Bicycling for Rehabilitation of Persons With Parkinson Disease: A Scoping Review.

Background And Purpose: Exercise is beneficial for persons with Parkinson disease (PwPD). The overarching purpose of this scoping review was to provide guidance to clinicians and scientists regarding current evidence for bicycling exercise for PwPD. A scoping review was conducted to examine the heterogeneous literature on stationary bicycling for PwPD to reduce motor symptoms and body function structure impairments, improve activities and motor performance, and reduce disease severity.

Modification of Huntington's disease by short tandem repeats.

Expansions of glutamine-coding CAG trinucleotide repeats cause a number of neurodegenerative diseases, including Huntington's disease and several of spinocerebellar ataxias. In general, age-at-onset of the polyglutamine diseases is inversely correlated with the size of the respective inherited expanded CAG repeat. Expanded CAG repeats are also somatically unstable in certain tissues, and age-at-onset of Huntington's disease corrected for individual CAG repeat length (i.

Expanding student nurse placement activity in Welsh care homes: An evaluation study.

Aim: Expanding and sustaining student nurse placements outside of the acute sector is a universal challenge. This paper aims to evaluate the Care Home Education Facilitator Role introduced in one area of Wales, United Kingdom, and to report on the outcomes achieved from this novel role.

Methods: Semi-structured interviews were undertaken with key stakeholders including the Care Home Education Facilitator postholder leading the pilot, care home managers, higher education institutions' placement managers/coordinators, student nurses and national health service staff.

Mutant huntingtin confers cell-autonomous phenotypes on Huntington's disease iPSC-derived microglia.

Huntington's disease (HD) is a neurodegenerative disorder caused by a dominantly inherited CAG repeat expansion in the huntingtin gene (HTT). Neuroinflammation and microglia have been implicated in HD pathology, however it has been unclear if mutant HTT (mHTT) expression has an adverse cell-autonomous effect on microglial function, or if they are only activated in response to the neurodegenerative brain environment in HD. To establish a human cell model of HD microglia function, we generated isogenic controls for HD patient-derived induced pluripotent stem cells (iPSC) with 109 CAG repeats (Q109).

Views and experiences of opioid access amongst palliative care providers and public representatives in a low-resource setting: A qualitative interview study.

Opioids (e.g. morphine) are affordable, effective interventions for cancer-related pain.

Large libraries of single-chain trimer peptide-MHCs enable antigen-specific CD8+ T cell discovery and analysis.

The discovery and characterization of antigen-specific CD8 T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapt single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We use this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality.

'It's tough. It is hard': A qualitative interview study of staff and volunteers caring for hospice in-patients with delirium.

Background: Delirium is a distressing condition often experienced by hospice in-patients. Increased understanding of current multidisciplinary care of delirium is needed to develop interventions in this setting.

Aim(s): To explore hospice staff and volunteers' practice, its influences and what may need to change to improve hospice delirium care.

Repeat Detector: versatile sizing of expanded tandem repeats and identification of interrupted alleles from targeted DNA sequencing.

Targeted DNA sequencing approaches will improve how the size of short tandem repeats is measured for diagnostic tests and preclinical studies. The expansion of these sequences causes dozens of disorders, with longer tracts generally leading to a more severe disease. Interrupted alleles are sometimes present within repeats and can alter disease manifestation.

Large libraries of single-chain trimer peptide-MHCs enable rapid antigen-specific CD8+ T cell discovery and analysis.

CD8 + cytotoxic T cell responses against viral infection represent a major element of the adaptive immune response. We describe the development of a peptide antigen - major histompatibility complex (pMHC) library representing the full SARS-CoV-2 viral proteome, and comprised of 634 pMHC multimers representing the A*02.01, A*24.

Introducing the '3 Fs model of complexity' for people with dementia accessing a NHS mental health inpatient dementia assessment ward: An interpretive description study.

Background: In the United Kingdom, the use of the terms 'complex' and 'complexity' alongside dementia is reflected in a number of policy and practice documents. However, there is a lack of evidence that explores how complexity is perceived, constructed and experienced by people with dementia, family carers and practitioners working in the NHS dementia inpatient assessment wards [dementia assessment wards].

Objective: To explore the meaning and concept of complexity in dementia from within the setting of a dementia assessment ward and develop a practice model.

Challenges and opportunities for cervical screening in women over the age of 50 years: a qualitative study.

Background: Cervical cancer is a preventable disease. Cases in women age >50 years are predicted to rise by 60% in the next two decades, yet this group are less likely to attend for screening than younger women.

Aim: To seek novel solutions to the challenges of cervical screening in women >50 years of age by examining practitioner and service-user experiences.

Huntington's disease age at motor onset is modified by the tandem hexamer repeat in TCERG1.

Huntington's disease is caused by an expanded CAG tract in HTT. The length of the CAG tract accounts for over half the variance in age at onset of disease, and is influenced by other genetic factors, mostly implicating the DNA maintenance machinery. We examined a single nucleotide variant, rs79727797, on chromosome 5 in the TCERG1 gene, previously reported to be associated with Huntington's disease and a quasi-tandem repeat (QTR) hexamer in exon 4 of TCERG1 with a central pure repeat.

Translating qualitative data into intervention content using the Theoretical Domains Framework and stakeholder co-design: a worked example from a study of cervical screening attendance in older women.

Background: Previous screening interventions have demonstrated a series of features related to social determinants which have increased uptake in targeted populations, including the assessment of health beliefs and barriers to screening attendance as part of intervention development. Many studies cite the use of theory to identify methods of behaviour change, but fail to describe in detail how theoretical constructs are transformed into intervention content. The aim of this study was to use data from a qualitative exploration of cervical screening in women over 50 in the UK as the basis of intervention co-design with stakeholders using behavioural change frameworks.

Exome sequencing of individuals with Huntington's disease implicates FAN1 nuclease activity in slowing CAG expansion and disease onset.

The age at onset of motor symptoms in Huntington's disease (HD) is driven by HTT CAG repeat length but modified by other genes. In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We discovered damaging coding variants in candidate modifier genes identified in previous genome-wide association studies associated with altered HD onset or severity.

Genetic modifiers of Huntington disease differentially influence motor and cognitive domains.

Genome-wide association studies (GWASs) of Huntington disease (HD) have identified six DNA maintenance gene loci (among others) as modifiers and implicated a two step-mechanism of pathogenesis: somatic instability of the causative HTT CAG repeat with subsequent triggering of neuronal damage. The largest studies have been limited to HD individuals with a rater-estimated age at motor onset. To capitalize on the wealth of phenotypic data in several large HD natural history studies, we have performed algorithmic prediction by using common motor and cognitive measures to predict age at other disease landmarks as additional phenotypes for GWASs.

Multiple early factors anticipate post-acute COVID-19 sequelae.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms.

Prostate cancer: unmet supportive and palliative care needs: national survey of patients and family carers.

Objectives: Men living with prostate cancer have supportive and palliative needs. However, few studies detail unmet needs (vs quality of life measurement) or include data from those with advanced disease. We aimed to identify unmet needs of people living with prostate cancer (men, family carers), including those with advanced disease.

The unique information and communication needs of men affected by prostate cancer: A qualitative study of men's experience.

Objective: The objective of this study is to explore the specific information and communication needs of men affected by prostate cancer to inform the development of educational materials for clinicians.

Methods: This is a qualitative descriptive study. A purposive sampling strategy was used to identify men at different cancer stages and with experience of different treatment regimens.

Association Analysis of Chromosome X to Identify Genetic Modifiers of Huntington's Disease.

Background: Huntington's disease (HD) is caused by an expanded (>35) CAG trinucleotide repeat in huntingtin (HTT). Age-at-onset of motor symptoms is inversely correlated with the size of the inherited CAG repeat, which expands further in brain regions due to somatic repeat instability. Our recent genetic investigation focusing on autosomal SNPs revealed that age-at-onset is also influenced by genetic variation at many loci, the majority of which encode genes involved in DNA maintenance/repair processes and repeat instability.

Timing and Impact of Psychiatric, Cognitive, and Motor Abnormalities in Huntington Disease.

Objective: To assess the prevalence, timing, and functional impact of psychiatric, cognitive, and motor abnormalities in Huntington disease (HD) gene carriers, we analyzed retrospective clinical data from individuals with manifest HD.

Methods: Clinical features of patients with HD were analyzed for 6,316 individuals in an observational study of the European Huntington's Disease Network (REGISTRY) from 161 sites across 17 countries. Data came from clinical history and the patient-completed Clinical Characteristics Questionnaire that assessed 8 symptoms: motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis.

What is the Pathogenic CAG Expansion Length in Huntington's Disease?

Huntington's disease (HD) (OMIM 143100) is caused by an expanded CAG repeat tract in the HTT gene. The inherited CAG length is known to expand further in somatic and germline cells in HD subjects. Age at onset of the disease is inversely correlated with the inherited CAG length, but is further modulated by a series of genetic modifiers which are most likely to act on the CAG repeat in HTT that permit it to further expand.

Huntington's Disease Pathogenesis: Two Sequential Components.

Historically, Huntington's disease (HD; OMIM #143100) has played an important role in the enormous advances in human genetics seen over the past four decades. This familial neurodegenerative disorder involves variable onset followed by consistent worsening of characteristic abnormal movements along with cognitive decline and psychiatric disturbances. HD was the first autosomal disease for which the genetic defect was assigned to a position on the human chromosomes using only genetic linkage analysis with common DNA polymorphisms.