Tiwanaku: entre el cielo y la tierra

Este trabajo es fruto del proyecto UNESCO de “Conservación y preservación de Tiwanaku y la pirámide de Akapana”, financiado por el Fondo Fiduciario Japonés, y con la participación de la Universidad Complutense de Madrid. Tiene como objetivo principal acercar el conocimiento científico sobre Tiwanaku a un público amplio. El libro está estructurado en cuatro etapas muy distintas. En la primera, Arriba, se hace un breve recorrido por las cuestiones básicas de la Teledetección, desde la primera toma fotográfica desde el aire, hasta la aplicación de las últimas técnicas de imágenes satelitales, y su aplicación al ámbito del Patrimonio. La segunda parte, Abajo, hará un breve recorrido por la historia del conocimiento de Tiwanaku, desde los primeros cronistas que hablaron sobre el papel de un espacio para ellos tan increíble como desconocido, hasta la aproximación general que ha hecho la Arqueología a lo largo de los últimos cien años, así como la manera de entender el sitio mediante la Geografía Física. El tercer apartado del libro, Adentro, muestra la aplicación de la técnica de teledetección al espacio intramuros de la ciudad, atendiendo a cuestiones tan interesantes como sus límites físicos, o los diferentes elementos que la componen, introduciendo algunos espectaculares descubrimientos que jalonan su paisaje urbano. El último capítulo, Afuera, hace referencia a dos elementos que, desde el entorno externo de la ciudad han condicionado de forma manifiesta la vida de sus habitantes a lo largo de toda su historia, que son el agua y la piedra. De ambos elementos mostraremos algunas evidencias absolutamente novedosas

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Geotechnical Design and Mitigation Measures for the Conservation of Akapana Pyramid in the Tiwanaku Archaeological Site (Bolivia)

[EN] Tiwanaku is an Archaeological World Heritage Site, located at an elevation of 3,885 m.a.s.l., south of Lake Titicaca (La Paz), in the high plateau region of Bolivia. The present paper reports the actions carried out in the frame of the project: “Preservacion y conservacion de Tiwanaku y la piramide de Akapana, Bolivia”. The consultancy was requested by UNESCO Office in Quito, following previous activities conducted since 2010 and directly by the CIAAAT. During the first mission in the archaeological site of Tiwanaku (from 9 to 16 May 2016), an interdisciplinary team, carried out the preliminary diagnosis concerning the geotechnical processes affecting the Akapana pyramid. After that, another filed mission was carried out in order to implement a general master plan of actions aimed at the conservation and risk reduction of the whole pyramid. For this scope during 2017 two different field survey were carried out. Main scope of the activities was: (i) prepare and develop a long term executive full proposal conservation project for the Pyramid; (ii) implement a Terrestrial Laser Scanning (TLS) survey in order to produce a very detail topographical setting of the whole pyramid; (iii) collect core drilling samples in the Akapana pyramid for laboratory analysis; (iv) perform stability analysis 3D Model; (v) identify mitigation measures for a test site. After the summer 2017 field mission, the main topographical outcomes of the TLS survey were elaborated, incorporated and adopted for the implementation a pilot project of mitigation measures. Final design has been implemented along the east flank of the pyramid, and support was given to local authorities and workers during all the mitigation measures implementation.The research and works described in this paper were funded by Japan Funds in Trust and managed by UNESCO Office in Quito and representation in Bolivia, Colombia, Ecuador and Venezuela ‘s international experts’ team, dispatched for attending “Pilot Project of Conservation of Akapana Pyramid”, in Tiwanaku (Bolivia), 2015 – 2018.Peer reviewe

Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior

Background: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. Methods: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. Results: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. Conclusions: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner

Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior

Background: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. Methods: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. Results: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. Conclusions: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective

Ciencia y persuasión social en la medicalización de la infancia en España, siglos XIX-XX Science and social persuasion in the medicalization of childhood in 19th- and 20th-century Spain

Este trabajo indaga la conversión en rutinaria de la visita del médico de niños en España. Estudia la sustitución de modelos de atención al embarazo, parto y crianza, tradicionalmente opacos para varones y objeto de cuidados mediante agentes populares, por otros accesibles a la medicina académica. A partir de la situación existente a nivel popular en el último tercio del siglo XIX, exploramos la repercusión de campañas de divulgación científica - entendidas como crítica sin cuartel a lo que se construyó como cultura popular - y la proliferación de dispositivos asistenciales gratuitos. La oferta de vigilancia sobre la alimentación de lactantes permitió familiarizar a las madres con la asistencia facultativa en la enfermedad, hasta que, en la segunda mitad del siglo XX, la Pediatría se centró preferentemente en las patologías y la Puericultura dejó de ser especialidad médica para convertirse en identidad profesional subalterna.<br>The article explores how childhood visits to doctors first became routine in Spain. The introduction of new models of prenatal care, childbirth, and childrearing required the extension of academic medicine into a terrain traditionally occupied by practitioners of popular medicine. Focusing on the status quo for most of the population in the final third of the nineteenth century, the study examines the repercussion of the era's scientific outreach campaigns (expressions of harsh criticism of what popular culture had constructed) and the spread of free health assistance. In particular, it highlights how attention to the nutritional needs of nursing mothers helped these women gain familiarity with the medical assistance available in the case of illness - so much so that by the second half of the twentieth century, the issues of health education and promotion had been relegated to a secondary plane within the medical profession