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.

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.

Response of accommodation and vergence systems to low dose atropine.

Purpose: Few studies have comprehensively investigated the effect of low dose atropine on the binocular vision system beyond accommodative amplitude. This study examined the effect of 0.05% atropine eye drops on a range of accommodation and vergence parameters across a 10-day period.

Current Practices for Mental Fatigue Quantification and Induction in Movement Science: Introducing the SPeCIFY Guidelines.

Mental fatigue (MF) is a complex phenomenon with significant implications for human performance, for which there are numerous studies investigating the effects of MF. Nevertheless, there is considerable variability in the approaches used to induce and quantify MF, making it hard to compare findings across studies and draw well-supported conclusions. This review addresses the methodological variability in the induction and quantification methods of MF in movement science in the following ways: on the one hand, by providing an overview of task design strategies to induce MF, emphasizing the importance of tailoring task duration, difficulty, and nature to individual participants and specific research contexts; on the other hand, by providing an overview of current methods used to quantify MF, including behavioural, subjective, and physiological measures, and highlighting the strengths and limitations of each.

Inequities in COVID-19 antiviral dispensation in Victoria, Australia: A retrospective cohort study using linked data.

Background And Objectives: Oral antiviral therapies are recommended for treatment of COVID-19 in people vulnerable to severe outcomes. This study examined COVID-19 antiviral dispensation and incidence of severe outcomes among eligible Victorians by socioeconomic status and cultural and linguistic diversity.

Method: A retrospective analysis was conducted using linked population data.

Estimating the preclinical Alzheimer's disease course with multimodal data.

Introduction: In observational studies of preclinical AD, an arbitrary "baseline" can obscure where an individual is located along a theoretical continuum. Optimizing longitudinal trajectories can distill multiple, non-linearly distributed observations into a single metric and inform where an individual may be along the disease course.

Methods: We developed a cognitive time (c-time) metric based on longitudinal cognitive data (mean = 7.

Macroevolutionary role reversals in the earliest radiation of bony fishes.

The evolution of jaws is hypothesized to have fueled radiations among vertebrates, contributing to their overwhelming success in the present day. Past work shows rapid early expansion of diversity in jaw structure in many lineages; however, the evolutionary dynamics underlying this pattern are unclear and hindered by the lack of a robust comparative framework. Here, using a macroevolutionary approach, we explore the diversification of lower jaws in early bony fishes, a major contributor to this initial radiation.

Increased ATP production and P-glycoprotein activity underlie the marked changes in blood-brain barrier transport of drugs in a mouse model of amyotrophic lateral sclerosis.

Background And Purpose: Patients with amyotrophic lateral sclerosis (ALS) are prescribed many medications for symptomatic relief. However, how potential alterations to the blood-brain barrier (BBB) affect the brain exposure of drugs in ALS remains under-investigated.

Experimental Approach: We used high-dimensional proteomic analysis, cellular metabolism, and mitochondrial functional assays to characterise isolated brain microvascular endothelial cells (BMECs) from wildtype and SOD1 transgenic mice, a mouse model of familial ALS, at a late-symptomatic age (P115-120), together with a transcardiac brain perfusion technique to assess BBB function in situ.

Results of a pilot randomized controlled trial of Tuning in to Kids for children with FASD in nonbiological parent care.

Background: Emotion regulation difficulties and placements with nonbiological parents are common in children with fetal alcohol spectrum disorders (FASD). We tested whether the Tuning in to Kids (TIK) intervention would improve emotion regulation in children with FASD living with nonbiological parents by targeting caregiver emotion socialization.

Method: A two-arm pilot randomized controlled trial of the 8-week, group-based TIK program was conducted from 8/2017 to 9/2021 (ClinicalTrials.

Balancing foetal disadvantage and seizure freedom in women capable of pregnancy - the Australian pregnancy register experience.

Objective: To determine which antiseizure medications (ASMs) provide the best overall compromise between a lower risk of foetal malformation and continuing control of maternal epilepsy during pregnancy.

Methods: Analysis of relevant data on women taking one of the 5 most commonly prescribed ASMs (levetiracetam (LEV), lamotrigine (LTG), carbamazepine (CBZ). Topiramate (TPM) and valproate (VPA)) in 2403 pregnancies of women with epilepsy (WWE) contained in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (APR).

The Impact of Strength Changes on Active Function Following Botulinum Neurotoxin-A (BoNT-A): A Systematic Review.

Botulinum neurotoxin-A (BoNT-A) injections are effective in reducing focal limb spasticity; however, their impact on strength and active function needs to be established. This review was a secondary analysis aimed at evaluating changes to active function in the context of muscle strength changes following BoNT-A intramuscular injection for adult upper and lower limb spasticity. The original review searched eight databases (CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Google Scholar, MEDLINE, PEDro, PubMed, Web of Science) and was conducted with methodology that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines as described in section 6.

Recent-onset atrial fibrillation: challenges and opportunities.

Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance.

The Mechanism and Kinetics of Hydroxyl Radical Polymerization of Nonionized Acrylic Acid and Its Derivatives in Aqueous Solution.

In the free-radical polymerization of acrylic acid derivatives (), including acrylic acid (), methyl acrylate (), acrylamide (), methacrylic acid (), and methyl methacrylate (), initiation and propagation occur via radical addition to . Although extensive experimental data exist about this industrial process, many mechanistic aspects of the reactions themselves remain unclear, largely because of the challenge that the characterization of reaction mechanisms poses to experimental methodology. Computational methods offer an alternative avenue to deliver fast and accurate results on the mechanistic details, as evidenced by various theoretical studies in the literature.

Neural correlates of human fear conditioning and sources of variability in 2199 individuals.

Pavlovian fear conditioning is a fundamental process in both health and disease. We investigate its neural correlates and sources of variability using harmonized functional magnetic resonance imaging data from 2199 individuals across nine countries, including 1888 healthy individuals and 311 with anxiety-related or depressive disorders. Using mega-analysis and normative modeling, we show that fear conditioning consistently engages brain regions within the "central autonomic-interoceptive" or "salience" network.

Efficacy and safety of B/F/TAF in treatment-naïve and virologically suppressed people with HIV ≥ 50 years of age: integrated analysis from six phase 3 clinical trials.

Introduction: Older adults with HIV, particularly those ≥ 50 years of age, face unique health challenges due to a higher prevalence of comorbidities and polypharmacy, which can impact medication adherence and increase the risk of adverse events. We assessed the efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) ≥ 50 years of age across treatment-naïve and virologically suppressed cohorts over a long-term follow-up.

Methods: This post hoc analysis included participants ≥ 50 and < 50 years of age from six phase 3 trials of B/F/TAF, comprising 2 treatment-naïve studies and 4 virologically suppressed studies.

C1'-Branched Acyclic Nucleoside Phosphonates as Inhibitors of Plasmodium Falciparum 6-Oxopurine Phosphoribosyltransferase.

Hypoxanthine-guanine-(xanthine) phosphoribosyltransferase [HG(X)PRT] is an excellent target for the development of new drugs to treat parasitic and bacterial infections as well as MYC-dependent triple-negative breast cancer. Inhibitors include compounds that mimic the transition state of the catalytic reaction and analogs of the two products of the reaction, the nucleoside monophosphates and pyrophosphate. One type of chemistry explored here is the design of purine-based C1'-branched acyclic nucleoside phosphonates bearing diverse structural attachments (secondary linkers) on the C1' atom.

Optimising pollutant degradation in reductant-mediated copper Fenton-like systems using mechanistically-based kinetic modelling.

A mechanistic kinetic model has been developed and validated for Cu(II)/AA (ascorbic acid) and Cu(II)/HO/AA systems under varying chloride concentrations and circumneutral pH. While the Cu(II)/AA system degraded the selected target contaminant (formate) via Cu(III) generation through a Fenton-like mechanism, observed efficiencies were inadequate for practical water treatment across a broad range of chloride concentrations. This limitation stemmed from insufficient HO production, leading to low Cu(III) concentrations, and scavenging of Cu(III) by AA and its oxidation products.

Translating the Transcriptome: A Connectomics Approach for Gene-Network Mapping and Clinical Application.

Gene expression shapes the brain's functional connectome, yet it is unclear whether genes linked to the same disorder converge on shared networks. We introduce gene network mapping-a framework combining spatial transcriptomics with normative functional connectivity to identify networks associated with gene expression. By generating -network maps, we captured distributed connectivity patterns for individual genes.

Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.

Background: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

Methods: We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

Results: We replicated the well-known association at the locus (lead single-nucleotide polymorphism [SNP]: rs147144681,  = 1.

Phase 1/2 study of H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive, HER2-negative breast cancer.

Background: Although endocrine therapies, alone or in combination with CDK4/6 inhibitors, have led to notable improvements in the treatment of estrogen receptor-positive (ER+) breast cancer, progression is inevitable for most patients. We report dose escalation and expansion data from a trial of H3B-6545 (a novel selective ER covalent antagonist that inactivates wild-type and mutant ERα) in women with locally advanced/metastatic ER+, HER2-negative breast cancer (BC).

Methods: This study was a multicenter, open-label, phase 1/2 trial.

European Society of Intensive Care Medicine Clinical Practice Guideline on fluid therapy in adult critically ill patients: Part 3-fluid removal at de-escalation phase.

Purpose: This is the third of three parts of the clinical practice guideline from the European Society of Intensive Care Medicine (ESICM) on fluid management in adult critically ill patients. This part addresses fluid removal in the de-escalation phase of shock management.

Methods: This guideline was formulated by an international panel of clinical experts, methodologists, and patient representatives.

Heme oxygenase-1 polymorphisms associate with ischemic cardiac complications and all-cause mortality in type 1 diabetes.

Background: Heme oxygenase 1 (HO-1), encoded by the HMOX1 gene is a highly inducible enzyme with multiple cardiovascular protective properties. Polymorphisms of the HMOX1 gene, especially a guanine-thymine dinucleotide repeat polymorphism (GTn), affects its transcriptional activity and is associated with cardiovascular complications in the general population. We studied the association of HMOX1 polymorphisms and HO-1 serum concentrations with vascular complications and all-cause mortality in individuals with type 1 diabetes (T1D).

Multivariate genome-wide association analysis of dyslexia and quantitative reading skill improves gene discovery.

The ability to read is an important life skill and a major route to education. Dyslexia, characterized by difficulties with accurate/ fluent word reading, and poor spelling is influenced by genetic variation, with a twin study heritability estimate of 0.4-0.

Red Cell Transfusion in Acute Myocardial Infarction: AABB International Clinical Practice Guidelines.

Description: Optimal transfusion strategies for patients with acute myocardial infarction (AMI) are uncertain. The aim of this guideline is to provide recommendations for red blood cell transfusion in patients with AMI.

Methods: These guidelines are based on evidence from randomized controlled trials of patients presenting with AMI and assigned to 2 different transfusion strategies (restrictive or liberal) based on hemoglobin concentrations or hematocrit levels before receipt of a transfusion.