Integrin beta-like 1 is regulated by DNA methylation and increased in heart failure patients.

Aims: Dynamic alterations in cardiac DNA methylation have been implicated in the development of heart failure (HF) with evidence of ischaemic heart disease (IHD); however, there is limited research into cell specific, DNA methylation sensitive genes that are affected by dysregulated DNA methylation patterns. In this study, we aimed to identify DNA methylation sensitive genes in the ischaemic heart and elucidate their role in cardiac fibrosis.

Methods: A multi-omics integrative analysis was carried out on RNA sequencing and methylation sequencing on HF with IHD (n = 9) versus non-failing (n = 9) left ventricular tissue, which identified Integrin beta-like 1 (ITGBL1) as a gene of interest.

Methanolic Extract of Phoenix Dactylifera Confers Protection against Experimental Diabetic Cardiomyopathy through Modulation of Glucolipid Metabolism and Cardiac Remodeling.

The incidence of cardiovascular disorders is continuously rising, and there are no effective drugs to treat diabetes-associated heart failure. Thus, there is an urgent need to explore alternate approaches, including natural plant extracts, which have been successfully exploited for therapeutic purposes. The current study aimed to explore the cardioprotective potential of (PD) extract in experimental diabetic cardiomyopathy (DCM).

Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta-analysis.

Introduction: Several landmark randomized-controlled trials (RCTs) have demonstrated the efficacy of sodium-glucose co-transport 2 (SGLT2) inhibitors in reducing all-cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanism of action and whether they have direct effects on reverse cardiac remodelling. Therefore, we conducted a meta-analysis of placebo controlled RCTs evaluating the impact of SGLT2 inhibition on imaging derived markers of reverse cardiac remodelling in patients with HF.

Unveiling impaired vascular function and cellular heterogeneity in diabetic donor-derived vascular organoids.

Vascular organoids (VOs), derived from induced pluripotent stem cells (iPSCs), hold promise as in vitro disease models and drug screening platforms. However, their ability to faithfully recapitulate human vascular disease and cellular composition remains unclear. In this study, we demonstrate that VOs derived from iPSCs of donors with diabetes (DB-VOs) exhibit impaired vascular function compared to non-diabetic VOs (ND-VOs).

Dose-dependent changes in cardiac function, strain and remodelling in a preclinical model of heart base irradiation.

Background And Purpose: Radiation induced cardiotoxicity (RICT) is as an important sequela of radiotherapy to the thorax for patients. In this study, we aim to investigate the dose and fractionation response of RICT. We propose global longitudinal strain (GLS) as an early indicator of RICT and investigate myocardial deformation following irradiation.

SGLT2 Inhibition in Heart Failure: Clues to Cardiac Effects?

Following the publication of several landmark clinical trials such as dapagliflozin in patients with heart failure and reduced ejection fraction, dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure, and empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction, sodium-glucose cotransport 2 inhibitors have been rapidly incorporated as a guideline-directed therapy in the treatment of heart failure. Moreover, their benefits appear to extend across the spectrum of left ventricular dysfunction which in some respects, can be seen as the holy grail of heart failure pharmacotherapy. Despite its plethora of proven cardioprotective benefits, the mechanisms by which it exerts these effects remain poorly understood, however, it is clear that these extend beyond that of promotion of glycosuria and natriuresis.

A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity.

Purpose: Despite technological advances in radiotherapy (RT), cardiotoxicity remains a common complication in patients with lung, oesophageal and breast cancers. Statin therapy has been shown to have pleiotropic properties beyond its lipid-lowering effects. Previous murine models have shown statin therapy can reduce short-term functional effects of whole-heart irradiation.

PLAC8-Mediated Activation of NOX4 Signalling Restores Angiogenic Function of Endothelial Colony-Forming Cells in Experimental Hypoxia.

Ischaemic cardiovascular disease is associated with tissue hypoxia as a significant determinant of angiogenic dysfunction and adverse remodelling. While cord blood-derived endothelial colony-forming cells (CB-ECFCs) hold clear therapeutic potential due to their enhanced angiogenic and proliferative capacity, their impaired functionality within the disease microenvironment represents a major barrier to clinical translation. The aim of this study was to define the specific contribution of NOX4 NADPH oxidase, which we previously reported as a key CB-ECFC regulator, to hypoxia-induced dysfunction and its potential as a therapeutic target.

Managing surgical waiting lists through dynamic priority scoring.

Prioritising elective surgery patients under the Australian three-category system is inherently subjective due to variability in clinician decision making and the potential for extraneous factors to influence category assignment. As a result, waiting time inequities can exist which may lead to adverse health outcomes and increased morbidity, especially for patients deemed to be low priority. This study investigated the use of a dynamic priority scoring (DPS) system to rank elective surgery patients more equitably, based on a combination of waiting time and clinical factors.

Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats.

Loss of retinal blood flow autoregulation is an early feature of diabetes that precedes the development of clinically recognizable diabetic retinopathy (DR). Retinal blood flow autoregulation is mediated by the myogenic response of the retinal arterial vessels, a process that is initiated by the stretch‑dependent activation of TRPV2 channels on the retinal vascular smooth muscle cells (VSMCs). Here, we show that the impaired myogenic reaction of retinal arterioles from diabetic animals is associated with a complete loss of stretch‑dependent TRPV2 current activity on the retinal VSMCs.

Spatial Gene Expression Changes in the Mouse Heart After Base-Targeted Irradiation.

Purpose: Radiation cardiotoxicity (RC) is a clinically significant adverse effect of treatment for patients with thoracic malignancies. Clinical studies in lung cancer have indicated that heart substructures are not uniformly radiosensitive, and that dose to the heart base drives RC. In this study, we aimed to characterize late changes in gene expression using spatial transcriptomics in a mouse model of base regional radiosensitivity.

Emergent craniotomy in rural and regional settings: recommendations from a tertiary neurosurgery unit: diagnosis and surgical decision-making.

Largely attributed to the tyranny of distance, timely transfer of patients with major traumatic brain injuries (TBI) from rural or regional hospitals to metropolitan trauma centres is not always feasible. This has warranted emergent craniotomies to be undertaken by non-neurosurgeons at their local hospitals with previous acceptable results reported in regional Australia. Our institution endorses this ongoing potentially life-saving practice when necessary and emphasize the need for neurosurgical units to provide ongoing TBI education to peripheral hospitals.

The Impact of COVID-19 on Acute Surgical Admissions at the Sunshine Coast University Hospital.

Purpose It has been noted in international literature that acute surgical admissions and number of operations reduced as a result of coronavirus disease2019 (COVID-19). This study assesses the impact of the COVID-19 pandemic on the number of acute surgical admissions, operations, and length of stay (LoS) at the Sunshine Coast University Hospital (SCUH), Queensland, Australia. Methodology A retrospective study was conducted on patients admitted to the Acute Surgical Unit (ASU) during March and April for the years 2018, 2019, and 2020.

A Rare Case of Intraperitoneal Desmoplastic Fibroblastoma.

Desmoplastic fibroblastoma is a benign soft tissue tumor of indolent nature. It is more prevalent in males in their fourth to sixth decades of life and typically presents in the upper extremities, feet, and back. Other, uncommon locations have been reported as well, including the oral cavity and retroperitoneum.

Emergent craniotomy in rural and regional settings - recommendations from a tertiary neurosurgery unit: surgical technique and future prospects.

Kenneth G Jamieson described the emergent craniotomy for traumatic brain injuries (TBI) in the rural and regional setting back in 1965 in his book 'A First Notebook Of Head Injury'. Since then, there has been successful use of the technique in peripheral hospitals prior to the safe transfer of patients to metropolitan trauma centres. Although the procedure can be daunting in inexperienced hands, our institution supports ongoing education to continue implementation of trauma craniotomies by non-neurosurgeons if it means another life is potentially saved.

FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail.

ECSIT is a critical limiting factor for cardiac function.

Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) is a protein with roles in early development, activation of the transcription factor NF-κB, and production of mitochondrial reactive oxygen species (mROS) that facilitates clearance of intracellular bacteria like Salmonella. ECSIT is also an important assembly factor for mitochondrial complex I. Unlike the murine form of Ecsit (mEcsit), we demonstrate here that human ECSIT (hECSIT) is highly labile.

Barriers-enablers-ownership approach: a mixed methods analysis of a social intervention to improve surgical antibiotic prescribing in hospitals.

Objectives: To assess an intervention for surgical antibiotic prophylaxis (SAP) improvement within surgical teams focused on addressing barriers and fostering enablers and ownership of guideline compliance.

Design: The Queensland Surgical Antibiotic Prophylaxis (QSAP) study was a multicentre, mixed methods study designed to address barriers and enablers to SAP compliance and facilitate engagement in self-directed audit/feedback and assess the efficacy of the intervention in improving compliance with SAP guidelines. The implementation was assessed using a 24-month interrupted time series design coupled with a qualitative evaluation.

Clearance of senescent cells during cardiac ischemia-reperfusion injury improves recovery.

A key component of cardiac ischemia-reperfusion injury (IRI) is the increased generation of reactive oxygen species, leading to enhanced inflammation and tissue dysfunction in patients following intervention for myocardial infarction. In this study, we hypothesized that oxidative stress, due to ischemia-reperfusion, induces senescence which contributes to the pathophysiology of cardiac IRI. We demonstrate that IRI induces cellular senescence in both cardiomyocytes and interstitial cell populations and treatment with the senolytic drug navitoclax after ischemia-reperfusion improves left ventricular function, increases myocardial vascularization, and decreases scar size.

Author Correction: Targeting QKI-7 in vivo restores endothelial cell function in diabetes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Epigenetic Regulation of Endothelial Cell Function by Nucleic Acid Methylation in Cardiac Homeostasis and Disease.

Pathological remodelling of the myocardium, including inflammation, fibrosis and hypertrophy, in response to acute or chronic injury is central in the development and progression of heart failure (HF). While both resident and infiltrating cardiac cells are implicated in these pathophysiological processes, recent evidence has suggested that endothelial cells (ECs) may be the principal cell type responsible for orchestrating pathological changes in the failing heart. Epigenetic modification of nucleic acids, including DNA, and more recently RNA, by methylation is essential for physiological development due to their critical regulation of cellular gene expression.