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Avian coccidiosis, a common disease caused by Eimeria species, results in significant losses in global poultry production. Mycotoxins are low-molecular-weight natural products (i.e., small molecules) produced as secondary metabolites by filamentous fungi and they have the potential to economically and significantly affect global poultry production. Little is known about the relationship between mycotoxins and avian coccidiosis, although they often co-occur in the field. This comprehensive review examines the intricate relationship between mycotoxins and avian coccidiosis, in particular how mycotoxins, including aflatoxins, ochratoxins, trichothecenes as well as Fusarium mycotoxins, compromise the health of the poultry flock and open the door to Eimeria parasites in the gut. In addition, this review sheds light on the immunosuppressive effects of mycotoxins, their disruption of cellular signaling pathways, and the consequent exacerbation of coccidiosis infections. The mechanisms of mycotoxin toxicity are also reviewed, emphasizing direct damage to intestinal epithelial cells, impaired nutrient absorption, inflammation, oxidative stress, and changes in the gut microbiota. Finally, the consequences for the prevention and treatment of coccidiosis when mycotoxins are present in the feed are discussed. This review emphasizes the need for effective management strategies to mitigate the combined risks of mycotoxins and coccidiosis and highlights the complexity of diagnosing and controlling these interrelated problems in poultry. The review advocates a holistic approach that includes strict feed management, disease prevention measures and regular monitoring to maintain the health and productivity of poultry against these significant challenges.
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Renal ischaemia and reperfusion (I/R) is caused by a sudden temporary impairment of the blood flow. I/R is a prevalent cause of acute kidney injury. As nitric oxide generated by inducible nitric oxide synthase (iNOS) has detrimental effects during I/R, the pharmacological blockade of iNOS has been proposed as a potential strategy to prevent I/R injury. The aim of this study was to improve the understanding of 1400W (an iNOS inhibitor) on renal I/R as a pharmacological strategy against kidney disease. BALB/c mice received 30 min of bilateral ischaemia, followed by 48 h or 28 days of reperfusion. Vehicle or 1400W (10 mg/kg) was administered 30 min before inducing ischaemia. We found that after 48 h of reperfusion 1400W decreased the serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin and proliferating cell nuclear antigen 3 in the I/R animals. Unexpectedly, we observed mRNA upregulation of genes involved in kidney injury, cell-cycle arrest, inflammation, mesenchymal transition and endothelial activation in the renal medulla of sham animals treated with 1400W. We also explored if 1400W promoted chronic kidney dysfunction 28 days after I/R and did not find significant alterations in renal function, fibrosis, blood pressure or mortality. The results provide evidence that 1400W may have adverse effects in the renal medulla. Importantly, our data point to 1400W-induced endothelial dysfunction, establishing therapeutic limitations for its use. KEY POINTS: Acute kidney injury is a global health problem associated with high morbidity and mortality. The pharmacological blockade of inducible nitric oxide synthase (iNOS) has been proposed as a potential strategy to prevent AKI induced by ischaemia and reperfusion (I/R). Our main finding is that 1400W, a selective and irreversible iNOS inhibitor with low toxicity that is proposed as a therapeutic strategy to prevent kidney I/R injury, produces aberrant gene expression in the medulla associated to tissue injury, cell cycle arrest, inflammation, mesenchymal transition and endothelial activation. The negative effect of 1400W observed in the renal medulla at 48 h from drug administration, is transient as it did not translate into a chronic kidney disease condition.
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Plasmacytoid dendritic cells (pDCs) are vital players in antiviral immune responses because of their high levels of IFN-α secretion. However, this attribute has also implicated them as critical factors behind the immunopathogenesis of inflammatory diseases, and no currently available therapy can efficiently inhibit pDCs' aberrant activation. Mesenchymal stromal cells (MSCs) possess stromal immunomodulatory functionality, regulating immune cell activation through several mechanisms, including the adenosinergic (CD39/CD73/adenosine) pathway. The IFN-γ preconditioning of bone marrow MSCs improves their inhibitory properties for therapy applications; however, isolating human gingival tissue-derived MSCs (hGMSCs) is more accessible. These cells have shown better immunomodulatory effects, yet the outcome of IFN-γ preconditioning and its impact on the adenosinergic pathway has not been evaluated. This study first validated the immunoregulatory properties of primary-cultured hGMSCs, and the results showed that IFN-γ preconditioning strengthens CD39/CD73 coexpression, adenosine production, and the regulatory properties of hGMSC, which were confirmed by describing for the first time their ability to reduce pDC activation and their IFN-α secretion and to increase the frequency of CD73+ pDC. In addition, when CD73's enzymatic activity was neutralized in hGMSCs, adenosine production and the IFN-γ preconditioning effect were restrained. This evidence might be applied to design hGMSCs- and adenosine-based immunotherapeutic strategies for treating inflammatory disorders that are associated with pDC overactivation.
Assuntos
5'-Nucleotidase , Adenosina , Células Dendríticas , Gengiva , Interferon gama , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/citologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Adenosina/metabolismo , Interferon gama/metabolismo , Gengiva/citologia , 5'-Nucleotidase/metabolismo , Células Cultivadas , Apirase/metabolismo , Proteínas Ligadas por GPIRESUMO
The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.
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Biomarcadores , Doenças Cardiovasculares , Vesículas Extracelulares , Proteínas de Choque Térmico HSP47 , Miócitos Cardíacos , Humanos , Vesículas Extracelulares/metabolismo , Biomarcadores/sangue , Masculino , Doenças Cardiovasculares/metabolismo , Feminino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Pessoa de Meia-Idade , Animais , Proteínas de Choque Térmico HSP47/metabolismo , Ratos , Canal de Potássio ERG1/metabolismo , Idoso , Adulto , Canais de Potássio Éter-A-Go-Go/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/sangueRESUMO
Sickle cell anemia has been classified as a noninfectious neglected tropical disease and, although not exclusively, affects African descendants more frequently. This study aimed to detect asymptomatic sickle cell hemoglobin carriers (HbAS) in marginalized and vulnerable populations during a public health screening in African descendants from Oaxaca, Mexico, and to validate an amplification refractory mutation system (ARMS)-PCR methodology to detect fetal-hemoglobin (HbF)-regulating genetic variants in BCL11A toward affordable routine association of single nucleotide variants (SNVs) with HbF concentrations. To this aim, hemoglobin variants were detected by acidic citrate agar and alkaline cellulose acetate electrophoreses. SNVs in the hemoglobin subunit beta gene (HBB) were identified by the ß-globin mutation detection assay (ß-GMDA) and ARMS-PCR, respectively, and validated by Sanger sequencing. The association between genotypes and HbF concentrations was evaluated using Spearman's correlation coefficient. The results obtained during a directed screening in 140 self-identified African descendants revealed 42 HbS-carriers (30%), of which 39 showed normal total hemoglobin concentrations (92.8%), only 3 presented anemia (7.2%), and 9 showed quantifiable HbF concentration (21.4%). As validated by Sanger sequencing, the designed ARMS-PCR efficiently detected homozygous and heterozygous variants in BCL11A. In a cohort of 42 heterozygous (HbAS) and 27 healthy (HbAA) individuals from the same population, only one SNV (rs766432) showed statistically significant association with increasing HbF concentration, and two new unrelated homozygous silent variants were identified. This study reveals the need to raise coverage of HbS screening in vulnerable populations and shows a feasible low-cost ARMS-PCR methodology to determine the presence of SNVs in quantitative trait loci affecting HbF.
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INTRODUCCION: Los niños con Síndrome de Down (SD) y sus cuidadores requieren de una atención de salud multidisciplinaria que responda a sus necesidades desde una perspectiva integral. OBJETIVO: conocer las experiencias y expectativas que tienen los cuidadores de niños con SD en relación con los cuidados brindados por la enfermera durante el control de supervisión de salud infantil. METOLOGÍA: Estudio cualitativo fenomenológico, muestra intencionada de casos por criterios conformada por 11 cuidadores de niños con SD entre 0 y 9 años, que recibieron prestaciones en el Control de Salud Infantil. Se realizaron entrevistas semiestructuradas, los datos se analizaron siguiendo el esquema de reducción progresiva. Contó con la aprobación de la Dirección de Carrera de Enfermería, Universidad Santo Tomás (Temuco-Chile) (Acta 07-2018). RESULTADOS: se generaron dos categorías: "Experiencia de atención otorgada por la enfermera" y "Expectativas vinculadas a la atención proporcionada por la enfermera", se develó que los cuidadores de niños con SD perciben que los cuidados brindados por la enfermera durante la atención son insuficientes en relación con las necesidades que estos niños presentan. Esto estaría vinculado con la falta de conocimientos sobre esta condición y su abordaje integral. Con respecto a sus expectativas, refieren necesidad de acompañamiento, apoyo, educación y de profesionales de enfermería capacitados. CONCLUSIONES: urge abordar las brechas con respecto a las competencias del profesional de enfermería que realiza controles de salud del niño para poder entregar una atención de calidad a ellos y sus familias.
INTRODUCTION: Children with Down Syndrome (DS) and their caregivers require multidisciplinary health care that meets their needs from a comprehensive perspective. OBJECTIVE: to know the experiences and expectations that caregivers of children with DS have concerning the care provided by the nurse in the Child Health Supervision Attention. METHOD: A qualitative phenomenological study was conducted, an intentional sample of cases by criteria made up of 11 caregivers of children with DS between 0 and 9 years of age, who received benefits at the Child Health Control. Semi-structured interviews were carried out; the data were analyzed following the progressive reduction scheme. It had the approval of the Nursing Career Department, Santo Tomás University (Temuco-Chile) (Acta 07-2018). RESULTS: two categories were generated: "Experience of care provided by the nurse" and "Expectations linked to the care provided by the nurse", it was revealed that caregivers of children with DS perceive that the care provided by the nurse during the control is insufficient with the children's needs also, data showed a link to the lack of knowledge about this condition and its comprehensive approach. Regarding their expectations, they report the need for accompaniment, support, and education from the nurse, in addition to being a trained professional. CONCLUSION: It is urgent to address the gaps regarding the competencies of the nursing professional who performs child health checks to deliver quality care to them and their families.
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This study aimed to optimize the 3D printing parameters of salmon gelatin gels (SGG) using artificial neural networks with the genetic algorithm (ANN-GA) and response surface methodology (RSM). In addition, the influence of the optimal parameters obtained using the two different methodologies was evaluated for the physicochemical and digestibility properties of the printed SGG (PSGG). The ANN-GA had a better fit (R2 = 99.98%) with the experimental conditions of the 3D printing process than the RSM (R2 = 93.99%). The extrusion speed was the most influential parameter according to both methodologies. The optimal values of the printing parameters for the SGG were 0.70 mm for the nozzle diameter, 0.5 mm for the nozzle height, and 24 mm/s for the extrusion speed. Gel thermal properties showed that the optimal 3D printing conditions affected denaturation temperature and enthalpy, improving digestibility from 46.93% (SGG) to 51.52% (PSGG). The secondary gel structures showed that the ß-turn structure was the most resistant to enzymatic hydrolysis, while the intermolecular ß-sheet was the most labile. This study validated two optimization methodologies to achieve optimal 3D printing parameters of salmon gelatin gels, with improved physicochemical and digestibility properties for use as transporters to incorporate high value nutrients to the body.
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El presente artículo aporta un acercamiento al ciberdelincuente identificando las características comunes en la personalidad de quienes delinquen en este escenario. Para llevar a cabo la investigación, se tomó una muestra de diecinueve expertos que forman parte de la Dirección de Investigación Criminal e INTERPOL, abordados por entrevista en profundidad. Los datos obtenidos fueron tratados desde un diseño hermenéutico con énfasis en la teoría fundamentada, por medio de tres fases elaboradas en análisis matricial de codificación abierta, selectiva y teórica; a partir de las cuales se establecen algunas de las tácticas del ciberdelincuente desplegadas en el ciberespacio a través de tecnologías de la información y las comunicaciones; su descripción desde el modelo big five y se identifican algunas de sus características como la falta de empatía, escrúpulos, incapacidad para el control de emociones, confianza y capacidad de innovar sus modus operandi(Sánchez y Robles, 2013). Finalmente, desde las teorías del control social se han estudiado el ciberdelito y los actos del ciberdelincuente de una manera formal que vela por encontrar estrategias de control del Estado, según González (2010), o informal, que busca los motivos que conducen a cometer delitos, como lo afirma López (2015), a partir de lo cual, al final, se presentan algunas recomendaciones.
This article provides an approach to cybercriminals by identifying the common characteristics in the personality of those who commit crimes in this scenario. In order to carry out the research, a sample of nineteen experts from the Criminal Investigation Directorate and INTERPOL were interviewed in depth. The data obtained were treated based on a hermeneutic design with emphasis on grounded theory, by means of three phases elaborated in matrix analysis of open, selective and theoretical coding; from which some of the tactics of cybercriminals deployed in cyberspace through information and communication technologies are established; their description based on the big five model and the identification of several of their characteristics such as lack of empathy, scruples, the inability to control emotions, confidence and the ability to innovate their modus operandi (Sánchez y Robles, 2013). Finally, theories of social control have studied cybercrime and the acts of cybercriminals in a formal way that seeks to find strategies to control the State, according to González (2010), or informally, seeking the motives that lead to committing crimes, as stated by López (2015), on the basis of which, at the end, some recommendations are presented.
Este artigo traz uma abordagem sobre os cibercriminosos, identificando as características comuns na personalidade de quem comete crimes nesse cenário. Para a realização da investigação foi recolhida uma amostra de dezanove peritos que integram a Direcção de Investigação Criminal e a INTERPOL, abordados através de entrevista em profundidade. Os dados obtidos foram tratados a partir de um desenho hermenêutico com ênfase na teoria fundamentada, por meio de três fases desenvolvidas em análise matricial de codificação aberta, seletiva e teórica; a partir da qual se estabelecem algumas das táticas cibercriminosas implantadas no ciberespaço através das tecnologias de informação e comunicação; A sua descrição baseia-se no modelo dos big five e são identificadas algumas das suas características, como a falta de empatia, escrúpulos, incapacidade de controlar emoções, confiança e capacidade de inovar o seu modus operandi (Sánchez y Robles, 2013). Por fim, a partir das teorias de controle social, o cibercrime e os atos dos cibercriminosos têm sido estudados de forma formal, que busca encontrar estratégias de controle do Estado, segundo González (2010), ou informalmente, que busca os motivos que levam ao cometimento dos crimes. , conforme afirma López (2015), a partir do qual, ao final, são apresentadas algumas recomendações.