Basic Science and Pathogenesis.

Background: Whilst numerous studies have explored the relationship between Alzheimer's disease (AD) and diabetes, there remains significant conflicting evidence as to their relationship. Some studies suggest an increased likelihood of developing AD in individuals with diabetes, especially type 2 diabetes (T2D) and that both diseases share pathological features. In contrast, other studies indicate that T2D is more aligned with vascular cognitive impairment and dementia and associated cerebrovascular/white matter pathology.

Basic Science and Pathogenesis.

Background: The glymphatic system has been suggested as an important clearance mechanism for amyloid-β (Aβ) during sleep. Animal and cellular models have suggested this clearance mechanism involves the water-channel protein, Aquaporin-4 (encoded by the AQP4 gene), located primarily in the astrocytic end-feet. We have previously reported on the interaction between genetic variants within AQP4, sleep and cross-sectional cortical amyloid-β (Aβ) burden.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) have identified numerous genetic variants associated with Alzheimer's disease (AD) risk, but genetic variation in the onset and progression of AD pathology is less understood. Accumulation of amyloid-β (Aβ) in the brain is a key pathological hallmark of AD beginning 10 - 20 years prior to cognitive symptoms. We investigated the genetic basis of variation in age at onset (AAO) of brain Aβ by comparing the performance of polygenic scores (PGSs) based on AD risk and resilience with a Aβ-AAO trait-specific PGS.

Basic Science and Pathogenesis.

Background: Observational studies have suggested a co-occurring relationship between Alzheimer's disease (AD) and asthma. However, the aetiology and biological mechanisms underlying AD and its potential association with asthma, an autoimmune condition, remain unclear.

Method: We examine the genetic relationship between AD and asthma by analysing large-scale genome-wide association study (GWAS) summary data from international research consortia and groups.

Basic Science and Pathogenesis.

Background: For large genomic studies of middle-aged individuals, the prevalence of Alzheimer's disease (AD) is extremely low, making it difficult to conduct genomic analysis of the condition. To enable genome-wide association studies of AD in such datasets, an approach called Genome-wide association by proxy (GWAX) uses family history of disease as a proxy for disease status. Borrowing from the machine learning (ML) literature, we treat the development of proxy phenotypes as a pseudo-labelling task, where an ideal proxy label accurately predicts the lifetime risk of AD.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) individuals, the PACC is widely used as a cognitive outcome measure and endpoint in observational studies and clinical trials. However, it has drawn criticism for being heavily weighted towards memory. Increasing evidence indicates a decline spanning multiple cognitive domains in CU individuals.

Nanoparticle-Based gene therapy strategies in retinal delivery.

Vision loss and blindness are significant issues in both developed and developing countries. There are a wide variety of aetiologies that can cause vision loss, which are outlined in this review. Although treatment has significantly improved over time for some conditions, nearly half of all people with vision impairment are left untreated.

FBP1 controls liver cancer evolution from senescent MASH hepatocytes.

Hepatocellular carcinoma (HCC) originates from differentiated hepatocytes undergoing compensatory proliferation in livers damaged by viruses or metabolic-dysfunction-associated steatohepatitis (MASH). While increasing HCC risk, MASH triggers p53-dependent hepatocyte senescence, which we found to parallel hypernutrition-induced DNA breaks. How this tumour-suppressive response is bypassed to license oncogenic mutagenesis and enable HCC evolution was previously unclear.

Placental cord insertion migration: Implications for ultrasound documentation and follow-up of abnormal placental cord insertion site.

Introduction/purpose: It is well-documented in the literature that the placenta migrates during pregnancy; however, studies regarding placental cord insertion (PCI) migration are scarce. This longitudinal, prospective study aimed to determine whether PCI migration is a true phenomenon, to assess whether the PCI can change classification during pregnancy and to determine the validity of PCI site documentation including follow-up of abnormal PCI.

Methods: Eighty-three participants who had first, second and third trimester ultrasound examinations at a Western Australian private imaging practice over a 12-month period between November 2021 and November 2022 were recruited.

The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA.

Expression of the compact mitochondrial genome is regulated by nuclear encoded, mitochondrially localized RNA-binding proteins (RBPs). RBPs regulate the lifecycles of mitochondrial RNAs from transcription to degradation by mediating RNA processing, maturation, stability and translation. The Fas-activated serine/threonine kinase (FASTK) family of RBPs has been shown to regulate and fine-tune discrete aspects of mitochondrial gene expression.

Exploring prevention and control mechanisms of youth substance use: a case of North Wollo and Waghimra, Northeast Ethiopia.

Background: Substance use among youths is a significant global and local issue. Youth who engage in substance use often experience various psychosocial, health, economic, and other problems. While governmental and non-governmental organizations in North Wollo and Waghimra Zones offer social services, their effectiveness in preventing and controlling substance use remains largely unstudied.

Characteristics and management of eosinophilic esophagitis in Australasian children: a decade of experience.

Background: The frequency of EoE has been increasing in Northern Hemisphere cohorts, yet there is a scarcity of data in our region. Regional climatic factors, and lifestyle habits may influence the presentation of EoE, and appropriate management is crucial to prevent complications. WIth this is mind we undertook the first comprehensive multisite study of EoE in Australasian children.

Contribution of the community pharmacist workforce to primary care through the lens of medicines classification: comparison of Aotearoa New Zealand and Australia.

Introduction Optimal use of the workforce in primary care is critical due to increasing complexity and demand resulting from multi-morbidity in ageing populations. Improving public access to medicines by making them available via a pharmacist without prescription can support self-care while ensuring oversight by a health professional. Aim The aim of this paper was to identify and explore key differences between New Zealand and Australia in medicines classified nationally for pharmacist-only non-prescription supply.

International Validation of a Novel PEACE Scale to Improve the Quality of Upper Gastrointestinal Mucosal Inspection During Endoscopy.

Introduction: The performance of a high quality esophagogastroduodenoscopy (EGD) is dependent on the mucosal cleanliness. Recently, the Polprep: Effective Assessment of Cleanliness in EGD (PEACE) scale was created to assess the degree of mucosal cleanliness during EGD. The aim of this study was to validate this scoring system in a cohort of international endoscopists.

Computational studies for pre-evaluation of pharmacological profile of gut microbiota-produced gliclazide metabolites.

Background: Gliclazide, a second-generation sulfonylurea derivative still widely used as a second-line treatment for type 2 diabetes mellitus, is well known to be subject to interindividual differences in bioavailability, leading to variations in therapeutic responses among patients. Distinct gut microbiota profiles among individuals are one of the most crucial yet commonly overlooked factors contributing to the variable bioavailability of numerous drugs. In light of the shift towards a more patient-centered approach in diabetes treatment, this study aimed to conduct a pharmacoinformatic analysis of gliclazide metabolites produced by gut microbiota and assess their docking potential with the SUR1 receptor to identify compounds with improved pharmacological profiles compared to the parent drug.

Artificial intelligence in community pharmacy practice: Pharmacists' perceptions, willingness to utilize, and barriers to implementation.

Background: Artificial intelligence (AI) has a significant potential to impact pharmacy practices worldwide. This study investigates pharmacists' perceptions of AI's role in pharmacy practices, their willingness to adopt it, and perceived barriers to its implementation at community pharmacies in Ethiopia.

Methods: A cross-sectional study was conducted among community pharmacists in Ethiopia.

Correction: An Artificial Therapist (Manage Your Life Online) to Support the Mental Health of Youth: Co-Design and Case Series.

[This corrects the article DOI: 10.2196/46849.].

Bovine tracheal organoids for studying Mycoplasma bovis respiratory infections.

In vitro three-dimensional organoid models simulate key aspects of the structure and function of in vivo organs and have been used to study physiology, host-pathogen interactions, pathogenesis and pharmacodynamics. Although most organoid studies have been developed using human or mouse tissues, recent advancements have enabled the establishment of intestinal and respiratory tract organoids from domestic animal samples. Mycoplasma bovis causes chronic respiratory tract infections in cattle with significant health and economic consequences.

Copper chelation redirects neutrophil function to enhance anti-GD2 antibody therapy in neuroblastoma.

Anti-disialoganglioside (GD2) antibody therapy has provided clinical benefit to patients with neuroblastoma however efficacy is likely impaired by the immunosuppressive tumor microenvironment. We have previously defined a link between intratumoral copper levels and immune evasion. Here, we report that adjuvant copper chelation potentiates anti-GD2 antibody therapy to confer durable tumor control in immunocompetent models of neuroblastoma.

Simulated achievement rate of β-lactams/nacubactam treatment in humans using instantaneous MIC-based PK/PD analysis.

Background: Nacubactam (NAC), a new diazabicyclooctane β-lactamase inhibitor, is being developed for use together with aztreonam (AZT) and cefepime (CFPM). However, the effective clinical dosages of AZT/NAC and CFPM/NAC have not yet been established. We have previously shown that free time above instantaneous MIC (fT > MICi) is a valuable pharmacokinetic (PK)/pharmacodynamic parameter for β-lactam (BL)/NAC in a mouse thigh infection model.

Effect of "In Use" Administration on Topical Product Metamorphosis and Skin Permeation of Acyclovir Creams: Implications for Bioequivalence.

Purpose: Typical clinical "in use" conditions for topical semisolids involve their application as a thin film, often with rubbing that can induce metamorphic stress. Yet, product quality and performance tests often characterize the manufactured product, and may not consider product metamorphosis (e.g.

Influence of Epithelial-Mesenchymal Transition on Risk of Relapse and Outcome to Eribulin or Cyclin-Dependent Kinase Inhibitors in Metastatic Breast Cancer.

Purpose: The presence of epithelial-mesenchymal transition (EMT) in breast cancer (BC) cells has been linked to worse prognosis and may influence response to systemic treatment. We explored the effect of EMT in tumor samples of patients with metastatic BC on disease-free interval and overall survival in those patients receiving eribulin or cyclin-dependent kinase 4/6 inhibitors (CDK4/6i).

Materials And Methods: Key inclusion criteria included available archived primary BC tissue and, where available, matched metastatic biopsy.

Introduction of the 'Blue Card' Concussion Policy to Semi-Elite Australian Football: Medical Staff Experiences and Perceptions.

Background: The Western Australian Football League (WAFL) introduced a new umpire driven 'blue-card rule' for concussion, but its benefit to the sports medicine team is unknown.

Purpose: To determine the experiences and perceptions of medical staff within the 2022-2023 Men's and Women's WAFL competitions following the introduction of the 'blue-card rule'.

Study Design: Cross-sectional study.

Parental Assessment of Postsurgical Pain in Infants at Home Using Artificial Intelligence-Enabled and Observer-Based Tools: Construct Validity and Clinical Utility Evaluation Study.

Background: Pain assessment in the infant population is challenging owing to their inability to verbalize and hence self-report pain. Currently, there is a paucity of data on how parents identify and manage this pain at home using standardized pain assessment tools.

Objective: This study aimed to explore parents' assessment and intervention of pain in their infants at home following same-day surgery, using standardized pain assessment tools.