Association of socioeconomic status with clinical characteristics, care quality and outcomes in patients undergoing transcatheter aortic valve implantation.

Background: Socioeconomic status (SES) is an important determinant of healthcare outcomes in many settings, but few studies have evaluated the impact of SES among patients with aortic stenosis (AS). We sought to explore the association between SES and clinical characteristics, care quality and outcomes among patients undergoing transcatheter aortic valve implantation (TAVI) for severe AS.

Methods: Consecutive patients undergoing TAVI for severe AS at three hospitals between August 2008 and February 2023 were prospectively enrolled in a multicentre registry.

Evidence for Radiation Therapy in Stage III Locoregionally Advanced Cutaneous Melanoma in the Post-Immunotherapy Era: A Literature Review.

In the landscape of Stage III locoregionally advanced cutaneous melanoma treatment, the post-immunotherapy era has sparked a number of questions on the management of the nodal basin. However, much of the available literature is not focused on radiation therapy as an adjuvant therapy. This literature review aims to illuminate the evidence surrounding radiation therapy's potential to mitigate regional recurrences in the adjuvant setting for melanoma.

The cost-effectiveness of semaglutide in reducing cardiovascular risk among people with overweight and obesity and existing cardiovascular disease, but without diabetes.

Background And Aims: The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial demonstrated significant reductions in cardiovascular outcomes in people with cardiovascular disease (CVD) and overweight or obesity (but without diabetes). However, the cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. This study explored whether use of semaglutide for the secondary prevention of CVD in overweight or obesity is cost-effective from the Australian healthcare perspective.

O-GlcNAc regulates anti-fibrotic genes in lung fibroblasts through EZH2.

Epigenetic modifications are involved in fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), and contribute to the silencing of anti-fibrotic genes. H3K27me3, a key repressive histone mark, is catalysed by the methyltransferase enhancer of Zeste homologue 2 (EZH2), which is regulated by the post-translational modification, O-linked N-Acetylglucosamine (O-GlcNAc). In this study, we explored the effects of O-GlcNAc and EZH2 on the expression of antifibrotic genes, cyclooxygenase-2 (Cox2) and Heme Oxygenase (Homx1).

Impact of socioeconomic status on presentation, care quality and outcomes of patients attended by emergency medical services for dyspnoea: a population-based cohort study.

Background: Low socioeconomic status (SES) has been linked to poor outcomes in many conditions. It is unknown whether these disparities extend to individuals presenting with dyspnoea. We aimed to evaluate the relationship between SES and incidence, care quality and outcomes among patients attended by emergency medical services (EMS) for dyspnoea.

Chest Pain Management Using Prehospital Point-of-Care Troponin and Paramedic Risk Assessment.

Importance: Prehospital point-of-care troponin testing and paramedic risk stratification might improve the efficiency of chest pain care pathways compared with existing processes with equivalent health outcomes, but the association with health care costs is unclear.

Objective: To analyze whether prehospital point-of-care troponin testing and paramedic risk stratification could result in cost savings compared with existing chest pain care pathways.

Design, Setting, And Participants: In this economic evaluation of adults with acute chest pain without ST-segment elevation, cost-minimization analysis was used to assess linked ambulance, emergency, and hospital attendance in the state of Victoria, Australia, between January 1, 2015, and June 30, 2019.

Epigenetic regulation of IPF fibroblast phenotype by glutaminolysis.

Objective: Excessive extra-cellular-matrix production and uncontrolled proliferation of the fibroblasts are characteristics of many fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). The fibroblasts have enhanced glutaminolysis with up-regulated glutaminase, GLS1, which converts glutamine to glutamate. Here, we investigated the role of glutaminolysis and glutaminolysis-derived metabolite α-ketoglutarate (α-KG) on IPF fibroblast phenotype and gene expression.

Cost-Effectiveness of Empagliflozin in Patients With Heart Failure and Preserved Ejection Fraction.

Background: Empagliflozin is the first medication to demonstrate clinical benefit in patients with heart failure with preserved ejection fraction, but its cost-effectiveness is unknown. We aimed to evaluate the cost-effectiveness of adding empagliflozin to standard therapy in patients with heart failure with preserved ejection fraction.

Methods: A Markov model from the perspective of the Australian health care system was constructed to compare empagliflozin plus standard care to standard care alone among a hypothetical cohort of patients with heart failure with preserved ejection fraction.

Epidemiology, outcomes and predictors of mortality in patients transported by ambulance for dyspnoea: A population-based cohort study.

Objectives: There are currently limited data to inform the management of patients transported by emergency medical services (EMS) with dyspnoea. We aimed to describe the incidence, aetiology and outcomes of patients transported by EMS for dyspnoea using a large population-based sample and to identify factors associated with 30-day mortality.

Methods: Consecutive EMS attendances for dyspnoea in Victoria, Australia from January 2015 to June 2019 were included.

Sex-Specific Outcomes Following Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Disease: A Systematic Review and Meta-Analysis.

Objective: To assess whether outcomes following percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease differ between men and women.

Background: Current guidelines recommend either PCI or CABG for patients with unprotected LMCA disease and low-to-intermediate anatomical complexity. However, it is unclear whether these guidelines apply to women, who are underrepresented in clinical trials.

Modulation of H4K16Ac levels reduces pro-fibrotic gene expression and mitigates lung fibrosis in aged mice.

Histone H4 lysine16 acetylation (H4K16Ac) modulates chromatin structure by serving as a switch from a repressive to a transcriptionally active state. This euchromatin mark is associated with active transcription. In this study, we investigated the effects of H4K16Ac on the expression of pro-fibrotic genes in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and in an aging murine model of lung fibrosis.

Thirst interneurons that promote water seeking and limit feeding behavior in .

Thirst is a motivational state that drives behaviors to obtain water for fluid homeostasis. We identified two types of central brain interneurons that regulate thirsty water seeking in , that we term the Janu neurons. Janu-GABA, a local interneuron in the subesophageal zone, is activated by water deprivation and is specific to thirsty seeking.

Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation: A Health Economic Analysis.

Background: There is increasing evidence that use of intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes compared with angiography guidance alone. However, concern regarding the cost-effectiveness of IVUS has limited use of this technology worldwide. In this study, we aimed to evaluate the cost-effectiveness of IVUS-guided PCI compared with angiography-guided PCI in patients undergoing drug-eluting stent implantation.

Cost-Effectiveness of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Severe Aortic Stenosis.

Background: Recent studies have shown that transcatheter aortic valve implantation (TAVI) is non-inferior to surgical aortic valve replacement (SAVR) for treatment of low-risk patients with severe aortic stenosis (AS). However, the cost-effectiveness of TAVI in this population is unknown. We sought to evaluate the cost-effectiveness of both balloon-expandable and self-expanding TAVI compared to SAVR in patients with severe AS at low operative risk.

Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice.

Tissue regeneration capacity declines with aging in association with heightened oxidative stress. Expression of the oxidant-generating enzyme, NADPH oxidase 4 (Nox4), is elevated in aged mice with diminished capacity for fibrosis resolution. Bromodomain-containing protein 4 (Brd4) is a member of the bromodomain and extraterminal (BET) family of proteins that function as epigenetic "readers" of acetylated lysine groups on histones.

SUMOylation Protects FASN Against Proteasomal Degradation in Breast Cancer Cells Treated with Grape Leaf Extract.

Existing therapeutic strategies for breast cancer are limited by tumor recurrence and drug-resistance. Antioxidant plant-derived compounds such as flavonoids reduce adverse outcomes and have been identified as a potential source of antineoplastic agent with less undesirable side effects. Here, we describe the novel regulation of fatty-acid synthase (FASN), the key enzyme in de novo fatty-acid synthesis, whereby L.

Cost-effectiveness of transcatheter aortic valve implantation compared to surgical aortic valve replacement in the intermediate surgical risk population.

Background: The recent PARTNER S3i trial compared transcatheter aortic valve implantation (TAVI) using the third-generation SAPIEN 3 device to surgical aortic valve replacement (SAVR) in intermediate-risk patients with severe symptomatic aortic stenosis. Using data from PARTNER S3i, we performed a contemporary cost-effectiveness analysis of current-generation TAVI versus SAVR from the Australian healthcare system perspective.

Methods: A Markov model with monthly cycles and a ten-year horizon was constructed to estimate costs, life-years and quality adjusted life-years (QALYs) associated with TAVI and SAVR.

A Click Chemistry Approach Reveals the Chromatin-Dependent Histone H3K36 Deacylase Nature of SIRT7.

Using an engineered pyrrolysyl-tRNA synthetase mutant together with tRNA, we have genetically encoded N-(7-azidoheptanoyl)-l-lysine (AzHeK) by amber codon in Escherichia coli for recombinant expression of a number of AzHeK-containing histone H3 proteins. We assembled in vitro acyl-nucleosomes from these recombinant acyl-H3 histones. All these acyl-nucleosomes contained an azide functionality that allowed quick click labeling with a strained alkyne dye for in-gel fluorescence analysis.

Star-related lipid transfer protein 10 (STARD10): a novel key player in alcohol-induced breast cancer progression.

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events.

Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes.

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.

Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence.

In primary mammalian cells, oncogenic ras induces premature senescence, depending on an active MEK-extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. It has been unclear how activation of the mitogenic MEK-ERK pathway by ras can confer growth inhibition. In this study, we have found that the stress-activated MAPK, p38, is also activated during the onset of ras-induced senescence in primary human fibroblasts.