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    Prolegomena to Philosophy as a Literary Genre in the Neoplatonic School of Alexandria

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    El programa filosófico de la escuela neoplatónica de Alejandría entre los siglos V y VI se estructura en torno a los Prolegómenos, o introducciones generales a la filosofía, junto con las introducciones a la filosofía de Platón y de Aristóteles. El objetivo de este artículo es analizar el género literario y filosófico de los Prolegómenos a la filosofía conservados, atribuidos a Ammonio, Elías, David y Pseudo-Elías. Las introducciones generales contienen seis definiciones de filosofía extraídas de autores a los que se otorga una autoridad epistémica ―tres atribuidas a Pitágoras, dos a Platón y una a Aristóteles―, y una descripción de la división de la filosofía en teoría y práctica, establecida por Aristóteles. La función de los Prolegómenos estriba en ofrecer una guía hermenéutica a las interpretaciones posteriores, colocándose al comienzo de los comentarios a la Isagoge de PorfirioThe philosophical programme of the Neoplatonic school of Alexandria between the 5th and 6th centuries is structured around the Prolegomena, or general introductions to philosophy, together with the introductions to the philosophy of Plato and Aristotle. The aim of this article is to analyse the literary and philosophical genre of the preserved Prolegomena to Philosophy, attributed to Ammonius, Elias, David and Pseudo-Elias. The general introductions contain six definitions of philosophy drawn from authors granted epistemic authority―three attributed to Pythagoras, two to Plato and one to Aristotle―and a description of the division of philosophy into theory and practice, established by Aristotle. The function of the Prolegomena is to provide a hermeneutical guide to later interpretations, and they are placed at the beginning of the commentaries on Porphyry’s IsagogeEste trabajo se enmarca en el Proyecto I+D PID2022-139027NA-I00 y forma parte de las actividades del Grupo de Investigación consolidado de la UAM: “Influencias de las éticas griegas en la filosofía contemporánea” (Ref. F-055

    Two photon-responsive gold nanocapsules enable targeted photothermal hyperthermia of chemoresistant melanoma: injection-route-dependent efficacy and renal evidence of fragment clearance

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    Melanoma is a highly aggressive skin cancer that often develops resistance to chemotherapy, underscoring the need for new treatment strategies. Here we evaluate plasmonic gold nanocapsules (AuNCs) as photoresponsive agents for two-photon luminescence-assisted photothermal therapy in chemoresistant melanoma models. The performance of the AuNCs was assessed in two-dimensional cell cultures, three-dimensional paclitaxel-resistant B16-F10 melanoma spheroids, and a subcutaneous melanoma mouse model under near-infrared excitation. In vitro, AuNCs alone exhibited no cytotoxicity, but under 830 nm two-photon excitation, they produced strong two-photon luminescence and thermal effects that increased with nanocapsule concentration and laser power. This led to transient oxidative stress, apoptosis induction, and effective melanoma cell ablation under optimal conditions (80 μg mL−1 AuNCs, 12 mW laser power). In vivo, the route of nanoparticle administration proved decisive. A single 4-min 806 nm irradiation after intratumoral injection uniformly heated the lesion (≈45–50 °C), yielded durable tumour eradication, and sequestered >99% of detected gold in the necrotic scab, with only trace renal clearance. In contrast, the same laser fluence after peritumoral injection generated a superficial hot rim, spared the tumour core, allowing eventual regrowth, and left ∼65% of the injected gold systemically redistributed, mainly in the spleen and liver. These findings highlight the potential of AuNCs as potent, image-guided photothermal agents for chemoresistant melanoma, offering targeted tumor destruction with limited systemic exposure. They reveal the injection route is a critical determinant of both therapeutic success and nanoparticle biodistributionThe study of the nanophotothermal therapy (nPTT) effects of gold nanocapsules (AuNCs) on melanoma cells using cryo soft X-ray tomography (CSXT) was conducted at the MISTRAL beamline of the ALBA Synchrotron (Project number: 2016091853). PRG acknowledges the Ministry of Science, Innovation and Universities (AEI-PID2022-140423NB-I00/AEI/10.13039/501100011033 and CNS2023 – 143700) and the AGAUR (2021 SGR 00175) for financial support. D. Jaque acknowledges theMinistry of Science, Innovation and Universities of Spain (PID2023-146775OB-I00). The authors thank Dr Vladimir Mulens Arias for fruitful discussions and Alba Riba for her contribution (Fig. S2A, ESI†

    El e-portfolio en la evaluación continua de la asignatura de Cooperación Internacional y Desarrollo

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    El proyecto de innovación docente que se presenta en este capítulo recoge el proceso de transformación del portafolio como herramienta de enseñanza-aprendizaje a un formato digital (e-portfolio) incorporando las tecnologías de la información y la comunicación (TIC), así como su mejora para hacerlo más adaptable a los diferentes contextos en los que se emplea. El objetivo de esta herramienta es desarrollar, fortalecer y aumentar las competencias digitales, de innovación, trabajo en equipo, creatividad, autonomía y pensamiento crítico entre los estudiantes en torno a la asignatura de Cooperación Internacional y Desarrollo. Una vez adaptado y mejorado, el e-portfolio se aplicó en los grados de Relaciones Internacionales y Derecho (4.º curso), Relaciones Internacionales y ADE (5.º curso), y Relaciones Internacionales y Comunicación Global (5.º curso) durante el curso 2022-2023. En este documento se presentan algunas reflexiones del proceso de mejora e implementación de la herramienta, evidenciando que el estudiantado se enfrentó a retos de aprendizaje al incorporar nuevas tecnologías, pero, al mismo tiempo, adquirió destrezas digitales, competencias colaborativas y creativas, y mejoró el uso de formas innovadoras para analizar y expresar de manera más efectiva el conocimiento adquirido durante el curs

    Controlling what’s written: aristocratic interference with Burgo’s Clerk office in the Late Middle Ages

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    The aim of this article is to examine the head clerk’s office in the realengo (under royal jurisdiction) city of Burgos during the fifteenth century. I will analyse the professional path that gave access to this office, its functions and its duties, and I will also go over the holders of this position in the fifteenth century. I will examine the appropriation of this post by the lineage of the Fernández de Velasco, Counts of Haro, condestables of Castile, and Dukes of Frías, members of the high Castilian nobility. Special attention will be paid to the mechanisms used by the nobility to access this public office, as well as to the scope and meaning of their control over the head clerk’s officeThis article is part of a research project entitled “Más allá de la palabra. Comunicación y discurso políticos en las Castilla Trastámara (1367-1504) / Beyond the Word. Political Communication and Discourse in Trastámara Castile (1367-1504)” (PID2021-125571NB-I00, MINECO 2022-2026/AEI/ FEDER, UE), funded by the Ministerio de Ciencia e Innovación (Spain). Used Abbreviations: AMB, Archivo Municipal de Burgos; AGS, Archivo General de Simancas; AHNOB, Archivo Histórico de la Noblez

    From Palace to castle: chronostratigraphic and structural analysis of the Late Medieval Old Castle of Manzanares El Real (Madrid). Archaeological work 2021-2024

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    Se dan a conocer los resultados más destacados de las investigaciones realizadas sobre el denominado Castillo Viejo de Manzanares El Real, enfocado tanto a la revisión de la documentaria escrita como a los resultados de las cuatro campañas arqueológicas realizadas entre 2021 y 2024. Las nuevas actuaciones confirman la presencia de un palacio del siglo XIV que conserva restos de la fachada decorada con esgrafiado segoviano que, a mediados del siglo XV, se fortifica siguiendo el modelo de los castillos propios del momentoThe most notable results of the research carried out on the so-called Castillo Viejo of Manzanares El Real have been released, focusing both on the review of written documentation and the findings from the four archaeological campaigns carried out between 2021 and 2024. These new efforts confirm the presence of a 14th-century palace that preserves remains of the façade decorated with Segovian sgraffito, which, in the mid-15th century, was fortified following the model of castles of this perio

    Sedimentation and metal accumulation in the Gulf of Urabá – Colombian Caribbean: A 150-year record of natural processes and human impacts

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    Natural and human factors control the sediment accumulation rates and metal deposition in estuaries. This study analyzes the changes in sedimentation rates and metal accumulation in the Gulf of Urab´a (southern Colombian Caribbean) over the last 150 years. The sedimentation rates of three cores (C1, C2, and C3) were determined using the constant flux (CF) model based on the 210 Pb isotope, averaging 0.14 cm/y, 0.22 cm/y and 0.10 cm/y, respectively. The temporal distribution of both major (Al, Fe, Ca, Mn) and minor (Zn, Cr, Cu, Ni) metals revealed important historical events, including the relocation of the main tributary mouth, intensive land use changes, and extreme climatic events. In agreement with previous studies in the area, moderate contamination and metal enrichment were found based on three geochemical indices (enrichment factor, anthropogenic factor and geo- accumulation index) considering global crust reference values. However, a lack of or minimal pollution was evident when considering the local background metal concentrations, which were determined in the bottom core sediments (2583 y BP). Therefore, this study evidences the relevance of using local background to determine metal pollution in surface sediments and cores. Despite high freshwater inputs and sediment supply, as well as anthropogenic activities in the gulf, sedimentation rates and metal accumulation are low compared to other marine environments worldwide, due to the presence of a salt wedge intrusion. The salt wedge creates a density difference, causing the clay fraction of the sediments, along with associated pollutants, to remain suspended for extended periods. As a result, sedimentation is hindered, and these materials are transported out of the gulf. Consequently, fine and medium silt dominate sedimentation and metal accumulation dynamics in the estuar

    Rentabilidad de la ecografía clínica multi-órgano como complemento al proceso diagnóstico en una consulta de Medicina Interna

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de Lectura: 08-07-2025Introducción: La ecografía supone una técnica diagnostica de imagen importante en radiología. Su accesibilidad y seguridad ha permitido ampliar su espectro hasta extenderse a un buen número de especialidades, que la emplean de forma rutinaria en consultas y hospitalización. El advenimiento de la ecografía clínica multiórgano ha permitido la evaluación diagnostica y tratamiento de los pacientes a pie de cama. Su incorporación a Medicina Interna es aún reciente y su modo de empleo y utilidad dista de estar establecido. Por ello nos planteamos valorar y medir la utilidad de la ecografía clínica-multiórgano en una consulta general de Medicina Interna. Métodos: Se trata de un estudio unicéntrico observacional prospectivo llevado a cabo en una consulta de medicina interna general en la que se realizaba ecografía clínica multiórgano de forma habitual. Se han recogido datos sociodemográficos, historia médica previa, exploración física, de seguimiento y variables ecográficas. Los hallazgos ecográficos fueron evaluados por el clínico responsable lo que, en base a su relevancia, podía implicar cambios en el manejo del paciente mediante cambios en el juicio clínico, tratamiento o pruebas complementarias. Resultados: Se incluyeron un total de 80 pacientes. La realización de la ecografía llevó una media de 13,1 (SD 2,32) minutos por paciente. Hubo un total de 319 hallazgos ecográficos de los que el 61,4% fueron agrupados dentro de los clínicamente relevantes. Suponiendo hallazgos ecográficos clínicamente relevantes en el 37,5% de los pacientes. El mayor número de estos se dieron a nivel abdominal (25%). Hubo un cambio de manejo en el 27,5% de los pacientes. El juicio clínico inicial cambió en el 16,3% de los pacientes, siendo la enfermedad oncológica la nueva sospecha diagnostica aislada más frecuente. Hubo nuevos juicios clínicos, independientes del motivo de consulta, en el 23,8%. Se modificaron las pruebas solicitadas en el 23,8%. En el 15% se produjo un cambio del tratamiento establecido. Se llevo a cabo una regresión logística y curva ROC para determinar el perfil de paciente que más se beneficiaba de la realización de la ecografía. Suponiendo la presencia de enfermedad cardiovascular y autoinmune como factores de riesgo y la obesidad como factor protector. No se detectaron efectos adversos. Conclusión: La realización de la ecografía clínica en consulta conlleva un cambio de manejo en los pacientes. Lo que permite una mejor aproximación a su diagnóstico y tratamient

    STING inhibition alleviates experimental peritoneal damage: Potential therapeutic relevance for peritoneal dialysis

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    Peritoneal dialysis (PD) is a widely used kidney replacement therapy for patients with end-stage kidney disease. Nevertheless, long-term exposure to PD fluid can damage the peritoneal membrane, leading to ultrafiltration failure and, ultimately, discontinuation of PD. Investigation of the molecular mechanisms underlying this damage is essential for identifying new therapeutic targets to mitigate peritoneal deterioration in PD patients. To this end, we employed RNA sequencing in a preclinical model of peritoneal injury, induced by prolonged chlorhexidine (CHX) exposure, which revealed cytosolic DNAsensing signaling as a novel pathway. Next, we demonstrated that key players in this pathway, such as the stimulator of interferon genes (STING) and its downstream signaling effectors (interferon regulatory factor 3, interferon-stimulated genes, and nuclear factor-κB signaling), were upregulated in experimental peritoneal damage. Moreover, increased STING expression was observed in human peritoneal biopsies from patients with PD. Subsequent studies in STING-deficient mice showed reduced proinflammatory gene expression and immune cell infiltration, together with inhibited nuclear factor-κB pathway activation at both early (10 days) and late (30 days) stages of CHX-induced peritoneal injury. STING deficiency also reduced peritoneal membrane thickening, fibrosis, and mesothelial-to-mesenchymal transition (MMT)-related changes in advanced CHX-induced damage. Furthermore, pharmacological inhibition of STING with C-176 attenuated CHX-induced peritoneal inflammation. Macrophages were identified as one of the STING-expressing cell types in the injured peritoneum. Hence, in vitro STING blockade in activated macrophages inhibited MMT in cultured mesothelial cells, suggesting that STING activation in this populationmay drive peritoneal fibrosis. Additionally, STING deficiency reduced peritoneal inflammation in S. epidermidis-induced peritonitis and decreased adhesion scores in a postsurgical intra-abdominal adhesion model. These findings identify STING as a pivotal mediator of peritoneal injury and support its potential as a novel therapeutic target to prevent PD-associated ultrafiltration failureThis study was funded by the Instituto de Salud Carlos III (ISCIII) through the projects PI20/00140, PI21/01453, PI23/00394, and RICORS2040-RD21/0005/0002, RD21/0005/0018, RD24/0004/0021, and RD24/0004/0001 and cofunded by the European Union-NextGenerationEU, Mecanismo para la recuperación y la resiliencia (MRR). The grant IMPROVE-PD from the European Union’s Horizon 2020 research and innovation program, under the Marie Skłodowska-Curie grant 812699, to ML-C, VM and MR-O. INNOREN ‘P2022/BMD-7221: Nuevas estrategias diagnósticas y terapéuticas en enfermedad renal crónica’ to VM and MR-O. Miguel Servet CP23/00025 to SR-

    Improved identification of T‐ALL paediatric patients with low MRD but poor prognosis using a transcriptional signature

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    Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number: RTI2018-0 93330-B -I 00; Ministerio de Economía y Competitividad, Grant/Award Number: SAF2015-7 0561-R ; Instituto de Investigación Sanitaria Fundación Jiménez Díaz; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2022- 137487OB- I0

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