Search Results (6,451)

(1) Background: Dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) are persistent organic pollutants (POPs), characterized by high toxicity and strong lipophilicity, which promote their bioaccumulation in human tissues. Their detection in breast milk raises concerns about early-life exposure during lactation. Although dietary intake is the primary route of maternal exposure, environmental pathways—including inhalation, dermal absorption, and residential proximity to contaminated sites—may also significantly contribute to the maternal body burden. (2) Methods: This narrative review examined peer-reviewed studies investigating maternal and environmental determinants of dioxin and dl-PCB concentrations in human breast milk. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science (2000–2024), identifying a total of 325 records. Following eligibility screening and full-text assessment, 20 studies met the inclusion criteria. (3) Results: The included studies consistently identified key exposure determinants, such as high consumption of animal-based foods (e.g., meat, fish, dairy), living near industrial facilities or waste sites, and maternal characteristics including age, parity, and body mass index (BMI). Substantial geographic variability was observed, with higher concentrations reported in regions affected by industrial activity, military pollution, or inadequate waste management. One longitudinal study from Japan demonstrated a declining trend in dioxin levels in breast milk, suggesting the potential effectiveness of regulatory interventions. (4) Conclusions: These findings highlight that maternal exposure to dioxins is influenced by identifiable environmental and behavioral factors, which can be mitigated through public health policies, targeted dietary guidance, and environmental remediation. Breast milk remains a critical bioindicator of human exposure. Harmonized, long-term research is needed to clarify health implications and minimize contaminant transfer to infants, particularly among vulnerable populations. Full article

Background/Objectives: Dental caries is the most prevalent oral condition worldwide. Consequences of untreated dental caries (CUDC) can range from pulp damage and soft tissue ulceration due to root debris to more severe issues, such as fistulas and abscesses. Rural communities might be more vulnerable to CUDC because of lower socioeconomic status, poorer access to healthcare, and lower education levels. The objective of this study was to evaluate and compare the prevalence of CUDC in rural and urban areas in schoolchildren aged 8 to 12 years in the State of Mexico. Methods: A cross-sectional study was conducted using the PUFA index, considering the presence of pulp involvement (P), soft tissue ulcerations due to root remnants (U), fistulas (F), and abscesses (A). The independent variable was the geographic area (rural or urban), and the covariates were nutritional status, hyposalivation, having one’s own toothbrush, and having received topical fluoride in the last year. Logistic regression models were fitted, calculating odds ratios (ORs) and 95% confidence intervals (CIs). Results: The prevalence of CUDC (PUFA > 0) was 42.9% in rural areas and 25.9% in urban areas. Residing in a rural area (OR: 2.15, 95% CI 1.38–3.34, p = 0.001), hyposalivation (OR: 1.93, 95% CI 1.11–3.37, p = 0.020), and professional fluoride application (OR: 0.15, 95% CI 0.07–0.32, p < 0.001) were associated with the prevalence of CUDC. Conclusions: To prevent caries and its clinical consequences due to the lack of treatment, it is important to promote timely care seeking and access to dental care services, considering the conditions of each geographic area. Full article

Electrospun nanofibrous membranes have gained considerable attention in bone tissue engineering due to their ability to mimic the extracellular matrix and provide a suitable environment for cell attachment and proliferation. This study investigates the fabrication, characterization, and biocompatibility of poly(L-lactic acid) (PLA)-based membranes enhanced with periclase (MgO) and gold nanoparticles (AuNPs). The membranes were fabricated using an optimized electrospinning process and subsequently characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FT-IR), and contact angle measurements. Additionally, in vitro biodegradation studies in simulated body fluid (SBF) and cytocompatibility tests with osteoblast-like cells were conducted. The results demonstrated that the incorporation of MgO and AuNPs significantly influenced the structural and chemical properties of the membranes, improving their wettability and bioactivity. SEM imaging confirmed uniform fiber morphology with well-distributed nanoparticles. FT-IR spectroscopy indicated successful integration of bioactive components into the PLA matrix. Cytocompatibility assays showed that modified membranes promoted higher osteoblast adhesion and proliferation compared to pristine PLA membranes. Furthermore, biodegradation studies revealed a controlled degradation rate suitable for guided bone regeneration applications. These findings suggest that electrospun PLA membranes enriched with MgO and AuNPs present a promising biomaterial for GBR applications, offering improved bioactivity, mechanical stability, and biocompatibility. Full article

Peanut cultivation is widely practiced using plastic mulch film, resulting in the accumulation of microplastics/nanoplastics (MPs/NPs) in agricultural soils, potentially negatively affecting peanut growth. To investigate the effects of two polystyrene (PS) sizes (5 μm, 50 nm) and three concentrations (0, 10, and 100 mg L⁻¹) on peanut growth, photosynthetic efficiency, and physiological characteristics, a 15-day hydroponic experiment was conducted using peanut seedlings as the experimental material. The results indicated that PS-MPs/NPs inhibited peanut growth, reduced soil and plant analyzer development (SPAD) values (6.7%), and increased levels of malondialdehyde (MDA, 22.0%), superoxide anion (O₂⁻, 3.8%) superoxide dismutase (SOD, 16.1%) and catalase (CAT, 12.1%) activity, and ascorbic acid (ASA, 12.6%) and glutathione (GSH, 9.1%) contents compared to the control. Moreover, high concentrations (100 mg L⁻¹) of PS-MPs/NPs reduced the peanut shoot fresh weight (16.1%) and SPAD value (7.2%) and increased levels of MDA (17.1%), O₂⁻ (5.6%), SOD (10.6%), POD (27.2%), CAT (7.3%), ASA (12.3%), and GSH (6.8%) compared to low concentrations (10 mg L⁻¹) of PS-MPs/NPs. Notably, under the same concentration, the impact of 50 nm PS-NPs was stronger than that of 5 μm PS-MPs. The peanut shoot fresh weight of PS-NPs was lower than that of PS-MPs by an average of 7.9%. Additionally, we found that with an increasing exposure time of PS-MPs/NPs, the inhibitory effect of low concentrations of PS-MPs/NPs on the fresh weight was decreased by 2.5%/9.9% (5 d) and then increased by 7.7%/2.7% (15 d). Conversely, high concentrations of PS-MPs/NPs consistently reduced the fresh weight. Correlation analysis revealed a clear positive correlation between peanut biomass and both the SPAD values as well as Fv/Fm, and a negative correlation with MDA, SOD, CAT, ASA, and GSH. Furthermore, the presence of PS-MPs/NPs in roots, stems, and leaves was confirmed using a confocal laser scanning microscope. The internalization of PS-MPs/NPs within peanut tissues negatively impacted peanut growth by increasing the MDA and O₂⁻ levels, reducing the SPAD values, and inhibiting the photosynthetic capacity. In conclusion, the study demonstrated that the effects of PS on peanuts were correlated with the PS size, concentration, and exposure time, highlighting the potential risk of 50 nm to 5 μm PS being absorbed by peanuts. Full article

Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) or with comorbidities. Methods: We conducted a retrospective observational cohort study from March to December 2024 in an Italian tertiary-care hospital. Adult patients treated in the ER with a single dose of dalbavancin (1500 mg) or oritavancin (1200 mg) for SSTIs were included. Demographic, clinical, and laboratory data were collected. Follow-up evaluations were performed at 14 and 30 days post-treatment to assess outcomes. Results: Nineteen patients were enrolled (median age 59 years; 53% female). Most had lower limb involvement and elevated inflammatory markers. Three patients (16%) were septic. Fourteen patients (74%) were discharged without hospital admission; hospitalization in the remaining cases was due to comorbidities rather than SSTI severity. No adverse drug reactions were observed. At 14 days, 84% of patients had clinical resolution; only 10% had recurrence by day 30, with no mortality nor readmission reported. Conclusions: LALs appear effective and well-tolerated in the ER setting, supporting early discharge and reducing healthcare burden. Broader use may require structured care pathways and multidisciplinary coordination. Full article

Background: Mediastinal staging plays a critical role in guiding treatment decisions for non-small cell lung cancer (NSCLC). While mediastinoscopy has been the gold standard for assessing mediastinal lymph node involvement, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a minimally invasive alternative with comparable diagnostic accuracy. This systematic review evaluates the diagnostic performance, safety, cost-effectiveness, and feasibility of EBUS-TBNA versus mediastinoscopy for mediastinal staging. Methods: A systematic literature review was conducted in accordance with PRISMA guidelines, including searches in Medline, Scopus, EMBASE, and Cochrane databases for studies published from 2010 onwards. A total of 1542 studies were identified, and after removing duplicates and applying eligibility criteria, 100 studies were included for detailed analysis. The extracted data focused on sensitivity, specificity, complications, economic impact, and patient outcomes. Results: EBUS-TBNA demonstrated high sensitivity (85–94%) and specificity (~100%), making it an effective first-line modality for NSCLC staging. Mediastinoscopy remained highly specific (~100%) but exhibited slightly lower sensitivity (86–90%). EBUS-TBNA had a lower complication rate (~2%) and was more cost-effective, while mediastinoscopy provided larger biopsy samples, essential for molecular and histological analyses. The need for general anaesthesia, longer hospital stays, and increased procedural costs make mediastinoscopy less favourable as an initial approach. Combining both techniques in select cases enhanced overall staging accuracy, reducing false negatives and improving diagnostic confidence. Conclusions: EBUS-TBNA has become the preferred first-line mediastinal staging method due to its minimally invasive approach, high diagnostic accuracy, and lower cost. However, mediastinoscopy remains crucial in cases requiring posterior mediastinal node assessment or larger tissue samples. The integration of both techniques in a stepwise diagnostic strategy offers the highest accuracy while minimizing risks and costs. Given the lower hospitalization rates and economic benefits associated with EBUS-TBNA, its widespread adoption may contribute to more efficient resource utilization in healthcare systems. Full article

Caffeine is a widely consumed psychoactive compound known to influence drug metabolism and efficacy through interactions with key enzymes such as cytochrome P450 3A4 (CYP3A4). This study investigates the molecular impact of caffeine on the binding behavior of imatinib, a first-line BCR-ABL tyrosine kinase inhibitor, using molecular docking simulations. Structural optimization and lipophilicity analyses were conducted using HyperChem, while docking was performed with HEX software (Version 8.0.0) against the CYP3A4 receptor (PDB ID: 1W0E). Two administration scenarios were evaluated: concurrent caffeine–imatinib complex formation and sequential administration with caffeine pre-bound to CYP3A4. The caffeine–imatinib complex exhibited a predicted increase in lipophilicity (logP = 3.09) compared to imatinib alone (logP = −1.29), which may indicate the potential for enhanced membrane permeability and tissue distribution. Docking simulations revealed stronger binding affinity of the complex to CYP3A4 (−350.53 kcal/mol) compared to individual compounds, and improved imatinib binding when CYP3A4 was pre-complexed with caffeine (−294.14 kcal/mol vs. −288.19 kcal/mol). Frontier molecular orbital analysis indicated increased reactivity of the complex (ΔE = 7.74 eV), supporting the hypothesis of altered pharmacodynamic behavior. These findings suggest that caffeine may modulate imatinib’s metabolic profile and therapeutic efficacy by enhancing receptor binding and altering drug distribution. The study underscores the importance of evaluating dietary components during drug development and therapeutic planning, particularly for agents metabolized by CYP3A4. Full article

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

The genus Colletotrichum is widely known for its phytopathological significance, especially as the causative agent of anthracnose in diverse agricultural crops. However, recent studies have unveiled its ecological versatility and biotechnological potential, particularly among endophytic species. These fungi, which asymptomatically colonize plant tissues, stand out as high-yielding producers of bioactive secondary metabolites. Given their scientific and economic relevance, this review critically examines endophytic Colletotrichum species, focusing on the chemical diversity and biological activities of the metabolites they produce, including antibacterial, antifungal, and cytotoxic activity against cancer cells, and antioxidant properties. This integrative review was conducted through a structured search of scientific databases, from which 39 relevant studies were selected, highlighting the chemical and functional diversity of these compounds. The analyzed literature emphasizes their potential applications in pharmaceutical, agricultural, and industrial sectors. Collectively, these findings reinforce the promising biotechnological potential of Colletotrichum endophytes not only as sources of bioactive metabolites but also as agents involved in ecological regulation, plant health promotion, and sustainable production systems. Full article

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial β-oxidation of fatty acids. To further characterize metabolic alterations associated with this condition, we conducted an untargeted lipidomic analysis of renal tissues using a murine model of TAC nephrotoxicity. TAC (1 mg/kg/day) or saline was subcutaneously administered to male ICR mice for 28 days, and kidney tissues were harvested for comprehensive lipidomic profiling. Lipidomic analysis was performed with liquid chromatography–tandem mass spectrometry (p < 0.05, n = 5/group). Triacylglycerols (TGs) were the predominant lipid class identified. TAC-treated mice exhibited reduced levels of unsaturated TG species with low carbon numbers, whereas TGs with higher carbon numbers and various degrees of unsaturation were increased. All detected TGs containing docosahexaenoic acid (DHA) showed an increasing trend in TAC-treated kidneys. Although accumulation of polyunsaturated TGs has been previously observed in chronic kidney disease, the preferential increase in DHA-containing TGs appears to be a unique feature of TAC-induced nephrotoxicity. These results suggest that DHA-enriched TGs may serve as a metabolic signature of TAC nephrotoxicity and offer new insights into its pathophysiology. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Bladder cancer (BC) is the most frequent cancer of the urinary system and one of the most common malignancies in the world. In the last decade, many studies have been conducted to better understand the pathophysiological mechanisms of BC to find innovative markers for disease monitoring and treatment. In this study, we aim to identify miRNAs whose expression is associated with specific tumoral characteristics and risks of disease progression. Forty-one BC patients were enrolled in this study. The expression of 84 miRNAs was evaluated by qRT-PCR analysis on tumoral and peritumoral tissues. The results highlighted the association of the miRNA-17-92 cluster with BC, with miR-17-5p, miR-18a-5p, miR-19a-3p, and miR-20a-5p (members of this cluster) being upregulated in the tumoral tissue and correlated with muscle invasion and tumor grading. Taken together, our study identified a panel of 26 dysregulated miRNAs in BC, some of which may be associated with aggressiveness and the risk of progression of this malignancy. Full article

Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This meta-analysis aims to determine which inotropic agent may be more effective in this clinical scenario. Methods: A systematic review and meta-analysis were conducted, including data from randomized clinical trials (RCTs) comparing levosimendan and dobutamine in patients with septic shock and persistent hypoperfusion. Summary effect estimates, including odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs), were calculated using a random-effects model. Trial sequential analysis (TSA) was also performed. Results: Of 244 studies screened, 11 RCTs were included. Levosimendan was associated with a reduction in in-hospital mortality (OR 0.64; 95% CI: 0.47; 0.88) and ICU length of stay (SMD 5.87; 95% CI: –8.37; 20.11) compared with dobutamine. Treatment with levosimendan also resulted in significant reductions in BNP (SMD –1.87; 95% CI: –2.45; −1.2) and serum lactate levels (SMD –1.63; 95% CI: –3.13; −0.12). However, TSA indicated that the current evidence is insufficient to definitively confirm or exclude effects on in-hospital and 28-day mortality. Conclusions: Levosimendan may improve hemodynamics, tissue perfusion, and biomarkers, and may reduce in-hospital mortality and ICU length of stay in patients with SICM compared with dobutamine. However, TSA highlights the need for further studies to inform clinical practice and optimize inotrope selection. Full article

This review presents a comprehensive overview of various ultrasound imaging techniques employed in the evaluation of the canine knee joint. It critically analyzes studies conducted on both human and animal subjects, with a focus on the diagnostic accuracy of B-mode ultrasound, Doppler examination, contrast-enhanced ultrasound, and elastography in both normal and pathological conditions. The review underscores the necessity of strict adherence to the protocols of each ultrasound modality and emphasizes the importance of a thorough understanding of the anatomical region to achieve optimal outcomes. The findings suggest that these ultrasound techniques can significantly enhance the diagnostic process, providing valuable insights into anatomy, size, blood supply, and tissue elasticity. Additionally, in cases where advanced imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI) are cost-prohibitive or less accessible, ultrasound serves as a reliable alternative, delivering high diagnostic accuracy and critical information regarding mechanical changes in the joint and neovascularization. Full article