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    Intracellular Synthesis of Indoles Enabled by Visible-Light Photocatalysis

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    Performing abiotic synthetic transformations in live cell environments represents a new, promising approach to interrogate and manipulate biology and to uncover new types of biomedical tools. We now found that photocatalytic bond-forming reactions can be added to the toolbox of bioorthogonal synthetic chemistry. Specifically, we demonstrate that exogenous styryl aryl azides can be converted into indoles inside living mammalian cells under photocatalytic conditions.We are thankful for the financial support of Spanish grants: RYC2020-029150-I and “ESF Investing in your future”, RTI2018-093813-J-I00, PID2019-108624RB-I00, and PID2022-137318OB-I00, funded by MCIN/AEI and by “ERDF A way of making Europe”. We also thank MCIN/ISCIII and the “European Union Next Generation EU/PRTR” (Grant IHRC22-00009), the ORFEO–CINQA network (RED2022-134287-T), the Consellería de Cultura, Educación e Ordenación Universitaria (Grant ED431C 2021/25 and Grant ED431G 2019/03: Centro Singular de Investigación de Galicia accreditation 2019-2022), and the European Union (European Regional Development Fund-ERDF corresponding to the multiannual financial framework 2014-2020). Figures have been created with https://BioRender.com.S

    Imagen molecular en el diagnóstico de la amiloidosis cardíaca con 99mTc-ácido 3,3- difosfono-1,2-propanodicarboxílico (99mTc-DPD)

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    La amiloidosis cardíaca es una miocardiopatía in iltrativa, en la que el uso de la gammagrafía con 99mTc-DPD permite su diagnóstico preciso mediante la valoración del área cardíaca con diversos métodos de interpretación. A pesar de las mejoras diagnósticas atribuidas a dichos métodos, persisten algunas limitaciones, como: la falta de un punto de corte estandarizado en el método cuantitativo, las discordancias inter-observador en el semicuantitativo y la falta de estandarización de un protocolo de adquisición de imágenes. El objetivo de esta tesis fue evaluar la rentabilidad diagnóstica de los estudios de imagen molecular y anatómica en pacientes con sospecha de AC y su aplicación en los diferentes subtipos de amiloidosis; así como correlacionarlos con las variables clínico-patológicas de interés

    Improved triamcinolone acetonide-eluting contact lenses based on cyclodextrins and high hydrostatic pressure assisted complexation

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    Contact lenses (CLs) constitute an advantageous platform for the topical release of corticosteroids due to their prolonged contact with the eye. However, the lipophilic nature of corticosteroids hampers CLs' ability to release therapeutic amounts. Two approaches to improve loading and release of triamcinolone acetonide (TA) from poly(2-hydroxyethyl methacrylate)-based hydrogels were investigated: adding 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to the monomers solution before polymerization (HEMA/i-CD) and an hydrogels' post-treatment with HP-β-CD (HEMA/p-CD). The effect of HP-β-CD and sterilization by high hydrostatic pressure (HHP) on the hydrogel properties (water content, oxygen and ion permeability, roughness, transmittance, and stiffness) was evaluated. The HEMA/i-CD hydrogels had stronger affinity for TA, sustaining its release for one day. HHP sterilization promoted the formation of cyclodextrin-TA complexes within the hydrogels, improving their drug-loading capacity »60 %. Cytotoxicity and irritability tests confirmed the safety of the therapeutic CLs. TA released from the hydrogels permeated through ocular tissues ex vivo and showed anti-inflammatory activity. Finally, a previously validated mathematical model was used to estimate the ability of the TA-loaded CLs to deliver therapeutic drug concentrations to the posterior part of the eye. Overall, HP-β-CD-containing CLs are promising candidates for the topical ocular application of TA as an alternative delivery system to intraocular injectionsWork supported by Fundação para a Ciência e a Tecnologia (FCT) through [doi: 10.54499/UIDB/00100/2020] and [doi: 10.54499/UIDP/00100/2020] (CQE), [doi: 10.54499/UIDB/04585/2020] (CiiEM) and [doi:10.54499/PTDC/CTM-CTM/2353/2021] (SOL project), University of Aveiro and FCT/MCT through [UIDB/50006/2020 and UIDP/50006/2020] (LAQV-REQUIMTE) co-funded by the FEDER within PT2020 Partnership Agreement, and MCIN/AEI/10.13039/501100011033 Spain [PID 2020-113881RB-I00], Xunta de Galicia [ED431C 2020/17], and FEDER. The authors acknowledge SICASAL - Indústria e Comércio de Carnes, S.A. for the kind supply of porcine fresh eyes and to Dr. Nuno Taveira from the University of Lisbon for providing THP-1 human monocytes cell line. ASHLAND kindly provided Cavasol® W7 HP PHARMA (HP-β-CD)S

    Cáncer de pulmón microcítico, ocupación y características en nunca fumadores. Aproximación epidemiológica

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    El cáncer de pulmón constituye un problema mundial de salud pública. El cáncer de pulmón de célula pequeña es el tipo histológico que presenta peores datos de supervivencia en la actualidad. Identificar factores de riesgo modificables es fundamental para poder incidir en la disminución de la incidencia de una enfermedad altamente letal. El tabaco es la causa principal pero no es el único factor de riesgo modificable del cáncer de pulmón de célula pequeña. Entre otros destaca la exposición al humo ambiental de tabaco, el radón, el humo de motores diésel y otras sustancias carcinogénicas presentes en el ámbito laboral y en el doméstico. El objetivo principal de esta tesis es valorar el impacto de la ocupación como factor de riesgo de cáncer de pulmón de célula pequeña, de manera independiente al consumo de tabaco

    El liderazgo en la era digital: revisión ética de las teorías de liderazgo organizativo

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    El objetivo es entender las relaciones organizativas entre personas y si las teorías tradicionales de liderazgo responden a los retos del contexto actual. Este está marcado por relaciones digitales y plataformas virtuales que cuestiona elementos relacionales comunicativos como la confianza. Un contexto dominado por los datos y la información ha puesto en duda el papel del líder. La digitalización transforma a las personas y a las organizaciones. Ante la mecanización de las relaciones, la toma de decisiones por agentes máquina y la crisis de los diferentes modelos de gestión organizativa, este trabajo pretende repensar las relaciones a través del liderazgo. Para cuestionar y repensar es necesario hacerlo desde una dimensión ética que proponga reflexiones y posibles soluciones al objetivo de estudio

    Langmuir monolayer studies of non-ionic surfactants and DOTMA for the design of ophthalmic niosomes

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    The worldwide increase in diabetes entails a rise in associated diseases, with diabetic retinopathy on the forefront of the ocular complications. To overcome the challenges posed by ocular barriers, self-assembled nanocarriers have gathered increasing attention in recent years, with niosomes revealing themselves to be suitable for the delivery of a variety of drugs. This study investigated the mechanical properties of Langmuir monolayers comprising cholesterol, Tween 60, and 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), both individually and in binary and ternary systems. The cholesterol monolayer was characterized by an L-shaped isotherm, reflecting two surface aggregation states. Tween 60 exhibited expanded conformation and progressive aggregation, transitioning through a phase change. The addition of cholesterol to Tween 60 resulted in a subtle reduction in surface compressional modulus. The compression isotherms highlighted the stabilizing effect of cholesterol on the monolayer, affecting the film's resistance to compression. The introduction of DOTMA in Tween 60 monolayers revealed concentration-dependent effects, where the compression resistance of the film was proportional to DOTMA concentration. Ternary systems of cholesterol, DOTMA and Tween 60 exhibited unique behavior, with DOTMA enhancing film stability and cholesterol modulating this effect. Temperature and subphase ionic strength variations further exacerbated the effects of DOTMA concentration. Brewster Angle Microscopy confirmed the absence of microdomains in the compressed monolayer, supporting the hypothesis of a monolayer collapse. Overall, the research provided valuable insights into the intricate interactions and mechanical behavior of these surfactant systems and the feasibility of obtaining cationic niosome-based drug delivery.S

    Environmental asymmetries in global value chains: The case of the European automotive sector

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    The European automotive sector is deeply integrated in the EU regional value chain. Each EU member show differences their economic and environmental performance. While central European countries perform more advanced, higher-value and lower-emission tasks, eastern economies specialize in manufacturing and have a higher share of exports from an environmental perspective. However, the environmental effects resulting from automotive production, as well as the distinctions among European economies based on their development levels, remain unexplored. Similarly, the implications of participation in global value chains (GVCs) in this context have not been examined. Therefore, the aim of this paper is to analyze the Environmental Kuznets Curve and the Pollution Haven/Halo Hypothesis in the case of the EU28 automotive sector under a value-added approach. The multi-regional input-output methodology along with a panel data estimation was used to verify the hypotheses. The results verify an inverted-N shape curve for the Kuznets hypothesis. Nevertheless, the results show no evidence of compliance with the haven or halo hypotheses. Moreover, participation in GVCs implies higher environmental impacts. Based on these findings, some policy recommendations are proposed to enhance the sector's circularity and optimize material use throughout the production chainThis research has been supported by the ICEDE research group, to which the authors belong, Galician Competitive Research Group ED431C 2022/15 financed by Xunta de Galicia and project “REVALEC” REFERENCE PID2022 141162NB-I00 Financed by MCIN/AEI/ 10.13039/501100011033/EFRD, EUS

    Acuerdo del Consejo de Gobierno de 10 de junio de 2024 que aprobó el Reglamento de estudios de doctorado de la USC

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    Documento en Galego Data de publicación no taboleiro electrónico da USC o 24/06/2024. Pendente de publicación no DOG

    Spanish–French leech trade and its consequences: From the increase in medical demand to resource depletion and technical innovation

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    This article studies the impact caused by the success and dissemination of Broussais’ theories on the use of leeches as a medical supply on Spanish–French trade relations, as well as its consequences for the Spanish market between 1821 and the 1860s. Analysing the documents produced by the different public administrations, together with newspaper and archival sources in both Spain and France and the literature and legislation of that period, allows us to understand the evolution of this trade and the heavy impact it had on the autochthonous population of this animal resource. The article reveals how, at the beginning of the 1820s, leeches became an important medical supply and how the demand for them increased significantly. This gave rise to a trade relation between Spain and France that led to the overexploitation of the resource, the issuing of regulations on the matter, and the search for technological solutions to increase the production of leechesS

    Determination of the urinary concentrations of six bisphenols in public servants by online solid-phase extraction-liquid chromatography tandem mass spectrometry

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    Bisphenols are widely used as monomers and additives in plastic production. Thus, bisphenol A (BPA) and its most prominent substitutes have been detected in many environmental and human samples. This study proposes an online solid-phase extraction analytical methodology coupled to liquid chromatography with tandem mass spectrometry for the determination of six bisphenols (BPA and bisphenols F (BPF), S (BPS), AF (BPAF), B (BPB), and E (BPE)) in urine samples as an efficient and automated methodology. The method was developed and validated for all bisphenols with good recoveries (92–112%) and repeatability (RSD ≤ 10%) despite the variable matrix effects, except BPAF (which would require a dedicated internal standard), achieving method quantification limits in the 0.05–2.2 ng mL−1 range. The methodology was subsequently applied to 435 urine samples from a non-occupational exposure population (civil servants for the regional government) from Santiago de Compostela (Galicia, Spain). Only BPA, BPF, and BPS were positively detected; the last two presented higher detection frequencies than BPA. When the urinary concentrations are extrapolated to human intake and compared to the European Food Safety Agency (EFSA) tolerable daily intake (TDI) of 2 × 10−4 µg kg−1 day−1 (TDI), all BPA positively identified samples would surpass this threshold. Although no TDI exists currently for the other two identified bisphenols, it is evident that human exposure to bisphenols should be limited. Finally, the results stratification by gender revealed higher levels of exposure to BPF in the women group.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was funded by the Spanish Agencia Estatal de Investigación MCIN/AEI/10.13039/501100011033 (ref. PID2020-117686RB-C32) and Consellería de Cultura, Educación y Universidades da Xunta de Galicia (ref. ED481A-2020/258 and ED431C 2021/06).S

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