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461 papers

Trajectories Associated With the Use and Deprescription of Benzodiazepines and Z-Drugs in a Network of Geriatric Outpatient Clinics.

do Carmo Júnior NM et al. · Jul 1, 2026

Purpose To determine the trajectories of benzodiazepine (BZD) and Z-drug use among older adults (n = 3590) followed in a network of geriatric outpatient clinics in Brazil. Methods This longitudinal study evaluated BZD and Z-drug use over a 24-month follow-up period. The proportion of use at baseline and at the end of the study period was compared using the McNemar test. Two trajectories were considered: started using and stopped using. Comparisons between trajectories and independent variables were performed using Pearson's chi-square test. Variables with p Results A small but significant reduction in overall BZD or Z-drug use was observed (17.4% to 16.0%; p = 0.007), with a marked decrease in isolated Z-drug use (6.1% to 4.0%; p Conclusions Clinical vulnerability and psychiatric conditions were associated with BZD or Z-drug use and initiation, while pharmacist consultations were associated with both initiation and discontinuation trajectories.

Psychology

Targeting the Lipid Metabolism Proteins FASN and GPAM in Alveolar Type II Cells Decreases Lung Metastasis.

Liu XZ et al. · Jul 1, 2026

Cancer cells that seed in the lung require lipids often produced by alveolar type II (AT2) cells. However, whether overt metastases depend on AT2 cell-derived lipids and whether AT2 cells can be targeted to reduce metastasis growth remains unknown. We discovered that breast cancer-derived lung metastases stimulate the proliferation of AT2 cells in their vicinity and reprogram them into lipid feeder cells in mice and patients using spatial analysis. Mechanistically, the metastasis secretome activates the transcription factor sterol regulatory element-binding transcription factor 1 (SREBP-1) in AT2 cells, enhancing the expression of key de novo lipid synthesis genes, including fatty acid synthase (FASN) and glycerol-3-phosphate acyltransferase 1 (GPAM). Deleting Fasn selectively in AT2 cells or targeting FASN and GPAM systemically significantly impairs lung metastasis growth in mice. In summary, we discovered that overt metastases reprogram AT2 cells and that targeting the lipid metabolism of AT2 cells impairs metastasis growth. Significance Current therapies in oncology targeting the cancer or immune cell compartment of tumors show limited efficacy against breast cancer-derived metastases. We discovered that decreasing the lipid metabolism of lung resident AT2 cells is sufficient to impair lung metastasis growth in mice without apparent adverse effects.

Biochemistry, Genetics and Molecular Biology

Myosin Post-Translational Modifications Associated With Critical Illness Myopathy.

Ribeiro F et al. · Jul 1, 2026

Background Critical illness myopathy is a common and devastating consequence of critical care, causing dramatic loss of muscle mass and function in intensive care unit patients. Functional deficits often exceed the loss in muscle mass and myosin content. However, the mechanisms underlying the loss of force and emergence of myosin-expressing non-force-generating fibers remain elusive. Methods Myosin dysfunction was investigated in six intensive care unit patients exposed to a 12-day mechanical ventilation and immobilization period using mass spectrometry-based proteomics and molecular dynamics simulations. Results Previous single muscle fiber analyses revealed decreased fiber size and specific force from the 1st to the 12th days in all patients. A subset of myosin-expressing fibers exhibiting a complete loss of contractile function was identified in three of the patients despite similar atrophy levels (~30%, p Conclusion In addition to muscle wasting and myosin loss, abnormal myosin post-translational modifications contribute to muscle weakness in ICU patients with CIM, including the development of muscle fibers incapable of generating contractile force.

Antioxidants in Plant-Based Food Matrices: From Structure-Activity and Degradation Kinetics to Formulation Design.

Vargas-Ramella M et al. · Jul 1, 2026

Plant-based antioxidants are widely incorporated into foods to retard oxidative deterioration and to deliver health-related benefits. Yet, their in-product and in vivo performance frequently diverges from predictions based on solution-phase chemical assays, because matrix interactions, processing history, and host metabolism reshape both stability and bioactivity. This review integrates molecular mechanisms, structure-activity relationships (SARs), and degradation kinetics with food-matrix and human-relevance considerations to explain when, where, and how plant-based antioxidants act. Evidence is collated across polyphenols, carotenoids, tocopherols and tocotrienols, and selected alkaloids, linking hydrogen-atom, single-electron, and proton-coupled transfer pathways. Together, with those evidences, transition-metal chelation, interactions with proteins and polysaccharides, interfacial partitioning in emulsions, and metal-catalyzed oxidation are discussed. The influence of conventional and emerging processing, storage, and delivery systems (Pickering and double emulsions, spray drying/chilling, complex coacervation, ionic gelation) on antioxidant stability, localization, and bioaccessibility is also examined. Across systems, efficacy is governed less by intrinsic reactivity or nominal polarity than by effective interfacial concentration, partitioning behavior, and metal management. Encapsulation, when matched to matrix and process, improves antioxidant retention. Combinations of antioxidants may act cooperatively under one set of conditions and become antagonistic, or even pro-oxidant, under high oxygen availability or at suboptimal molar ratios. In this review, solution-phase rankings (DPPH, ABTS, FRAP, ORAC) are interpreted as descriptors of intrinsic reactivity. They cannot, on their own, predict performance in real food matrices or the post-digestion metabolite pool reaching systemic circulation. Effective use of plant antioxidants in foods therefore requires that formulation choices be informed by interfacial kinetics, food-component interactions during digestion, gut-microbiota metabotypes, and biomarker-validated estimates of dietary intake.

Agricultural and Biological Sciences

Glucagon-Like Peptide-1 Agonist vs. Placebo and Pulmonary Decline After Open-Heart Surgery: A Substudy of the GLORIOUS Randomised Clinical Trial.

Mikkelsen AD et al. · Jul 1, 2026

Background Postoperative pulmonary decline is an established complication of open-heart surgery extending beyond the immediate postoperative phase. Inflammation-mediated lung damage and ischaemia-reperfusion injury secondary to extracorporeal circulation is a proposed pathophysiological driver. GLP-1 receptor agonists (GLP-1RA) have emerged as promising protective agents in this setting. Aim Investigate whether infusion of the GLP-1RA, exenatide during cardiopulmonary bypass and weaning thereof, can mitigate the decline in diffusing capacity and ventilatory performance 3 months postoperative, compared to placebo. Methods In this predefined explorative substudy of the randomised, clinical GLORIOUS trial, 878 adult patients undergoing non-emergent coronary artery bypass grafting (CABG) and/or surgical aortic valve replacement (SAVR) were randomised to a continuous infusion of the GLP-1RA, exenatide or placebo during cardiopulmonary bypass, extending into the early postoperative period. Diffusing capacity of the lung for carbon monoxide (DLCO) and ventilatory performance (FEV 1 /FVC) were measured preoperatively and 3 months postoperatively. Results Median DLCO (% predicted corrected) declined from 80% preoperative to 72% 3 months postoperative, corresponding to a -7.7 percentage point (pp) difference (95% CI 6.2 to 9.1; p 1 /FVC declined from 0.75 preoperative to 0.73 postoperative, corresponding to a -1.6 difference (95% CI 1.0 to 2.1; p 0.3). Findings were consistent across subgroup analyses. Conclusion While both diffusing capacity and ventilatory performance exhibited a mild-to-moderate decline 3 months after open-heart surgery, the GLP-1RA exenatide did not mitigate this decline compared with placebo. Editorial comment Pulmonary dysfunction is one of the most common complications to open-heart surgery. The present study confirms a decline in diffusing capacity of the lung for carbon monoxide (DLCO) and in ventilatory performance measured as FEV 1 /FVC at 3 months postoperatively compared to preoperative measurements. Infusion of GLP-1 receptor antagonist during cardiopulmonary bypass and weaning did not mitigate the pulmonary decline compared to placebo.

Medicine

BeeGees: A High-Throughput Protein-Coding DNA Barcode Recovery Pipeline Tailored for Genome Skims of Museum Specimens.

Parsons DAJ et al. · Jul 1, 2026

Natural history collections are unparalleled archives of global biodiversity, yet most specimens remain molecularly uncharacterised due to the technical challenges of historical DNA (hDNA), including degradation, low endogenous content and contamination. Genome skimming offers a scalable alternative to PCR-based barcoding, but existing bioinformatic workflows are not optimised for the heterogeneous, metagenomic nature of museum-derived data. Here we present BeeGees (Barcode Extraction and Evaluation from Genome Skims), a high-performance computing (HPC) integrated, Snakemake-based workflow designed for protein-guided recovery and validation of mitochondrial and plastid barcode genes from degraded short-read genome sequences. BeeGees integrates dual read pre-processing, systematic per-sample parameter sweeps, sequential consensus cleaning to remove contaminant sequences and rigorous structural and taxonomic validation against curated reference databases. We benchmarked BeeGees on 1518 museum specimen-derived genome skims spanning eight phyla. The workflow completed in approximately 120 h (< 5 min per sample) on HPC infrastructure. When excluding sequencing failures (< 1 M reads), validated COI barcodes were recovered for 73.2% of specimens (1050/1435). Barcode recovery success was influenced by endogenous content, preservation quality and parameter choice rather than raw read count alone, highlighting the importance of systematic parameter optimisation. Sequential consensus cleaning eliminated ambiguous bases and reduced chimeric artefacts, proving essential for robust museomic analyses. BeeGees provides a reproducible, scalable framework for high-throughput barcode recovery and biodiversity genomics and reference gap-filling initiatives from natural history collections. The BeeGees pipeline is available at: https://github.com/bge-barcoding/BeeGees/.

Environmental Science

Paediatric Practitioners' Acceptance of the National Paediatric Early Warning System (PEWS).

Kaye LK et al. · Jul 1, 2026

Early detection of deterioration in children in hospital is essential for improving patient outcomes, prompting NHS England to introduce a digital National Paediatric Early Warning System (PEWS) in November 2023. Our service evaluation examined a locally delivered digital version of the PEWS system, introduced in July 2025 to explore paediatric staffs' acceptance before and after implementation, measured by the Technology Integration Evaluation Resource (TIER), based on the Technology Integration Model. Online surveys were completed pre- and post-implementation. Acceptance did not significantly change over time. However, user motivation, agency and perceived cost-benefit as well as perceptions of PEWS as an extension of self, were positively associated with acceptance, highlighting key psychological factors influencing digital health adoption.

Medicine

Antibiotics in Veterinary Ophthalmology: Resistance, Stewardship, and Emerging Antibiotic-Sparing Strategies.

Sebbag L et al. · Jul 1, 2026

Antimicrobial resistance (AMR) is a growing challenge in veterinary ophthalmology, particularly in cases of bacterial keratitis, where progressive stromal infection can threaten vision and globe integrity within hours to days. This review synthesizes current evidence on pathogen distribution, antimicrobial susceptibility profiles, multidrug resistance (MDR) prevalence, and determinants of nonsusceptibility in veterinary patients, highlighting the emerging role of antibiotic-sparing alternatives. Across contemporary studies, Staphylococcus pseudintermedius, β-hemolytic streptococci, and Pseudomonas aeruginosa are consistently among the most frequently isolated pathogens. The highest MDR burdens are reported in referral populations and among methicillin-resistant staphylococci worldwide. Feline data remain comparatively limited but show regional variability in resistance patterns, while equine studies reveal temporal shifts in isolate distribution and a rising prevalence of methicillin-resistant organisms in tertiary settings. Recent topical antimicrobial exposure is the most consistently identified predictor of reduced culture positivity and elevated resistance rates in subsequent ocular isolates, highlighting the importance of early microbiologic sampling and judicious antibiotic use. Interpreting antimicrobial susceptibility testing (AST) in ophthalmology remains challenging because clinical breakpoints are generally derived from systemic dosing regimens, despite substantially higher, albeit transient, drug concentrations being achieved at the ocular surface following topical administration. Moreover, the ocular surface microenvironment, including tear proteins, inflammation, biofilm formation, and concurrent serum therapy, may substantially influence antimicrobial activity and therapeutic response. The review concludes with practical ophthalmology-specific stewardship recommendations, a One Health perspective on resistant ocular pathogens, and a forward-looking discussion of antibiotic-sparing adjuncts within a broader multimodal strategy to preserve antimicrobial effectiveness.

Medicine

Bayesian Analysis of Postoperative Complication Risk Associated With Preoperative Exposure to Fine Particulate Matter: A Single-Center Cohort Study.

Pearson JF et al. · Jul 1, 2026

Background Air pollution, especially particle pollution, is increasingly recognized as a potential perioperative risk factor, yet modeling environmental exposures in surgical cohorts remains methodologically underdeveloped. We demonstrate a Bayesian hierarchical framework to quantify probabilistic associations between preoperative fine particulate matter (PM 2.5 ) exposure and postoperative complications, highlighting its interpretability and flexibility for clinical environmental epidemiology. Methods We conducted a single center, retrospective cohort study using data from 49,615 surgical patients in Utah who underwent elective surgical procedures from 2016 to 2018. Patients' addresses were geocoded and linked to daily Census-tract level PM 2.5 estimates. The exposure variable was defined as the maximum PM 2.5 concentrations in the 7 days prior to surgery. The binary outcome was a composite of postoperative complications: pneumonia, surgical site infection, urinary tract infection, sepsis, stroke, myocardial infarction, or thromboembolic event. A hierarchical Bayesians regression model with weakly informative priors was used adjusting for age, sex, season, neighborhood disadvantage, and the Elixhauser index of comorbidities with census tract as a group (random) effect. We present posterior estimates with credible intervals, highlight model transparency and sensitivity, and discuss contrasts with standard frequentist methods. Results Postoperative complications were associated in a dose-dependent manner with higher concentrations of PM 2.5 exposure. We found a relative increase of 8.2% in the odds of complications (OR = 1.082) for every 10.ug/m 3 increase in the highest single-day 24-h PM 2.5 exposure during the 7 days prior to surgery. For an increase in PM 2.5 from 1 to 30 ug/m 3 , the odds of complication rose to over 27% (95% CI: 4%-55%). The results were robust across prior choices and model specifications. We report full posterior distributions and highlight advantages of Bayesian modeling for uncertainty quantification and clinical interpretability. Conclusions This case study demonstrates the application of hierarchical Bayesian modeling to quantify the probabilistic associations between preoperative PM 2.5 exposure and postoperative complications, highlighting transparent risk estimation and uncertainty characterization that may inform the design of future multicenter perioperative environmental studies. Editorial comment Using Bayesian statistical analysis, the authors demonstrate a dose-dependent risk for postoperative complications in patients exposed to air polluted with fine particulate matter with a size of less than 2.5 μm.

Environmental Science

Accuracy and Documentation of Richmond Agitation-Sedation Scale Assessments in a Cardiothoracic Critical Care Unit: A Prospective, Cross-Sectional Audit.

Szentgyorgyi L et al. · Jul 1, 2026

Background Sedation is a fundamental component of critical care and requires regular, accurate assessment to support its safe titration and minimise harm. International guidelines and local policy at the Wythenshawe Hospital's Cardiothoracic Critical Care Unit mandate hourly documentation of the Richmond Agitation-Sedation Scale (RASS). Aims This audit evaluated adherence to these standards and explored factors associated with documentation completeness and assessment accuracy. Study design A prospective, cross-sectional audit of bedside RASS assessment was conducted without prior notification. Nursing RASS scores were compared with expert auditor ratings. Data were collected using an anonymous, secure, auditor-completed online survey. Statistical analysis examined the relationship between documentation completion and RASS accuracy. Results Seventy-six nursing assessments were included. Most nurses were Band 5, with a median of 3.5 years of experience. Patients were predominantly male, mechanically ventilated and receiving sedation. Overall, 75% of nurse RASS assessments (n = 57) were accurate; however, only 33% (n = 25) were documented hourly as required by policy. Greater nursing experience was associated with improved accuracy in RASS. Deeper sedation was associated with lower agreement between nurse and expert assessments. Higher self-reported confidence was associated with poorer completion of documentation. Most discrepancies were small, with nurse and expert ratings differing by one RASS point. Conclusions This audit identified important gaps in the accuracy and documentation of nurse-led RASS assessment in a cardiothoracic critical care setting. The findings suggest that perceived familiarity and confidence may not be sufficient to ensure accurate and consistently documented sedation assessment. Relevance to clinical practice Suboptimal RASS documentation and scoring accuracy may limit reliable titration of sedation in critically ill patients and reduce the effectiveness of protocolised sedation strategies. These findings support targeted staff education, reinforcement of standardised assessment processes and improvements in documentation systems to strengthen sedation monitoring and patient safety.

Medicine