Publications by authors named "Lancaster G"

Oxidation of lipids, excessive cell death and iron deposition are prominent features of human atherosclerotic plaques. While extensive research has established the detrimental roles of lipid oxidation and apoptosis in atherosclerosis development, the involvement of iron in atherogenesis is not yet fully understood. With the emergence of an iron-dependent form of cell death termed ferroptosis, new attention has been brought to the complex interplay among iron, ferroptosis and atherosclerosis.

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Background: Liver cirrhosis is not included in surgical risk prediction models despite being a significant risk factor associated with high periprocedural morbidity and mortality in patients undergoing cardiac surgery. Limited contemporary data exists assessing the outcomes of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with cirrhosis.

Methods: Patients with cirrhosis who underwent TAVR or SAVR were identified from the Nationwide Readmissions Database.

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Background: Self-harm in young people is a growing concern and reducing rates a global priority. Rates of self-harm documented in general practice have been increasing for young people in the UK in the last two decades, especially in 13-16-year-olds. General practitioners (GPs) can intervene early after self-harm but there are no effective treatments presently available.

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Background: General practitioners (GPs) are key to the frontline assessment and treatment of young people after self-harm. Young people value GP-led self-harm care, but little is known about how GPs manage young people after self-harm.

Aim: This study aimed to understand the approaches of GPs to self-harm in young people and explore their perspectives on ways they might help young people avoid repeat self-harm.

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The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis. Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell function and when disrupted immune cell function is impaired. There are numerous metabolic diseases whereby systemic lipid metabolism and cellular function is impaired.

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Infective endocarditis (IE), with its high morbidity and mortality, is a frequent complication of injection drug use (IDU). We present a case highlighting the complexities in the management of IDU-associated IE (IDU-IE) in a 46-year-old male with active IDU who presented with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia and a large tricuspid valve vegetation. Urgent tricuspid valve surgery was indicated due to the size of the vegetation measuring up to 4 cm, along with recurrent pulmonary septic emboli.

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Article Synopsis
  • Huntington's disease is a neurodegenerative disorder caused by a mutation in the huntingtin protein, leading to symptoms like chorea and cognitive decline due to neuronal death.
  • Recent research highlights the importance of the neurovascular unit in understanding the disease, particularly the effects of the mutant huntingtin protein on brain function.
  • A study compared presymptomatic and symptomatic Huntington's disease patients to healthy controls, revealing reduced neurovascular phase coherence and lower efficiency of oxygen transport to the brain, indicating impaired neurovascular function in both patient groups.
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Introduction: Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals.

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The cellular lipidome comprises thousands of unique lipid species. Here, using mass spectrometry-based targeted lipidomics, we characterize the lipid landscape of human and mouse immune cells ( www.cellularlipidatlas.

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Aim: Acyl-coenzyme A dehydrogenase family member 10 (ACAD10) is a mitochondrial protein purported to be involved in the fatty acid oxidation pathway. Metformin is the most prescribed therapy for type 2 diabetes; however, its precise mechanisms of action(s) are still being uncovered. Upregulation of ACAD10 is a requirement for metformin's ability to inhibit growth in cancer cells and extend lifespan in Caenorhabditis elegans.

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Alzheimer's disease (AD) is associated with both extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles (NFT). We characterized the behavioral, metabolic and lipidomic phenotype of the 5xFADxTg30 mouse model which contains overexpression of both Aβ and tau. Our results independently reproduce several phenotypic traits described previously for this model, while providing additional characterization.

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The risk of neurodegenerative disorders increases with age, due to reduced vascular nutrition and impaired neural function. However, the interactions between cardiovascular dynamics and neural activity, and how these interactions evolve in healthy aging, are not well understood. Here, the interactions are studied by assessment of the phase coherence between spontaneous oscillations in cerebral oxygenation measured by fNIRS, the electrical activity of the brain measured by EEG, and cardiovascular functions extracted from ECG and respiration effort, all simultaneously recorded.

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Objective: Caring for a child with cystic fibrosis (CF) is a rigorous daily commitment for caregivers and treatment burden is a major concern. We aimed to develop and validate a short form version of a 46-item tool assessing the Challenge of Living with Cystic Fibrosis (CLCF) for clinical or research use.

Design: A novel genetic algorithm based on 'evolving' a subset of items from a pre-specified set of criteria, was applied to optimise the tool, using data from 135 families.

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Objectives: The leading cause of mortality in patients with rheumatoid arthritis is atherosclerotic cardiovascular disease (CVD). We have shown that murine arthritis impairs atherosclerotic lesion regression, because of cellular cholesterol efflux defects in haematopoietic stem and progenitor cells (HSPCs), causing monocytosis and impaired atherosclerotic regression. Therefore, we hypothesised that improving cholesterol efflux using a Liver X Receptor (LXR) agonist would improve cholesterol efflux and improve atherosclerotic lesion regression in arthritis.

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Article Synopsis
  • - The study aimed to determine the impact of colchicine and high-intensity rosuvastatin on the progression of COVID-19 in hospitalized patients, compared to standard care alone.
  • - Conducted as a randomized controlled trial across four centers within the Yale New Haven Health System, it involved 250 non-critically ill hospitalized COVID-19 patients, with a follow-up period of 30 days.
  • - The trial was halted early for futility, as there was no notable difference in severe disease progression or thromboembolic events between the treatment group and the control group.
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In 2016, we published a conceptual framework outlining the conclusions of our work in defining pilot and feasibility studies. Since then, the CONSORT extension to randomised pilot and feasibility trials has been published and there have been further developments in the pilot study landscape. In this paper, we revisit and extend our framework to incorporate the various feasibility pathways open to researchers, which include internal pilot studies.

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Introduction: Children's early development is affected by caregiving experiences, with lifelong health and well-being implications. Governments and civil societies need population-based measures to monitor children's early development and ensure that children receive the care needed to thrive. To this end, the WHO developed the Global Scales for Early Development (GSED) to measure children's early development up to 3 years of age.

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Introduction: With the ratification of the Sustainable Development Goals, there is an increased emphasis on early childhood development (ECD) and well-being. The WHO led Global Scales for Early Development (GSED) project aims to provide population and programmatic level measures of ECD for 0-3 years that are valid, reliable and have psychometrically stable performance across geographical, cultural and language contexts. This paper reports on the creation of two measures: (1) the GSED Short Form (GSED-SF)-a caregiver reported measure for population-evaluation-self-administered with no training required and (2) the GSED Long Form (GSED-LF)-a directly administered/observed measure for programmatic evaluation-administered by a trained professional.

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Article Synopsis
  • The low dose short Synacthen test (LDSST) was found to be more sensitive but less specific than the standard test for diagnosing adrenal insufficiency based on meta-analyses.
  • A retrospective study analyzed outcomes of LDSSTs conducted between 2008-2014 and 2016-2020, involving a total of 495 patients, investigating factors like cortisol levels, age, and sex.
  • Results indicated that 70% of participants had a normal cortisol response, with abnormal results more common in patients with prior glucocorticoid treatment, suggesting rare occurrences of overdiagnosis within the clinical setting.
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Objective: Treatments for cystic fibrosis (CF) are complex, labour-intensive, and perceived as highly burdensome by caregivers of children with CF. An instrument assessing burden of care is needed.

Design: A stepwise, qualitative design was used to create the CLCF with caregiver focus groups, participant researchers, a multidisciplinary professional panel, and cognitive interviews.

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Adipose-tissue-resident macrophages (ATMs) maintain metabolic homeostasis but also contribute to obesity-induced adipose tissue inflammation and metabolic dysfunction. Central to these contrasting effects of ATMs on metabolic homeostasis is the interaction of macrophages with fatty acids. Fatty acid levels are increased within adipose tissue in various pathological and physiological conditions, but appear to initiate inflammatory responses only upon interaction with particular macrophage subsets within obese adipose tissue.

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Temporary central venous hemodialysis (HD) catheters are commonly used in end-stage renal disease (ESRD) patients while awaiting peritoneal dialysis catheter, arterio-venous fistula or graft placement and maturation. Catheter-related right atrial thrombus (CRAT) is a common finding in patients with central venous catheters (CVCs) and can cause CVC to malfunction. The incidence of CRAT is about 29% with a mortality of 18.

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Background: Despite improvement in the standard of care (SOC) for hospitalized COVID-19 patients, rates of morbidity and mortality remain high. There continues to be a need for easily available and cost-effective treatments. Colchicine and rosuvastatin are both safe and well-studied medications with anti-inflammatory and other pleiotropic effects that may provide additional benefits to hospitalized COVID-19 patients.

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