Search Results (958)

Introduction: The early stages of fish represent a critical phase for survival and recruitment, as they are highly vulnerable to both biotic and abiotic factors, as well as anthropogenic pressures. To enhance survival, many marine species use estuaries as nursery areas. However, these ecosystems are increasingly exposed to contaminants such as microplastics (MPs; plastic particles < 5 mm) that can cause several direct or indirect negative impacts on fish larvae, namely impairing their development or survival. Objective: This study aimed to quantify and compare temporal changes in the ratio of microplastics (MPs) to fish larvae (FL) (MP:FL) in the Douro estuary (NW Portugal), assessing how exposure to MPs varies across years and seasons. Methodology: Seasonal sampling campaigns were conducted in the Douro estuary during 2021/2022 and 2025. Multiple stations along the estuary were sampled using plankton tows with a 0.5 mm mesh size. In the laboratory, fish larvae were sorted and identified, and the remaining material was processed to isolate and quantify MPs. The recovered MPs were subsequently characterized according to type, size, and color. Results: Data from 2022 indicated that Clupeidae, Gobiidae, and Gadidae were the most abundant fish families, while colorless and blue fibers between 2 and 3 mm were the dominant MP types. Data from 2025 showed that Gobiidae, Labridae, and Atherinidae were the most abundant families, with similar MP types observed in water in 2022. The ratio of MPs:FL in summer and autumn of 2021/2022 was 36 and 65 MPs:1 FL, respectively, whereas in 2025 it was 0.26 and 3.80 MPs:1 FL, respectively. Conclusions: These preliminary results indicate a decreasing trend in the ratio of MP:fish larvae over time. Although further data analysis is ongoing, the observed interannual differences highlight the importance of long-term monitoring of estuarine nursery areas to better understand contamination dynamics and their potential effects on early fish life stages. Full article

This article examines the transformation of the concepts of contingency and providence from Aristotle to Augustine. For Aristotle, contingency defines the sublunary world: singular future events are neither determined nor already true, as he argues in De Interpretatione 9, 19a7–19b4, and action takes place among particulars that could be otherwise, τὸ ἐνδεχόμενον ἄλλως ἔχειν (“that which could be otherwise”). Φρόνησις (“practical wisdom”) enables deliberation in this realm by discerning the means to εὐδαιμονία (“happiness,” “the good life”), where rules do not exhaust judgment and outcomes remain exposed to risk. For Augustine, apparent contingency is encompassed within divine providence; casus (“chance,” “case”) or fortuitum (“the fortuitous”) expresses human ignorance, not the absence of an ordo causarum (“order of causes”). In De Civitate Dei V.9, nothing occurs without a cause known to God, and chance occurs occulto quodam ordine (“by a certain hidden order”). The relationship between the two is not one of direct influence, given that Augustine had limited and indirect access to Aristotle. The comparison is thematic: it analyzes how problems initially formulated by Aristotle—the open future, deliberation, particulars—are reconfigured through creatio ex nihilo (“creation out of nothing”), praescientia (“foreknowledge”), and gratia (“grace”). Both affirm human responsibility, though within distinct horizons: Aristotle, in an open field measured ὡς ἐπὶ τὸ πολύ (“for the most part”); Augustine, in a created order in which the will itself is foreknown and sustained by God. Prudence thus becomes twofold: navigating what might be otherwise without a guarantee of success and ordering temporal goods toward the unchanging Good, trusting that no risk escapes providence. Full article

Despite increasing efforts to improve cardiovascular disease (CVD) risk evaluation and management, it remains a leading cause of mortality and morbidity worldwide. This has driven interest in high-density lipoprotein (HDL)-related biomarkers as indicators of oxidative stress and atherogenic processes not fully captured by traditional lipid measurements. In this study, we examined specific paraoxonase 1 (PON1) activity and its relationship with anthropometric, blood pressure, and lipid metabolism measures in 100 middle-aged Lithuanian individuals at high cardiovascular risk. HDL fractions were isolated using iodixanol-based density gradient centrifugation. PON1 concentration and arylesterase activity were measured, and specific activity was defined as arylesterase activity normalized to PON1 concentration. No significant associations were observed between specific PON1 activity and age, body mass index, waist circumference, blood pressure, smoking status, or statin use. Specific PON1 activity was independently associated with lower risk-weighted apolipoprotein B and lower low-density lipoprotein cholesterol levels. These exploratory findings suggest that higher specific PON1 activity may reflect a less atherogenic lipid profile in individuals at high cardiovascular risk, as indicated by its association with LDL-C and with risk-weighted apolipoprotein B. Because direct oxidative stress and inflammatory markers were not measured, interpretations regarding oxidative burden should be considered indirect and hypothesis-generating. Given the cross-sectional nature of the study and the relatively small sample size, these results should be interpreted as exploratory and hypothesis-generating. Further longitudinal studies in larger populations are needed to confirm these observations. Full article

Aphasia is a complex neurological syndrome that includes a multitude of signs and symptoms that describe a patient’s inability to use language (understanding and producing spoken and/or written language) after it has already been acquired, which is caused by cerebral lesions situated in the dominant (left) cerebral hemisphere in right-handed people. Aphasia has a prevalence of 25–30% in acute ischemic stroke (especially in arterial infarcts). In patients who suffered cerebral venous and dural sinuses thrombosis (CVST), aphasia has been noticed in almost 20% of cases, its presence being considered a negative predictive factor. We report the case of a 22-year-old right-handed woman with obesity and active smoking (10 cigarettes/day), undergoing treatment with oral contraceptives who presented to the Emergency Department with an intense headache, resistant to usual analgesic treatment, accompanied by language disorders onset within 24 h. The neurological examination was normal, except for language assessment, which revealed the severe impairment of the repetition domain (she was unable to repeat simple words), and difficulty in naming objects with some hesitations and mild comprehension difficulties (especially in complex orders). She underwent neuroimaging examinations at admission. Native Head Computed Tomography revealed spontaneous hyperdensity (parenchymatous hematoma) in the left temporal lobe. Cranial magnetic resonance imaging (MRI) confirmed venous infarction in the left temporal area and a hypointense signal on MRI T2*SW (susceptibility-weighted) in the region of the left lateral sinus and left jugular vein bulb, which confirmed the thrombosis at this level. Associated cortical vein thrombosis was diagnosed on indirect radiological grounds, since hemorrhagic transformation obscured the direct visualization of the adjacent cortical veins. MR venography was not performed at that time, but instead at the 1-month follow-up, MR venography confirmed the chronic, partial thrombosis of the left lateral sinus and left jugular vein bulb. Laboratory data demonstrated an elevated D-dimer and the presence of homozygosity for MTHFR C677T and PAI-1 4G/4G. Anticoagulation in the form of low-molecular-weight heparin was immediately started, followed by chronic treatment with oral anticoagulant (apixaban) and folic acid. The headaches resolved within three days, and her neurological examination was almost normal: the repetition continued being altered for complex phrases. We did not observe any left lateral sinus thrombosis recurrence, or other extra-cerebral embolic events (deep vein thrombosis or pulmonary embolism) during the follow-up year. The immediate anticoagulation since the admission resulted in a favorable outcome. Taking into consideration our interest in monitoring patients with aphasia secondary to CVST, we also analyzed data from the literature regarding the incidence of conduction aphasia and other aphasic syndromes in this CVST. Due to the limited number of articles identified in the last 21 years (2005–2026) in the literature, we concluded that conduction aphasia is an extremely rare clinical presentation in this kind of pathology and further studies should be conducted in order to identify significant statistical data. Full article

The coexistence of microplastics (MPs) and heavy metals (Cd, Pb) in agricultural soils has become a global environmental and ecological risk. In this study, a pot experiment was conducted to investigate the effects of different concentrations of polyethylene (PE) microplastics and combined Cd/Pb contamination on the growth and development, heavy metal accumulation, and antioxidant system of tobacco (Nicotiana tabacum L. cv. Yunyan 87). The results showed that low-dose PE and low concentrations of heavy metals had minor impacts on tobacco growth and the antioxidant system; in contrast, high-dose PE and elevated heavy metal treatments markedly induced increases in malondialdehyde content (MDA) and enhanced the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). Under co-contaminated conditions, the addition of low-dose PE reduced the translocation capacity of heavy metals, alleviated heavy metal-induced oxidative stress responses, and promoted tobacco growth. Conversely, high-dose PE promoted the translocation of Cd into tobacco plants and increased Cd contents in tobacco leaves, leading to marked decreases in soluble protein and soluble sugar contents, and causing severe reductions in plant height, number of functional leaves, and biomass. Structural equation modeling (SEM) analysis revealed that the direct effect of PE on tobacco growth was not significant; instead, it primarily acted as a regulatory factor, exerting either promotional or inhibitory effects on tobacco growth at different doses. The impact of Cd/Pb on tobacco growth appeared to involve two potential pathways. On the one hand, Cd/Pb induced direct toxicity through their accumulation within tobacco tissues. On the other hand, they exerted indirect regulation primarily by modulating the activities of the tobacco antioxidant system. Full article

Background/Objectives: The incidence of melanoma in situ (MIS) has increased markedly in several high-income countries, often outpacing invasive melanoma without a proportional rise in mortality. This divergence has raised concerns regarding overdiagnosis, defined as the detection of biologically indolent disease that would not have caused harm if left untreated. This review aims to synthesize contemporary evidence on the overdiagnosis of MIS, focusing on epidemiological patterns, screening-related detection, pathological interpretation, quantitative estimates, and clinical consequences. Methods: A narrative review with systematic search elements was conducted using a structured approach informed by PRISMA principles. PubMed was searched for studies published between January 2017 and March 2026, and eligible studies were selected based on relevance to melanoma overdiagnosis, MIS incidence, screening, and diagnostic variability. Results: The literature consistently demonstrates that increases in melanoma incidence are largely driven by MIS and thin invasive lesions rather than advanced disease. Screening and surveillance preferentially increase detection of low-risk lesions, while variability in dermatopathological interpretation contributes to diagnostic drift. Quantitative studies suggest that a substantial proportion of MIS diagnoses may represent overdiagnosis, exceeding 60–80% in some settings. All of this entails significant direct and indirect social costs in several countries. Conclusions: Overdiagnosis of MIS is a significant and multifactorial phenomenon. MIS represents a heterogeneous entity, and future strategies should focus on improving diagnostic precision, risk stratification, and minimizing harm associated with unnecessary diagnosis. Full article

Oxidative stress occurs when reactive oxygen species exceed the capacity of antioxidant defenses, causing molecular damage and alterations in cellular signaling. This process is characterized by interindividual variability, particularly based on biological sex. Hormones such as estrogens, which exert antioxidant effects, and androgens, which can act as pro-oxidants in certain contexts, along with genetic and epigenetic factors linked to sex chromosomes, contribute to the sex-specific regulation of redox homeostasis. Nutraceuticals, including polyphenols, vitamins, carotenoids, and omega-3 fatty acids, influence oxidative processes through both direct and indirect mechanisms. This review evaluates the impact of biological sex on oxidative stress mechanisms and responses to nutraceutical antioxidants, synthesizing the results of molecular, metabolic, and clinical studies published over the past decade. The current literature indicates that biological sex influences both basal redox balance and individual responses to antioxidant mechanisms. Generally, males have a higher oxidative load and may benefit more from supplementation, while females typically possess greater antioxidant capacity, primarily due to hormonal influences. Greater consideration of sex as a biological variable is essential to optimize nutraceutical strategies and develop personalized interventions for oxidative stress-related diseases. Full article

Background/Objectives: Schisandrin B (Sch B), a bioactive lignan of Schisandra chinensis has been commonly investigated for its antitumor activities, yet its radiosensitizing effect and mechanism remain unclear. This study was conducted to investigate the radiosensitizing effects of Sch B in breast cancer (BC) and elucidate its molecular mechanisms, with a specific focus on the gut microbiota–immune axis. Methods: In vitro, CCK-8, colony formation, and 3D spheroid assays were used to evaluate the effects of Sch B on proliferation inhibition and radiosensitization, flow cytometry and immunofluorescence were used to elucidate the mechanisms involved. In vivo, 4T1 tumor-bearing mice were treated with Sch B, and 16S rDNA sequencing and LC-MS/MS were used to analyze the gut microbiota and short-chain fatty acid (SCFA) metabolism. IHC and qPCR detected antitumor immune responses. Results: Sch B inhibited the proliferation of BC cells in a time- and dose-dependent manner with negligible toxicity to the mammary epithelial cell line MCF-10A. Furthermore, Sch B enhanced the radiosensitivity (sensitization enhancement ratio: 1.20~1.77) of BC by inducing G1 phase cell cycle arrest and delaying radiation-induced DNA double-strand break repair. In vivo, Sch B suppressed BC growth in BALB/c mice without causing obvious systemic toxicity. Sch B reversed tumor-induced gut microbiota dysbiosis (restoring species abundance and the Firmicutes/Bacteroidetes ratio, enriching beneficial genera such as Lactobacillus and Butyrobacter) and normalized SCFA profiles (correlative evidence). Furthermore, Sch B modulated systemic immune responses by increasing the expression of Ifng, Cxcl10, Ddx58 and promoting CD3⁺ and CD8⁺ T-cell infiltration in tumors. Conclusions: Sch B exerts BC radiosensitization through dual mechanisms, direct regulation of the cell cycle and DNA repair, and indirect modulation of the gut microbiota-immune axis (correlative evidence), highlighting it as a safe and effective candidate for improving the efficacy of BC radiotherapy. Full article

Causal graphs are powerful instruments for structuring information and analyzing the extent to which an observed effect can be attributed to a given cause. In this work, we demonstrate how edge-weighted causal graphs can be used to quantify whether a sentence acts as a direct or indirect cause. We introduce methods to identify the causal path with the highest total strength between two concepts and, given a specific context, to determine the pair of concepts with the strongest causal connection. In addition, we propose centrality measures that incorporate causality scores and graph weights, enabling the ranking of sentences by causal importance and identifying the most relevant ones. Full article

Antimicrobial resistance in Mycoplasma gallisepticum (MG), a primary causative agent of chronic respiratory disease in poultry, has reached alarming levels, underscoring the urgent need for alternative strategies. Natural products have emerged as promising candidates owing to their multi-target mechanisms of action. This review synthesizes current evidence on natural anti-MG agents, critically appraising their in vitro and in vivo efficacy, molecular mechanisms, and translational potential. A mechanistic taxonomy is proposed for distinguishing direct pathogen-directed mechanisms (membrane disruption, adhesion inhibition, virulence factor neutralization) from indirect host-directed mechanisms, notably NF-κB/MAPK pathway modulation and gut–lung axis immunoregulation. Emphasis is placed on anti-infective polypharmacology, exemplified by luteolin’s dual inhibition of the TatD virulence factor and host inflammatory cascades. The gut–lung axis represents a novel therapeutic frontier, with Bacillus subtilis KC1 controlling respiratory mycoplasmosis through intestinal microbiome remodeling and systemic AhR activation. Despite encouraging efficacy data, critical knowledge gaps persist, including a scarcity of rigorous in vivo trials under commercial conditions, incomplete mechanistic characterization, and challenges in standardizing complex natural product formulations. Natural products are best positioned not as wholesale antibiotic replacements but as integral components of integrated, antibiotic-sparing strategies aligned with antimicrobial stewardship and One Health principles. Full article

Background/Objectives: Maternal mortality remains an important indicator of health inequities, reflecting social, regional, and racial inequalities, as well as the responsiveness of health systems. This study aimed to analyze and compare maternal mortality between Brazil and Portugal from 2020 to 2023. Methods: This is a binational ecological and observational study based on secondary data from official records of live births and maternal deaths in both countries. Maternal mortality rates were calculated per 100,000 live births and stratified by sociodemographic and regional variables. Poisson regression models offset by the logarithm of live births were used to estimate adjusted incidence ratios (IRR) and 95% confidence intervals. Analyses were conducted using R and Stata software. Results: Brazil presented rates between 55 and 62 per 100,000 live births, while Portugal maintained lower values, ranging from 8 to 20 per 100,000. In Brazil, higher risks were observed among Black and Indigenous women, residents of the North and Northeast regions, and in age groups above 30 years. Direct and indirect causes showed similar proportions, with an increase in indirect causes during the pandemic. In Portugal, mortality showed low magnitude, but annual fluctuation was attributed to the small number of events and the limitation of microdata. Conclusions: The study highlights strong structural and racial inequalities in Brazilian maternal mortality, contrasting with the lower magnitude and greater stability observed in Portugal. This reinforces the need for intersectoral actions, strengthening the obstetric network, and continuous surveillance to reduce preventable deaths and promote equity in maternal care. Full article

Aristolochic acid (AA), a naturally occurring compound found in Aristolochia plants, is a well-established nephrotoxin and Group 1 carcinogen. Emerging evidence suggests a potential link between AA exposure and hepatocellular carcinoma (HCC), one of the leading causes of cancer-related mortality worldwide. This review critically evaluates current knowledge on AA’s hepatic metabolism, its formation of persistent DNA adducts, and the induction of inflammatory responses in the liver. Based on preclinical and indirect human evidence, we propose a working hypothesis that AA may contribute to hepatocarcinogenesis through a dual mechanism: genotoxic (primarily via H-ras and p53 mutations resulting from AA-DNA adducts) and non-genotoxic (via chronic inflammation involving IL-6, TNF-α, and NF-κB activation, as well as epithelial–mesenchymal transition). We note, however, that these mechanisms remain to be validated in human cohorts and do not yet establish causality. Recent studies have identified novel mechanisms, including PDK4-mediated mitochondrial dysfunction, ferroptosis inhibition via p53 hijacking, and ARID1A deficiency as a susceptibility factor. A recent meta-analysis quantified a significantly increased risk of liver cancer following AA exposure in epidemiological studies. While direct causal evidence in humans remains limited, the high mutational burden observed in AA-exposed liver tissues warrants caution. Nevertheless, the primary public health priority pertains to the prevention of AA exposure. Further epidemiological and mechanistic studies are urgently needed. Full article

Advances in wearable device and sensor technologies progressively shift respiratory monitoring from the clinical setting to real-world conditions. This rapidly developing field allows for more accurate diagnostics. However, reliable monitoring during dynamic activities remains challenging due to artifacts caused by movement, postural changes, electrode drift, and variability in breathing patterns. Therefore, this review focuses on wearable methodologies capable of determining respiratory rate and potentially tidal volume during strenuous physical activities. Direct sensing approaches, including chest and abdominal belts, bioimpedance principles, and inertial sensing units, are complemented by indirect methods derived from ECG and PPG signals. Hybrid systems, which are also discussed, represent a very promising approach. Special attention is paid to signal processing, machine learning, and multimodal sensor fusion algorithms that improve robustness and reliability. By systematically analyzing hardware and software combinations, validation protocols, and current limitations, this article identifies emerging trends in adaptive respiratory monitoring. This review aims to guide the development of next-generation wearable systems. Full article

Railway cable-stayed bridge construction is characterized by high complexity and substantial safety risk. Deficiencies in safety control may result in serious accidents (e.g., collapse and falls), causing significant casualties and economic losses; therefore, clarifying risk interactions and accident-causing mechanisms is essential. This study proposes a fuzzy DEMATEL–ISM approach in which fuzzy sets capture uncertainty in experts’ linguistic assessments. DEMATEL quantifies influence strengths and causal relationships among factors, and ISM constructs a multi-level hierarchy to explain accident causation. Twenty safety influencing factors are identified and grouped into five categories: management, human, material and equipment, construction technology, and environmental conditions. The obtained accident-causing mechanism comprises seven hierarchical levels: L₁: collapse and fall accidents, L₂: direct factors, L₃–L₅: indirect factors, and L₆–L₇: root factors. This mechanism is a chain of events that leads to an accident, with the nodes improper prestressing, structural deformation and differential settlement. These key nodes can be avoided by reinforcing safety management system implementation, daily supervision and inspection, and education and training on the subject of safety to ensure the safety of railway cable-stayed bridge construction. Full article

Background: Pulmonary fibrosis (PF) is a major global health issue associated with substantial morbidity across all age groups. One of the important etiological factors contributing to PF is drug-induced lung injury, which can result from both direct and indirect damage to the pulmonary parenchyma caused by various pharmacological agents, including chemotherapeutics, antirheumatic drugs, cardiovascular medications, and certain antimicrobial agents. The aim of our study was to assess the structure of antibacterials involved in drug-induced PF (DIPF) and analyze signals of DIPF, calculating the reporting odds ratio (ROR) and proportional reporting ratio (PRR) using spontaneous reports (SRs) extracted from the Russian National Pharmacovigilance database. Methods: A retrospective, descriptive pharmacoepidemiological analysis of SRs from the AIS database for the period 1 April 2019–31 March 2025 was conducted. Results: A total of 130 SRs with data on DIPF associated with antibacterial agents were identified, with patients’ mean age of 59.1 ± 14.46 years. Death was reported in 65 SRs (50%) with a mean age of 53.0 ± 13.66 years. Next, antibacterials were identified as leaders: sulfamethoxazole (used alone or in combination with trimethoprim, 20.7% (n = 50)), azithromycin (18.2%, n = 44), levofloxacin (12.4%, n = 30), doxycycline (11.6%, n = 28), and cefuroxime (10.7%, n = 26). Disproportionality analysis performed with PRR and ROR calculation revealed the strongest association with DIPF for cefuroxime (PRR = 15.11, 95% confidence interval, CI: 10.25–22.27; ROR = 15.31, 95% confidence interval, CI: 10.33–22.68). Conclusions: Cefuroxime was revealed as a drug with an unexpected but robust safety signal for DIPF, warranting heightened clinical awareness and further investigation. The observed associations between antibacterial agents and DIPF should be interpreted with caution, as they may reflect protopathic bias (antibiotics prescribed for early symptoms of unrecognized pulmonary fibrosis) or context-dependent biological effects rather than true pro-fibrotic drug properties. Our findings do not establish causality but rather generate safety signals that warrant validation through prospective studies with detailed clinical phenotyping and mechanistic investigations using human cell lines. Full article