Antimicrobial risk assessment-Aggregating aquatic chemical and resistome emissions.

Urban water systems receive and emit antimicrobial chemicals, resistant bacterial strains, and resistance genes (ARGs), thus representing "antimicrobial hotspots". Currently, regional environmental risk assessment (ERA) is carried out using drug consumption data and threshold concentrations derived based on chemical-specific minimum inhibitory concentration values. A legislative proposal by the European Commission released in 2022 addresses the need to include selected ARGs besides the chemical concentration-based ERAs.

Effects of statins on kidney function in older adults.

Background: The effect of statin therapy on kidney function among older adults is unclear.

Objectives: To examine the association between statin use and changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), positive or negative, in an older adult cohort with versus without chronic kidney disease (CKD) at baseline.

Methods: This analysis included 18,056 participants aged ≥65 years with versus without CKD at baseline in a randomized trial of low-dose aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially.

Estimating surgical blood loss: A review of current strategies in various clinical settings.

The estimation of surgical blood loss is routinely performed during and after surgical procedures and has morbidity and mortality implications related to the risk of under- and over-resuscitation. The strategies for estimating surgical blood loss include visual estimation, the gravimetric method, the colorimetric method, formula-based methods, and other techniques (e.g.

Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain.

Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due to the blood-brain barrier (BBB) and the tendency of delivery vehicles to accumulate in the liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA delivery to the brain. We utilize click chemistry to functionalize LNPs with peptides that target receptors overexpressed on brain endothelial cells and neurons, namely the RVG29, T7, AP2, and mApoE peptides.

Classification of chronic kidney disease in older Australian adults by the CKD-EPI 2009 and 2021 equations: secondary analysis of ASPREE study data.

Objectives: To assess the clinical impact on generally healthy older Australians of changing from the 2009 CKD-EPI (CKD-EPI) to the 2021 CKD-EPI (CKD-EPI) equation for calculating the estimated glomerular filtration rate (eGFR).

Study Design: Secondary analysis of data from the prospective ASPirin in Reducing events in the Elderly (ASPREE) cohort study.

Setting, Participants: Australians aged 70 years or older living in the community and without life-limiting medical conditions, recruited 1 March 2010 - 31 December 2014 for the ASPREE trial.

Caregiver Experiences with Prescribed Antibiotic Access After a Pediatric Emergency Department Visit: A Qualitative Study.

Objective: Approximately one third of caregivers do not obtain a prescribed medication after their child's pediatric emergency department visit. We sought to explore the facilitators and barriers that caregivers experience in accessing prescribed antibiotics after their child's pediatric emergency department visit.

Methods: We conducted semi-structured interviews with caregivers of children who presented to a quaternary academic pediatric emergency department and were discharged with prescribed antibiotics.

Potent antitumor activity of a designed interleukin-21 mimic.

Long-standing goals of cancer immunotherapy are to activate cytotoxic antitumor T cells across a broad range of affinities while dampening suppressive regulatory T (Treg) cell responses, but current approaches achieve these goals with limited success. Here, we report a IL-21 mimic, 21h10, designed to have augmented stability and high signaling potency in both humans and mice. In multiple animal models and in human melanoma patient derived organotypic tumor spheroids (PDOTS), 21h10 showed robust antitumor activity.

Non-criteria antiphospholipid antibody profiles and thrombotic outcomes in a cohort of patients with systemic lupus erythematosus.

Objectives: Antiphospholipid syndrome (APS) is characterised by the presence of antiphospholipid antibodies (aPLs) and clinical outcomes of thrombosis and/or obstetric morbidity and is associated with systemic lupus erythematosus (SLE). IgG antiphosphatidylserine/prothrombin complex (aPS/PT), IgM aPS/PT and IgG anti-beta 2 glycoprotein 1-domain 1 (aβ2GP1-D1) are novel aPLs that have been associated with thrombosis; however, conclusive data are still lacking. It remains unclear how best to incorporate non-criteria autoantibodies into clinical decision-making.

Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia.

Pre-eclampsia is a placental disorder that affects 3-5% of all pregnancies and is a leading cause of maternal and fetal morbidity worldwide. With no drug available to slow disease progression, engineering ionizable lipid nanoparticles (LNPs) for extrahepatic messenger RNA (mRNA) delivery to the placenta is an attractive therapeutic option for pre-eclampsia. Here we use high-throughput screening to evaluate a library of 98 LNP formulations in vivo and identify a placenta-tropic LNP (LNP 55) that mediates more than 100-fold greater mRNA delivery to the placenta in pregnant mice than a formulation based on the Food and Drug Administration-approved Onpattro LNP (DLin-MC3-DMA).

An unusual case of a dry cough.

https://bit.ly/4dXUOX4.

A survey study on the availability of anaesthetic breathing systems and their use in dogs weighing 5-10 kg.

Objective: To investigate which breathing systems are available and why they are selected in dogs weighing 5-10 kg.

Study Design: Anonymous online voluntary open survey.

Methods: An online survey, designed following CHERRIES guidelines, was advertised through the American College of Veterinary Anesthesiologists - List, Association of Veterinary Anaesthesia and European College of Veterinary Anaesthesia and Analgesia (February-March 2022).

Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity.

Inorganic nitrate (NO) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the Metabolic Syndrome (MetS), type-II diabetes and metabolic dysfunction associated steatotic liver disease (MASLD). Administration of NO to endothelial nitric oxide synthase-deficient mice reversed aspects of MetS, however the impact of NO supplementation in diet-induced obesity is not well understood. Here we investigated the whole-body metabolic phenotype and cardiac and hepatic metabolism in mice fed a high-fat high-sucrose (HFHS) diet for up to 12-months of age, supplemented with 1 mM NaNO (or NaCl) in their drinking water.

Understanding Training Load in Golf: A Survey of Swing Coaches, Performance Practitioners, and Medical Staff.

Watson, A, Murray, A, Coughlan, D, Wells, J, Ehlert, A, Xu, J, Turner, A, and Bishop, C. Understanding training load in golf: A survey of swing coaches, performance practitioners, and medical staff. J Strength Cond Res 39(1): e20-e29, 2025-The present study aimed to investigate the current opinions and practices of golf coaches, performance practitioners, and medical staff working in golf, on the topic of monitoring training load in the sport.

Depression Symptoms Do Not Worsen Over Time in a Cohort of CKD Patients: The BRINK Study.

Background: The prevalence of depression is high in the chronic kidney disease (CKD) (20-40%) and dialysis (30-50%) populations. Less is known about how depressive symptoms change over time in patients with CKD.

Methods: Participants in the Brain in Kidney Disease (BRINK) cohort study completed a depressive symptom questionnaire (PHQ-9) and serum creatinine testing annually.

Tolerability of linezolid in patients with drug-resistant TB in Daru, Western Province, PNG.

Setting: Linezolid (LZD) has emerged as a critical agent and core component of regimens to treat drug-resistant TB (DR-TB); however, there are ongoing uncertainties regarding its safety and the optimal dosing approach. Since 2016, linezolid has been used in the treatment of patients diagnosed with DR-TB at Daru Provincial Hospital, PNG.

Objective: To describe the patient characteristics, treatment outcomes, and tolerability of linezolid-containing regimens used to treat DR-TB in Daru, Western Province.

TB programme outcomes in South Fly District, Papua New Guinea, were maintained through COVID-19.

Setting: An established response to an outbreak of drug-resistant TB (DR-TB) on Daru Island, South Fly District (SFD), Western Province, Papua New Guinea (PNG).

Objective: To describe and evaluate the trends in TB case notification disaggregated by demographic and clinical characteristics, programmatic interventions for TB and COVID-19 and treatment outcomes in 2017-2022.

Design: A cohort study of routinely collected programmatic data of all patients registered for TB treatment in SFD comparing pre-COVID (2017-2019) to COVID (2020-2022) periods.

Accurate design of high-affinity protein binding macrocycles using deep learning.

The development of macrocyclic binders to therapeutic proteins typically relies on large-scale screening methods that are resource-intensive and provide little control over binding mode. Despite considerable progress in physics-based methods for peptide design and deep-learning methods for protein design, there are currently no robust approaches for design of protein-binding macrocycles. Here, we introduce RFpeptides, a denoising diffusion-based pipeline for designing macrocyclic peptide binders against protein targets of interest.

Disruption of the Physical Interaction Between Carbonic Anhydrase IX and the Monocarboxylate Transporter 4 Impacts Lactate Transport in Breast Cancer Cells.

It has been previously established that breast cancer cells exhibit high expression of the monocarboxylate (lactate) transporters (MCT1 and/or MCT4) and carbonic anhydrase IX (CAIX) and form a functional metabolon for proton-coupled lactate export, thereby stabilizing intracellular pH. CD147 is the MCT accessory protein that facilitates the creation of the MCT/CAIX complex. This study describes how the small molecule Beta-Galactose 2C (BGal2C) blocks the physical and functional interaction between CAIX and either MCT1 or MCT4 in Xenopus oocytes, which reduces the rate of proton and lactate flux with an IC of ~90 nM.

Age-Related Hearing Loss: A cross-sectional study of healthy older Australians.

Introduction Hearing loss is common in ageing populations, but thorough investigation of factors associated with objective hearing loss in otherwise healthy, community dwelling older individuals is rare. We examined prevalence of age-related hearing loss (ARHL) in healthy, community-dwelling older adults, and determined whether sociodemographic, lifestyle or health factors associate with hearing thresholds. Audiometry assessment was investigated with self-reports of hearing loss and hearing handicap.

Preventing troublesome variability in clinical blood pressure measurement.

The importance of accurate blood pressure (BP) measurement is well-established. However, there is little quantitative comparative data on the influence of different measurement conditions on BP or the stability of the oscillometric pulse waveform from which BP is calculated. This study investigates the effect of six different measurement conditions (Quiet, Reading, Speaking, Deep Breathing, Moving, and Tapping) on BP readings in 30 healthy normotensive subjects.