Perfluorohexyloctane (F6H8) is a semifluorinated alkane recently approved for ophthalmic treatment of dry eye disease. Although considered locally safe for topical use, its structural similarity to persistent per- and polyfluoroalkyl substances (PFAS) raises concerns about systemic accumulation and long-term toxicity. To investigate potential hepatic effects, we examined the metabolic impact of F6H8 exposure in human HepaRG hepatocytes across a broad concentration range representing short- and long-term exposure scenarios. Combined targeted and untargeted metabolic profiling by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) was performed on intracellular extracts and extracellular media. F6H8 induced pronounced, concentration-dependent metabolic alterations, many of which exhibited non-monotonic responses. Low concentrations primarily affected amino acid, fatty acid, and lipid metabolism, while central carbon metabolism was disrupted only at the highest exposures. Notably, a putative biotransformation product, perfluorohexyloctanoic acid, was detected, suggesting metabolic persistence and conversion to a PFAS-like structure. This metabolite showed strong associations with cellular metabolic profiles and elicited metabolic changes that only partially overlapped with those induced by the parent compound, indicating distinct biological activity following biotransformation. These findings indicate that F6H8 elicits broad metabolic reprogramming and may not be metabolically inert as previously assumed. Given its clinical use and structural similarity to persistent fluorochemicals, the results highlight the need for comprehensive, long-term safety assessment of F6H8 and related semifluorinated alkanes.

Background Dilatation of the common bile duct (CBD) after cholecystectomy is frequently observed during follow-up imaging; however, its extent and clinical implications remain incompletely defined. Distinguishing physiological postoperative ductal enlargement from pathological dilatation is essential to avoid unnecessary diagnostic evaluation. This study aimed to compare CBD diameter in post-cholecystectomy patients with non-operated controls and to assess its association with time since surgery, age, and body mass index (BMI). Materials and methods This retrospective observational study included 165 adult patients who underwent abdominal ultrasound examination, comprising 91 post-cholecystectomy patients and 74 controls with an intact gallbladder. The CBD diameter was measured in the suprahilar segment. Group differences were evaluated using independent t-tests and chi-square tests. Logistic and linear regression analyses were used to assess predictors of CBD dilatation and continuous diameter change. All multivariable models were adjusted for age, sex, and BMI. Results CBD diameter was significantly greater in post-cholecystectomy patients compared with controls (6.61 mm vs. 4.56 mm; p < 0.001). Dilatation ≥7 mm occurred in 38.5% of post-cholecystectomy patients versus 5.4% of controls (p < 0.001), and prior cholecystectomy remained a strong independent predictor of dilatation after adjustment (aOR = 14.583; 95% CI: 4.449-47.807). Using a fixed ≥7 mm cutoff, increasing age was associated with lower odds of categorical CBD dilatation, whereas sex and BMI were not significant predictors. Linear regression analyses demonstrated a significant positive association between CBD diameter and both time elapsed since surgery and age, indicating gradual ductal enlargement over time. Marked dilatation (>10 mm) was uncommon and did not reach statistical significance in relation to cholecystectomy. Conclusion Cholecystectomy is associated with measurable and progressive enlargement of the CBD. While CBD diameter increases gradually with advancing age and postoperative duration, categorical dilation thresholds are more strongly influenced by surgical status than by age alone. Recognition of this expected postoperative anatomical pattern may help clinicians avoid unnecessary imaging and interventions in asymptomatic patients.

Type 1 conventional dendritic cells (cDC1s) acquire and cross-present tumor antigens to prime CD8⁺ T cells. Whether this selects for specific neoantigens is unclear. DNGR-1 (CLEC9A), a cDC1 receptor for F-actin exposed on dead cells, promotes cross-presentation of cell-associated antigens. Here we show that DNGR-1-deficient mice develop chemically induced tumors more rapidly and at higher incidence, and these are more frequently rejected on transplantation into wild-type recipients. Whole-exome sequencing reveals enrichment of predicted neoantigens derived from mutated F-actin-binding proteins. Consistent with this observation, tethering model antigens to F-actin enhances DNGR-1-dependent cross-presentation. These results suggest that DNGR-1-mediated recognition of F-actin exposed by dead cancer cells favors priming of CD8⁺ T cells specific for cytoskeletal neoantigens, which can then drive immune escape of cancer cells lacking or reverting those mutations. Thus, neoantigen cross-presentation by cDC1 can determine the immune visibility of the tumor mutational landscape and sculpt cancer evolution by immunoediting. Here the authors show DNGR-1 expressed by cDC1s promotes CD8⁺ T cell priming to cytoskeletal neoantigens from dying tumor cells, thereby shaping cancer immune visibility and tumor evolution through immunoediting.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disorder that typically affects young adults and is primarily characterized by demyelinating lesions in the central nervous system (CNS). According to the Revised McDonald Criteria, the clinical diagnosis of MS can be established based on a combination of clinical observations, the presence of focal lesions in at least two distinct CNS areas on magnetic resonance imaging (MRI) and the detection of specific oligoclonal bands in the cerebrospinal fluid. Conventional MRI remains a cornerstone of MS diagnosis and disease monitoring, providing high-resolution assessments of lesion burden and brain atrophy. In addition, advanced MRI methods are increasingly applied in research settings to probe myelin integrity, iron deposition, and biochemical changes, with the potential to complement established diagnostic workflows in the future. Despite remarkable advances in the management of MS over the past two decades, complex differential diagnoses and the lack of effective imaging tools for therapy monitoring remain major obstacles, thus channeling the development of innovative molecular imaging probes that can be harnessed in clinical practice. Indeed, positron emission tomography (PET) has a significant potential to advance the contemporary diagnosis and management of MS. Given the solid body of evidence implicating myelin dysfunction in the pathophysiology of MS, myelin-targeted imaging probes have been developed, and are currently under clinical evaluation for MS diagnosis and therapy monitoring. In parallel, ligands for the 18 kDa translocator protein (TSPO) and the cannabinoid receptor type 2 (CB2R) have been employed to capture neuroinflammatory processes by visualizing microglial activation, while other tracers allow the assessment of synaptic integrity across various disease stages of MS. Further, PET probes have been employed to delineate the role of activated microglia and facilitate the assessment of synaptic dysfunction across all disease stages of MS. This review discusses the challenges and opportunities of translational molecular imaging by highlighting key molecular concepts that are currently leveraged for diagnostic imaging, patient stratification, therapy monitoring and drug development in MS. Moreover, we shed light on potential future developments that hold promise to advance our understanding of MS pathophysiology, with the ultimate goal to provide the best possible patient care for every individual MS patient.

Introduction Spinal tumor surgery mandates complete removal with preserved neurological function and stability. Total Laminectomy (TL) provides access but risks complications (pain, deformity) from extensive tissue removal. The safer, tissue-sparing Unilateral Hemilaminectomy (UHL) is limited by concerns about complete resection via its narrower corridor. Research question This study was comparing the clinical and radiological characteristic between unilateral TL and total laminectomy UHL and they clinical outcomes and complications. Material and methods This was a retrospective cohort study comparing UHL and TL for intradural/extradural spinal tumors. We analyzed consecutive patients operated between January 2018 and December 2024, excluding those with confounding factors. Surgical approach was selected based on tumor location and intraoperative needs. Data on patient demographics, pre/postoperative neurological status, surgical parameters, and tumor characteristics were collected. Primary outcomes were postoperative neurological status and complications rate. Statistical analysis compared variables between groups using appropriate tests, with significance at p = 0.05. Results Baseline characteristics were similar between groups, and the overall postoperative complication rate was low (6.3 %) and comparable. The postoperative KPS score between UHL and TL showed improvement, without significant difference between them. Both approaches yielded significant improvements in functional status and neurological recovery from preoperative baselines. Discussion and conclusion Our findings indicate that the tissue-sparing UHL approach can achieve similar functional outcomes and complication rates as TL for similarly sized tumors. This supports UHL as a safe and effective option, although the final surgical approach must remain individualized based on specific tumor complexity and radiological findings.

The Balkan mountain ranges are major hotspots of genetic diversity and endemism, yet many species remain poorly studied. One such species is Alyssum bosniacum, a narrow endemic of the Central Dinaric Alps. To fill this gap, we examined 143 individuals from 15 populations across the species’ range using flow-cytometric ploidy determination, amplified fragment length polymorphisms (AFLPs), nuclear microsatellites, and chloroplast DNA sequences. Microsatellite data revealed two genetic clusters, showing moderate differentiation and relatively high diversity. AFLP profiles indicated shallow but geographically structured variation, while chloroplast haplotypes showed limited divergence and regional clustering. Our data suggest possible persistence in multiple microrefugia within the Central Dinaric Alps, although further evidence is needed to confirm this scenario. Despite range fragmentation, genetic variation within the population remains high, indicating evolutionary resilience and supporting the species’ long-term future population stability under current conditions.

Studies have rarely examined the effects of changes in legal anti-doping knowledge (LADK) on doping tendencies in athletes. This study aimed to evaluate the effectiveness of a structured educational intervention focused on LADK and to analyze how LADK changes affect elite athletes’ doping tendency. The participants were athletes (n = 310; 156 females; 24.1 ± 4.2 years of age), all actively competing at the senior national or international level in either individual (N = 119) or team sports (N = 191), tested on sociodemographic-, sport-, doping-factors (including doping tendency—DT), and LADK. Participants were randomly divided into an experimental group (E: N = 140) and a control group (C: N = 170). The E group participated in a structured educational program on LADK. A pre- and posttest design was used to evaluate changes in LADK (dependent variable). Logistic regression was calculated to evaluate the association between LADK and binarized DT (negative vs. neutral/positive DT). Factorial ANOVA for repeated measurements revealed significant improvement in LADK in the E group, with significant ANOVA effects for time (F test = 35.8, p < 0.05) and time × group interaction (F test = 12.27, p < 0.05). The logistic regression did not reveal significant correlations between LADK and DT. Further studies exploring younger athletes, as well as long-term, multidimensional interventions, are warranted.

Seed biopriming is increasingly recognized as a strategy capable of inducing molecular memory that enhances plant performance under heavy-metal stress. Here, we investigated how biopriming Silene sendtneri seeds with Paraburkholderia phytofirmans PsJN establishes a transcriptional state that predisposes seedlings for improved cadmium (Cd) tolerance. RNA-seq profiling revealed that primed seeds exhibited differential gene expression prior to Cd exposure, with strong upregulation of detoxification enzymes, antioxidant machinery, metal transporters, photosynthetic stabilizers, and osmoprotectant biosynthetic genes. Enrichment of gene ontology categories related to metal ion detoxification, redox homeostasis, phenylpropanoid metabolism, and cell wall organization indicated that biopriming imprints a preparatory transcriptional signature resembling early stress responses. Upon Cd exposure, primed plants displayed enhanced physiological performance, including preserved integrity, elevated antioxidant activity, particularly peroxidases in roots, higher osmolyte accumulation, stabilized micronutrient levels, and substantially increased Cd uptake and sequestration. These coordinated responses demonstrate that biopriming induces a sustained molecular memory that accelerates and strengthens downstream defense activation. These findings demonstrate that PGPR-based biopriming establishes a stable transcriptomic memory in seeds that enhances cadmium tolerance, metal sequestration, and stress resilience, highlighting its potential for improving hyperaccumulator performance in phytoremediation and stress adaptation strategies.

Background The role of pharmacists in managing urinary tract infections (UTIs) is crucial, yet there is no instrument to assess their attitudes and practices in this area. The study aimed to develop and initially validate a questionnaire to evaluate pharmacists' attitudes and practices concerning patient counselling for UTIs, with the ultimate goal of supporting improvements in pharmacy practice and enhancing the quality of patient care. Methods The questionnaire was developed and initially validated (content and face) through a multi-phase mixed-methods approach consisting of: 1) initial item generation applying a comprehensive literature review, 2) first expert panel discussion, 3) content and cultural validation by pharmacists (focus group discussion), 4) second expert panel discussion, and 5) pretesting by the target population. The necessity, relevance, and clarity were assessed by calculating the Content Validity Ratio (CVR), Item-Level Content Validity Index (I-CVI), and Scale-Level Content Validity Index (S-CVI/Ave). Qualitative data was analyzed using an ethnographic content analysis. Results The initial questionnaire consisted of 33 items, divided into two domains: pharmaceutical practice and attitudes. After phases 2–4, all items were rated with satisfactory CVR and I-CVI values (over 0.99 and 0.83, respectively). The final phase of content validation resulted in the questionnaire final version of 25 items with S-CVI/Ave = 0.98 for relevance and S-CVI/Ave = 1 for clarity. Internal consistency analysis demonstrated high reliability for the attitudes toward antibiotics subscale (Cronbach's α = 0.850) and acceptable reliability for the attitudes toward herbal products subscale (Cronbach's α = 0.735). Conclusions The developed questionnaire is concise, easy to use and has satisfactory content and face validity. The developed questionnaire can be used to assess pharmacists' practices and attitudes in counselling patients with UTI symptoms, contributing to the identification of areas for improvement in pharmacy practice and patient safety.

Human gustatory function is a complex trait combining taste, smell, and touch required for the safety and quality assessment of ingested food. Taste dysfunction is one of the most prominent symptoms of COVID‐19 that was reversible in most cases, but some patients reported permanent changes in their perception of different food sources. This symptom brought attention to the complexity of the regulation of smell and taste and their potential use in diagnostics and treatment of acute and chronic taste disorders. We investigated the genetic association of candidate genes with SARS‐CoV‐2 infection–related dysgeusia. A total of 96 individuals with confirmed virus infection were divided into groups according to the presence of self‐reported taste dysfunction and genotyped using a custom Illumina gene panel. Out of 18 functionally related taste genes, statistically significant differences were observed for HCN4 variants c∗2393C > G ( p = 0.013) and c.2556G > A ( p = 0.026), PLCB2 variants c.3037‐55T > C ( p = 0.019) and c.582+958_582+959inv ( p = 0.021), and TAS1R1 variant c.1594+41G > A ( p = 0.03), which indicate possible association to taste dysfunction in response to virus infection.

For patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) who are not considered to be at very high mortality risk at the time of admission, current clinical guidelines advocate for coronary angiography (CAG) to be performed during hospitalization. Therefore, in these patients, introduction of novel non-invasive methods for prediction of severity of coronary artery disease is needed in order to identify patients who could benefit from CAG earlier during their hospital stay. The aim of this study was to evaluate the association between severity of CAD and echocardiographically assessed global longitudinal strain (GLS) and post-systolic shortening (PSS) of left ventricular myocardium in patients with NSTE-ACS. This prospective cross-sectional study included patients admitted to the cardiology clinic with the diagnosis of NSTE-ACS. Inclusion criteria were: preserved left ventricular ejection fraction (>50%), absence of regional wall motion abnormalities and indication for CAG set by interventional cardiologist and performed during the hospital stay. Patients who were estimated to be at very high mortality risk were excluded from the study. In addition to conventional echocardiography parameters, post-systolic shortening index (PSI), LAD specific PSI (PSI-LAD) and GLS were measured. PSI was calculated as the average PSS across all 17 myocardial segments, generated from strain curves, while PSI-LAD was calculated as the average PSS across 10 myocardial segments vascularized by LAD. The severity of CAD was assessed using the SYNTAX score. Significant coronary artery stenosis was defined as ≥90% narrowing in one of the three main epicardial arteries. Among the 70 enrolled patients, 45.7% (n=32) were diagnosed with unstable angina, while 54.3% (n=38) were diagnosed with NSTEMI. There was a significant positive correlation between SYNTAX score and both GLS (rho=0.504; p<0.001) and PSI (rho=0.249; p=0.035). Patients with significant LAD stenosis had higher GLS values (-14.88±2.53% vs. -17.02±3.23%, p=0.001) and higher PSI-LAD values (10.65 [3.13–18.53] vs. 4.2 [2.53–8.3], p=0.015) compared to those without significant LAD stenosis. GLS emerged as an independent predictor of significant stenosis on one of three main epicardial arteries (p=0.001; OR 1.43; 95% CI: 1.16–1.76). Both PSI-LAD and GLS demonstrated significant predictive value for LAD stenosis, with AUCs of 0.672 (p=0.020) and 0.675 (p=0.019), respectively. In addition to other known clinical factors, GLS and PSI may serve as feasible non-invasive echocardiographic parameters for additional risk stratification in NSTE-ACS patients who are not at very high risk. These measures could help identify individuals who might benefit from earlier CAG during hospitalization. Further research is warranted to develop precise risk assessment models incorporating these parameters.

Humans are exposed to environmental or occupational air pollution from combustion emissions in outdoor and indoor environments. Irrespective of the sources, combustion emissions are characterized by being a complex mixture of particles, volatile compounds and gases. The present systematic review summarizes results on DNA strand breaks measured by the comet assay in leukocytes, from studies on human exposure to traffic-related vehicle exhaust, biomass combustion and coke oven work environments. These exposures have in common the combustion of fuel, which generates particles and polycyclic aromatic hydrocarbons. Standardized mean differences (SMDs) have been calculated by random effects models. Meta-analyses show increased levels of DNA strand breaks in studies on traffic-related exhausts (SMD = 0.62, 95% CI: 0.36, 0.89, n = 21), biomass combustion (1.73, 95% CI: 0.72, 2.74, n = 10) and coke oven emission (0.84, 95% CI: 0.30, 1.37, n = 10). Studies from high-income countries have reported much smaller differences in DNA strand break levels than have studies from middle-income countries. These differences may be attributed to higher exposures related to less strict emission control, and more susceptible populations in middle-income populations; unrecognized confounding despite efforts to match subjects on traditional confounders; or higher risk of comet assay measurement bias and exposure misclassification. In conclusion, this systematic review and meta-analysis show that exposure to combustion-derived air pollution, with clear exposure gradients in terms of particulate matter or polycyclic aromatic hydrocarbons, is associated with increased levels of DNA strand breaks in human leukocytes.