Papel de la ICAM-1, COX-2 y el Receptor de Manosa en la modulación de la respuesta estromal durante la metástasis hepática por cáncer colorrectal

xxvi, 229 p.La ICAM-1, la COX-2 y el Receptor de Manosa son moléculas implicadas en el desarrollo tumoral hepático por células de cáncer colorrectal. Las células tumorales colonizan el hígado formando un microambiente tumoral único, en el cual, las poblaciones estromales hepáticas, fibroblastos y macrófagos (HSCs y KCs) juegan un papel clave durante la colonización hepática. Pese a la importancia de estas poblaciones hepáticas, el papel de la ICAM-1, la COX-2 y el Receptor de Manosa apenas se ha estudiado en la formación del microambiente tumoral y en la respuesta estromal hepática

Los organismos de gestión de destino en enoturismo: casos internacionales de éxito

La actividad enoturística ha evolucionado en España de forma más lenta que en otras zonas del mundo, entre otras causas por una gestión de destinos de menor éxito en su implementación. Por ello resulta esencial identificar y analizar casos de éxito enoturístico en organismos de gestión de destinos (OGDs) a nivel internacional, permitiendo formular un conjunto de recomendaciones potencialmente extrapolables a desti‑nos enoturísticos españoles. En un ejercicio de benchmarking se mapea una tríada de variables relevantes. En primer lugar, las variables culturales (“Viejo Mundo” y “Nuevo Mundo”); luego, los distintos niveles adminis‑trativos de gestión (nacional‑regional‑local); y en tercer lugar, el aspecto geográfico, con análisis de casos en tres continentes: Francia, Condado de Sonoma (California, EEUU), y Cabo Wineland (Sudáfrica). Con este acopio de datos y un análisis de la situación del enoturismo en España se formulan algunas propuestas de mejora potencialmente aplicables a la gobernanza y gestión en destinos enoturísticos españoles.Wine tourism has developed in Spain at a slower rate than elsewhere, because of a less success‑ful destination management approach among other reasons. In this framework, it is relevant to identify and analyse successful wine tourism destinations worldwide, as their policy and governance practice may be inspiring even for destination management organizations and entrepreneurs in Spain. A benchmark‑ing exercise is thus carried out – taking into consideration cultural and institutional variables as well as geolocation characteristics – for case studies in France, Sonoma County (California, U.S.A.) and Cape Wineland (South Africa). A comparison of best practices there and for wine tourism (enotourism) in Spain permits to enunciate some conclusions and recommendations

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

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

Coronavirus disease 2019 in patients with rheumatic immune-mediated diseases in a single university hospital, matched case-control study and literature review

Background: COVID-19 may present different degrees of severity. Viral infections in patients with rheumatic inflammatory diseases (R-IMID) trend to present more severe disease. However, data comparing the severity of the disease between R-IMID and the general population are scarce. Objectives: To compare predisposing factors, clinical, serological features, and severity of COVID-19 infection in patients with and without R-IMID. Methods: Case-control study in a single University Hospital. We included all consecutive patients with a diagnosis of an R-IMID and COVID-19 infection up to March 31st, 2021. This cohort was compared to patients without R-IMID and not receiving immunosuppressive therapy, matched for sex and age (±5 years). Confirmed infection was defined if a patient had a positive nasopharyngeal swab for SARS-CoV-2. Severity was divided into mild, moderate, severe and critical according to the United States National Institute of Health (NIH) guidelines. Results: We included 274 R-IMID patients (185 women/89 men), mean age 59.1 ± 18 years. More frequent R-IMID were: Rheumatoid arthritis (28.8%), Psoriatic Arthritis (20.1%), axial Spondyloarthritis (12.4%), Polymyalgia Rheumatica (8%) and Systemic Lupus Erythematosus (8%). Hypertension and dyslipidemia were more frequent in patients with R-IMID. Although most of the cases were mild, critical cases and deaths were more frequent in R-IMID. When adjusted by comorbidities, no statistical differences were observed. Conclusion: R-IMID have a very similar clinical presentation when compared to the general population. There is a trend to an increased severity of the disease in patients with R-IMID

SHARDS: A global view of the star formation activity at z~0.84 and z~1.23

In this paper, we present a comprehensive analysis of star-forming galaxies (SFGs) at intermediate redshifts (z~1). We combine the ultra-deep optical spectro-photometric data from the Survey for High-z Absorption Red and Dead Sources (SHARDS) with deep UV-to-FIR observations in the GOODS-N field. Exploiting two of the 25 SHARDS medium-band filters, F687W17 and F823W17, we select [OII] emission line galaxies at z~0.84 and z~1.23 and characterize their physical properties. Their rest-frame equivalent widths (EW$_{\mathrm{rf}}$([OII])), line fluxes, luminosities, star formation rates (SFRs) and dust attenuation properties are investigated. The evolution of the EW$_{\mathrm{rf}}$([OII]) closely follows the SFR density evolution of the universe, with a trend of EW$_{\mathrm{rf}}$([OII])$\propto$(1+z)$^3$ up to redshift z~1, followed by a possible flattening. The SF properties of the galaxies selected on the basis of their [OII] emission are compared with complementary samples of SFGs selected by their MIR and FIR emission, and also with a general mass-selected sample of galaxies at the same redshifts. We demonstrate observationally that the UVJ diagram (or, similarly, a cut in the specific SFR) is only partially able to distinguish the quiescent galaxies from the SFGs. The SFR-M$_*$ relation is investigated for the different samples, yelding a logarithmic slope ~1, in good agreement with previous results. The dust attenuations derived from different SFR indicators (UV(1600), UV(2800), [OII], IR) are compared and show clear trends with respect to both the stellar mass and total SFR, with more massive and highly star-forming galaxies being affected by stronger dust attenuation.Comment: Replaced to match the accepted version (24 pages, 1 table, 17 figures). Published in ApJ, 812, 155 (2015): http://stacks.iop.org/0004-637X/812/15

Metodología de la ecoinnovación PDCA, aplicada al prototipo de fachada vegetal aljibe Naturpanel en el Proyecto SOS-Natura

Este artículo expone la metodología de trabajo desarrollada en las investigaciones del Departamento de Construcción y Tecnología Arquitectónicas de la UPM, basada en el concepto de ecoinnovación, y en la normativa AENOR de Ecodiseño (UNE-EN ISO 14006), en normativas relacionadas como la UNE-EN ISO 9001 y 14001, entre otras. Dicha metodología considera los aspectos medioambientales desde las primeras fases de la investigación, para aumentar la ecoeficiencia de las propuestas producidas, de manera que satisfagan las necesidades humanas y proporcionen una mejor calidad de vida, a la vez que reduzcan progresivamente los impactos ambientales y la intensidad de consumo de recursos a lo largo de su ciclo de vida, hasta un nivel, al menos, en línea con la capacidad de asimilación de la Tierra. El objetivo de esta comunicación es explicar y dar a conocer, mediante ejemplos concretos, dicha metodología; los beneficios de la misma y cómo influye su utilización en el diseño arquitectónico de fachadas vegetales

Evaluación formativa entre pares. Experiencias en todos los niveles universitarios

[ES] El objetivo de este trabajo es describir tres tipos de experiencia de evaluación entre pares diseñados con el fin de mejorar no solo el aprendizaje de las materias, sino también las competencias profesionales tanto de evaluados como de evaluadores. Otro de los fines fue estimular la reflexión de los docentes implicados para que, tras un debate sobre las ventajas e inconvenientes del proceso, generasen protocolos y repertorios de buenas prácticas transferibles entre asignaturas y campos de conocimiento. El primer tipo de experiencia, llevada a cabo entre estudiantes en grupos pequeños o medianos en once asignaturas de grado y máster, consistió en la evaluación de trabajos en grupo escritos y/o de sus exposiciones orales. La segunda, realizada entre pares de alumnos en gran grupo, se centró en pruebas “clásicas” escritas utilizadas como parte de la evaluación formativa de una asignatura. Por último, en la tercera experiencia profesores expertos evaluaron la actuación docente de sus pares noveles. Tras concluir las fases de preparación, evaluación y recogida de resultados de las mismas, y a falta del análisis final de los datos de las encuestas de satisfacción y el rendimiento académico, podemos decir que los resultados parecen prometedores: se ha producido un aumento de la motivación y la familiarización con instrumentos de evaluación como las escalas de valoración. Los participantes parecen haber mejorado también sus competencias comunicativas, su capacidad reflexiva y “habilidades blandas” (soft skills) como la capacidad crítica y la colaboración, además de avanzar en su autonomía personal y profesional. Como conclusión, podemos decir que este es un paso adelante en la búsqueda de experiencias de evaluación eficaces desde el punto de vista formativo, sostenibles para el sistema universitario, el docente y la asignatura, y transferibles entre asignaturas de todos los niveles educativos

Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune Mediated Inflammatory Diseases. A Multicenter Study

We aimed to assess the e cacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 13.9 years). The underlying diseases were Bechet?s disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean SD BCVA (0.8 0.3 LogMAR vs. 0.6 0.3 LogMAR; p = 0.03), mean SD RNFL (190.5 175.4 m vs. 183.4 139.5 m; p = 0.02), mean SD MT (270.7 23.2 m vs. 369.6 137.4 m; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10?61.5) mg/day at baseline to. 2.5 (0?5) mg/day after one year of follow-up; p = 0.001. After a mean SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is e ective in patients with refractory non-MS ON

The Spatial parameters of gait and their association with falls, functional decline and death in older adults: a prospective study

Association between spatial gait parameters and adverse health outcomes in the elderly has not been sufficiently studied. The goal of this study is to evaluate whether the stride length or the step width predict falls, functional loss and mortality. We conducted a prospective cohort study on a probabilistic sample of 431 noninstitutionalized, older-than-64-years subjects living in Spain, who were followed-up for five years. In the baseline visit, spatial gait parameters were recorded along with several control variables, with special emphasis on known medical conditions, strength, balance and functional and cognitive capacities. In the follow-up calls, vital status, functional status and number of falls from last control were recorded. We found that a normalized-to-height stride length shorter than 0.52 predicted recurrent falls in the next 6 months with 93% sensitivity and 53% specificity (AUC: 0.72), and in the next 12 months with 81% sensitivity and 57% specificity (AUC: 0.67). A normalized stride length <0.5 predicted functional loss at 12 months with a sensitivity of 79.4% and specificity of 65.6% (AUC: 0.75). This predictive capacity remained independent after correcting for the rest of risk factors studied. Step-with was not clearly related to functional loss or falls. Both shorter normalized stride length (OR1.56; AUC: 0.62; p < 0.05) and larger step width (OR1.42; AUC: 0.62; p < 0.05) were associated with risk of death at 60 months; however, none of them remained as independent predictor of death, after correcting for other risk factors. In summary, spatial gait parameters may be risk markers for adverse outcomes in the elderly. Step length is independently associated with functional loss and falls at one year, after correction for numerous known risk factors