Chemical alteration of UO micro-particles in model lung systems.

Uranium dioxide (UO) particles can be released from mines, nuclear fuel manufacturing, reactor accidents, and weapons use. They pose inhalation risks, yet their behavior in the human lung remains poorly understood. This study investigates the long-term chemical alteration and dissolution of µm-sized UO particles in two model lung fluids: Simulated Lung Fluid (SLF) and Artificial Lysosomal Fluid (ALF), representing extracellular and intracellular lung environments, respectively.

The role of low subcortical iron, white matter myelin, and oligodendrocytes in schizophrenia: a quantitative susceptibility mapping and diffusion tensor imaging study.

Iron-the most abundant magnetic brain substance-is essential for many biological processes, including dopamine and myelin synthesis. Quantitative susceptibility mapping (QSM) MRI has recently linked altered subcortical magnetic susceptibility (χ) to schizophrenia. Since χ is increased by iron and decreased by myelin, abnormal levels of either could underlie these QSM differences.

Multimodality curative-intent treatment in NSCLC: an unprecedented era of change 2017-2025.

Curative-intent multimodality treatment-combining local treatments such as surgery or radiotherapy with systemic therapy-is the cornerstone of care in stage II-III non-small cell lung cancer (NSCLC). Since 2017, the systemic therapy backbones with multimodality treatment have undergone a dramatic transformation, driven by a series of pivotal, practice-changing clinical trials. Immunotherapy and targeted therapies, previously confined to the advanced/metastatic setting, are now firmly embedded in curative-intent regimens.

An Electronic Health Record-Wide Association Study to identify populations at increased risk of E. coli bloodstream infections.

Objectives: Escherichia coli bacteraemias have been under mandatory surveillance in the UK for fifteen years, but cases continue to rise. Systematic searches of all features present within electronic healthcare records (EHRs), described here as an EHR-wide association study (EHR-WAS), could potentially identify under-appreciated factors that could be targeted to reduce infections.

Methods: We used data from Oxfordshire, UK, and an EHR-WAS method developed for use with large-scale COVID-19 data to estimate associations between E.

Community-based hearing aid fitting model for adults in low-income communities facilitated by community health workers: a feasibility study.

Background: Hearing loss affects more than 1.5 billion people worldwide, yet fewer than 10% of those who could benefit from hearing aids are able to access them. Barriers such as high costs, limited availability, and a critical shortage of trained professionals in low- and middle-income countries contribute to this gap, while emerging models of care-such as task-shifting to community healthcare workers (CHWs) supported by mHealth technologies-show promise in improving access, affordability, and outcomes in underserved communities.

Diagnostic stewardship - optimization of superficial wound swab cultures can reduce the environmental impact of the microbiology laboratory.

Optimization of diagnostic testing is essential for the sustainable delivery of laboratory services. To date, little consideration has been given to the potential benefits of diagnostic stewardship to laboratories looking to reduce their environmental footprint. Implementing a pre-analytical diagnostic stewardship intervention for the testing of superficial wound swabs would result in a measurable reduction in the environmental footprint of the microbiology laboratory.

Pharyngeal electrical stimulation to treat dysphagia in acute stroke: learnings from cases in the PhEED clinical trial.

Objective: To assess the efficacy of pharyngeal electrical stimulation in improving dysphagia post-stroke.

Design: A randomized, sham-controlled, blinded multicentre clinical trial.

Subjects/patients: Seventeen patients with acute ischaemic or haemorrhagic stroke experiencing dysphagia, indicated by a penetration aspiration scale score of 4-8 on videofluoroscopy.

Mechanistic Divergence in Sulfur-Ligated Iron(III)-Alkylperoxo Reactivity: Aldehyde Oxidation Prevails over Deformylation.

Metalloenzymes activate molecular oxygen within their catalytic cycles to generate a reactive species capable of substrate transformation. In many iron-containing enzymes, it is a high-valent iron(IV)-oxo complex that is synthesized from an iron(III)-alkylperoxo intermediate, although direct observation and characterization of such species have remained elusive, leaving their mechanistic role uncertain. To address this gap in our understanding, we present here the synthesis, comprehensive characterization, and reactivity of a novel thioether-ligated iron(III)-alkylperoxo complex supported by the ligand 2-((2-(pyridin-2-yl)ethyl)thio)-N,N-bis(pyridin-2-ylmethyl)ethan-1-amine.

Concentration-dependent blood binding: assessing implications through physiologically based Pharmacokinetic modeling of tacrolimus as a case example.

Concentration-dependent binding to red blood cells is a characteristic of several drugs, complicating the understanding of how pathophysiological factors influence drug behavior. This study utilized user-friendly, physiologically-based pharmacokinetic (PBPK) models to compare concentration-dependent and independent blood-to-plasma drug concentration ratios (B/P), using tacrolimus as a case study. Two models were developed and validated for tacrolimus using clinical data from healthy volunteers; Model 1 accounted for saturable blood binding, and Model 2 used a constant B/P level.

Meal timing trajectories in older adults and their associations with morbidity, genetic profiles, and mortality.

Background: Older adults are vulnerable to mistimed food intake due to health and environmental changes; characterizing meal timing may inform strategies to promote healthy aging. We investigated longitudinal trajectories of self-reported meal timing in older adults and their associations with morbidity, genetic profiles, and all-cause mortality.

Methods: We analyzed data from 2945 community-dwelling older adults from the University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, with up to five repeated assessments of meal timing and health behaviors conducted between 1983 and 2017.

Impact of prehospital delay on postoperative complications and 5-year mortality in older adults with hip fractures.

Purpose: Guidelines recommended early surgery for hip fracture to improve outcomes, yet it is often hindered by prehospital delays. However, it remains unclear whether prehospital delay independently leads to poor outcomes of the well-recognized impact of in-hospital delay for hip fracture surgery.

Methods: We included patients aged over 60 years old who underwent surgery for their first acute hip fracture between 2000 and 2022 at a national trauma center in Beijing, China.

Cerebrovascular Reactivity at Rest and Its Association With Cognitive Function in People With Genetic Frontotemporal Dementia.

Background And Objectives: Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular health, and its signature in familial frontotemporal dementia (FTD) remains unknown. The primary aim was to investigate CVR in genetic FTD using an fMRI index of vascular contractility termed resting-state fluctuation amplitudes (RSFAs) and to assess whether RSFA differences are moderated by age. A secondary aim was to study the relationship between RSFA and cognition.

Adaptation and pilot testing of the Early Learning Outcome Measure (ELOM) (4&5) Years Assessment tool in South African Sign Language.

Early Childhood Development is a key national priority in South Africa which has developed the Early Learning Outcome Measure (ELOM 4&5) specifically designed to measure the progress of 4- and 5-year-old children across 5 domains of early childhood development. This age-validated, population-standardised instrument has been shown to have measurement equivalence and lack of bias across South Africa's 11 official spoken languages. In 2023, South African Sign Language was formally recognised as 12th official language of South Africa, but no ELOM (4&5) exists in SASL despite over 6,000 deaf children being born annually.

Effects of age, sex, language ability and second language listening on children's recognition of nonwords and sentences in noise and reverberation.

Objectives: To evaluate children's ability to recognise speech and its relationship to language ability using two newly developed tests: the Listening in Spatialised Noise and Reverberation test (LiSN-R) and the Test of Listening Difficulties - Universal (ToLD-U).

Design: LiSN-R and ToLD-U used nonword and sentence recognition in spatially separated noise and reverberation. Language ability was assessed using the Clinical Evaluation of Language Fundamentals (CELF) sentence recall.

The influence of ethnicity on frailty in a United Kingdom (UK) population.

Background: Frailty is an important and increasing clinical and public health problem. Within the United Kingdom (UK). Most data relating to the occurrence of frailty is derived from Caucasian groups.

A Journey between Neurons and Astrocytes: A Tribute to Giorgio Carmignoto.

The intimate relation between astrocytes and blood vessels was proposed by Camillo Golgi in 1870. Santiago Ramon y Cajal subsequently introduced the idea of astrocytes as regulators of functional hyperaemia accompanying neuronal activity in 1895. In 2003 Giorgio Carmignoto, Micaela Zonta, Tullio Pozzan and their colleagues revealed mechanisms of astrocytic control over vasodilatation.

Divergent Synthesis of 1-Azabicyclo[n.1.1]alkane Bioisosteres via Photoinduced Palladium Catalysis.

Nitrogen heterocycles are indispensable structural motifs in pharmaceuticals, agrochemicals, and materials science. However, the development of new synthetic methods to access these frameworks remains a significant challenge. Here, we describe a switchable radical approach for the synthesis of 1-azabicyclo[2.

Impacts of mitochondrial dysfunction on axonal microtubule bundles as a potential mechanism of neurodegeneration.

Mitochondrial dysfunction is an important cause for neurodegeneration, often associated with dyshomeostasis of reactive oxygen species, i.e., oxidative stress.

Unprecedented UK heatwave harmonised drivers of fuel moisture creating extreme temperate wildfire risk.

Climate change is resulting in more extreme fire weather during major heatwaves. Across temperate Europe, shrub landscapes dominate the area burned, with the moisture content of fuels during these events determining the threat posed. Current controls on the moisture content of temperate fuel constituents and their response to future extreme heatwaves are not known.

Bacteria-phage infection network structure and genomic defence system content predict efficacy of a phage therapy cocktail against from chronic lung infections.

chronic lung infections pose serious challenges for phage therapy due to high between-patient strain diversity and rapid within-patient phenotypic and genetic diversification, necessitating simple predictors of efficacy to streamline phage cocktail design. We quantified bacteria-phage infection networks (BPINs) for six phages against 900 clones previously isolated from 10 bronchiectasis infections ( = 90 isolates per patient). BPIN structure varied extensively between patients.