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Biofilms, first described by Anthony van Leeuwenhoek (1632-1723), are surface-attached, organized microbial communities. They form when single cells embed within an extracellular matrix (ECM) composed mainly of extracellular polymeric substances (EPS), enabling a multicellular lifestyle. Extracellular DNA (eDNA), a major EPS component, makes up a substantial portion of biofilm biomass. It interacts with polysaccharides, proteins, and nucleic acids to create a stable network that reinforces biofilm structure. eDNA, present in all biofilm ECM, plays a paradoxical role in bacterial survival. It is vital for structural integrity, guiding the biofilm from initial attachment through maturation and dispersion, yet this dependence also creates a critical vulnerability. Recent research highlights that while eDNA supports biofilm growth, disrupting its release, interactions, or structure destabilizes the matrix and drives depletion. Recognizing eDNA as both a structural scaffold and a therapeutic target enables more effective strategies to inhibit and disperse resilient biofilm communities. This review highlights recent advances in eDNA-releasing mechanisms, its multifunctional roles in biofilm support, and how its structures and interactions regulate development. We further show that modulating eDNA provides a targeted strategy for antibiofilm therapy and clinical dispersal. Notably, eDNA itself may also act as a cue for biofilm inhibition.

Medical gaslighting, defined as the dismissal or minimization of patient-reported symptoms in the absence of adequate justification, has emerged as a relevant yet insufficiently examined phenomenon in gastroenterology. Patients with gastrointestinal disorders are particularly vulnerable due to the prevalence of conditions that rely on subjective symptom reporting, evolving diagnostic criteria, and limited availability of definitive biomarkers, especially among functional gastrointestinal disorders and disorders of gut-brain interaction as defined by the Rome IV criteria. This narrative review provides an overview of medical gaslighting in both pediatric and adult gastroenterology, including its conceptual foundations, clinical manifestations, and consequences. Drawing on established theoretical frameworks and contemporary clinical literature, we examine how diagnostic uncertainty, implicit bias, time constraints, and communication gaps contribute to diagnostic invalidation across care settings. Attention is given to populations at increased risk, including children, women, and patients from marginalized racial or socioeconomic backgrounds, as well as to pediatric-specific challenges related to caregiver-mediated symptom reporting and developmental variability. Importantly, this review distinguishes medical gaslighting from appropriate diagnostic uncertainty and from persistent patient concern despite appropriate evaluation, emphasizing the role of transparent diagnostic reasoning and therapeutic alliance. We also highlight validated diagnostic criteria and symptom assessment tools for both functional and inflammatory gastrointestinal disorders as mechanisms to support diagnostic confidence and patient validation. Finally, this review outlines practical, clinically actionable strategies to reduce medical gaslighting in gastroenterology, including bias-aware communication, structured reassurance, use of standardized diagnostic frameworks, and multidisciplinary care models. Addressing medical gaslighting is essential to improving diagnostic accuracy, patient trust, and equitable, patient-centered gastrointestinal care.

This study investigated the effects of docosahexaenoic acid (DHA) supplementation on delayed onset muscle soreness (DOMS), physical function, and inflammation following eccentric exercise-induced muscle damage in physically trained male and female adults (training&#x2009;&#x2265;&#x2009;5d/wk). Thirty-eight participants (12 Control, 26 DHA) completed a 12-week double-blind, placebo-controlled matched-pair trial. The Control group received high-oleic acid tablets. The DHA group received 715&#xa0;mg/d of microencapsulated DHA tablets. Participants performed eccentric cycling at weeks 0 and 12, with assessments conducted pre-exercise, 0-h, 24-h, and 48-h post-exercise. The primary outcomes were DOMS (visual analogue scale) and the Omega-3 Index (O3I) (estimated by finger-stick dry blood spot). Secondary outcomes included neuromuscular function and inflammatory cytokines. O3I was not different between groups at week 0 but was elevated in the DHA group (&#x2206;2.43%, [95% CI; 2.10, 2.77], P&#x2009;<&#x2009;0.001) and between Control at week 12 (P&#x2009;<&#x2009;0.001). DOMS was lower at 24-h and 48-h post-exercise in the DHA group and between Control at week 12 (P&#x2009;<&#x2009;0.01). At week 12, jump height and peak vertical force improved at 48-h post-exercise in the DHA group (P&#x2009;<&#x2009;0.05), resulting in moderate (d&#x2009;=&#x2009;0.60) and small (d&#x2009;=&#x2009;0.32) effect sizes for 48-h post-exercise area under the curve (AUC) between groups, respectively. There were interaction effects for 48-h post-exercise AUC of IL-6 (P&#x2009;=&#x2009;0.049), TNF-&#x3b1; (P&#x2009;=&#x2009;0.010), and IL-10 (P&#x2009;=&#x2009;0.026). A dietary achievable dose of DHA elevated the O3I and reduced DOMS in physically trained adults. These outcomes support protracted intake of DHA to attenuate the physiological impact of eccentric exercise and promote recovery.

Climate change poses significant threats to global health, impacting physical, mental, and socio-economic well-being across diverse settings. Understanding these impacts on non-communicable diseases (NCDs) and prevention strategies is critical for informing public health policy and practice. This study aimed to systematically synthesise existing evidence on the public health challenges of climate change-induced NCDs in vulnerable populations and low-resource settings and inform policymakers about developing interventions to protect vulnerable populations from the adverse impacts of climate change on health. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted by searching six databases: PubMed, Scopus, Web of Science, Embase, EBSCOhost, and Cochrane Library. Studies that addressed the link between environmental changes and NCD risks or evaluated prevention strategies were included, with 27 studies meeting the inclusion criteria. The data were analysed using thematic synthesis, and the quality of the studies was evaluated using standardised appraisal instruments. The review synthesised evidence from (n&#x2009;=&#x2009;27) studies and identified multiple ways climate and environmental changes exacerbate NCD risks, including heat stress, air pollution, and food insecurity. Vulnerable populations, such as low-income households and displaced communities, were disproportionately affected. The global health challenges of climate change can be averted by utilising multiple and cost-effective strategies such as community engagement, establishing climate-inclusive health policies, and improving the effectiveness of resilient healthcare systems. However, data availability scarcity, inadequate policy implementation, gaps in multisectoral collaboration, and acclimatisation measures continue to be key obstacles to climate change-induced NCD challenges. Climate change is a prominent cause of NCDs and public health challenges in the 21st century, particularly among vulnerable populations and healthcare systems in low-resource settings. An integrated systems approach with multisectoral collaboration and involvement is required to establish a climate-resilient public healthcare system that mitigates climate-induced public health challenges and impacts. Future research should focus on addressing data gaps, scaling effective interventions, and prioritising the needs of vulnerable populations.

The diesel exhaust constituent 1-nitropyrene (1-NP) is classified as a probable human carcinogen and other constituents 1,8-dinitropyrene (1,8-DNP) and 3-nitrobenzanthrone (3-NBA) are classified as possible human carcinogens by the International Agency for Research on Cancer. These nitroarenes are activated by nitroreduction via nitroso- and hydroxylamino- intermediates on route to the corresponding amine product(s). Two types of DNA adduct can occur in this sequence. First, the hydroxylamino- intermediate can undergo sulphonation or acetylation giving rise to a strong leaving group so that stable covalent adducts can form. Second, back oxidation of these air sensitive intermediates can give rise to reactive oxygen species and nitrogen species (ROS, RNS) so that oxidatively damaged bases can form. Human aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 play prominent roles in the nitroreduction of these nitroarenes in human lung cell lines. We now report that when AKR1C1-AKR1C3 are transfected into V79-4 cells we observe a significant increase in HPRT gene mutation. The mutation is dependent on AKR1C enzyme activity since isoform specific inhibitors reduced the number of mutant colonies formed. ROS scavengers reduced the number of mutant colonies formed with 1-NP, 1-8-DNP and 3-NBA in the presence of transfected AKR1C1. Ethyl gallate and the superoxide dismutase mimetic (MnTBAP) reduced the number of mutant colonies formed. Nitric oxide scavengers, 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazoyl-1-oxy-3-oxide and uric acid, also reduced the number of mutant colonies formed. Our results suggest that both 8-oxo-dG and 8-nitro-dG lesions may contribute to the mutation observed. Since AKR1C1-AKR1C3 are potently induced by NRF2, its activation might increase the mutagenicity of nitroarenes in the context of diesel exhaust exposure.

This study reports the first documented detection of 123Xe in the context of the CTBTO's International Monitoring System (IMS), in samples collected by the SPALAX-NG system (CEA/DIF, France). 123Xe is a short-lived radioisotope (T1/2&#x202f;=&#x202f;2.05&#x202f;h) produced during medical 123I synthesis; atmospheric releases from medical facilities can lead to 123Xe capture by nearby IMS stations, potentially causing false 131mXe detections due to spectral overlaps in regions of interest (ROIs). Using high-resolution gamma and coincidence spectroscopy, we confirmed the presence of 123Xe and its decay product, 123I, in collected air samples. To mitigate interference, we developed an analytical adaptation for SPALAX-NG that identifies 123Xe via its 149&#x202f;keV gamma peak and adjusts ROIs 5 and 6, with minimal efficiency loss (&#x2264;2.8%). This solution ensures accurate discrimination between 123Xe and CTBT-relevant isotopes. Our findings demonstrate the need to account for non-CTBT radioxenon isotopes in IMS analyses, particularly near medical isotope production sites, and advocate for high-resolution detection systems to improve monitoring reliability under the CTBT.

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Cyanobacterial harmful algae blooms (cyanoHABs) are increasingly common in freshwater around the world, impairing freshwater ecosystems as well as access to water used for drinking, agriculture, fishing, and industry. A combined coagulant-clay flocculation strategy is a promising method to remove harmful algal cells, yet the optimally efficient application protocol and dosage remain unclear, making cost estimation difficult. Here we investigate how (1) the application procedure and (2) the relative dosages of clay and chitosan affect the removal efficiency of M. aeruginosa, a representative freshwater cyanobacterium. Bentonite was chosen for its abundance and high cation exchange capacity, and chitosan was chosen for its biodegradability and regulatory approval in the United States. We conducted lab-scale flocculation experiments that showed (i) a stepwise application of chitosan and bentonite, regardless of application order, results in a higher cell removal efficiency than a single-step chitosan-modified bentonite application (CMB); (ii) in all three approaches, there is an optimal chitosan dose that is sensitive to both cyanobacterial cell density and the bentonite dose; and (iii) upon optimization according to application procedure and dosage, the addition of chitosan at 2-4 mg/L can reduce the required bentonite dose to remove 80 % of cyanobacteria to <80 mg/L. Though experimental, our findings indicate a sensitivity of flocculation efficiency to chitosan dose and application procedure, suggesting that important care should be taken to optimize these two parameters in field campaigns that use the EPA-approved materials, chitosan and bentonite, to efficiently remove cyanoHABs-cells in freshwater ecosystems.

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HLA compatibility has been a cornerstone for safe and successful allogeneic haematopoietic cell transplantation (HCT), with human leukocyte antigen (HLA)-mismatched transplants consistently associated with inferior survival. However, recent advances in typing technologies, supportive care, and novel graft-versus-host disease (GvHD) prophylaxes have prompted the revisiting of HLA mismatch relevance in contemporary HCT. Within the framework of the 3rd Workshops of the Practice Harmonization & Guidelines Committee, the EBMT convened a group of experts in histocompatibility & immunogenetics, HCT immunobiology, and clinical HCT, to review the current state of the art and develop a set of consensus-based recommendations on the role of HLA in current HCT. The topics included technological aspects of HLA typing, the role of HLA mismatches in donor selection, and the detection and management of anti-HLA antibodies in HLA-mismatched transplantation. Moreover, the role of HLA matching relative to other non-HLA factors and in the context of novel GvHD prophylaxes, non-malignant disease, and pediatric populations was defined. Finally, the relevance of special models for HLA matching and of post-HCT monitoring of HLA-loss in malignant disease relapse was reviewed. The present document summarizes the expert consensus on these topics, to provide evidence-based recommendations for clinical decision-making.

While knee osteoarthritis (OA) is incurable, end-stage OA can be managed surgically with partial knee arthroplasty (PKA) or total knee arthroplasty (TKA). Most studies that compare PKA and TKA cohorts rely on patient-reported outcome measures (PROMs) and lack objective joint-level biomechanics. The purpose of this study was to examine preoperative joint-level kinematics during multiple functional tasks including preferred-pace walking, fast-paced walking, and sit-to-stand alongside self-reported outcomes in patients that received partial versus total knee arthroplasty. Participants with end-stage knee osteoarthritis were recruited from St. Joseph's Healthcare Hamilton. Self-reported measures included the Oxford knee score, pain ratings, quality of life, and depression. Functional tasks were recorded using markerless motion capture, and joint-level kinematics were analyzed with linear mixed models to test main and interaction effects of surgery type and task condition. The study included 15 patients that received partial knee arthroplasty and 56 patients that received total knee arthroplasty. No significant differences were observed in self-reported outcomes, nor in single-speed gait or sit-to-stand performance. However, differences emerged when examining walking patterns across speeds. Compared to the total knee arthroplasty group, patients that received partial knee arthroplasty demonstrated greater changes in stride length, peak stance and swing knee flexion, knee excursion, peak stance hip flexion, and overall hip range of motion when going from preferred- to fast-paced walking. These findings suggest that multi-speed gait assessments may provide a more sensitive approach to detecting kinematic differences in osteoarthritis patients and may be valuable in other clinical contexts.

Plant metabolism underpins the food, fiber, and fuel that support our economy, driving strong interest in new strategies to rewire plant metabolism for emerging applications. While most synthetic biology efforts are reliant on genetic engineering, plants can be manipulated in many other ways that remain comparatively underexplored. Across nature, diverse organisms, including bacteria, fungi, and insects, have evolved sophisticated mechanisms to exploit plant metabolic richness, reshaping it for purposes that span from basic nutrition to the construction of complex, novel structures for shelters. These interspecies interactions and non-model systems represent unique manners in which plants can be reprogrammed or hijacked by other organisms, offering inspiration for novel approaches to engineering plant metabolism. By better understanding the basis of how organisms induce these remarkable transformations in plants, we can expand the conceptual boundaries of synthetic biology and reveal alternative routes to manipulating plants for the production of a diverse array of valuable compounds and materials. Deeper insight into these mechanisms will yield novel blueprints for rethinking the scope and breadth in which we can redesign plant metabolism across many applications.

Background/Objectives: To identify predictors of successful fusion and adjacent segment disease (ASD) following ALIF. Methods: Records of patients undergoing one- or two-level ALIF were queried for baseline and postoperative radiographic data, demographics, operative notes, and implant characteristics. All had &#x2265;1 year of follow-up with CT, and multivariable Cox regression was used to identify predictors of radiographic fusion through the interbody, ASD, and ASD requiring reoperation. Results: In total, 177 patients (median 59 yr; 52.5% male) were treated at 245 unique levels, of which 193 fused (81.3% with posterior fixation and 59.6% with standalone), 43 had ASD (17.6%), and 14 had ASD requiring reoperation (5.7%). Fusion was predicted by anterior cage placement (HR 0.94/mm; 95% CI [0.90, 0.98]; p = 0.003) and BMP use (HR 1.92; [1.15, 3.18]; p = 0.012). Radiographic ASD was predicted by older age (HR 1.08 per year; [1.03, 1.14]; p < 0.001), undergoing a revision [vs. index] fusion operation (HR 3.51; [1.44; 8.59]; p = 0.006), lower preoperative disc height (HR 0.83/mm; [0.74, 0.94]; p = 0.003), and preoperative facet vacuum phenomenon (HR 2.46; [1.18, 5.15]; p = 0.017). None of the extracted variables predicted reoperation for ASD. Conclusions: BMP use along with anterior cage placement and posterior fixation may improve the odds of fusion through the interbody following one- or two-level ALIF. Adjacent segment pathology is more common in patients with greater preoperative degenerative pathology (vacuum sign; more collapsed disc) and advanced age. Pelvic fixation did not improve fusion odds, but the data highlight the benefits of supplementary posterior fixation vs. standalone ALIF.

In neuronal dysfunction, there is a disruption of synthesis and release of neurotransmitters including dopamine. Oxidative stress is a major contributor to neuronal dysfunction. Oxidative stress affects tetrahydrobiopterin (BH4), an essential cofactor in the synthesis of several neurotransmitters such as dopamine and nitric oxide. BH4 supports the activity of enzyme tyrosine hydroxylase (TH) and initiates dopamine synthesis. Studies have reported contradictory results on neuronal dysfunction and disease progression following treatments to reduce oxidative stress and BH4 supplementation. In this study, we developed a computational model of TH biochemical pathway in dopaminergic nerve cells. Using this model, we quantitatively analyzed the impact of reduced BH4 synthesis and oxidative stress on L-dopa and dopamine synthesis. The base case concentration of L-dopa was 382.5 nM and cytosolic dopamine was 12.4 nM. The results showed a significant decrease in the concentrations of L-dopa and dopamine with reduction in BH4 synthesis. The presence of oxidative stress further exacerbated these decreases in concentration. The mechanistic analysis suggests that this computational model provides an initial framework for evaluating how BH4-related perturbations influence species concentrations in the TH biochemical pathway in dopaminergic nerve cells. Our findings indicate that under the simulated conditions, BH4 supplementation produced short-term changes in species concentrations and that sustained improvement in nerve cell dysfunction likely requires a multi-target approach that simultaneously enhances de novo BH4 synthesis and reduces cellular oxidative stress. The online version contains supplementary material available at 10.1007/s11571-026-10486-4.

Fungal symbionts play essential roles in ecosystems influencing plant development and biodiversity. Mycorrhizal fungi can form common mycorrhizal networks (CMNs) where a fungus connects the roots of at least two plants via continuous extraradical mycelium and transfers resources such as nitrogen and carbon. In addition to mycorrhizal fungi, there is another group of fungal mutualists known as endophytes. They also support plant development and may form common endophyte networks (CENs). Whether endophytes can transfer soil resources like nitrogen, carbon, and water through such networks remains an open question. To test this, we established a CEN experiment in split petri dishes involving Arabidopsis thaliana hosts and three phylogenetically diverse endophytes (Trichoderma viride, Mucor hiemalis, and Fusarium temperatum) to test whether resources like isotopically labelled amino acid 15nitrogen (N), amino acid 13carbon (C), 15N-ammonium, or deuterated water can be transferred by donor to receiver plants connected via CENs. We show that the tested endophytes can form CENs and transfer growth limiting resources from donor plant soil to receiver plant tissues. F. temperatum boosted plant growth by 38% relative to the uninoculated control, and it enriched plant 15N content derived from amino acids by 55%. Surprisingly, we also observed amino acid-derived 13C transport from donor plant soil to receiver plant tissues by T. viride (+&#x2009;2.83% > control). We also demonstrate that soil resource transfer, evaluated as isotope enrichment, by all three endophytes shifted in the presence of two versus a single host plant even when root systems were physically separated to avoid competition, underscoring that endophytic functioning, not just that of plants, also shifts when CENs are formed. Our results demonstrate that non-mycorrhizal fungi, like endophytes, can form networks similar to the idea of CMNs and transfer plant growth relevant resources. Endophytes display a broad array of symbiotic functions with their hosts, and formation of CENs may be a newly discovered component of their symbiotic tool kit.

Pediatric cerebral venous sinus thrombosis (CVST) is being increasingly recognized and can pose substantial risks of morbidity and mortality. Data on the epidemiology, management, and outcomes of CVST in the PICU remain limited. To describe the clinical characteristics, management, and outcomes of critically ill children with CVST during their admission to the PICU. We conducted a retrospective observational cohort study in a quaternary PICU in Toronto, Canada, between 2018 and 2023. Patients 18 years old and younger with acute primary CVST (CVST being the primary indication for ICU admission) and secondary CVST (diagnosis during an admission for an alternative diagnosis) were included in this study. The primary outcome was in-hospital mortality. Descriptive statistics were used to describe characteristics and outcomes. Thirty patients were admitted with a diagnosis of CVST: 19 (63%) primary, 11 (37%) secondary. Fourteen (47%) had an associated cerebral infarct, and nine (30%) had an associated intracranial hemorrhage. The most common condition associated with secondary CVST was a brain disease requiring neurosurgical intervention (5/11). Five (17%) children with CVST died in this study, of which four had a primary CVST. Children residing in neighborhoods with increased marginalization were disproportionally represented in this cohort. Primary CVST is more common than secondary and is associated with significant mortality. The disproportionate impact on marginalized children emphasizes the need for heightened awareness and determination of factors associated with this finding.

Disseminated histoplasmosis is a severe systemic mycosis typically seen in immunocompromised individuals. Though CNS involvement occurs in a small subset of patients, associated intracranial hemorrhage is an exceptionally rare and poorly documented complication. A 26-year-old woman with untreated HIV from an endemic region presented with weight loss, jaundice, and lymphadenopathy. Her clinical course progressed to seizures and meningeal signs, initially suggesting tuberculous meningitis. However, neuroimaging revealed a left temporo-occipital hematoma and subarachnoid hemorrhage. Despite severe thrombocytopenia, a lymph node biopsy and positive Histoplasma urinary antigen confirmed Histoplasma capsulatum. Following targeted treatment with amphotericin B and subsequent antiretroviral therapy, the patient achieved a remarkable neurological recovery. Disseminated histoplasmosis can involve CNS and cause rare intracranial hemorrhage, which may mimic cerebral tuberculosis. In endemic regions and immunocompromised patients, early diagnosis and immediate antifungal therapy are vital, serving as primary determinants for a favorable neurological prognosis.

Publicly available cancer indicators are increasingly used to guide regional health-care planning and investment. Their robustness for decision-making in remote or insular regions remains insufficiently examined. We analysed publicly available incidence, mortality, standardised incidence ratios, standardised mortality ratios, mortality-to-incidence ratios (MIR), premature mortality and temporal trends using Corsica as a stress test and comparing with other French regions using national datasets. Indicators were compared using confidence intervals, temporal aggregation and rank-stability analyses. No causal inference was attempted. Across multiple indicators, Corsica's relative position varied substantially depending on indicator choice, time window and statistical representation. Several indicators showed wide confidence-interval overlap with most French regions and marked rank instability, despite large apparent position changes. MIR and trend-based indicators were particularly sensitive to temporal aggregation and data structure. Our findings suggest that commonly used national cancer indicators are frequently insufficiently robust to support decision-grade regional planning in remote settings. Apparent "good" or "poor" performance in such contexts can reflect statistical instability rather than meaningful differences. For remote regions, cancer indicators should be interpreted with particular caution. Routinely published cancer indicators are insufficiently robust to support decision-grade regional health-care planning in small or insular populations.

Longitudinal studies allow the modelling of disease progression through repeated measurement of health outcomes, such as biomarkers. Changes in measurement tools over time, due to logistical or financial constraints, may challenge the statistical modeling of outcome trajectories. This study aims to compare two methods for managing changes in blood biomarkers assays over time, in the context of modeling their longitudinal trajectories. We analyzed data from 2299 individuals in the French MEMENTO cohort, focusing on two Alzheimer's disease blood biomarkers: 181-phosphorylated tau (p-tau181) and neurofilament light chain (NfL). Baseline blood samples were quantified using an initial assay kit in 2021, while samples collected at 2- and 4-year follow-ups with updated kits in 2023. Two approaches were applied to derive conversion equations for aligning measurements from the initial to the updated assay: (i) a bridging study, requiring biomarker quantification using both the initial and the updated assay in a subsample of individuals and (ii) Latent Process Models (LPM), which established links between the two assays as measures of the same latent process over age, using biomarker measurements available at the 3 timepoints. Prediction error rates were computed, and biomarker trajectories estimated with linear mixed models according to two variables of interest (education level, cognitive impairment). Prediction error rates were slightly higher for LPM than for bridging for both NfL and p-tau181. While the two methods yielded similar predictions around the median, discrepancies were observed at the tails of the distribution of the observed values. Longitudinal trajectories showed consistent associations for the variables of interest at baseline and during follow-up for both biomarkers. LPM provide a feasible and efficient method for managing changes in biomarker quantification assays in longitudinal studies. LPM yields results comparable to traditional bridging studies without requiring additional sample analysis. This approach is particularly advantageous in studies with long-term follow-up, where changes in measurement tools cannot always be avoided, offering a straightforward and resource-efficient solution.