Disfunción sexual como efecto adverso de la quimioterapia en mujeres con cáncer de mama

Introducción: la disfunción sexual se considera un efecto secundario de la quimioterapia, aspecto importante para las pacientes en la fase libre de enfermedad; momento donde los profesionales sanitarios encuentran un desafío en la atención al paciente por la intimidad del tema. Objetivos: aportar y conocer datos sobre la disfunción sexual y aspectos relacionados, en mujeres que han sufrido cáncer de mama y que alternativas y apoyos tienen para solucionarlos. Metodología: se desarrolló un estudio descriptivo transversal. Se recogieron datos personales y sobre su calidad de vida mediante diferentes encuestas. La imagen corporal se mide mediante la escala de Imagen Corporal de Hopwood, la autoestima con la escala de RSES y la disfunción sexual con la escala de FSFI. Las variables cuantitativas se describieron con su media y desviación típica, y las cualitativas con su porcentaje. Resultados: de la muestra de 30 mujeres, prevalecen aquellas casadas durante el tratamiento. La mayoría presentó no tener disfunción sexual y un nivel de autoestima elevado-normal, y muy pocas presentaron alteración en su imagen corporal. Ninguna de las variables recogidas estuvo dentro del rango de normalidad y las diferencias entre ellas resultó ser no significativa estadísticamente. Conclusiones: la disfunción sexual en las mujeres con cáncer de mama es un aspecto poco estudiado. No existen datos concluyentes sobre el tema, pero otros estudios destacan su importancia, dato a tener en cuenta por los profesionales de salud así como la falta de una encuesta “gold standard”

Rings, Hexagons, Petals, and Dipolar Moment Sink-Sources: The Fanciful Behavior of Water around Cyclodextrin Complexes

The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to design new products and to optimize their use. Computational simulations are well suited to fill this gap, especially in the case of CD systems due to their low number of degrees of freedom compared with typical macromolecular systems. Thus, the design and validation of solid and efficient methods to simulate and analyze CD-based systems is key to contribute to this field. The behavior of supramolecular complexes critically depends on the media where they are embedded, so the detailed characterization of the solvent is required to fully understand these systems. In the present work, we use the inclusion complex formed by two α-CDs and one sodium dodecyl sulfate molecule to test eight different parameterizations of the GROMOS and AMBER force fields, including several methods aimed to increase the conformational sampling in computational molecular dynamics simulation trajectories. The system proved to be extremely sensitive to the employed force field, as well as to the presence of a water/air interface. In agreement with previous experiments and in contrast to the results obtained with AMBER, the analysis of the simulations using GROMOS showed a quick adsorption of the complex to the interface as well as an extremely exotic behavior of the water molecules surrounding the structure both in the bulk aqueous solution and at the water surface. The chirality of the CD molecule seems to play an important role in this behavior. All together, these results are expected to be useful to better understand the behavior of CD-based supramolecular complexes such as adsorption or aggregation driving forces, as well as to introduce new methods able to speed up general MD simulationsThis work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (RTI2018-098795-A-I00), and by the Xunta de Galicia and the ERDF (ED431C 2017/25 and Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09). P.F.G. is funded by a predoctoral research grant (BES-2016-076761) from the Spanish Ministry of Economy and Competitiveness and the European Social Fund. M.C. is funded by a predoctoral fellowship from Xunta de Galicia. R.G.-F. is a “Ramón y Cajal” fellowship (RYC-2016-20335) from the Ministerio de Ciencia, Innovación y UniversidadesS

Effect of water models on transmembrane self-assembled cyclic peptide nanotubes

Self-assembling cyclic peptide nanotubes can form nanopores when they are inserted in lipid bilayers, acting as ion and/or water permeable channels. In order to improve the versatility of these systems, it is possible to specifically design cyclic peptides with a combination of natural and non-natural amino acids, enabling the control of the nature of the inner cavity of the channels. Here, the behavior of two types of self-assembling peptide motifs, alternating α-amino acids with γ- or δ-aminocycloalkanecarboxylic acids, is studied via molecular dynamics (MD) simulations. The behavior of water molecules in nanopores is expected to affect the properties of these channels and therefore merits detailed examination. A number of water models commonly used in MD simulations have been validated by how well they reproduce bulk water properties. However, it is less clear how these water models behave in the nanoconfined condition inside a channel. The behavior of four different water models—TIP3P, TIP4P, TIP4P/2005, and OPC—are evaluated in MD simulations of self-assembled cyclic peptide nanotubes of distinct composition and diameter. The dynamic behavior of the water molecules and ions in these designed artificial channels depends subtly on the water model used. TIP3P water molecules move faster than those of TIP4P, TIP4P/2005, and OPC. This demeanor is clearly observed in the filling of the nanotube, in water diffusion within the pore, and in the number and stability of hydrogen bonds of the peptides with water. It was also shown that the water model influences the simulated ion flux through the nanotubes, with TIP3P producing the greatest ion flux. Additionally, the two more recent models, TIP4P/2005 and OPC, which are known to reproduce the experimental self-diffusion coefficient of bulk water quite well, exhibit very similar results under the nanoconfined conditions studied here. Because none of these models have been parametrized specifically for waters confined in peptide nanotubes, this study provides a point of reference for further validationThis work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (CTQ2016-78423-R, PID2019-111126RB-100, and RTI2018-098795-A-I00) and by the Xunta de Galicia and the ERDF (ED431F 2020/05, ED431C 2017/25, and Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09). M.C. thanks Xunta de Galicia for a predoctoral fellowship (ED481A-2017/068). R.G.-F. thanks Ministerio de Ciencia, Innovación y Universidades for a Ramón y Cajal contract (RYC-2016- 20335). Research in MSPS’s group is supported by EPSRC (EP/R004722/1; EP/V010948/1) BBSRC (BB/R00126X/1) and Wellcome Trust (208361/Z/17/Z)S

Highly Enantioselective Iridium(I)-Catalyzed Hydrocarbonation of Alkenes: A Versatile Approach to Heterocyclic Systems Bearing Quaternary Stereocenters

We report a versatile, highly enantioselective intramolecular hydrocarbonation reaction that provides a direct access to heteropolycyclic systems bearing chiral quaternary carbon stereocenters. The method, which relies on an iridium(I)/bisphosphine chiral catalyst, is particularly efficient for the synthesis of five-, six- and seven-membered fused indole and pyrrole products, bearing one and two stereocenters, with enantiomeric excesses of up to >99 %. DFT computational studies allowed to obtain a detailed mechanistic profile and identify a cluster of weak non-covalent interactions as key factors to control the enantioselectivityThis work received financial support from the Spanish MINECO (SAF2016-76689-R, PID2019-108624RB-I00, CTQ2017-84767-P, PID2020-118579GB-I00), the Xunta de Galicia (ED431C 2017/19, 2015-CP082, Centro Singular de Investigación de Galicia accreditation 2019-2022, ED431G 2019/03, a predoctoral Fellowship to A. A. and M. C. and a postdoctoral Fellowship to D. F. F, ED481B-2019-005) and the ERDF, ERC (Adv. Grant No. 340055). The Orfeo-Cinqa network (CTQ2016-81797-REDC)S

Iridium(I)-Catalyzed Intramolecular Cycloisomerization of Enynes: Scope and Mechanistic Course

NOTICE: This is the peer reviewed version of the following article: David F. Fernández, Catarina A. B. Rodrigues, Martín Calvelo, Moisés Gulías, José L. Mascareñas and Fernando López (2018), Iridium(I)-Catalyzed Intramolecular Cycloisomerization of Enynes: Scope and Mechanistic Course. ACS Catalysis, 2018, 8 (8), 7397–7402 [DOI: 10.1021/acscatal.8b02139]. This article may be used for non-commercial purposes in accordance with American Chemical Society Terms and Conditions for self-archivingWe report an Ir(I)-catalyzed cycloisomerization methodology that provides access to carbocyclic systems bearing exo-alkene moieties from alkynyl-equipped acyclic precursors. The method relies on the C–H activation of olefinic and (hetero)aromatic C(sp2)–H bonds, followed by an exocyclization to a tethered alkyne, and provides interesting cyclic diene products that are amenable of further elaboration. Importantly, DFT calculations suggests that, in contrast to related hydrocarbonations of alkenes in which either migratory insertions or C–C reductive eliminations have been suggested to be rate-determining, in our reactions, the energetic barrier of these steps is lower than that of the previous C–H activationThis work received financial support from the Spanish MINECO (Nos. SAF2016-76689-R, CTQ2016-77047-P, and CTQ2017-84767-P, as well as an FPI fellowship to D.F.F.), the Xunta de Galicia (Nos. ED431C 2017/19 and 2015-CP082, as well as Centro Singular de Investigación de Galicia accreditation 2016-2019 ED431G/09 and predoctoral fellowship to M.C.), the ERDF, ERC (Adv. Grant No. 340055) and the Orfeo-Cinqa network (No. CTQ2016-81797-REDC). Dr. Rebeca García-Fandiño is acknowledged for helpful suggestions on DFT studiesS

Pd-Catalyzed (3 + 2) Heterocycloadditions between Alkylidenecyclopropanes and Carbonyls: Straightforward Assembly of Highly Substituted Tetrahydrofurans

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Catalysis, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acscatal.0c01827A Pd catalyst made from a Pd(0) source and a bulky biaryl phosphine ligand promotes highly efficient intramolecular (3 + 2) heterocycloadditions between alkylidenecyclopropanes (ACPs) and carbonyls. The annulations provide a straightforward access to fused polycyclic systems featuring β-methylene tetrahydrofuran moieties. DFT data support a pallada–ene process and shed light on the critical role of hemilabile interactions between the Pd center and the bulky biaryl phosphine. Significantly, these Pd(0) catalysts are also effective for promoting intermolecular formal cycloadditions between ACPs and trifluoromethyl ketones, thus providing for a direct entry to chiral tetrahydrofuran moieties (THFs) bearing trifluoromethyl–substituted carbonsThis work received financial support from the Spanish MINECO (SAF2016-76689-R, CTQ2017-84767-P), the Xunta de Galicia (ED431C 2017/19, 2015-CP082, Centro Singular de Investigación de Galicia accreditation 2019-2022, ED431G 2019/03, and a predoctoral Fellowship to E.d.C. and M.C.), CONICYT (grant to F.V.), and the ERDF, ERC (Adv. Grant 340055). The Orfeo–Cinqa network (CTQ2016-81797-REDC) is also acknowledgedS

Human O-GlcNAcase Uses a Preactivated Boat-skew Substrate Conformation for Catalysis. Evidence from X-ray Crystallography and QM/MM Metadynamics

Human O-linked β-N-acetylglucosaminidase (hOGA) is one of the two enzymes involved in nuclear and cytoplasmic protein O-GlcNAcylation, an essential post-translational modification. The enzyme catalyzes the hydrolysis of the GlcNAc-O-(Ser/Thr) glycosidic bonds via anchimeric assistance through the 2-acetamido group of the GlcNAc sugar. However, the conformational itinerary of the GlcNAc ring during catalysis remains unclear. Here we report the crystal structure of wild type hOGA in complex with a nonhydrolyzable glycopeptide substrate and elucidate the full enzyme catalytic mechanism using QM/MM metadynamics. We show that the enzyme can bind the substrate in either a chair- or a boat-like conformation, but only the latter is catalytically competent, leading to the reaction products via 1,4B/1S3 → [4E]‡ → 4C1 and 4C1 → [4E]‡ → 1,4B/1S3 conformational itineraries for the first and second catalytic reaction steps, respectively. Our results reconcile previous experimental observations for human and bacterial OGA and will aid the development of more effective OGA inhibitors for diseases associated with impaired O-GlcNAcylation

Real and virtual biological science living laboratory for science teachers' formation : promoting global scientific literacy and critical thinking for sustainable development

Global attempts to renew scientific education aim to stop the decline of young people's interest in science and technology, and to promote the development of citizens' scientific literacy for sustainable development. Among other changes, these aims require the adaptation of K12 Biological Science Teacher’s training to meet the new objectives. Scientific literacy involves knowing science and how knowledge is developed and validated, recognizing the interactions between science, technology and society, that is, the nature of science (NoS; a set of meta-scientific contents that encompass historical, epistemological and sociological aspects of science with great value for scientific education). It also involves grasping of cognitive skills underlying critical thinking (CT; a set of cognitive abilities, including self-regulation and metacognitive processes) and creative problem solving. Therefore, scientific literacy contributes to making informed decisions, facilitating the participation of citizens in situations and dilemmas of scientific tenor. In addition, CT is closely related to the performance of educators in their professional work. Particularly, in the teaching of science, CT skills favour and enhance the learning of concepts and theories linked not only to science but also to the NoS. Considering the current conditions of middle-higher K12 Biological Science Teachers’ formation and classrooms´ limitations in our country and the region, we propose a pilot project aiming to promote the transformation of initial teachers´ training, seeking to improve the development of CT skills and to deepen NoS comprehension. It will involve the immersion of K12 Biological Science Teacher students in Biological Science Living Physical and "mirror" Virtual Reality Laboratories. These laboratories will be equipped with "do it yourself" (DIY), "do it with others" (DIWO) and "bring your own device" (BYOD) technologies for the implementation of research-type activities framed in the philosophy of the "fabrication laboratories". The virtual platform will also comprise a library with didactic resources under permissive licenses to ensure a broader impact. Within these environments, K12 Biological Science Teacher students will engage in the creation of didactic units involving problem solving and knowledge building in parallel to deeper understanding of scientific processes. We also hope to promote the creativity and innovation of the participants, and the appropriation of DIY/DIWO/BYOD and virtual reality technologies as educational resources in the classroom and everyday life. Thanks to the virtual environment, this approach would also allow to reach both National and International K12 Biological Science Teacher students and graduate Biological Science Teachers. Considering the universal access to the Internet and free access to educational platforms in several countries, we also hope to impact on the non-formal and informal Biological Science education and contribute to achieving quality education for all (Objective # 4 of the Agenda for Sustainable Development 2030, UNESCO) beyond geographical and cultural barriers. This pilot project will be implemented by an interinstitutional, multidisciplinary and international team. It will capitalize on confluent groups´ previous experience and complementary strengths in Science didactics (particularly biology), engineering, arts, virtual reality, fabrication, as well as open hardware and open software culture. The experimental approach corresponds to a quasi-experimental pre-test/post-test design with control groups, and formative and summative evaluation. As a result of the implementation of this educational innovation we expect to contribute to the improvement of Biological Science Teachers students´ CT skills and promote their active involvement in practical activities that should enhance their professional activity

Virtualizing university teaching through Open Educational Resources by means of ArcGIS Online (REARGOL)

La pandemia provocada por el virus SARS-CoV-2 (COVID19) ha demostrado la necesidad de acelerar la digitalización de la docencia universitaria. Las herramientas digitales para la transferencia ciencia-educación, que ya eran esenciales para asegurar la calidad de la docencia presencial, se han transformado en imprescindibles cuando las circunstancias han impuesto la docencia virtual. El proyecto REARGOL ha desarrollado y ensayado en ArcGIS online instrumentos para la virtualización de contenidos en asignaturas de grado y máster, sobre geomorfología, gestión de desastres, patrimonio natural y patrimonio cultural. Ha sido un ensayo piloto, replicable en todas las titulaciones y temáticas susceptibles de generar información geoespacial (prácticamente todos los títulos y áreas de conocimiento). El único límite es la imaginación. El proyecto ha priorizado la participación de estudiantes de grado, máster y doctorado, que han desarrollado 4 tipos de aplicaciones: Mapas Web y Web AppBuilder (visores cartográficos interactivos), encuestas Survey 123 (formularios recogida de datos), Cuadros de Mandos (plataformas online que permiten combinar varias aplicaciones) y Story Maps (presentaciones para mostrar conjuntamente información y aplicaciones ArcGIS online). Las aplicaciones que se ensayaron con éxito durante el curso 2020-2021, en asignaturas de grado y máster, así como en TFMs y TFGs, continúan utilizándose en el curso 2021-2022.The SARS-CoV-2 (COVID19) pandemic has shown the urgent need to improve university teaching. Digital resources for Science-Education transfer, which already were crucial for ensuring the quality of face-to-face teaching, turned to be indispensable when the health crisis forced virtual teaching. The REARGOL project has developed and tested ArcGIS Online tools for the virtualization of Bachelor’s and Master’s courses focused on geomorphology, natural disaster management, and natural and cultural heritage. This has been a preliminary test that could be applied to all undergraduate and postgraduate degrees, that can produce geospatial information in all knowledge areas. Imagination is the only constraint. The project has prioritized the participation of undergraduate and postgraduate students (Master and PhD). The project has priorized the participation of undergraduate and postgraduate (Master’s and PhD) students. They have developed four types of applications: Web Maps and Web AppBuilder (interactive cartographical viewers), Survey 123 (data collection forms), Dashboards (online platforms allowing to combine several applications) and Story Maps (presentations for displaying information and ArcGIS online applications). The tools successfully tested during the 2020-2021 academic year are still being used in the current one, in Bachelor’s and Master’s degrees, as well as in Bachelor’s and Master’s final dissertations.Depto. de GeografíaFac. de Geografía e HistoriaFALSEsubmitte