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Many anticancer agents used in clinics induce premature senescence in healthy tissues generating accelerated aging processes and adverse side-effects in patients. Cardiotoxicity is a well-known limiting factor of anticancer treatment with doxorubicin (DOX), a very effective anthracycline widely used as antitumoral therapy in clinical practice, that leads to long-term morbidity and mortality. DOX exposure severely affects the population of cardiac cells in both mice and human hearts by inducing premature senescence, which may represent the molecular basis of DOX-induced cardiomyopathy. Here, we demonstrate that senescence induction in the heart contributes to impaired cardiac function in mice upon DOX treatment. Concomitant elimination of senescent cells with the senolytic Navitoclax in different formulations produces a significant decrease in senescence and cardiotoxicity markers together with the restoration of the cardiac function in mice followed by echocardiography. These results evidence the potential clinical use of senolytic therapies to alleviate cardiotoxicities induced in chemotherapy-treated patients.

La lesión de Dieulafoy es una causa infrecuente de hemorragia digestiva, producida por la erosión de vasos aberrantes en la submucosa, habitualmente gástrica. La localización yeyunal es inusual. Su diagnóstico es complicado por la característica intermitente del sangrado, recomendándose inicialmente el abordaje endoscópico. Se trata de una situación excepcional que debe tenerse en cuenta en el diagnóstico diferencial de la hemorragia digestiva. Puede producirse una hemorragia masiva que comprometa la vida del paciente. Es recomendable un manejo endoscópico/radiológico inicial; el abordaje quirúrgico se reserva para hemorragias refractarias a los tratamientos menos invasivos.

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.

Resumen:El itinerario geográfico es un recurso didáctico motivador de conocimientos significativos y de valoración del paisaje desde el área de Conocimiento del Medio, aunque desde la transversalidad de Educación Ambiental. Su enfoque didáctico persigue la funcionalidad como recurso inductor del aprendizaje significativo. El desarrollo de la propuesta didáctica se articula en tomo a las transformaciones humanas en el paisaje.Palabras clave:Aprendizaje significativo, itinerario geográfico, valoración del paisaje. Abstract:The Geographic Itinerary is a didactic resource that motivates learners, encourages their knowledge and assessment on the landscape, and awakes their sensibility with the help of the transversal area of Environmental Education. Its methodological approach focuses on functionality as an inducement of significant learning. Tbe proposed method is built up on project-based working as a means to gather together and evaluate the leaming contents. A project on landscape alteration by human action is put forward in the syllabus design. Key words:Landscape Assessment, Functional and Significant Learning, Geographical Itinerary. Résumé:L'ltinéraire géographique se montre comme une ressource didactique qui favorise I'acquisition des connaissances et la valorisation du paysage au méme temps qui sensibilise grasce au domaine traversier de l'Éducation à faveur de l'environnement. L'approche didactique poursuit la fonctionnalité qui conduise á I'apprentissage significatif. La méthode se base sur le travail autour d'un projet qui sert a agglutiner et a évaluer les contenus d'apprentissage. Un projet sur la transformation du paysage par I'action humaine est développé dans le propos d'unité méthodologique. Mots-Clés:L'apprentissage significatif, l'itinéraire géographique, la valorisation du paysage.

Resumen: El itinerario geográfico es un recurso didáctico motivador de conocimientos significativos y de valoración del paisaje desde el área de Conocimiento del Medio, aunque desde la transversalidad de Educación Ambiental. Su enfoque didáctico persigue la funcionalidad como recurso inductor del aprendizaje significativo. El desarrollo de la propuesta didáctica se articula en tomo a las transformaciones humanas en el paisaje. Palabras clave: Aprendizaje significativo, itinerario geográfico, valoración del paisaje. Abstract: The Geographic Itinerary is a didactic resource that motivates learners, encourages their knowledge and assessment on the landscape, and awakes their sensibility with the help of the transversal area of Environmental Education. Its methodological approach focuses on functionality as an inducement of significant learning. Tbe proposed method is built up on project-based working as a means to gather together and evaluate the leaming contents. A project on landscape alteration by human action is put forward in the syllabus design. Key words: Landscape Assessment, Functional and Significant Learning, Geographical Itinerary. Résumé: L'ltinéraire géographique se montre comme une ressource didactique qui favorise I'acquisition des connaissances et la valorisation du paysage au méme temps qui sensibilise grasce au domaine traversier de l'Éducation à faveur de l'environnement. L'approche didactique poursuit la fonctionnalité qui conduise á I'apprentissage significatif. La méthode se base sur le travail autour d'un projet qui sert a agglutiner et a évaluer les contenus d'apprentissage. Un projet sur la transformation du paysage par I'action humaine est développé dans le propos d'unité méthodologique. Mots-Clés: L'apprentissage significatif, l'itinéraire géographique, la valorisation du paysage.

Chronic obstructive pulmonary disease is progressive and in its advanced stage is associated with major disability. Previous studies suggest that patients with this disease receive little palliative care, even in very advanced stages. Given this, our objectives were to describe the clinical practice of Spanish pulmonologists in the care of patients with end-stage chronic obstructive pulmonary disease, to identify potential barriers to implementing palliative care in these patients and to correlate these responses with doctor's years of experience. A link to an online survey was sent to pulmonologists on (a) symptom management, (b) structure of their department and collaboration with other services, (c) specialized medical training in palliative care, (d) communication with patients and their families, and (e) limiting barriers identified in the management of these patients. A total of 387 responses were received. The majority used opioids to treat dyspnea (52.9%) or pain (54.2%) and many treated anxiety/depression (41%). Around half of the respondents had no established routines in their departments to offer palliative care to patients with chronic obstructive pulmonary disease. There was little communication with end-of-life patients and their families on disease course, mainly associated with a lack of medical training (83% of cases) and changes in patient wishes regarding care through the disease course (81%). In our setting, communication with end-of-life patients with chronic obstructive pulmonary disease is poor. The key challenges identified are insufficient medical training and changing desires of patients. No substantial differences in attitude were found as a function of experience. [ABSTRACT FROM AUTHOR]

Abstract Background Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular and functional studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression. Results To address these challenges, we established an approach to study human astrocytes within the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains. Xenografted hiPSC-derived astrocyte progenitors differentiated into astrocytes that integrated functionally within the mouse host brain and matured in a cell-autonomous way retaining human-specific morphologies, unique features, and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes responded to the presence of amyloid plaques undergoing morphological changes that seemed independent of the APOE allelic background. Conclusions In sum, we describe here a promising approach that consist of transplanting patient-derived and genetically modified astrocytes into the mouse brain to study human astrocyte pathophysiology in the context of Alzheimer´s disease.

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The synthesis of ferrocene-based heteroditopic receptors in which the ferrocene moiety is attached to an imidazo[4,5-e]benzothiadiazole or imidazo[4,5-f]quinoxaline is reported. These nitrogen-rich ferrocene derivatives show remarkable ion-sensing properties because of the presence of the redox active ferrocene unit and the polyazaheteroaromatic ring systems which act as a dual binding site for anions and metal cations. They display an anodic shift of the oxidation wave (ΔE1/2= 67–200 mV) upon complexation with metal cations and a strong cathodic shift (ΔE1/2= −82 to −100 mV) in the presence of F−and HP2O73−anions. For the Zn2+, Cd2+, Hg2+and Pb2+metal cations tested, the change in the absorption spectra is accompanied by a dramatic colour change which allows the potential for “naked eye” detection. [ABSTRACT FROM AUTHOR]

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer’s among others. Recent data provide compelling evidence that distinct astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

ABSTRACT: Objective: Nivolumab, anti–programmed cell death 1 monoclonal antibody, is a newly Food and Drug Administration–approved biologic for the treatment of metastatic melanoma. New indications for treatment of other cancers have been recently granted. Nivolumab package insert reads: “Warnings and Precautions: immune-mediated pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, hypothyroidism and hyperthyroidism may occur.” Development of type 1 diabetes as an adverse event was not documented in the New England Journal of Medicine article that introduced its successful use for melanoma treatment.Methods: We present the case of an adult patient who developed autoimmune diabetes after treatment with nivolumab, accompanied by the presence of high serum titers of glutamic acid decarboxylase 65 (GAD65) isoform antibodies and a clinical presentation of diabetic ketoacidosis.Results: Although endocrine autoimmunity has been described following treatment with nivolumab, type 1 diabetes has only been shown after the treatment of 2 patients with melanoma that happened to be antibody (GAD65, insulin, and islet cell antibody) negative.Conclusion: Clinicians prescribing this drug need to be aware of this life-threatening adverse effect. At a minimum, patient education should be offered to every patient treated with this biologic.Abbreviations:GAD65glutamic acid decarboxylase 65PD-1programmed cell death 1

El objetivo de este estudio fue determinar los efectos que tiene el sedentarismo en la composición corporal, condición física y rendimiento académico a lo largo de las etapas de Educación Primaria y Secundaria. La muestra incluyó 70 niños evaluados durante 5 años. Se obtuvieron datos de composición corporal (Índice de Masa Corporal, Índice de Cintura Cadera, % de grasa corporal y % de masa muscular), condición física (salto de longitud, salto de altura, Test de agilidad o Test de Tapping, Test de Cooper, presión manual) y rendimiento académico en cada asignatura cursada en ambas etapas educativas. Los resultados mostraron que a mayor edad existe un mayor número de alumnado con comportamiento sedentario, un empeoramiento de la condición física y, además, el rendimiento académico se ve afectado por estos comportamientos sedentarios y la inactividad física.

La gestión del conocimiento tiene una fuerte relación con la organización de la información y su transformación en conocimiento, de esta manera sus principales objetos de estudio son los factores humanos, organizativos y tecnológicos que intervienen en el flujo de transferencia del conocimiento y su ciclo de vida. La incorporación de las prácticas de gestión del conocimiento en las Instituciones de Educación Superior (IES) se ha acentuado en la última década (Quarchioni et al., 2020). También han aumentado los procesos de evaluación y acreditación institucional con los que se busca medir la calidad mínima aceptable en los procesos académico-administrativos. Así, los sistemas de gestión de conocimiento se convierten en herramientas de gran valor para una gestión óptima de documentos e información propios de un proceso de acreditación. Esta revisión de literatura de tipo hermenéutica contribuye con la descripción de la gestión del conocimiento como disciplina académica y su aplicación en la comprensión de diez (10) modelos de gestión del conocimiento para IES. Los resultados muestran que los modelos de sistemas de gestión de conocimiento en las IES son específicos a cada contexto e institución, buscan mejorar las funciones sustantivas de las universidades. La mayoría de los modelos estudiados son híbridos, pero requieren ser validados con la puesta en marcha. Se fundamentan principalmente en revisiones de literatura y estudios de contexto. Ninguno de los modelos estudiados se sustenta en una auditoría de conocimiento, ni se conciben para apoyar a la institución en los procesos de evaluación y acreditación universitaria.

Abstract Background Psychopathology and side effects of antipsychotic drugs contribute to worsening physical health and long-term disability, and increasing the risk of mortality in these patients. The efficacy of exercise on these factors is not fully understood, and this lack of knowledge may hamper the routine application of physical activity as part of the clinical care of schizophrenia. Aims To determine the effect of exercise on psychopathology and other clinical markers in patients with schizophrenia. We also looked at several moderators. Method MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, PsycINFO, and Cochrane Library databases were systematically searched from inception to October 2022. Randomized controlled trials of exercise interventions in patients 18–65 years old diagnosed with schizophrenia disorder were included. A multilevel random-effects meta-analysis was conducted to pool the data. Heterogeneity at each level of the meta-analysis was estimated via Cochran’s Q, I2, and R2. Results Pooled effect estimates from 28 included studies (1,460 patients) showed that exercise is effective to improve schizophrenia psychopathology (Hedges’ g = 0.28, [95% CI 0.14, 0.42]). Exercise presented stronger effects in outpatients than inpatients. We also found exercise is effective to improve muscle strength and self-reported disability. Conclusions Our meta-analysis demonstrated that exercise could be an important part in the management and treatment of schizophrenia. Considering the current evidence, aerobic and high-intensity interval training exercises may provide superior benefits over other modalities. However, more studies are warranted to determine the optimal type and dose of exercise to improve clinical outcomes in people with schizophrenia.