of life implications for elevated trait impulsivity in people with Parkinson's disease.

Background: Several non-motor features of Parkinson's disease (PD) are known to adversely affect patient health-related quality of life (HRQL). However, the specific impact of neuropsychiatric complications, such as impulsive behaviour, is yet to be elucidated.

Objectives: The present cross-sectional, observational study aimed to investigate the effects of heightened trait impulsivity on HRQL in individuals with PD.

Impact of Gastrointestinal Symptoms on Health-Related Quality of Life in an Australian Parkinson's Disease Cohort.

Background: Gastrointestinal symptoms (GIS) in people with Parkinson's disease (PwP) are often underreported and may remain untreated. Constipation is a common nonmotor symptom that can adversely affect health-related quality of life (QoL); however, the impact of other GIS has not been adequately investigated.

Objectives: To investigate the relationship between QoL and constipation using the Bristol Stool Chart, bowel movement frequency, and a perceived constipation measure; and to explore the relationship between QoL and other GIS in an Australian PD cohort.

Immunoregulatory effects of testosterone supplementation combined with exercise training in men with Inclusion Body Myositis: a double-blind, placebo-controlled, cross-over trial.

Objectives: Sporadic Inclusion Body Myositis (IBM) is an inflammatory muscle disease affecting individuals over the age of 45, leading to progressive muscle wasting, disability and loss of independence. Histologically, IBM is characterised by immune changes including myofibres expressing major histocompatibility complex molecules and invaded by CD8 T cells and macrophages, and by degenerative changes including protein aggregates organised in inclusion bodies, rimmed vacuoles and mitochondrial abnormalities. There is currently no cure, and regular exercise is currently the only recognised treatment effective at limiting muscle weakening, atrophy and loss of function.

Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.

Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleotide (TTTA) repeat variant in NEFH was selected using an in-silico short structural variant (SSV) evaluation algorithm and investigated in two cohorts of North American sALS patients, both separately and combined (Duke cohort n = 138, Coriell cohort n = 333; combined cohort n = 471), compared to a group of healthy controls from the Coriell Institute biobank (n = 496). Stratification according to site of disease onset revealed that the 9 TTTA allele was associated with reduced disease risk, specifically confined to spinal-onset sALS patients in the Duke cohort (p = 0.

Muscle B mode ultrasound and shear-wave elastography in idiopathic inflammatory myopathies (SWIM): criterion validation against MRI and muscle biopsy findings in an incident patient cohort.

Background: B mode ultrasound (US) and shear wave elastography (SWE) are easily accessible imaging tools for idiopathic inflammatory myopathies (IIM) but require further validation against standard diagnostic procedures such as MRI and muscle biopsy.

Methods: In this prospective cross-sectional study we compared US findings to MRI and muscle biopsy findings in a group of 18 patients (11 F, 7 M) with active IIM (dermatomyositis 6, necrotising autoimmune myopathy 7, inclusion body myositis 4, overlap myositis 1) who had one or both procedures on the same muscle. US domains (echogenicity, fascial thickness, muscle bulk, shear wave speed and power doppler) in the deltoid and vastus lateralis were compared to MRI domains (muscle oedema, fatty infiltration/atrophy) and muscle biopsy findings (lymphocytic inflammation, myonecrosis, atrophy and fibro-fatty infiltration).

Assessment of the safety of the cationic arginine-rich peptides (CARPs) poly-arginine-18 (R18 and R18D) in models of mast cell degranulation and red blood cell hemolysis.

Our laboratory focuses on the development of novel neuroprotective cationic peptides, such poly-arginine-18 (R18: 18-mer of l-arginine; net charge +18) and its d-enantiomer R18D in stroke and other brain injuries. In the clinical development of R18/R18D, their cationic property raises potential safety concerns on their non-specific effects to induce mast cell degranulation and hemolysis. To address this, we first utilised primary human cultured mast cells (HCMCs) to examine anaphylactoid effects.

Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome.

Objective: To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT).

Methods: sNfL levels were measured using a sensitive single-molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB-PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.

Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson's Disease Cohort.

There has been increasing recognition of the importance of the gut microbiome in Parkinson's disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP). The study involved recruitment and assessment of 87 PwP from multiple Movement Disorders Clinics in Australia and 47 healthy controls.

Supporting Patient-Clinician Interaction in Chronic HIV Care: Design and Development of a Patient-Reported Outcomes Software Application.

Background: The consideration of health-related quality of life (HRQL) is a hallmark of best practice in HIV care. Information technology offers an opportunity to more closely engage patients with chronic HIV infection in their long-term management and support a focus on HRQL. However, the implementation of patient-reported outcome (PRO) measures, such as HRQL in routine care, is challenged by the need to synthesize data generated by questionnaires, the complexity of collecting data between patient visits, and the integration of results into clinical decision-making processes.

TOMM40 '523' poly-T repeat length is a determinant of longitudinal cognitive decline in Parkinson's disease.

The translocase of outer mitochondrial membrane 40 (TOMM40) '523' polymorphism has previously been associated with age of Alzheimer's disease onset and cognitive functioning in non-pathological ageing, but has not been explored as a candidate risk marker for cognitive decline in Parkinson's disease (PD). Therefore, this longitudinal study investigated the role of the '523' variant in cognitive decline in a patient cohort from the Parkinson's Progression Markers Initiative. As such, a group of 368 people with PD were assessed annually for cognitive performance using multiple neuropsychological protocols, and were genotyped for the TOMM40 '523' variant using whole-genome sequencing data.