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Besnoitia besnoiti is a cyst-forming apicomplexan parasite and the causal agent of bovine besnoitiosis. During early phase of infection, tachyzoites replicate within host endothelial cells in a host cell cholesterol-dependent process. By applying U18666A treatments, we here evaluated the role of Niemann-Pick type C protein 1 (NPC1) in both, intracellular B. besnoiti replication and host cellular cholesterol distribution. Additionally, B. besnoiti-driven changes in NPC1 gene transcription were studied by qPCR. Overall, U18666A treatments significantly reduced B. besnoiti proliferation and induced cholesterol accumulation in host cytoplasmic dense vesicles. However, NPC1 gene transcription was not affected by B. besnoiti infection.
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In recent years, contaminants of emerging concern have been reported in several environmental matrices due to advances in analytical methodologies. These anthropogenic micropollutants are detected at residual levels, representing an ecotoxicological threat to aquatic ecosystems. In particular, the pharmacotherapeutic group of non-steroidal anti-inflammatories (NSAIDs) is one of the most prescribed and used, as well as one of the most frequently detected in the aquatic environment. Bivalves have several benefits as a foodstuff, and also as an environment bioindicator species. Therefore, they are regarded as an ideal tool to assess this issue from both ecotoxicological and food safety perspectives. Thus, the control of these residues in bivalves is extremely important to safeguard environmental health, also ensuring food safety and public health. This paper aims to review NSAIDs in bivalves, observing their consumption, physicochemical characteristics, and mechanisms of action; their environmental occurrence in the aquatic environment and aquatic biota; and their effects on the ecosystem and the existent legal framework. A review of the analytical methodologies for the determination of NSAIDs in bivalves is also presented.
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Pulmonary rehabilitation (PR) is the bedrock of non-pharmacological treatment for people with COPD. Nonetheless, it is well described in the literature that unless the patient changes his behaviour, the benefits of PR programmes will decline in six to twelve months after finishing the programme. Therefore, maintenance programmes can address the problem of PR programmes' effect loss over time.Community care units can provide multidisciplinary care in the current Portuguese primary health care context. These units have an interdisciplinary team that aims to develop competencies in COPD patients to self-manage the disease.This study aims to test the effectiveness of a 12-month home-based PR programme (Rehab2Life) compared to usual care through a single-blind randomised controlled trial with two parallel groups. The Rehab2Life programme includes two distinct phases. The first is an 8-week PR programme delivered to both groups, and the second is a PR maintenance programme delivered to the intervention group after the initial eight weeks. The control group receive the usual care and regular appointments. The primary outcome is functional capacity, and secondary outcomes are dyspnea, Health-Related Quality of Life (HRQoL), number of exacerbations, symptoms burden, anxiety and depression symptoms, and physical activity.We expect to observe that the home-based PR programme brings clinically relevant benefits to the participants at the end of the first eight weeks and that, at 12 months after the maintenance phase of the programme, benefits are less dissipated than in the control group. We expect to identify the characteristics of the patients who benefit the most from home-based programmes.The trial was registered on 7 April 2022 at ClinicalTrials.gov (NCT05315505).
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BACKGROUND: The emergence of smartphones has sparked a transformation across multiple fields, with health care being one of the most notable due to the advent of mobile health (mHealth) apps. As mHealth apps have gained popularity, there is a need to understand their energy consumption patterns as an integral part of the evolving landscape of health care technologies. OBJECTIVE: This study aims to identify the key contributors to elevated energy consumption in mHealth apps and suggest methods for their optimization, addressing a significant void in our comprehension of the energy dynamics at play within mHealth apps. METHODS: Through quantitative comparative analysis of 10 prominent mHealth apps available on Android platforms within the United States, this study examined factors contributing to high energy consumption. The analysis included descriptive statistics, comparative analysis using ANOVA, and regression analysis to examine how certain factors impact energy use and consumption. RESULTS: Observed energy use variances in mHealth apps stemmed from user interactions, features, and underlying technology. Descriptive analysis revealed variability in app energy consumption (150-310 milliwatt-hours), highlighting the influence of user interaction and app complexity. ANOVA verified these findings, indicating the critical role of engagement and functionality. Regression modeling (energy consumption = ß0 + ß1 × notification frequency + ß2 × GPS use + ß3 × app complexity + ε), with statistically significant P values (notification frequency with a P value of .01, GPS use with a P value of .05, and app complexity with a P value of .03), further quantified these bases' effects on energy use. CONCLUSIONS: The observed differences in the energy consumption of dietary apps reaffirm the need for a multidisciplinary approach to bring together app developers, end users, and health care experts to foster improved energy conservation practice while achieving a balance between sustainable practice and user experience. More research is needed to better understand how to scale-up consumer engagement to achieve sustainable development goal 12 on responsible consumption and production.
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Aplicativos Móveis , Humanos , Estados Unidos , Smartphone , Telemedicina/métodosRESUMO
Background Pulmonary rehabilitation (PR) is formally indicated to all COPD patients in groups B and E. It positively impacts dyspnoea, health-related quality of life and exercise tolerance, reducing admissions among people with chronic obstructive pulmonary disease (COPD) who have had a recent exacerbation and symptoms of anxiety and depression. There is limited access to PR programmes in Portugal, partially due to insufficient resources or referrals. This study aims to characterise COPD patients and assess whether they have criteria for PR programmes. Data from this study may provide strategic information for healthcare organisations to differentiate and innovate their response to COPD patients. Methodology A cross-sectional study was conducted in an urban municipality in the northern region of Portugal. The sample was randomly extracted from the national primary electronic health records. The sample size (n = 339) was determined considering the population of COPD patients in this region (N = 2818), a 95% confidence level and a margin of error of 5%. Results In this population, the prevalence of COPD is 1.8%. Furthermore, in this sample, 40% (n = 136) of people diagnosed with COPD have a formal indication to participate in PR programmes, although only 14.2% (n = 48) of these patients had access to PR. Conclusion COPD is probably underdiagnosed in this Portuguese region. Most COPD patients have eligibility criteria to be offered PR programmes, although most of them do not benefit from this vital treatment. Investing in community and home-based programmes may increase PR access, reducing acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admissions.
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Critical aspects of physiology and cell function exhibit self-sustained ~24-hour variations termed circadian rhythms. In the liver, circadian rhythms play fundamental roles in maintaining organ homeostasis. Here, we established and characterized an in vitro liver experimental system in which primary human hepatocytes display self-sustained oscillations. By generating gene expression profiles of these hepatocytes over time, we demonstrated that their transcriptional state is dynamic across 24 hours and identified a set of cycling genes with functions related to inflammation, drug metabolism, and energy homeostasis. We designed and tested a treatment protocol to minimize atorvastatin- and acetaminophen-induced hepatotoxicity. Last, we documented circadian-dependent induction of pro-inflammatory cytokines when triggered by LPS, IFN-ß, or Plasmodium infection in human hepatocytes. Collectively, our findings emphasize that the phase of the circadian cycle has a robust impact on the efficacy and toxicity of drugs, and we provide a test bed to study the timing and magnitude of inflammatory responses over the course of infection in human liver.
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Ritmo Circadiano , Hepatócitos , Inflamação , Fígado , Humanos , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Inflamação/metabolismo , Fígado/metabolismo , Acetaminofen/farmacologia , Atorvastatina/farmacologia , Citocinas/metabolismo , Inativação Metabólica , Lipopolissacarídeos/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Células CultivadasRESUMO
AbstractLong-term social and genetic monogamy is rare in animals except birds, but even in birds it is infrequent and poorly understood. We investigated possible advantages of monogamy in a colonial, facultative cooperatively breeding bird from an arid, unpredictable environment, the sociable weaver (Philetairus socius). We documented divorce and extrapair paternity of 703 pairs over 10 years and separated effects of pair duration from breeding experience by analyzing longitudinal and cross-sectional datasets. Parts of the colonies were protected from nest predation, thereby limiting its stochastic and thus confounding effect on fitness measures. We found that 6.4% of sociable weaver pairs divorced and 2.2% of young were extrapair. Longer pair-bonds were associated with more clutches and fledglings per season and with reproducing earlier and later in the season, when snake predation is lower, but not with increased egg or fledgling mass or with nestling survival. Finally, the number of helpers at the nest increased with pair-bond duration. Results were similar for protected and unprotected nests. We suggest that long-term monogamy is associated with a better capacity for exploiting a temporally unpredictable environment and helps to form larger groups. These results can contribute to our understanding of why long-term monogamy is frequently associated with unpredictable environments and cooperation.
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Ligação do Par , Pardais , Animais , Estudos Transversais , Comportamento Predatório , ReproduçãoRESUMO
Predation risk can influence behavior, reproductive investment, and, ultimately, individuals' fitness. In high-risk environments, females often reduce allocation to reproduction, which can affect offspring phenotype and breeding success. In cooperative breeders, helpers contribute to feed the offspring, and groups often live and forage together. Helpers can, therefore, improve reproductive success, but also influence breeders' condition, stress levels and predation risk. Yet, whether helper presence can buffer the effects of predation risk on maternal reproductive allocation remains unstudied. Here, we used the cooperatively breeding sociable weaver Philetairus socius to test the interactive effects of predation risk and breeding group size on maternal allocation to clutch size, egg mass, yolk mass, and yolk corticosterone. We increased perceived predation risk before egg laying using playbacks of the adults' main predator, gabar goshawk (Micronisus gabar). We also tested the interactive effects of group size and prenatal predator playbacks on offspring hatching and fledging probability. Predator-exposed females laid eggs with 4% lighter yolks, but predator-calls' exposure did not clearly affect clutch size, egg mass, or egg corticosterone levels. Playback-treatment effects on yolk mass were independent of group size, suggesting that helpers' presence did not mitigate predation risk effects on maternal allocation. Although predator-induced reductions in yolk mass may decrease nutrient availability to offspring, potentially affecting their survival, playback-treatment effects on hatching and fledging success were not evident. The interplay between helper presence and predator effects on maternal reproductive investment is still an overlooked area of life history and physiological evolutionary trade-offs that requires further studies.
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This article summarises some of the outstanding sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the 2023 European Respiratory Society International Congress. Two sessions from each Assembly group are outlined, covering the following topics: Group 9.01 focuses on respiratory physiology techniques, specifically on predicted values and reference equations, device development and novel applications of cardiopulmonary exercise tests; Group 9.02 presents an overview of the talks given at the mini-symposium on exercise training, physical activity and self-management at home and outlines some of the best abstracts in respiratory physiotherapy; Group 9.03 highlights the nursing role in global respiratory health and presents nursing interventions and outcomes; and Group 9.04 provides an overview of the best abstracts and recent advances in behavioural science and health psychology. This Highlights article provides valuable insight into the latest scientific data and emerging areas affecting the clinical practice of Allied Respiratory Professionals.
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In this work, inelastic neutron scattering (INS) spectroscopy is used to investigate the impact of entropic factors on the behaviour of deep eutectic solvents (DES). Periodic density functional theory calculations (DFT) provide a reliable assignment of the vibrational modes of pure compounds. This assignment guides the analysis of INS spectra of binary mixtures - with particular attention to methyl torsional modes. Deviations from ideality in the mixtures of tetraalkylammonium salts with urea are readily determined through a simplified thermodynamic approach. This study reports and discusses the relationship between the cation's asymmetry, the INS spectra of the eutectic mixture and its deviation from ideality. Contrary to the majority of systems studied so far, the deep eutectic system comprised of [N2,2,2,1]Cl and urea appears to owe its deviation from ideality to entropic rather than enthalpic factors.
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Fasciola hepatica causes liver fluke disease, a worldwide neglected and re-emerging zoonotic disease, leading to hepatitis in humans and livestock. In the pathogenesis, flukes actively migrate through liver parenchyma provoking tissue damage. Here, parasites must confront leukocytes of the innate immune system in vivo. Polymorphonuclear neutrophils (PMN) are the most abundant granulocytes and first ones arriving at infection sites. PMN may display neutrophil extracellular traps (NETs), consisting of nuclear DNA, decorated with histones, enzymes, and antimicrobial peptides. We investigated for the first time whether F. hepatica soluble antigens (FhAg) can also trigger NETosis and innate immune reactions in exposed ovine PMN. Thus, isolated PMN were co-cultured with FhAg and NET formation was visualized by immunofluorescence and scanning electron microscopy analyses resulting in various phenotypes with spread NETs being the most detected in vitro. In line, NETs quantification via Picogreen®-fluorometric measurements revealed induction of anchored- and cell free NETs phenotypes. Live cell 3D-holotomographic microscopy revealed degranulation of stimulated PMN at 30 min exposure to FhAg. Functional PMN chemotaxis assays showed a significant increase of PMN migration (p = 0.010) and intracellular ROS production significantly increased throughout time (p = 0.028). Contrary, metabolic activities profiles of FhAg-exposed PMN did not significantly increase. Finally, in vivo histopathological analysis on F. hepatica-parasitized liver tissue sections of sheep showed multifocal infiltration of inflammatory cells within liver parenchyma, and further fluorescence microscopy analyses confirmed NETs formation in vivo. Overall, we hypothesized that NET-formation is a relevant host defence mechanism that might have a role in the pathogenesis of fasciolosis in vivo.
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Armadilhas Extracelulares , Fasciola hepatica , Humanos , Animais , Ovinos , Neutrófilos , Imunidade Inata , Armadilhas Extracelulares/metabolismo , Técnicas de Cocultura/veterináriaRESUMO
Cryptosporidium parvum is a zoonotic-relevant parasite belonging to the phylum Alveolata (subphylum Apicomplexa). One of the most zoonotic-relevant etiologies of cryptosporidiosis is the species C. parvum, infecting humans, cattle and wildlife. C. parvum-infected intestinal mucosa as well as host cells infected in vitro have not yet been the subject of extensive biochemical investigation. Efficient treatment options or vaccines against cryptosporidiosis are currently not available. Human cryptosporidiosis is currently known as a neglected poverty-related disease (PRD), being potentially fatal in young children or immunocompromised patients. In this study, we used a combination of atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization (AP-SMALDI) mass spectrometry imaging (MSI) and liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to determine and locate molecular biomarkers in in vitro C. parvum-infected host cells as well as parasitized neonatal calf intestines. Sections of C. parvum-infected and non-infected host cell pellets and infected intestines were examined to determine potential biomarkers. Human ileocecal adenocarcinoma cells (HCT-8) were used as a suitable in vitro host cell system. More than a thousand different molecular signals were found in both positive- and negative-ion mode, which were significantly increased in C. parvum-infected material. A database search in combination with HPLC-MS/MS experiments was employed for the structural verification of markers. Our results demonstrate some overlap between the identified markers and data obtained from earlier studies on other apicomplexan parasites. Statistically relevant biomarkers were imaged in cell layers of C. parvum-infected and non-infected host cells with 5 µm pixel size and in bovine intestinal tissue with 10 µm pixel size. This allowed us to substantiate their relevance once again. Taken together, the present approach delivers novel metabolic insights on neglected cryptosporidiosis affecting mainly children in developing countries.
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Criptosporidiose , Cryptosporidium parvum , Cryptosporidium , Criança , Humanos , Animais , Bovinos , Pré-Escolar , Espectrometria de Massas em Tandem , Diagnóstico por ImagemRESUMO
Inhibition of eukaryotic initiation factor 4A has been proposed as a strategy to fight pathogens. Rocaglates exhibit the highest specificities among eIF4A inhibitors, but their anti-pathogenic potential has not been comprehensively assessed across eukaryotes. In silico analysis of the substitution patterns of six eIF4A1 aa residues critical to rocaglate binding, uncovered 35 variants. Molecular docking of eIF4A:RNA:rocaglate complexes, and in vitro thermal shift assays with select recombinantly expressed eIF4A variants, revealed that sensitivity correlated with low inferred binding energies and high melting temperature shifts. In vitro testing with silvestrol validated predicted resistance in Caenorhabditis elegans and Leishmania amazonensis and predicted sensitivity in Aedes sp., Schistosoma mansoni, Trypanosoma brucei, Plasmodium falciparum, and Toxoplasma gondii. Our analysis further revealed the possibility of targeting important insect, plant, animal, and human pathogens with rocaglates. Finally, our findings might help design novel synthetic rocaglate derivatives or alternative eIF4A inhibitors to fight pathogens.
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Fator de Iniciação 4A em Eucariotos , RNA , Animais , Humanos , Simulação de Acoplamento Molecular , RNA/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , RNA Helicases DEAD-box/metabolismoRESUMO
Prenatal resource allocation to offspring can be influenced by maternal environment and offspring value, and affect offspring survival. An important pathway for flexible maternal allocation is via egg components such as nutrients and hormones. In cooperative breeders, females with helpers may increase resource allocation to eggs-'differential allocation'-or reduce it-'load-lightening'. Yet, helper effects on egg composition have been poorly studied. Moreover, it is unknown how helpers' presence modulates laying order effects on egg content and survival. Here, we investigated how maternal allocation varied with group size and laying order in the cooperatively breeding sociable weaver (Philetairus socius). We estimated interactive effects of helpers and laying order on allocation to egg mass, yolk nutrients-yolk mass, proteins, lipids, carotenoids, vitamin A and vitamin E-and hormones-testosterone, androstenedione, and corticosterone. Results concurred with the 'differential allocation' predictions. Females with more helpers produced later-laid eggs with heavier yolks and more lipids, and laid eggs overall richer in lipids. Proteins, antioxidants, and hormones were not found to vary with helper number. We then analyzed how helper number modulated laying order effects on survival. Females with more helpers did not specifically produce later-laid eggs with higher survival, but eggs laid by females with more helpers were overall more likely to fledge. These findings show that some egg components (yolk mass, lipids) can positively vary according to females' breeding group size, which may improve offspring fitness.
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Lipídeos , Testosterona , Feminino , Animais , Testosterona/metabolismo , Gema de Ovo/metabolismoRESUMO
The presence of pharmaceuticals in aquatic ecosystems mostly originates from wastewater treatment plants (WWTPs) and such a situation can be responsible for significant negative impacts on natural ecosystems, such as estuarine and coastal areas. Bioaccumulation of pharmaceuticals, namely antibiotics, in exposed organisms is known to have remarkable effects on different trophic levels of non-target organisms such as algae, invertebrates and vertebrates, including the emergence of bacterial resistance. Bivalves are a highly appreciated seafood product, as they are fed by filtering water, and can bioconcentrate chemicals, being ideal for biomonitoring environmental health hazards in coastal and estuarine ecosystems. To use this sentinel species, an analytical strategy was developed to be used in accessing antibiotics, from human and veterinary medicine, and evaluate their occurrence as emerging pollutants in aquatic environments. The optimized analytical method was fully validated according to the European requirements defined by the Commission Implementing Regulation 2021/808. The validation comprised the following parameters: specificity, selectivity, precision, recovery, ruggedness, linearity, and the decision limit CCα, as well as the limit of detection (LoD) and limit of quantification (LoQ). The method was validated for 43 antibiotics to allow their quantification in both contexts, environmental biomonitoring and food safety.
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In this article, we provide a brief overview of some of the outstanding sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the 2022 European Respiratory Society International Congress, which was held in a hybrid format. Early Career Members from Assembly 9 summarised the content of the sessions, with the support of the Officers from the four Assembly groups: Respiratory Function Technologists and Scientists (Group 9.01); Physiotherapists (Group 9.02); Nurses (Group 9.03); and Psychologists and Behavioural Scientists (Group 9.04). The sessions covered the following topics: recent advances in cardiopulmonary exercise and challenge testing; the role and new trends in physiotherapy, exercise and physical activity promotion interventions in chronic respiratory diseases; development of the international curriculum for respiratory nurses and nursing aspects in disease management; and treatment adherence, e-health interventions and post-coronavirus disease 2019 challenges. This Highlights article targets delegates who attended the Congress sessions, as well as those who were unable to attend, and provides valuable insight into the latest scientific data and emerging areas affecting the clinical practice of Allied Respiratory Professionals.
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Rice is the second most important cereal crop and is vital for the diet of billions of people. However, its consumption can increase human exposure to chemical contaminants, namely mycotoxins and metalloids. Our goal was to evaluate the occurrence and human exposure of aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEN), and inorganic arsenic (InAs) in 36 rice samples produced and commercialized in Portugal and evaluate their correlation. The analysis of mycotoxins involved ELISA, with limits of detection (LODs) of 0.8, 1 and 1.75 µg kg-1 for OTA, AFB1, and ZEN, respectively. InAs analysis was carried out by inductively coupled plasma mass spectrometry (ICP-MS; LOD = 3.3 µg kg-1). No sample showed contamination by OTA. AFB1 was present in 2 (4.8%) samples (1.96 and 2.20 µg kg-1), doubling the European maximum permitted level (MPL). Concerning ZEN, 88.89% of the rice samples presented levels above the LOD up to 14.25 µg kg-1 (average of 2.75 µg kg-1). Regarding InAs, every sample presented concentration values above the LOD up to 100.0 µg kg-1 (average of 35.3 µg kg-1), although none surpassed the MPL (200 µg kg-1). No correlation was observed between mycotoxins and InAs contamination. As for human exposure, only AFB1 surpassed the provisional maximum tolerable daily intake. Children were recognized as the most susceptible group.
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Micotoxinas , Oryza , Zearalenona , Criança , Humanos , Micotoxinas/análise , Oryza/química , Projetos Piloto , Portugal , Contaminação de Alimentos/análise , Zearalenona/análise , Aflatoxina B1/análise , Medição de RiscoRESUMO
In the recent years, several "omics" technologies based on specific biomolecules (from DNA, RNA, proteins, or metabolites) have won growing importance in the scientific field. Despite each omics possess their own laboratorial protocols, they share a background of bioinformatic tools for data integration and analysis. A recent subset of bioinformatic tools, based on available templates or remote homology protocols, allow computational fast and high-accuracy prediction of protein structures. The quickly predict of actually unsolved protein structures, together with late omics findings allow a boost of scientific advances in multiple fields such as cancer, longevity, immunity, mitochondrial function, toxicology, drug design, biosensors, and recombinant protein engineering. In this chapter, we assessed methodological approaches for the integration of omics and remote homology inferences to decipher protein functionality, opening the door to the next era of biological knowledge.
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Genômica , Neoplasias , Humanos , Genômica/métodos , Biologia ComputacionalRESUMO
The poultry industry, in order to prevent and control coccidiosis caused by Eimeria spp., widely uses coccidiostats as feed additives. The main objective of this study was to evaluate the presence of nine coccidiostats in 62 egg samples by UHPLC-MS/MS. Overall, detection frequency and average concentration were 90.3% (56/62) and 106.3 µg kg-1, respectively. Only diclazuril and nicarbazin were detected. Diclazuril, only found in home-raised eggs, showed an overall detection frequency of 8.1% (5/62), with average and maximum concentrations of 0.46 ± 1.90 µg kg-1 and 13.6 µg kg-1, respectively. Nicarbazin presented an overall higher frequency, 88.7% (55/62), with levels up to 744.8 µg kg-1. Additionally, four samples (6.5%) presented both nicarbazin and diclazuril. Home-raised egg samples (n = 28) showed a detection frequency of 89.3%, with nicarbazin found in more samples (85.7% vs. 17.9%) and at higher levels (266.3 ± 169.4 µg kg-1 vs. 0.91 ± 2.78 µg kg-1) when compared to diclazuril. In supermarket samples (n = 34), only nicarbazin was detected in 31 samples (91.1%), with an average of 167.6 ± 62.2 µg kg-1. Considering the average contamination scenario, consumers' health should not be adversely affected by egg consumption. In every scenario considered, children were the most vulnerable population group.