PROTO-COL. La experiencia de una red interuniversitaria para la formación en protocolo y eventos (2010-2014)

En este proyecto de innovación docente denominado “Proto-col: red interuniversitaria de trabajo colaborativo en protocolo y gestión de eventos” se ha realizado durante los cursos académicos 2010-2011, 2011-2012, 2012-2013 y 2013-2014 un ejercicio de reflexión, en primer término, sobre la idoneidad del perfil de los estudiantes en protocolo y gestión de eventos, a partir de los nuevos Grados en Publicidad y Relaciones Públicas ofertados por la Universidad de Alicante y la Universitat Jaume I de Castellón; en segundo término, sobre la metodología didáctica aplicada en las asignaturas optativas vinculadas a dicho ámbito formativo, e integradas en las nuevas propuestas educativas, así como diferentes investigaciones exploratorias sobre la presencia de materias vinculadas a la gestión de eventos, el protocolo y las relaciones institucionales en las universidades españolas. Todas estas aportaciones, junto con la dirección de TFGs, TFMs y direcciones de tesis doctorales reflejan el trabajo en red de un grupo de profesores especializados en esta materia y justifica la pertinencia de este proyecto interuniversitario que se ha traducido en diversas contribuciones académicas y experiencias docentes

Inhibition of COX-2 Impairs Colon Cancer Liver Metastasis through Reduced Stromal Cell Reaction

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE 2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE 2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.This work was supported by the Department of Industry and Research of the Basque Government SAIOTEK SPE12UN075 and S-PE11UN043 to B.A., IT-487-09 to E.O., and by the Spanish Science and Technology Ministry MINECOR18/P32

Liver sinusoidal endothelial cell ICAM-1 mediated tumor/endothelial crosstalk drives the development of liver metastasis by initiating inflammatory and angiogenic responses

The prometastatic stroma generated through tumor cells/host cells interaction is critical for metastatic growth. To elucidate the role of ICAM-1 on the crosstalk between tumor and primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), implicated in tumor adhesion and angiogenesis, we performed in vitro cocultures and an in vivo model of liver metastasis of colorectal cancer (CRC). ICAM-1 blockade in the LSECs decreased the adhesion and transmigration of tumor cells through an LSEC in vitro and vivo. Cocultures of C26 cells and LSECs contained higher amounts of IL-1 beta, IL-6, PGE-2, TNF-alpha and ICAM-1 than monocultures. C26 cells incubated with sICAM-1 secreted higher amounts of PGE-2, IL-6, VEGF, and MMPs, while enhanced the migration of LSECs and HSCs. HSCs cultures activated by media from C26 cells pretreated with sICAM-1 contained the largest amounts of VEGF and MMPs. C26 cell activation with sICAM-1 enhanced their metastasizing potential in vivo, while tumor LFA-1 blockade reduced tumor burden and LSECs and HSC-derived myofibroblasts recruitment. In vivo ICAM-1 silencing produced similar results. These findings uncover LSEC ICAM-1 as a mediator of the CRC metastatic cascade in the liver and identifies it as target for the inhibition of liver colonization and metastatic progression.This work has been supported by a predoctoral grant from the University of the Basque Country to the principal author and from the Department of Industry and Research of the Basque Government SAIOTEK S-PE12UN075 and S-PE11UN043 to BA, and IT-487-09 to EO

Silencing of Sinusoidal DDR1 Reduces Murine Liver Metastasis by Colon Carcinoma

Liver metastasis depends on the collagenous microenvironment generated by hepatic sinusoidal cells (SCs). DDR1 is an atypical collagen receptor linked to tumor progression, but whether SCs express DDR1 and its implication in liver metastasis remain unknown. Freshly isolated hepatic stellate cells (HSCs), Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs), that conform the SCs, expressed functional DDR1. HSCs expressed the largest amounts. C26 colon carcinoma secretomes increased DDR1 phosphorylation in HSCs and KCs by collagen I. Inhibition of kinase activity by DDR1-IN-1 or mRNA silencing of DDR1 reduced HSCs secretion of MMP2/9 and chemoattractant and proliferative factors for LSECs and C26 cells. DDR1-IN-1 did not modify MMP2/9 in KCs or LSECs secretomes, but decreased the enhancement of C26 migration and proliferation induced by their secretomes. Gene array showed that DDR1 silencing downregulated HSCs genes for collagens, MMPs, interleukins and chemokines. Silencing of DDR1 before tumor inoculation reduced hepatic C26 metastasis in mice. Silenced livers bore less tumor foci than controls. Metastatic foci in DDR1 silenced mice were smaller and contained an altered stroma with fewer SCs, proliferating cells, collagen and MMPs than foci in control mice. In conclusion, hepatic DDR1 promotes C26 liver metastasis and favors the pro-metastatic response of SCs to the tumor.We would like to acknowledge the following core facilities and individuals for their support: CIC bioGUNE Center for Cooperative Research in Biosciences, University of the Basque Country Animal Core Facility and SGIker Advanced Light Microscopy Core Facility. We thank Iratxe Basaldua for the in situ MMPs assay

Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection

Approximately 25% of elite controllers (ECs) lose their virological control by mechanisms that are only partially known. Recently, immunovirological and proteomic factors have been associated to the loss of spontaneous control. Our aim was to perform a metabolomic approach to identify the underlying mechanistic pathways and potential biomarkers associated with this loss of control. Methods: Plasma samples from EC who spontaneously lost virological control (Transient Controllers, TC, n=8), at two and one year before the loss of control, were comparedwith a control group of ECwho persistently maintained virological control during the same follow-up period (Persistent Controllers, PC, n=8). The determination of metabolites and plasma lipids was performed by GC-qTOF and LC-qTOF using targeted and untargeted approaches. Metabolite levels were associated with the polyfunctionality of HIV-specific CD8+T-cell response. Findings: Our data suggest that, before the loss of control, TCs showed a specific circulating metabolomic profile characterized by aerobic glycolytic metabolism, deregulated mitochondrial function, oxidative stress and increased immunological activation. In addition, CD8+ T-cell polyfunctionality was strongly associated with metabolite levels. Finally, valine was the main differentiating factor between TCs and PCs. Interpretation: All these metabolomic differences should be considered not only as potential biomarkers but also as therapeutic targets in HIV infection.Instituto Carlos III PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186 INT11/240 INT12/282 INT15/226Fondos Europeos para el Desarrollo Regional PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186FEDER PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186FEDER PI10/02635 PI13/00796 PI16/00503 PI12/02283 PI16/00684 CPII014/00025 FI14/00431 FI17/00186Programa de Suport als Grups de Recerca 2017SGR948 2014SGR250Gilead Fellowship Program GLD14/293 GLD17/00299Red de Investigación en Sida RD12/0017/0005 RD16/0025/0006 RD12/0017/0029 RD16/0025/0020Junta de Andalucía C-0032/17Generalitat de Catalunya PERIS SLT002/16/0010

PROTO-COL. Aportaciones de una red interuniversitaria para la formación en protocolo y eventos (2010-2015)

Este proyecto de innovación docente denominado “Proto-col: red interuniversitaria de trabajo colaborativo en protocolo y gestión de eventos” se ha desarrollado durante los últimos cinco cursos académicos (2010-2011, 2011-2012, 2012-2013, 2013-2014, 2014-2015) y constituye en la actualidad un grupo de trabajo consolidado, en el que sus miembros han compartido un ejercicio de reflexión sobre las capacidades, habilidades y destrezas en este ámbito, por parte de los estudiantes de los Grados en Publicidad y Relaciones Públicas ofertados por la Universidad de Alicante y la Universitat Jaume I de Castellón. Para ello, durante estos años, se ha trabajado en el diseño de metodología didáctica aplicada a las asignaturas optativas vinculadas al protocolo y la gestión de eventos, y se han realizado diferentes investigaciones exploratorias sobre perfiles profesionales o la presencia de materias vinculadas a la gestión de eventos, el protocolo y las relaciones institucionales en las universidades españolas. Todas estas aportaciones, junto con la participación en cursos de especialización y másteres universitarios, la realización de proyectos académicos, la dirección de TFGs, TFMs y tesis doctorales reflejan el trabajo colaborativo de un grupo de profesores especializados en esta materia y justifica la pertinencia de este proyecto interuniversitario que se ha traducido en diversas contribuciones académicas y experiencias de enseñanza-aprendizaje

Few-layer antimonene electrical properties

Antimonene -a single layer of antimony atoms- and its few layer forms are among the latest additions to the 2D mono-elemental materials family. Numerous predictions and experimental evidence of its remarkable properties including (opto)electronic, energetic or biomedical, among others, together with its robustness under ambient conditions, have attracted the attention of the scientific community. However, experimental evidence of its electrical properties is still lacking. Here, we characterized the electronic properties of mechanically exfoliated flakes of few-layer (FL) antimonene of different thicknesses (∼ 2–40 nm) through photoemission electron microscopy, kelvin probe force microscopy and transport measurements, which allows us to estimate a sheet resistance of ∼ 1200 Ω sq−1 and a mobility of ∼ 150 cm2V−1s−1 in ambient conditions, independent of the flake thickness. Alternatively, our theoretical calculations indicate that topologically protected surface states (TPSS) should play a key role in the electronic properties of FL antimonene, which supports our experimental findings. We anticipate our work will trigger further experimental studies on TPSS in FL antimonene thanks to its simple structure and significant stability in ambient environmentsWe acknowledge financial support through the “Maríade Maeztu” Programme for Units of Excellence in R&D (CEX2018-000805-M), the Spanish MINECO through projects PCI2018-093081, FIS2016-80434-P, PID2019-109539GB-C43, PID2019- 106268GB-C31 and -C32, MAT2016-77608-C3-1-P and -3-P, MAT2013-46753-C2-2-P and MAT2017-85089-C2-1R, the EU Graphene Flagship funding (Graphene Flagship Core3 881603 and JTC2017/2D-Sb&Ge), the EU via the ERC-Synergy Program (GrantERC-2013-SYG-610256 NANOCOSMOS), the Comunidad Autónoma de Madrid through MAD2D-CM, S2018/NMT-4321 (NanomagCOST-CM) and the European StructuralFunds via FotoArt CM project (S2018/NMT-4367), and the Fundación Ramón Areces. S.P. acknowledges financial support by the VILLUM FONDEN via the Centre of Excellence for Dirac Materials (Grant No. 11744

LDR brachytherapy offers superior tumor control to single-fraction HDR prostate brachytherapy: A prospective study

[Purpose]: To compare the clinical outcomes of single-fraction high-dose-rate (HDR) brachytherapy and single-fraction low-dose-rate (LDR) brachytherapy as the sole treatment for primary prostate cancer. [Material and Methods]: A quasi-randomized study that allocated, from March 2008 to February 2012, 129 low and intermediate risk prostate cancer patients to one single-fraction HDR of 19 Gy (61 patients) or to a 145 Gy 125I LDR permanent implant (68 patients. Biochemical relapse-free survival (bRFS) and overall survival (OS) were compared using the Kaplan–Meier method and Cox regression analysis. [Results]: After a median follow-up of 72 months in the HDR group, 26 patients relapsed, and after a median follow-up of 84 months in the LDR group, 7 patients relapsed (p < 0.0001). The 5-year bRFS was significantly better for the LDR group than for the HDR group (93.7% and 61.1%, respectively) (p < 0.0001). The 5-year OS also was significantly better in the LDR group (95.5% vs. 89.9%) (p = 0.0436). [Conclusions]: Permanent LDR prostate implant brachytherapy offers better clinical outcomes than single-fraction HDR for prostate cancer.Peer reviewe

Randomized controlled trial evaluating the benefit of a novel clinical decision support system for the management of COVID-19 patients in home quarantine: A study protocol

Producción Científica(1) Background: We present the protocol of a randomized controlled trial designed to evaluate the benefit of a novel clinical decision support system for the management of patients with COVID-19. (2) Methods: The study will recruit up to 500 participants (250 cases and 250 controls). Both groups will receive the conventional telephone follow-up protocol by primary care and will also be provided with access to a mobile application, in which they will be able to report their symptoms three times a day. In addition, patients in the active group will receive a wearable smartwatch and a pulse oximeter at home for real-time monitoring. The measured data will be visualized by primary care and emergency health service professionals, allowing them to detect in real time the progression and complications of the disease in order to promote early therapeutic interventions based on their clinical judgement. (3) Results: Ethical approval for this study was obtained from the Drug Research Ethics Committee of the Valladolid East Health Area (CASVE-NM-21-516). The results obtained from this study will form part of the thesis of two PhD students and will be disseminated through publication in a peer-reviewed journal. (4) Conclusions: The implementation of this telemonitoring system can be extrapolated to patients with other similar diseases, such as chronic diseases, with a high prevalence and need for close monitoring.Junta de Castilla y León e Instituto de Salud Carlos III - (grant COV20/00539

PROTO-COL. Red interuniversitaria para la formación en protocolo, eventos y relaciones institucionales (2010-2016)

Este proyecto de innovación docente denominado “Proto-col: red interuniversitaria de trabajo colaborativo en protocolo y gestión de eventos” se ha desarrollado durante los últimos seis cursos académicos (2010-2011, 2011-2012, 2012-2013, 2013-2014, 2014-2015, 2015-2016) y constituye en la actualidad un grupo de trabajo consolidado, en el que sus miembros han compartido un ejercicio de reflexión sobre las capacidades, habilidades y destrezas en este ámbito, por parte de los estudiantes de los Grados en Publicidad y Relaciones Públicas ofertados por la Universidad de Alicante, la Universitat Jaume I de Castellón, y la Universidad Miguel Hernández (a través de su centro adscrito IMEP), con la implantación del Grado en Organización de Eventos, Protocolo y Relaciones Institucionales desde el curso 2012-2013 y del Máster Universitario como posgrado desde el curso 2013-2014. Para ello, durante todos estos años, se ha trabajado en el diseño de propuestas educativas y metodología didáctica aplicada a las asignaturas vinculadas al protocolo, la gestión de eventos y las relaciones institucionales. Se han realizado diferentes investigaciones exploratorias sobre perfiles profesionales y la presencia de materias vinculadas al protocolo, la gestión de eventos y las relaciones institucionales en las universidades españolas. Todas estas aportaciones, junto con la participación en cursos de especialización y másteres universitarios, la realización de proyectos académicos, la dirección de TFGs, TFMs y tesis doctorales reflejan el trabajo colaborativo de un grupo de profesores especializados en esta materia y justifica la pertinencia de este proyecto interuniversitario que se ha traducido en diversas contribuciones académicas y experiencias de enseñanza-aprendizaje