Connections Reduce Rheumatic Heart Disease-Related Mortality in Western Australia: A Mixed Methods Study.

Introduction: Preventable rheumatic heart disease (RHD) deaths continue to occur in Australia, with Aboriginal people disproportionately affected. Despite research into structural drivers and the lived experience of people with RHD, and national guidelines focusing on RHD prevention and treatment, recent coronial inquests have highlighted that systemic failures are ongoing. Few studies describe RHD service delivery and/or mortality within the Western Australian (WA) context.

Navigating challenges and adherence in time-restricted eating: A qualitative study.

Aims: Adherence to any dietary approach is crucial for achieving long-term benefits. This qualitative study aims to explore the facilitators and barriers to adherence, and how individuals in community settings navigate time-restricted eating in their daily lives.

Methods: Semi-structured, in-depth interviews were conducted with 21 participants who had practised time-restricted eating (confining the daily eating window to <10h a day; and excluding periodic fasting methods like the 5:2 approach or alternate day fasting) for periods ranging from 3 months to more than 5 years.

Time-Restricted Eating in Real-World Healthcare Settings: Utilisation and Short-Term Outcomes Evaluation.

Background: Time-restricted eating (TRE) shows promise for managing weight and metabolic issues, yet its application in real-world healthcare settings remains underexplored. This study aims to assess the real-world utilisation and short-term outcomes of TRE in clinical practice.

Methods: This observational study used a retrospective chart review of 271 adults who attended a metabolic specialist clinic between 2019 and 2023.

Phthalates Impair Estrogenic Regulation of HIF2α and Extracellular Vesicle Secretion by Human Endometrial Stromal Cells.

Di(2-ethylhexyl) phthalate (DEHP), a known endocrine-disrupting chemical, is a plasticizer found in many common consumer products. High levels of DEHP exposure have been linked to adverse pregnancy outcomes, yet little is known about how it affects human uterine functions. We previously reported that the estrogen-regulated transcription factor hypoxia-inducible factor 2 alpha (HIF2α) promotes the expression of Rab27b, which controls the trafficking and secretion of extracellular vesicles (EVs).

Comparative Algorithms for Identifying and Counting Hospitalisation Episodes of Care for Coronary Heart Disease Using Administrative Data.

Purpose: Measures of disease burden using hospital administrative data are susceptible to over-inflation if the patient is transferred during their episode of care. We aimed to identify and compare measures of coronary heart disease (CHD) and myocardial infarction (MI) episodes using six algorithms that account for transfers.

Patient And Methods: We used person-linked hospitalisations for CHD and MI for 2000-2016 in Western Australia based on the interval between discharge and subsequent admission (date, datetime algorithms), pathway (admission source, discharge destination) and any combination to generate machine learning models (random forest [RF], gradient boosting machine [GBM]).

Prevalence of dementia among Indigenous populations of countries with a very high Human Development Index: a systematic review.

Dementia is a health priority for Indigenous peoples. Here, we reviewed studies on the prevalence of dementia or cognitive impairment among Indigenous populations from countries with a very high Human Development Index (≥0·8). Quality was assessed using the Joanna Briggs Institute risk-of-bias tool and CONSolIDated critERia for strengthening the reporting of health research involving Indigenous peoples (CONSIDER), with oversight provided by an Indigenous Advisory Board.

Discovery of ERD-12310A as an Exceptionally Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα).

Inhibition of estrogen receptor alpha (ERα) signaling is an established therapeutic approach for the treatment of ER-positive (ER+) breast cancers, but new therapeutic strategies are urgently needed to overcome clinical resistance. In the present study, we describe the discovery and extensive evaluation of ERD-12310A as an exceptionally potent and orally efficacious PROTAC degrader of ERα. ERD-12310A achieved a DC value of 47 pM and is 10 times more potent than ARV-471.

"It just made sense to me!" A Qualitative Exploration of Individual Motivation for Time-Restricted Eating.

Time-Restricted Eating (TRE), a form of intermittent fasting, has gained popularity for weight control and metabolic health. It is not incorporated into dietary and clinical guidelines, and hence is generally not being recommended to the public. This qualitative study explores how individuals have discovered TRE as a form of dietary practice and their motivations for practising it.

Iterative Catalyst-Controlled Diastereoselective Matteson Homologations Enable the Selective Synthesis of Benzestrol Isomers.

We report the development of an iterative Matteson homologation reaction with catalyst-controlled diastereoselectivity through the design of a new catalyst. This reaction was applied to the selective synthesis of each stereoisomer of benzestrol, a bioactive compound with estrogenic activity featuring three contiguous stereocenters. The different stereoisomers were assayed to determine their binding affinity for the estrogen receptor α (ERα), and the absolute configuration of the compound having uniquely high activity was determined.

Pattern of hospital admissions and costs associated with acute rheumatic fever and rheumatic heart disease in Australia, 2012-2017.

Objective This study aims to describe the pattern and trends in acute rheumatic fever (ARF)/rheumatic heart disease (RHD)-related hospitalisations and costs for Australians aged <65 years. Methods This retrospective linked data study measured trends in hospitalisations and costs for ARF, RHD and complications of ARF/RHD in Northern Territory, South Australia, Western Australia, Queensland and New South Wales between 1 July 2012 and 30 June 2017. Persons with ARF/RHD were identified from RHD registers and/or hospital records.

NEARER SCAN (LENO BESIK) evaluation of a task-sharing echocardiographic active case finding programme for rheumatic heart disease in Australia and Timor-Leste: protocol for a hybrid type II effectiveness-implementation study.

Introduction: Rheumatic heart disease (RHD) is underdiagnosed globally resulting in missed treatment opportunities and adverse clinical outcomes. We describe the protocol for a study which aims to co-design, implement and conduct an evaluation of a task-sharing approach to echocardiographic active case finding for early detection and management of RHD in high-risk settings in Australia and Timor-Leste.

Methods And Analysis: Echocardiograms will be obtained by trained local staff using hand-held echocardiographic devices employing the 'Single Parasternal Long Axis view with a Sweep of the Heart' (SPLASH) technique and interpreted by experts remote from the site of acquisition.

Estimating the true number of people with acute rheumatic fever and rheumatic heart disease from two data sources using capture-recapture methodology.

Objective In Australia, accurate case ascertainment of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) diagnoses for disease surveillance and control purposes requires the use of multiple data sources, including RHD registers and hospitalisation records. Despite drawing on multiple data sources, the true burden of ARF/RHD is likely to be underestimated. Methods This study used capture-recapture methods to quantify the missing number of ARF/RHD cases in data from hospitals and jurisdictional RHD registers.

Incidence and Predictors of Stroke in Australian Adults With Congenital Heart Disease (2000-2017).

Background: Adults with congenital heart disease (CHD) are at increased risk of stroke but high-quality population level data on stroke incidence in these patients are scant.

Methods And Results: A retrospective whole-population Western Australian cohort of adult patients with CHD aged 18 to 64 years was created and followed from January 2000 to December 2017 using linked hospital data. Stroke incidence rates within the adult cohort with CHD were calculated and compared with the general population via direct standardization.

Process evaluation of a randomised controlled trial intervention designed to improve rehabilitation services for Aboriginal Australians after brain injury: the Healing Right Way Trial.

Background: Healing Right Way (HRW) aimed to improve health outcomes for Aboriginal Australians with stroke or traumatic brain injury by facilitating system-level access to culturally secure rehabilitation services. Using a stepped-wedge randomised controlled trial (RCT) design (ACTRN12618000139279, 30/01/2018), a two-pronged intervention was introduced in four rural and four urban hospitals, comprising 1.Cultural security training (CST) for staff and 2.

Clinical profile of paediatric acute rheumatic fever and rheumatic heart disease in Western Australia: 1987 to 2020.

Aim: To describe the clinical profile of acute rheumatic fever (ARF) presentations to paediatric cardiology tertiary services in Western Australia (WA).

Methods: A retrospective clinical audit of individuals with confirmed ARF referred to the only paediatric tertiary cardiac service in WA (1 January 1987 to 31 December 2020). Comparisons between inpatient, outpatient, remote and non-remote groups were assessed.

Are we missing opportunities to detect acute rheumatic fever and rheumatic heart disease in hospital care? A multijurisdictional cohort study.

Objective This study aimed to investigate potential missed diagnoses of acute rheumatic fever and rheumatic heart disease during hospital-based care among persons subsequently identified with these conditions. Methods This retrospective cohort study used linked emergency department and inpatient administrative records from Queensland, Northern Territory, South Australia, and New South Wales during 2003-2018 (varying between jurisdictions by completeness of data) of all persons first identified with acute rheumatic fever or rheumatic heart disease while aged 8-24years. Using coded discharge diagnoses from the preceding 3years, we identified presentations (e.

Resistance to FOXM1 inhibitors in breast cancer is accompanied by impeding ferroptosis and apoptotic cell death.

Purpose: Cancer treatments often become ineffective because of acquired drug resistance. To characterize changes in breast cancer cells accompanying development of resistance to inhibitors of the oncogenic transcription factor, FOXM1, we investigated the suppression of cell death pathways, especially ferroptosis, in FOXM1 inhibitor-resistant cells. We also explored whether ferroptosis activators can synergize with FOXM1 inhibitors and can overcome FOXM1 inhibitor resistance.

Asymmetric allostery in estrogen receptor-α homodimers drives responses to the ensemble of estrogens in the hormonal milieu.

The estrogen receptor-α (ER) is thought to function only as a homodimer but responds to a variety of environmental, metazoan, and therapeutic estrogens at subsaturating doses, supporting binding mixtures of ligands as well as dimers that are only partially occupied. Here, we present a series of flexible ER ligands that bind to receptor dimers with individual ligand poses favoring distinct receptor conformations-receptor conformational heterodimers-mimicking the binding of two different ligands. Molecular dynamics simulations showed that the pairs of different ligand poses changed the correlated motion across the dimer interface to generate asymmetric communication between the dimer interface, the ligands, and the surface binding sites for epigenetic regulatory proteins.

NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells.

Background: Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 inhibitors in HGSOC cell models.

Results: We treated HGSOC and fallopian tube epithelial (FTE) cells with a panel of previously reported FOXM1 inhibitors.

Asymmetric Allostery in Estrogen Receptor-α Homodimers Drives Responses to the Ensemble of Estrogens in the Hormonal Milieu.

Unlabelled: The estrogen receptor-α (ER) is thought to function only as a homodimer, but responds to a variety of environmental, metazoan, and therapeutic estrogens at sub-saturating doses, supporting binding mixtures of ligands as well as dimers that are only partially occupied. Here, we present a series of flexible ER ligands that bind to receptor dimers with individual ligand poses favoring distinct receptor conformations -receptor conformational heterodimers-mimicking the binding of two different ligands. Molecular dynamics simulations showed that the pairs of different ligand poses changed the correlated motion across the dimer interface to generate asymmetric communication between the dimer interface, the ligands, and the surface binding sites for epigenetic regulatory proteins.

Healing Right Way randomised control trial enhancing rehabilitation services for Aboriginal people with brain injury in Western Australia: translation principles and activities.

Background This report provides the theory, method and practice of culturally secure translation and knowledge exchange in the Healing Right Way Clinical Trial (2017-2022), outlining activities to date. Healing Right Way was a stepped wedge cluster randomised controlled trial conducted in Western Australia, aimed at enhancing rehabilitation services and quality of life for Aboriginal Australians following acquired brain injury. The trial translation plan was aspirational and action-oriented, with its implementation iterative and ongoing.