Generation of mice with combined Hexa Gly269Ser KI or KO and Neu3 KO alleles to create new models of GM2 gangliosidoses.

The GM2 gangliosidoses are lysosomal storage disorders exhibiting a spectrum of neurological phenotypes ranging from childhood death to debilitating adult-onset neurological impairment. To date, no mouse model harbouring a specific human mutation causing GM2 gangliosidosis has been created. We used CRISPR/Cas9 to generate knockin (KI) mice with the common adult-onset Hexa Gly269Ser variant as well as knockout (KO) mice with Hexa mutations expected to cause complete HexA deficiency.

Understanding the Determinants of Use of the Australian Guide to Diagnosis of Fetal Alcohol Spectrum Disorder: Informing the Review, Development and Dissemination of New National Clinical Practice Guidelines.

Introduction: The Australian Guide to the Diagnosis of fetal alcohol spectrum disorder (FASD), developed in 2016, is currently under review. This study aimed to understand how the Guide is used in practice and identify factors influencing its implementation.

Methods: A cross-sectional online survey was conducted with Australian health practitioners involved in the assessment and diagnosis of FASD.

Conducting Eating Disorder Research in the Era of Generative AI: Researcher Perspectives and Guidelines From the International Journal of Eating Disorders.

Objectives: Generative Artificial Intelligence (AI) could transform how science is conducted, supporting researchers with writing, coding, peer review, and evidence synthesis. However, it is not yet known how eating disorder researchers utilize generative AI, and uncertainty remains regarding its safe, ethical, and transparent use. The Executive Committee of the International Journal of Eating Disorders disseminated a survey for eating disorder researchers investigating their practices and perspectives on generative AI, with the goal of informing guidelines on appropriate AI use for authors, reviewers, and editors.

Steps to manage treatment-refractory migraine in adults.

Introduction: Refractory migraine (RM) is characterized by a lack of response to both migraine-specific and repurposed treatments, significantly impairing quality of life. Risk factors for RM include, among others, overuse of symptomatic medications, nonadherence to treatment and comorbid conditions that limit the use of anti-migraine medications.

Areas Covered: This critical perspective addresses the diagnosis and management of patients with RM.

Treatment modifiers and predictors of risperidone response in dementia: An individual participant data meta-analysis of six randomized controlled trials.

Introduction: Risperidone is approved for behaviors and psychological symptoms of dementia (BPSD), despite modest efficacy and known risks. Identifying responsive symptoms, treatment modifiers, and predictors is crucial for personalized treatment.

Method: A one-stage individual participant data meta-analysis of six randomized controlled trials (risperidone: n = 1009; placebo: N = 712) was conducted.

An Intervention to Build Grit, Resilience and a Growth Mindset in Physiotherapy Students.

Background: Grit, resilience and a growth mindset are traits that help health professional students respond positively and adapt to the challenges of the clinical learning environment. The aim of this study was to determine if a 5-week education-based intervention can enhance grit, resilience and a growth mindset in physiotherapy students on clinical placement.

Methods: In this single group intervention study, physiotherapy students participated in a 5-week group-based, online educational intervention for 1 h per week during their first clinical placement.

Targeted deletion of Cyp24a1 in the intestine reduces mucosal injury and preserves epithelial proliferation after 5-fluorouracil treatment.

Vitamin D has been proposed to attenuate chemotherapy-induced gastrointestinal mucositis (GM). In the intestine, local catabolism of active vitamin D [1,25-dihydroxyvitamin D₃] is mediated by the enzyme Cyp24a1. This study assessed whether deletion of Cyp24a1 specifically in intestinal epithelial cells can protect against 5-fluorouracil (5-FU)-induced intestinal injury and microbiome disruption in mice.

The temporal change in heat-related mortality in relation to the Heat Health Action Plans in the five major cities of Australia.

Heat-Health Action Plans (HHAPs) are essential public health interventions to reduce heat-related mortality and morbidity, yet how heat-related health risks have changed following their implementation remains scarce. This study aimed to examine the temporal changes in heat-related mortality in relation to the implementation of the HHAPs across five major cities of Australia, including Melbourne, Sydney, Brisbane, Adelaide, and Perth. Daily mortality and temperature data from 1999-2019 were analysed using distributed lag non-linear models to compare the heat-related mortality attributable fractions (AF%) between pre- and post-HHAP periods.

Established and Emerging Therapies for Cardiovascular-Kidney-Metabolic Syndrome: Harnessing the Benefits of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and Beyond.

Cardiovascular-kidney-metabolic (CKM) syndrome is a term that is increasingly used to describe interconnected conditions that lead to poor health outcomes, including cardiovascular disease, chronic kidney disease, type 2 diabetes, and obesity. Historically, there have been very few targeted pharmacotherapies available that have changed cardiovascular outcomes for people with CKM syndromes; however, over the past decade, new pharmacologic options have rapidly expanded, with strong evidence for cardiovascular and kidney protective benefits in CKM conditions. Of note, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists have emerged as key therapeutic options and are now widely guideline-endorsed.

Effects of aperiodic neural activity on sleep-based emotional memory consolidation across the lifespan.

Sleep neurophysiology undergoes significant changes across the lifespan, which coincide with age-related differences in memory, particularly for emotional information. However, the mechanisms that underlie these effects remain poorly understood. One potential mechanism is the aperiodic component, which reflects "neural noise", differs across age, and is predictive of perceptual and cognitive processes.

Overview of evidence synthesis types and modes.

Background And Objectives: Evidence syntheses systematically compile and analyze information from multiple sources to support health care decision making. As many different types of questions need to be answered in health care, different evidence synthesis types have emerged. In this article, we introduce the most common types of evidence synthesis.

Recyclable Cu-Catalyzed -Methylation and C5-Methylthiomethylation of Isatins with DMSO.

An unprecedented recyclable system of copper-catalyzed C-C/N coupling of isatins and DMSO without any oxidant and acidic/basic additive has been unlocked. The -isatins occur tandem -methylation and C5-methylthiomethylation in order, while -substituted isatins proceed C5-methylthiomethylation only. DMSO serves as Me and MeSCH sources as well as the solvent.

Trends in Use of Direct-Acting Antivirals for Treatment of Hepatitis C Virus Infection in Australia 2016-2024.

Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) treatment in Australia since their inclusion on the Pharmaceutical Benefits Scheme (PBS) in 2016. Treatment has shifted from genotype-specific to pan-genotypic regimens, with glecaprevir/pibrentasvir and sofosbuvir/velpatasvir now recommended in clinical guidelines. This study examined trends in DAA dispensing in light of evolving treatment regimens.

Mepolizumab treatment and reduced oral corticosteroid exposure improves symptoms of depression and anxiety in severe eosinophilic asthma: data from the Australian Mepolizumab Registry.

Background: The benefits of oral corticosteroid (OCS) stewardship approaches -including monoclonal antibody treatments for severe asthma- on reducing toxic OCS exposure and related comorbidities such as depression and anxiety require real-world evaluation.

Methods: This real-world observational study investigated OCS exposure and associated complications over 24 months in patients enrolled in the Australian Mepolizumab Registry (n = 412).

Results: Patients were median age 59 years, 58 % were female.

Multiscale non-covalent assembly of proteins and polysaccharides from mechanisms to functional enhancements and applications: A review.

In the context of the escalating global emphasis on healthy food and sustainable development, non-covalent assembly systems formed between proteins and polysaccharides have garnered substantial attention. As natural biomolecules, proteins and polysaccharides synergize to form multiscale complexes through mechanisms such as electrostatic interactions, hydrophobic interactions, and hydrogen bonding, thus exhibiting enhanced stability and functionality. This review identifies five major research hotspots in this field using bibliometric analysis, covering complex formation mechanisms, performance enhancement strategies, and application-expansion directions.

Effect of a delay discounting intervention on soft drink and alcohol demand.

Excessive soft drink and alcohol consumption have been associated with negative health outcomes. This study tested whether an intervention to reduce preferences for smaller, immediate rewards over larger, delayed rewards (i.e.

Otolith-derived chemical chronologies reveal distinct patterns in physiology and environmental life histories of deep-sea snappers.

Otolith chemical approaches are widely used to inform fisheries management, supporting the identification of population structure, connectivity, and natal origins. Chemical transects combined with fish age and growth data can reveal individual life histories, highlighting movement patterns and environmental influences within populations. Scaling these distinct variations to the population-level through novel chronological approaches could further boost our understanding of long-term physiological and environmental processes, and their interactions across regions and species.

The Breath of Revolution: Illness and Metaphor in the Life of Ernesto "Che" Guevara.

This article examines the chronic asthma of Ernesto "Che" Guevara not merely as a biomedical condition, but as a metaphorical and existential element of his revolutionary identity. Drawing on Aristotle's theory of metaphor and S. Sontag's cultural critique of illness, it explores how Guevara's lifelong struggle with asthma shaped his medical vocation and informed his political radicalism.

Forms of interventions for problematic usage of the internet: A scoping review.

Background And Aims: This scoping review aims to identify current forms of interventions for Problematic Usage of the Internet (PUI) to inform more effective intervention and policy-making initiatives grounded in robust empirical evidence.

Methods: The search was conducted in the PubMed, Scopus, and PsycINFO databases until October 12, 2024. Empirical research presenting data on interventions for PUI and written in English was included without restrictions of age groups, types of interventions, or types of PUI.

Addressing Safety, Quality, and Cost of Care Through a Telehealth Outpatient Transitional Care Model: Protocol for a Pragmatic Randomized Controlled Trial.

Background: People with multimorbidity have complex health care needs, resulting in high health service use, hospital readmission rates, and support needs. To prevent unnecessary hospital readmissions, effective coordination during the transition from hospital to primary care is essential; the transitional care model (TCM) is an effective approach to achieve this. This study will adapt the TCM, focusing on a nurse-led telehealth-based follow-up transition coordination service to enhance continuity between hospital and primary care, aiming to reduce unnecessary hospital readmissions and improve patient transitions.

Twenty-Eight Days Later: Emergency Diagnoses Associated With Increased Risk of Readmission, a Retrospective Observational Study of Older Adults.

Aims: To describe diagnostic categories and comorbidities associated with increased risk of readmission within 28 days among older adults.

Methods: Retrospective observational study of all hospital admissions following ED attendance by patients aged ≥ 60 years between July 2020 and June 2023. Index and subsequent 28-day readmission were identified using ED data and hospital discharge records.

Relational factors influencing implementation in aged care: a literature review.

Introduction: There are widespread efforts to implement change and innovation to improve care for older people in aged care. Relational factors are among the key determinants of implementation in care settings, and are an emerging area of implementation research attention.

Aim: This study aimed to identify relational factors that influence implementation in aged care.