Urological outcomes in nonagenarians with prostate cancer.

Introduction: Nonagenarians represent a growing patient population. Herein, we report on the largest cohort of Canadian nonagenarian patients, to our knowledge, with prostate cancer.

Methods: A retrospective chart of 44 nonagenarian men diagnosed with localized or metastatic prostate cancer between 2006 and 2019 was performed.

Tissue physiology revolving around the clock: circadian rhythms as exemplified by the intervertebral disc.

Circadian clocks in the brain and peripheral tissues temporally coordinate local physiology to align with the 24 hours rhythmic environment through light/darkness, rest/activity and feeding/fasting cycles. Circadian disruptions (during ageing, shift work and jet-lag) have been proposed as a risk factor for degeneration and disease of tissues, including the musculoskeletal system. The intervertebral disc (IVD) in the spine separates the bony vertebrae and permits movement of the spinal column.

Fifteen-minute consultation: Fractures in non-ambulant children with cerebral palsy.

Objective: To describe a safeguarding decision pathway for the assessment of osteopenic fractures in non-ambulant children with cerebral palsy.

Method: Literature review and consensus practice of a child safeguarding team, including clinicians and social workers.

Conclusion: Low-energy fractures of the lower limb in non-ambulant children with cerebral palsy are relatively common and explained by the presence of reduced bone strength, in the absence of any other unexplained injuries or safeguarding concerns.

Vitamin D testing: Impact of changes to testing guidelines on detection of patients at risk of vitamin D deficiency.

Background: Changes were made to the Australian guidelines for vitamin D testing in November 2014 which restricted the patients who could be tested and reimbursed under the Medical Benefits Schedule. A retrospective study was conducted to assess the impact of the changes.

Methods: Data from 588,021 cases tested for vitamin D over the period of 2014 to 2017 were obtained and the results in 149,808 cases tested before the change in guidelines were compared to 438,213 cases tested afterwards.

Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study.

Background: The genetic basis of variation in the progression of primary tauopathies has not been determined. We aimed to identify genetic determinants of survival in progressive supranuclear palsy (PSP).

Methods: In stage one of this two stage genome-wide association study (GWAS), we included individuals with PSP, diagnosed according to pathological and clinical criteria, from two separate cohorts: the 2011 PSP GWAS cohort, from brain banks based at the Mayo Clinic (Jacksonville, FL, USA) and in Munich (Germany), and the University College London PSP cohort, from brain banks and the PROSPECT study, a UK-wide longitudinal study of patients with atypical parkinsonian syndromes.

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts.

Atypical UV Photoproducts Induce Non-canonical Mutation Classes Associated with Driver Mutations in Melanoma.

Somatic mutations in skin cancers and other ultraviolet (UV)-exposed cells are typified by C>T and CC>TT substitutions at dipyrimidine sequences; however, many oncogenic "driver" mutations in melanoma do not fit this UV signature. Here, we use genome sequencing to characterize mutations in yeast repeatedly irradiated with UV light. Analysis of ~50,000 UV-induced mutations reveals abundant non-canonical mutations, including T>C, T>A, and AC>TT substitutions.

Investigation of Somatic Mutations in Human Brains Targeting Genes Associated With Parkinson's Disease.

Somatic single nucleotide variant (SNV) mutations occur in neurons but their role in synucleinopathies is unknown. We aimed to identify disease-relevant low-level somatic SNVs in brains from sporadic patients with synucleinopathies and a monozygotic twin carrying 2 G2019S, whose penetrance could be explained by somatic variation. We included different brain regions from 26 Parkinson's disease (PD), one Incidental Lewy body, three multiple system atrophy cases, and 12 controls.

The Effectiveness of Transition Interventions to Support Older Patients From Hospital to Home: A Systematic Scoping Review.

Background: Interventions supporting older adults' transition from hospital to home can address geriatric needs. Yet this evidence base is fragmented. This review describes transitional interventions that provide pre- and post-discharge support for older adults and evaluates their implementation and effectiveness in improving health and well-being.

Genome-Wide Association Studies of Cognitive and Motor Progression in Parkinson's Disease.

Background: There are currently no treatments that stop or slow the progression of Parkinson's disease (PD). Case-control genome-wide association studies have identified variants associated with disease risk, but not progression. The objective of the current study was to identify genetic variants associated with PD progression.

Bridging the research-practice gap in healthcare: a rapid review of research translation centres in England and Australia.

Background: Large-scale partnerships between universities and health services are widely seen as vehicles for bridging the evidence-practice gap and for accelerating the adoption of new evidence in healthcare. Recently, different versions of these partnerships - often called academic health science centres - have been established across the globe. Although they differ in structure and processes, all aim to improve the integration of research and education with health services.

The Original Anatomic Reconstruction of Palmar and Dorsal Radioulnar Ligaments for Distal Radioulnar Joint Instability.

Thirty years ago, the first anatomic reconstruction of the palmar and dorsal radioulnar ligaments for chronic distal radioulnar joint (DRUJ) instability was proposed by Sanders. In this surgical technique, the midpoint of a free tendon autograft is firmly secured in a bony tunnel at the ulnar fovea. The 2 graft limbs anchored at the fovea traverse the DRUJ and are securely woven into the periarticular soft tissues radially, reproducing the ligamentous anatomy while not overconstraining the joint.

Psychosocial volunteer support for older adults with cognitive impairment: development of MyCare Ageing using a codesign approach via action research.

Background And Objectives: Older adults with cognitive impairment are vulnerable to frequent hospital admissions and emergency department presentations. The aim of this study was to use a codesign approach to develop MyCare Ageing, a programme that will train volunteers to provide psychosocial support to older people with dementia and/or delirium in hospital and at home when discharged from hospital.

Setting: Melbourne, Victoria, Australia.

The Cortical Basal ganglia Functional Scale (CBFS): Development and preliminary validation.

Objective: To develop a patient/care-giver reported scale capable of easily and reliably assessing functional disability in 4 repeat tauopathies (4RTs).

Background: 4R tauopathies including progressive supranuclear palsy, corticobasal degeneration and a subset of frontotemporal dementias manifest a range of overlapping clinical phenotypes. No available rating scale is capable of evaluating the functional impact of these complex disorders.

Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project.

Hereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity. Fifty percent of HSP patients remain yet genetically undiagnosed. The 100,000 Genomes Project (100KGP) is a large UK-wide initiative to provide genetic diagnosis to previously undiagnosed patients and families with rare conditions.

Site-specific characterization of SARS-CoV-2 spike glycoprotein receptor-binding domain.

The novel coronavirus SARS-CoV-2, the infective agent causing COVID-19, is having a global impact both in terms of human disease as well as socially and economically. Its heavily glycosylated spike glycoprotein is fundamental for the infection process, via its receptor-binding domains interaction with the glycoprotein angiotensin-converting enzyme 2 on human cell surfaces. We therefore utilized an integrated glycomic and glycoproteomic analytical strategy to characterize both N- and O- glycan site-specific glycosylation within the receptor-binding domain.

An Iterative Process for Identifying Pediatric Patients With Type 1 Diabetes: Retrospective Observational Study.

Background: The incidence of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in children and youth is increasing. However, the current approach for identifying pediatric diabetes and separating by type is costly, because it requires substantial manual efforts.

Objective: The purpose of this study was to develop a computable phenotype for accurately and efficiently identifying diabetes and separating T1DM from T2DM in pediatric patients.

Diabetes medication regimens and patient clinical characteristics in the national patient-centered clinical research network, PCORnet.

We used electronic medical record (EMR) data in the National Patient-Centered Clinical Research Network (PCORnet) to characterize "real-world" prescription patterns of Type 2 diabetes (T2D) medications. We identified a retrospective cohort of 613,203 adult patients with T2D from 33 datamarts (median patient number: 12,711) from 2012 through 2017 using a validated computable phenotype. We characterized outpatient T2D prescriptions for each patient in the 90 days before and after cohort entry, as well as demographics, comorbidities, non-T2D prescriptions, and clinical and laboratory variables in the 730 days prior to cohort entry.