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Abstract Piscine orthoreovirus (PRV) is a virus that is widely distributed among global aquaculture populations of salmonid species. The coho salmon (Oncorhynchus kisutch) is a species of increasing productive and economic importance in Chile. The presence of PRV has generated concern about its impact on the health and welfare of this species. The objective of this study was to comparatively describe the clinical manifestations, pathological changes, and pathogenesis associated with PRV infection in two different farms of farmed coho salmon in Chile through a prospective longitudinal descriptive observational study. The results demonstrated that PRV-1b and PRV-3a are independently associated with the same clinical and pathological presentation in farmed coho salmon. Microscopic pathology of the disease associated with PRV-1b and PRV-3a was primarily characterized by degenerative and inflammatory findings in the heart and liver. Hematological and blood biochemistry biomarkers in fish exhibited alterations, manifesting as hemolytic anemia and prehepatic jaundice likely due to indirect hyperbilirubinemia. Pathogenesis of infection associated with both PRV-1b and PRV-3a would indicate a specific tropism for erythrocytes and cardiomyocytes of the spongy myocardium. It is noteworthy that despite a notable reduction in viral load of both PRV subgroups in tissues, the frequency of macroscopic lesions increased during the final phase of the study. In conclusion, the results indicate a strong correlation between infection by both PRV subgroups and the proposed orthoreoviral cardiomyopathy and hemolytic jaundice (OCHJ) disease. Further research on the pathogenesis and surveillance of PRV-1b and PRV-3a subgroups is pivotal to develop effective strategies for the control of OCHJ in farmed coho salmon.

Abstract Cellular senescence connects aging and cancer. Cellular senescence is a common program activated by cells in response to various types of stress. During this process, cells lose their proliferative capacity and undergo distinct morphological and metabolic changes. Senescence itself constitutes a tumor suppression mechanism and plays a significant role in organismal aging by promoting chronic inflammation. Additionally, age is one of the major risk factors for developing breast cancer. Therefore, while senescence can suppress tumor development early in life, it can also lead to an aging process that drives the development of age-related pathologies, suggesting an antagonistic pleiotropic effect. In this work, we identified Rian/MEG8 as a potential biomarker connecting aging and breast cancer for the first time. We found that Rian/MEG8 expression decreases with age; however, it is high in mice that age prematurely. We also observed decreased MEG8 expression in breast tumors compared to normal tissue. Furthermore, MEG8 overexpression reduced the proliferative and stemness properties of breast cancer cells both in vitro and in vivo by activating apoptosis. MEG8 could exemplify the antagonistic pleiotropic theory, where senescence is beneficial early in life as a tumor suppression mechanism due to increased MEG8, resulting in fewer breast tumors at an early age. Conversely, this effect could be detrimental later in life due to aging and cancer, when MEG8 is reduced and loses its tumor-suppressive role.

Antecedentes y objetivo. El entrenamiento muscular inspiratorio (EMI) genera efectos positivos en el rendimiento físico, pero existen pocas pruebas sobre los efectos en la resaturación muscular en adultos mayores. El objetivo del estudio fue evaluar el impacto de un programa de entrenamiento muscular inspiratorio (EMI) de 4 semanas sobre la fuerza inspiratoria dinámica máxima, la función pulmonar, la oxigenación muscular y la capacidad funcional en adultos mayores funcionalmente independientes. Material y métodos. Doce adultos mayores aleatorizados (EG= n6; 68,8 ± 2,6 años; SCG=n6, 71,5 ± 4,7años) completaron el estudio. Se aplicó un programa de EMI de 4 semanas, junto con recomendaciones generales de actividad física. Se evaluaron las actividades de la vida diaria, el flujo y los volúmenes pulmonares, la fuerza inspiratoria dinámica máxima (índice S), el flujo inspiratorio máximo (FIM), la velocidad de resaturación muscular (ΔTSIreoxy) mediante NIRS y la batería Senior Fitness Test antes y después de la intervención. Resultados. Mejoras en el GE en la prueba de pararse y sentarse de la silla (p=0,013; η²p=0,474), test de curl de bíceps (p=0,015; η²p=0,463) y test de caminata de 6 minutos (p=0,011; η²p=0,495), mientras que en el grupo control sólo se observaron cambios en el test de curl de bíceps (p=0,004; η²p=0,589). Se observó un aumento del GE en el índice S (p=0,038; η²p=0,363) con un elevado efecto sobre el flujo inspiratorio máximo (FIM) (p=0,138; η²p=0,206), finalmente el GE mostró un elevado tamaño del efecto sobre la velocidad de resaturación muscular al final del ejercicio (p=0,213; η²p=0,187; Δ=-31%). Conclusiones. Un programa corto de EMI aumenta el índice S, la capacidad física y la velocidad de oxigenación muscular. El EMI puede ser una estrategia de intervención complementaria en adultos mayores para mejorar su forma física y su respuesta vascular periférica.

IntroductionOverdiagnosis in PSA-based prostate cancer (PCa) screening is primarily studied in younger, healthier populations from clinical trials. This study aimed to evaluate the probability of overdiagnosis in PCa screening within a clinical practice context, focusing on its relationship with PSA levels, Gleason scores, and subsequent clinical procedures.MethodsWe conducted a retrospective cohort analysis of 1,070 asymptomatic men over 40 years old diagnosed with PCa between 2004 and 2022, following a positive PSA test. The patients were followed until December 31, 2022, with a median follow-up time of 5.7 years (IQR 3.2-8.6). The primary outcome was the probability of overdiagnosis, assessed through life expectancy and the Charlson Comorbidity Index, considering lead times of 5, 10, and 15 years.ResultsWe found that patients with PSA levels >10 ng/dL and/or Gleason scores ≥8 were generally older and had more comorbidities than those with PSA levels 4-10 ng/dL and/or Gleason scores ≤7. The probability of overdiagnosis was significantly higher in patients with PSA levels >10 ng/dL (41.4%, IQR 21.5-73.9) and Gleason scores ≥8 (42.6%, IQR 14.9-38.9), compared to those with PSA levels 4-10 ng/dL (20.1%, IQR 12.8-30.4) and Gleason scores ≤7 (26.6%, IQR 23.6-68.6). Notably, 71.7% of patients did not receive pharmacological treatment. Patients with higher PSA levels also experienced greater radiation exposure from diagnostic imaging (median 19.9 mSv vs. 14.7 mSv, p = 0.004).ConclusionsThese findings underscore the high likelihood of overdiagnosis in older patients with elevated PSA levels and significant comorbidities, highlighting the need for careful consideration of patient comorbidities before PSA testing.

Introduction and objectives: Migraine is the most common reason for neurology outpatient consultation; more than 80% of patients with migraine suffer some degree of associated disability. Migraine is an underdiagnosed disorder and patients frequently receive inappropriate treatment, which is why it is necessary to establish recommendations to improve patient management. The objective of this document is to establish a consensus position on the pharmacological treatment of migraine, including general measures and detailed analysis of the different options for the treatment of attacks and their prevention, from the perspective of Ibero-American countries. Methods and results: Based on the recommendation documents published by the scientific societies of different Ibero-American countries, 2 surveys were prepared; through the application of the Delphi methodology and discussions in subsequent meetings, a document was developed in consensus format, supported by evidence from the literature and expert recommendations. Conclusions: A series of recommendations were agreed upon for the treatment of episodic migraine and chronic migraine, both for the acute management of attacks and for their prevention. These recommendations are based on the consensus process and a literature review, and are adapted to the regional conditions of the Ibero-American countries. Resumen: Introducción y objetivos: La migraña es el motivo ambulatorio neurológico de consulta más frecuente, más del 80% de los pacientes con migraña sufre algún grado de discapacidad asociada. La migraña es un trastorno subdiagnosticado y frecuentemente los pacientes reciben un tratamiento inadecuado por lo que es necesario establecer recomendaciones que ayuden a un mejor manejo de los pacientes. El objetivo de este trabajo es realizar un consenso sobre el tratamiento farmacológico de la migraña, incluyendo medidas generales y el análisis pormenorizado de las diferentes opciones para el tratamiento de las crisis y de la prevención de las mismas con la óptica de los países iberoamericanos. Métodos y resultados: Partiendo de los documentos de recomendaciones publicados por las sociedades científicas de diferentes países latinoamericanos se elaboraron dos encuestas y mediante la aplicación de la metodología Delphi y discusiones en reuniones posteriores, se desarrolló un documento en formato de consenso soportado en literatura y recomendaciones de expertos. Conclusiones: Se han consensuado una serie de recomendaciones para el tratamiento de la migraña episódica (ME)y de la migraña crónica (MC), tanto para el manejo de los ataques como para su prevención. Dichas recomendaciones se han basado en el consenso y en la revisión bibliográfica y se han adaptado a las condiciones regionales de los países iberoamericanos.

Interpretation: These findings support the nuclear localization of p-ASyn in skin cells and show that its presence decreases PD and almost disappears in the malignant transformation of melanocytes, redistributing to the cytoplasm and intercellular spaces. This confirms the association between PD and melanoma, providing crucial insights into the role of p-ASyn in both diseases.

Much of the current available literature on leisure characterizes it as an additional consumer good: a derivative of capitalist society, featured as a commodity and, for the most part, an industry. This paper argues that recovering the concept of leisure from the ancients, with a contemporary focus on culture and the practice of living artfully, will help us create a new understanding of leisure that will break free from the reigning popular focus on "free time." The concept of leisure (scholé) will here be set against an existential backdrop that will situate it entirely within the realm of education, to reveal important connections to what it means to be an educated self and to lead a flourishing collective life in the form of culture. This discussion will conclude with a portrait of the concept that will be of interest to democracy-oriented educators, as we set the groundwork for actualizing the concept in the practice and lives of teachers and students in today's world.

Ligation of retinoic acid receptor alpha (RARα) by RA promotes varied transcriptional programs associated with immune activation and tolerance, but genetic deletion approaches suggest the impact of RARα on TCR signaling. Here, we examined whether RARα would exert roles beyond transcriptional regulation. Specific deletion of the nuclear isoform of RARα revealed an RARα isoform in the cytoplasm of T cells. Extranuclear RARα was rapidly phosphorylated upon TCR stimulation and recruited to the TCR signalosome. RA interfered with extranuclear RARα signaling, causing suboptimal TCR activation while enhancing FOXP3+ regulatory T cell conversion. TCR activation induced the expression of CRABP2, which translocates RA to the nucleus. Deletion of Crabp2 led to increased RA in the cytoplasm and interfered with signalosome-RARα, resulting in impaired anti-pathogen immunity and suppressed autoimmune disease. Our findings underscore the significance of subcellular RA/RARα signaling in T cells and identify extranuclear RARα as a component of the TCR signalosome and a determinant of immune responses.

Background: Ifosfamide-induced Fanconi syndrome is a relatively infrequent complication that generally occurs in young patients with a high cumulative dose of ifosfamide; and is commonly characterized by glycosuria, proteinuria, electrolyte abnormalities, and a normal anion gap metabolic acidosis. Case Presentation: In this study, we present the case of a 16-year-old male patient with of osteosarcoma of the right femur with pulmonary metastasis, who received ifosfamide as part of chemotherapy 1 year and 2 months ago and required hospitalization for cellulitis. During inpatient management, he presented with hypokalemia, hypophosphatemia, polyuria, glycosuria, and proteinuria, by which he was diagnosed with Fanconi syndrome and nephrogenic diabetes insipidus, induced by ifosfamide. Management was focused on the control of the internal environment and use of potassium supplements and potassium-sparing diuretics. Conclusion: Patients receiving ifosfamide should be periodically monitored for kidney function and internal environment to detect any potential complications. It is thus important to carefully observe the cumulative dose of ifosfamide to prevent its associated nephrotoxicity, since its appearance can impoverish the prognosis in patients with neoplasms. Therefore, physicians should always be aware about the possibility of nephrotoxicity development.

La fijación biológica de nitrógeno (FBN) es un proceso natural que puede suministrar hasta el 90% del nitrógeno necesario para algunas leguminosas, por lo que representa una opción sustentable para reducir los efectos adversos de fertilizantes químicos en la agricultura. Para evaluar la eficiencia en FBN de cinco cultivares de frijol de hábito arbustivo, cinco de hábito enredador y 10 poblaciones de frijol silvestre, se inocularon plántulas con un compuesto de tres cepas de Rhizobium spp. Se usó un diseño experimental completamente al azar con cinco repeticiones y se registraron ocho variables cuantitativas. Se hicieron análisis de varianza, se obtuvieron índices de eficiencia en nodulación y fijación de nitrógeno y se realizaron análisis de componentes principales (CP). Los análisis de varianza y los índices de eficiencia en nodulación y fijación mostraron diferencias entre genotipos. Las variedades Peruano 16, Cuarenteño y Pinto Saltillo de hábito arbustivo fueron eficientes en nodulación y en fijación de nitrógeno. Las poblaciones silvestres ROL 633 y ROL 486, fueron eficientes en nodulación y de baja eficiencia en fijación. Los contrastes ortogonales de las variables número y peso seco de nódulos, nitrógeno total y contenido de clorofila y los índices de eficiencia en nodulación y fijación de nitrógeno ambos por grupos de genotipos, permiten afirmar que las variedades de frijol arbustivo mostraron un comportamiento sobresaliente, superando de manera general a las variedades cultivadas de hábito trepador y a los genotipos silvestres. El CP1 separó a los genotipos por longitud de vástago y raíz y el CP2 por número y peso seco de nódulos. Los resultados confirman variabilidad entre genotipos de frijol en FBN, la existencia de cultivares de hábito arbustivo eficientes en nodulación y fijación y que existe potencial para selección de genotipos de frijol eficientes en FBN.

Anaerobic digestion is an alternative for wastewater treatment and its effluent could be used in agricultural production because it may contain nutrients; however, its harmlessness is a limiting factor. This research evaluated the potential of a self-cleaning biodigester (SCB) effluent to increase corn and sunflower production of a school plot. The SCB was located at the Telebachillerato Comunitario in San Felipe del Progreso, State of Mexico, Mexico. A randomized block design was used with three fertilization levels of N, P and K, irrigated with SCB effluent and potable water and 3 replications. Physical, chemical and biological parameters (total and fecal coliforms, Salmonella and Escherichia coli) were evaluated in the SCB effluent before being used as fertilizer on the corn and sunflower crops. Finally, the grain yield and the harvested seeds' safety were determined. In the SCB effluent, high K and Ca, high salinity, moderate total coliforms, fecal coliforms and E. coli were observed; Salmonella was not detected. In corn and sunflower seed, 98% of total coliforms were reduced, with no presence of fecal coliforms and E. coli compared to the SCB effluent. The grain yield of sunflower irrigated with SCB effluent increased up to 72% compared to that irrigated with potable water and in corn no significant differences were found between SCB effluent and potable water irrigation.

Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins-including gene expression, chromatin occupancy and three-dimensional conformation-we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.