4,683 results match your criteria: "University of Exeter College of Medicine & Health[Affiliation]"

Expanding the genetic and phenotypic landscape of replication factor C complex-related disorders: RFC4 deficiency is linked to a multisystemic disorder.

Am J Hum Genet

September 2024

National Institutes of Health Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Article Synopsis
  • DNA replication is crucial for cell division and maintaining genetic stability, with the RFC complex playing a key role by loading important proteins onto DNA.
  • While RFC1's involvement in certain disorders is recognized, the impact of RFC2-5 subunits, particularly RFC4, on human genetic diseases remains under-researched.
  • Our study identifies harmful variants in RFC4 linked to a new disorder marked by muscle weakness and hearing issues, showing how these variants disrupt RFC complex formation and ultimately affect DNA replication and cell cycle processes.
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Aims/hypothesis: Although statistical models for predicting type 1 diabetes risk have been developed, approaches that reveal the heterogeneity of the at-risk population by identifying clinically meaningful clusters are lacking. We aimed to identify and characterise clusters of islet autoantibody-positive individuals who share similar characteristics and type 1 diabetes risk.

Methods: We tested a novel outcome-guided clustering method in initially non-diabetic autoantibody-positive relatives of individuals with type 1 diabetes, using the TrialNet Pathway to Prevention study data (n=1123).

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Introduction: This study developed a proposed set of person-centred quality indicators (PC-QIs) for services that assess older adults' care and support needs to determine their eligibility to receive government-funded aged care services in Australia. Individual proposed PC-QIs amenability for change within current organizational structures were explored. Barriers and opportunities to adapt service elements of the aged care assessment service to better align with the intent of the proposed PC-QIs were identified.

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Using Organoids to Model Sex Differences in the Human Brain.

Biol Psychiatry Glob Open Sci

September 2024

Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages.

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Article Synopsis
  • Current estimates of genetic variants linked to Parkinson's disease (PD) show limitations and biases across different populations, complicating patient recruitment for clinical trials focused on genetic therapies.
  • The Rostock Parkinson's disease (ROPAD) study analyzes data from 12,580 PD patients across 16 countries, revealing that 14.8% had a genetic test positive for PD-related variants, particularly in specific genes like GBA1 and LRRK2.
  • Findings indicate higher positivity rates in patients with earlier onset (age ≤ 50) or a positive family history, emphasizing the need for more extensive genetic investigation to improve patient stratification for future clinical trials.
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[This corrects the article DOI: 10.3389/fnins.2023.

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Limited evidence of a shared genetic relationship between C-reactive protein levels and cognitive function in older UK adults of European ancestry.

Front Dement

August 2023

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.

Introduction: Previous studies have shown associations between cognitive function and C-reactive protein (CRP) levels in older adults. Few studies have considered the extent to which a genetic predisposition for higher CRP levels contributes to this association.

Methods: Data was analyzed from 7,817 UK participants aged >50 years as part of the PROTECT study, within which adults without dementia completed a comprehensive neuropsychological battery.

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Introduction: The National Registry of Rare Kidney Diseases (RaDaR) collects data from people living with rare kidney diseases across the UK, and is the world's largest, rare kidney disease registry. We present the clinical demographics and renal function of 25,880 prevalent patients and sought evidence of bias in recruitment to RaDaR.

Methods: RaDaR is linked with the UK Renal Registry (UKRR, with which all UK patients receiving kidney replacement therapy [KRT] are registered).

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We introduce a novel AI-driven approach to unsupervised fundus image registration utilizing our Generalized Polynomial Transformation (GPT) model. Through the GPT, we establish a foundational model capable of simulating diverse polynomial transformations, trained on a large synthetic dataset to encompass a broad range of transformation scenarios. Additionally, our hybrid pre-processing strategy aims to streamline the learning process by offering model-focused input.

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Mortality of patients with COPD.

Expert Rev Respir Med

June 2024

College of Medicine and Health, University of Exeter Medical School, University of Exeter, Exeter, UK.

Introduction: Chronic obstructive pulmonary disease (COPD) is the third most common cause of death worldwide and 24% of the patients die within 5 years of diagnosis.

Areas Covered: The epidemiology of mortality and the interventions that reduce it are reviewed. The increasing global deaths reflect increases in population sizes, increasing life expectancy and reductions in other causes of death.

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Penetrance is the probability that an individual with a pathogenic genetic variant develops a specific disease. Knowing the penetrance of variants for monogenic disorders is important for counseling of individuals. Until recently, estimates of penetrance have largely relied on affected individuals and their at-risk family members being clinically referred for genetic testing, a 'phenotype-first' approach.

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Impedance threshold device as a countermeasure for spaceflight associated neuro-ocular syndrome (SANS): Mitigating mechanisms in proposed pathophysiology.

Life Sci Space Res (Amst)

August 2024

Center for Space Medicine, Baylor College of Medicine, Houston, Texas, United States; Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, United States; The Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas, United States; Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medicine, New York, New York, United States; Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, United States; University of Texas MD Anderson Cancer Center, Houston, Texas, United States; Texas A&M College of Medicine, Bryan, Texas, United States; Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States. Electronic address:

Article Synopsis
  • - Long-duration spaceflight (LDSF) poses specific health risks, notably Spaceflight Associated Neuro-ocular Syndrome (SANS), linked to changes in fluid dynamics and increased pressure in the brain due to microgravity.
  • - SANS is unique to space environments, as there is no equivalent condition on Earth, although some studies attempt to simulate space conditions through bed rest and head-down tilting.
  • - Proposed solutions to combat SANS include using thigh cuffs for blood flow regulation and devices like the impedance threshold device (ITD) to help reduce intracranial pressure.
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Following the development of a value of vaccination (VoV) framework for health technology assessment/cost-effectiveness analysis (HTA/CEA), and identification of three vaccination benefits for near-term inclusion in HTA/CEA, this final paper provides decision makers with methods and examples to consider benefits of health systems strengthening (HSS), equity, and macroeconomic gains. Expert working groups, targeted literature reviews, and case studies were used. Opportunity cost methods were applied for HSS benefits of rotavirus vaccination.

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Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardiopulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer.

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A novel developmental critical period of orexinergic signaling in the primary visual thalamus.

iScience

July 2024

Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University in Krakow, Krakow, Poland.

The orexinergic system of the lateral hypothalamus plays crucial roles in arousal, feeding behavior, and reward modulation. Most research has focused on adult rodents, overlooking orexins' potential role in the nervous system development. This study, using electrophysiological and molecular tools, highlights importance of orexinergic signaling in the postnatal development of the rodent dorsolateral geniculate nucleus (DLG), a primary visual thalamic center.

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Pharmacists' Willingness to Offer Vaccination Services: A Systematic Review and Meta-Analysis.

Pharmacy (Basel)

June 2024

School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Pharmacy-based vaccination (PBV) services increase coverage and enhance access to lifesaving vaccines. This systematic review assessed the proportion of pharmacists willing to offer PBV services. PubMed/MEDLINE, CINAHL, EMBASE and Scopus electronic databases were searched from inception to identify relevant literature.

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The benefits of exercise have been widely explored among people with Parkinson's (PwP). Exercise can improve non-motor (fatigue, pain, sleep, etc.) and motor features (balance, muscle strength, gait speed, etc.

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Article Synopsis
  • The study analyzed how depressive symptoms changed in South Africa from March 2020 to 2021, focusing on individuals with and without pre-pandemic depression and the impact of food security.
  • High levels of depression were consistently found among those with pre-pandemic depression and food insecurity, while those without these factors reported the lowest levels.
  • The findings stress the need to prioritize mental health support and food security, especially during crises, as the relationship between these factors evolved throughout the pandemic.
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What do medical students think are characteristics of a good ultrasound tutor? A qualitative study.

BMC Med Educ

July 2024

Institute of Primary Health Care (BIHAM), University of Bern, Mittelstrasse 43, Bern, CH-3012, Switzerland.

Purpose: This study was designed to elicit medical students' opinions on the characteristics of a good ultrasound tutor. The results should help educators to create an optimal teaching environment and inform tutor training.

Materials And Methods: The qualitative study recruited 15 participants from a larger mixed-methods study of 64 medical students who underwent a basic course on abdominal ultrasound taught by faculty and near-peer tutors.

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Excess adipose tissue may promote chronic systemic inflammation and oxidative stress, causing endothelial damage. Early evidence indicates that obesity may be associated with poorer cerebral perfusion. The purpose of this study was to examine the relationship between body composition and cerebral hemodynamics.

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Article Synopsis
  • - This study seeks to better classify individuals with multiple long-term health conditions (MLTCs) by identifying specific clusters of these conditions across various age groups and their links to negative health outcomes and healthcare utilization.
  • - Researchers employed latent class analysis on data from large cohorts, including over 1.8 million individuals, to determine how different MLTC clusters impact mortality, hospital hospitalizations, and general practitioner usage over ten years.
  • - Findings indicated that certain MLTC clusters, particularly those involving cardiometabolic and pain/mental health issues, showed strong associations with higher risks of mortality and healthcare use, particularly in younger and middle-aged individuals, while data from the UKHLS group did not reveal significant risks.
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