Protocol for a randomised controlled unblinded feasibility trial of HD-DRUM: a rhythmic movement training application for cognitive and motor symptoms in people with Huntington's disease.

Introduction: Huntington's disease (HD) is an inherited neurodegenerative disease causing progressive cognitive and motor decline, largely due to basal ganglia (BG) atrophy. Rhythmic training offers promise as therapy to counteract BG-regulated deficits. We have developed HD-DRUM, a tablet-based app to enhance movement synchronisation skills and improve cognitive and motor abilities in people with HD.

Estimation of Gait Parameters in Huntington's Disease Using Wearable Sensors in the Clinic and Free-living Conditions.

In Huntington's disease (HD), wearable inertial sensors could capture subtle changes in motor function. However, disease-specific validation of methods is necessary. This study presents an algorithm for walking bout and gait event detection in HD using a leg-worn accelerometer, validated only in the clinic and deployed in free-living conditions.

Language-Independent Acoustic Biomarkers for Quantifying Speech Impairment in Huntington's Disease.

Purpose: Changes in voice and speech are characteristic symptoms of Huntington's disease (HD). Objective methods for quantifying speech impairment that can be used across languages could facilitate assessment of disease progression and intervention strategies. The aim of this study was to analyze acoustic features to identify language-independent features that could be used to quantify speech dysfunction in English-, Spanish-, and Polish-speaking participants with HD.

Searching for information about stem cells online in an age of artificial intelligence: How should the stem cell community respond?

Patients and their families routinely use the Internet to learn about stem cell research. What they find, is increasingly influenced by ongoing changes in how information is filtered and presented online. This article reflects on recent developments in generative artificial intelligence and how the stem cell community should respond.

A systematic review on adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in individuals with mild cognitive impairment and Alzheimer's disease dementia.

Obstructive sleep apnoea (OSA) is highly prevalent in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The gold standard treatment for OSA is continuous positive airway pressure (CPAP). Long-term, well-powered efficacy trials are required to understand whether CPAP could slow cognitive decline in individuals with MCI/AD, but its tolerability in this group remains uncertain.

Considerations for clinical trial design and conduct in the evaluation of novel advanced therapeutics in neurodegenerative disease.

The recent advances in the development of potentially disease modifying cell and gene therapies for neurodegenerative disease has resulted in the production of a number of promising novel therapies which are now moving forward to clinical evaluation. The robust evaluation of these therapies pose a significant number of challenges when compared to more traditional evaluations of pharmacotherapy, which is the current mainstay of neurodegenerative disease symptom management. Indeed, there is an inherent complexity in the design and conduct of these trials at multiple levels.

Physical activity and exercise outcomes in Huntington's disease (PACE-HD): results of a 12-month trial-within-cohort feasibility study of a physical activity intervention in people with Huntington's disease.

Introduction: While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention.

Methods: Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.

Monitoring and Managing Lifestyle Behaviors Using Wearable Activity Trackers: Mixed Methods Study of Views From the Huntington Disease Community.

Background: There are early indications that lifestyle behaviors, specifically physical activity and sleep, may be associated with the onset and progression of Huntington disease (HD). Wearable activity trackers offer an exciting opportunity to collect long-term activity data to further investigate the role of lifestyle, physical activity, and sleep in disease modification. Given how wearable devices rely on user acceptance and long-term adoption, it is important to understand users' perspectives on how acceptable any device might be and how users might engage over the longer term.

Translating cell therapies for neurodegenerative diseases: Huntington's disease as a model disorder.

There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain.

Objectively characterizing Huntington's disease using a novel upper limb dexterity test.

Background: The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent validity of the C3t as a simple, objective assessment of impairment that is reflective of disease severity in Huntington's, that is not reliant on clinical expertise for administration.

Methods: One-hundred-and-five participants presenting with pre-manifest (n = 16) or manifest (TFC-Stage-1 n = 39; TFC-Stage-2 n = 43; TFC-Stage-3 n = 7) Huntington's disease completed the Unified Huntington's Disease Rating Scale and the C3t at baseline.

Protocol for an open label: phase I trial within a cohort of foetal cell transplants in people with Huntington's disease.

Huntington's disease is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric symptoms. Currently, no disease-modifying therapies are available to slow or halt disease progression. Huntington's disease is characterized by relatively focal and specific loss of striatal medium spiny neurons, which makes it suitable for cell-replacement therapy, a process involving the transplantation of donor cells to replace those lost due to disease.

A randomised feasibility study of computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD).

Background: Huntington's disease (HD) is associated with a range of cognitive deficits including problems with executive function. In the absence of a disease modifying treatment, cognitive training has been proposed as a means of slowing cognitive decline; however, the impact of cognitive training in HD patient populations remains unclear. The CogTrainHD study assessed the feasibility and acceptability of home-based computerised executive function training, for people impacted by HD.

Pregnancy and weight monitoring: A feasibility study of weight charts and midwife support.

Around half of pregnant women in the United Kingdom are overweight or obese. The antenatal period provides an opportunity for encouraging women to adopt positive lifestyle changes, and in recent years, this has included development of strategies to support women in avoiding excessive gestational weight gain. The objective of this interventional cohort study was to incorporate individualised gestational weight monitoring charts supported by motivational interviewing (MI)-based conversations into midwifery-led antenatal care and assess potential of the intervention for further development and evaluation.

A protocol for a randomised controlled, double-blind feasibility trial investigating fluoxetine treatment in improving memory and learning impairments in patients with mesial temporal lobe epilepsy: Fluoxetine, Learning and Memory in Epilepsy (FLAME trial).

Background: People with temporal lobe epilepsy (TLE) report significant problems with learning and memory. There are no effective therapies for combatting these problems in people with TLE, resulting in an unmet therapeutic need. The lack of treatment is, in part, due to a poor understanding of the neurobiology underlying these memory deficits.

Physical Activity and Exercise Outcomes in Huntington Disease (PACE-HD): Protocol for a 12-Month Trial Within Cohort Evaluation of a Physical Activity Intervention in People With Huntington Disease.

Background: Exercise is emerging as an important aspect in the management of disease-related symptoms and functional decline in people with Huntington disease (HD). Long-term evaluation of physical activity and exercise participation in HD has yet to be undertaken.

Objective: The objective is to investigate the feasibility of a nested randomized controlled trial (RCT) alongside a longitudinal observational study of physical activity and exercise outcomes in people with HD.

Exploring computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD): protocol for a randomised feasibility study.

Background: Cognitive impairments, especially deficits of executive function, have been well documented as a core and early feature in Huntington's disease (HD). Cognitive impairments represent considerable burden and can be devastating for people and families affected by HD. Computerised cognitive training interventions that focus on improving executive function present a possible non-pharmacological treatment option.

Seal or Varnish? A randomised controlled trial to determine the relative cost and effectiveness of pit and fissure sealant and fluoride varnish in preventing dental decay.

Background: Fissure sealant (FS) and fluoride varnish (FV) have been shown to be effective in preventing dental caries when tested against a no-treatment control. However, the relative clinical effectiveness and cost-effectiveness of these interventions is unknown.

Objective: To compare the clinical effectiveness and cost-effectiveness of FS and FV in preventing dental caries in first permanent molars (FPMs) in 6- and 7-year-olds and to determine their acceptability.

Physical Activity Self-Management and Coaching Compared to Social Interaction in Huntington Disease: Results From the ENGAGE-HD Randomized, Controlled Pilot Feasibility Trial.

Background: Self-management and self-efficacy for physical activity is not routinely considered in neurologic rehabilitation.

Objective: This study assessed feasibility and outcomes of a 14-week physical activity self-management and coaching intervention compared with social contact in Huntington disease (HD) to inform the design of a future full-scale trial.

Design: Assessor blind, multisite, randomized pilot feasibility trial.

Integrating technology into complex intervention trial processes: a case study.

Background: Trials of complex interventions are associated with high costs and burdens in terms of paperwork, management, data collection, validation, and intervention fidelity assessment occurring across multiple sites. Traditional data collection methods rely on paper-based forms, where processing can be time-consuming and error rates high. Electronic source data collection can potentially address many of these inefficiencies, but has not routinely been used in complex intervention trials.

The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial.

Background: Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers.

Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy.

Background: Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy.

Methods: We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy.

Development and Delivery of a Physical Activity Intervention for People With Huntington Disease: Facilitating Translation to Clinical Practice.

Background And Purpose: We studied the development and delivery of a 14-week complex physical activity intervention for people with Huntington disease, where detailed information about the intervention was fully embedded in the trial design process.

Methods: Intervention Development: The intervention was developed through a series of focus groups. The findings from the focus groups informed the development of a logic model for the physical activity intervention that was broadly consistent with the framework of self-determination theory.

New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms.

Hyperekplexia is a syndrome of readily provoked startle responses, alongside episodic and generalized hypertonia, that presents within the first month of life. Inhibitory glycine receptors are pentameric ligand-gated ion channels with a definitive and clinically well stratified linkage to hyperekplexia. Most hyperekplexia cases are caused by mutations in the α1 subunit of the human glycine receptor (hGlyR) gene (GLRA1).