Organoids and colorectal cancer

Organoids were first established as a three‐dimensional cell culture system from mouse small intestine. Subsequent development has made organoids a key system to study many human physiological and pathological processes that affect a variety of tissues and organs. In particular, organoids are becoming very useful tools to dissect colorectal cancer (CRC) by allowing the circumvention of classical problems and limitations, such as the impossibility of long‐term culture of normal intestinal epithelial cells and the lack of good animal models for CRC. In this review, we describe the features and current knowledge of intestinal organoids and how they are largely contributing to our better understanding of intestinal cell biology and CRC genetics. Moreover, recent data show that organoids are appropriate systems for antitumoral drug testing and for the personalized treatment of CRC patients.The work in the authors’ laboratory is funded by the Agencia Estatal de Investigación (PID2019‐104867RB‐I00/AEI/10.13039/501100011033), the Ministerio de Ciencia e Innovación (SAF2017‐90604‐REDT/NuRCaMeIn), and the Instituto de Salud Carlos III—Fondo Europeo de Desarrollo Regional (CIBERONC/CB16/12/00273, CIBERONC/CB16/12/00398 and ICI20/00057)

Clinico-pathological features, outcomes and impacts of COVID-19 pandemic on patients with early-onset colorectal cancer: A single-Institution Experience

The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. Methods: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old. Results: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%). Conclusions: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determinedThe work in the authors’ laboratory is funded by the Instituto de Salud Carlos III (ISCIII) and the Fondo Europeo de Desarrollo Regional (FEDER) (ICI20/00057, CIBERONC/CB16/12/00273, and CIBERONC/CB16/12/00398), as well as the Comunidad de Madrid (S2022/BMD-7212

Leadership, self-concept and sex: a deep analysis of transformational leadership

Una parte de la investigación sobre liderazgo se ha centrado en los efectos del liderazgo transformacional (TF) y transaccional (TA) en el autoconcepto del propio líder. Esta investigación se ha focalizado esta cuestión, debido a la importancia que encierra. Si se distingue qué tipo de liderazgo conlleva poseer un autoconcepto más positivo, es decir, una mayor autoestima, podremos concluir que existe una forma de liderar que, al menos en ese aspecto, es más recomendable. Según Sosik y Cameron (2010), el líder transformacional poseerá una personalidad más ascética y una excelencia moral; y por ello, un autoconcepto más positivo. Además, también analizaremos si existe diferencia en cuanto al sexo a la hora de ejercer un tipo de liderazgo u otro; pues se espera que las mujeres tiendan a desarrollar un liderazgo más transformacional (Eagly y col., 1992). Utilizando como muestra a 56 profesores/as de secundaria de Granada procedimos a pasar una serie de instrumentos que miden el tipo de liderazgo y el autoconcepto, con el fin de poner a prueba nuestras hipótesis. Finalmente, éstas fueron contrastadas, pues se encontró una clara tendencia por parte de las mujeres al liderazgo transformacional, además de comprobar que éste conllevaba un mayor autoconcepto personal y social en las personas que lo elegían como forma de liderazgo a ejercer.Part of the research about leadership has been focused on the effects that both transformational and transactional leadership have on the leader’s self-concept. This study is focused on that question, due to the importance that it has nowadays. Thus, if we can determine which form of leadership is related to a more positive self-concept, we will be able to conclude that it actually exists a way to lead that is more advisable than others, at least in this respect. Sosik and Cameron (2010) claim that transformational leaders have a more ascetic personality and also a moral excellence, so their self-concept will be more positive. Also, we will analyze the difference between men and women when it comes to lead: we expect that women tend to develop a transformational leadership (Eagly et al., 1992). For that aim, it was drawn a sample of 56 secondary school teachers from Granada, who had to complete different tests about their form of leadership and their self-concept. We finally found that, in general, women tend to have a transformational leadership, and this kind of leadership is related to a better self-concept, both social and personal.Universidad de Granada. Departamento de Psicología Social. Proyecto de Innovación Docente ReiDoCre

Hepatic encephalopathy-associated cerebral vasculopathy in acute-on-chronic liver failure: Alterations on endothelial factor release and influence on cerebrovascular function

The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F releases were increased, whereas thromboxane (TX) B was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI synthase, and TXA S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE. 1α 2 2 2This research was funded by the Ministerio de Economía y Competitividad (SAF2016-80305-P), CiberCV (Grant number: CB16/11/00286), the European Regional Development Grant (FEDER) (Comunidad de Madrid, grant number B2017/BMD- 3676), and R C D projects for young researchers, Universidad Autónoma de Madrid-Comunidad de Madrid (SI1-PJI-2019- 00321). RR-D received a fellowship from Juan de la Cierva Program (IJCI-2017-31399)

Supplementation with the Symbiotic Formulation Prodefen® Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats

In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen® (108 colony forming units/day, 4 weeks). Prodefen® diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen®. Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen®, through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen® caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen® could be an interesting non-pharmacological approach to ameliorate hypertensionThis research was funded by CiberCV (Grant number: CB16/11/00286), the Ministerio de Ciencia e Innovación (PID2020-116498RB-I00, and CDTI -Center for Industrial Technological Development-project PID 2020-FEDER Funds), and R+D projects for young researchers, Universidad Autónoma de Madrid-Comunidad de Madrid (SI1-PJI-2019-00321

Starkeya nomas sp. nov., a prosthecate and budding bacterium isolated from an immunocompromized patient

Strain HF14-78462T is an environmental bacterium found in clinical samples from an immunocompromized patient in 2014 at Hospital Universitari i Politècnic La Fe (Valencia, Spain). Phenotypically, strain HF14-78462T cells were Gram-stain-negative, aerobic, non-spore forming and non-motile small rods which formed mucous and whitish-translucent colonies when incubated at 20-36 °C. Phylogenetic analyses based on the 16S rRNA genes and the whole genomes of closest sequenced relatives confirmed that strain HF14-78462T is affiliated with the genus Starkeya. The strain was oxidase, catalase and urease positive; but indole, lysine decarboxylase, ornithine decarboxylase and DNase negative, did not produce H2S and was able to utilize a wide variety of carbon sources including acetamide, adonitol, amygdalin, l-arabinose, citric acid, glucose, mannitol and melibiose. Unlike Starkeya novella and Starkeya koreensis, strain HF14-78462T failed to grow in thiosulphate-oxidizing media and had a narrower temperature growth range. Its genome was characterized by a size of 4.83 Mbp and a C+G content of 67.75 mol%. Major fatty acids were C18:1 ω7c, cyclo C19 : 0 and C16 : 0, its polar acids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an aminophospholipid; while the ubiquinones were Q9 (1.8 %) and Q10 (98.2 %). Digital DNA-DNA hybridization values were 41 and 41.4 against S. novella and S. koreensis, respectively, while average nucleotide identity values were around 84 %. Phenotypic, average nucleotide identity and phylogenomic comparative studies suggest that strain HF14-78462T is a new representative of the genus Starkeya and the name Starkeya nomas sp. nov. is proposed. The type strain is HF14-78462T (=CECT 30124T=LMG 31874T).Financial support was obtained by the IIS project 2013/0437.S

Local wind speed forecasting based on WRF-HDWind coupling

[EN] Wind speed forecasts obtained by Numerical Weather Prediction models are limited for fine interpretation in heterogeneous terrain, in which different roughnesses and orographies occur. This limitation is derived from the use of low-resolution and grid-box averaged data. In this paper a dynamical downscaling method is presented to increase the local accuracy of wind speed forecasts. The proposed method divides the wind speed forecasting into two steps. In the first one, the mesoscale model WRF (Weather Research and Forecasting) is used for getting wind speed forecasts at specific points of the study domain. On a second stage, these values are used for feeding the HDWind microscale model. HDWind is a local model that provides both a high-resolution wind field that covers the entire study domain and values of wind speed and direction at very located points. As an example of use of the proposed method, we calculate a high-resolution wind field in an urban-interface area from Badajoz, a South-West Spanish city located near the Portugal border. The results obtained are compared with the values read by a weathervane tower of the Spanish State Meteorological Agency (AEMET) in order to prove that the microscale model improves the forecasts obtained by the mesoscale model

CX3CL1–CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis

Background: The CX3CL1–CX3CR1 axis has been related to numerous diseases. The aim of our study was to investigate its involvement in coeliac disease (CD) pathogenesis, particularly in the early phase of the disease. Methods: We collected peripheral blood from CD patients and controls, enrolled in a 3-day gluten challenge, to study soluble CX3CL1, I-TAC and MIG by Luminex, CX3CL1 and CX3CR1 gene expression by qPCR, and CX3CR1 protein expression in monocytes and CD8+, CD4+ and γδ+ T cells, by flow cytometry. We also analysed the expression of the CX3CL1 and CX3CR1 mRNA and protein in the duodenal biopsies of CD patients with active and treated disease, and in non-CD control individuals, by qPCR and immunohistochemistry. Results: After the gluten challenge, increased levels of CX3CL1, I-TAC and MIG proteins were observed in the peripheral blood of CD patients, with no changes in CX3CL1 mRNA, or CX3CR1 mRNA and protein. Regarding duodenal tissue, CX3CL1 was absent or barely present in the superficial and basal epithelium of CD patients, contrasting with the moderate to high levels present in controls. Conclusions: CX3CL1 seems to be involved in the appearance and progression of CD, and it appears to be a potential diagnostic biomarker. Its use as an alternative therapeutic target in CD deserves further research

Cultura urbana en televisión. Programa cultural realizado por profesores y alumnos de la Facultad de Ciencias de la Información

Con un enfoque para la docencia que plantea una universidad basada en el entusiasmo y en la participación a través de un modelo de aprendizaje que motive y sepa entusiasmar a los estudiantes, planteamos como proyecto de innovación para mejora de la calidad docente la creación de un programa de televisión sobre la cultura urbana vinculado a las asignaturas de: - "Producción y realización publicitaria" (Grado en Publicidad y Relaciones Públicas) - "Realización publicitaria" (Grado en Comunicación Audiovisual) - "Dirección cinematográfica" (Grado en Comunicación Audiovisual) - "Realización televisiva" (Grado en Comunicación Audiovisual) Y a los TFG relacionados con las áreas de conocimiento de realización y producción.Se crearían tres categorías en las que los alumnos podrían participar con sus trabajos: rodajes,reportajes audiovisuales y reportajes fotográficos y spots publicitarios. Los alumnos, tras haber pasado por alguna de las asignaturas o TFG propuestos, con sus respectivas prácticas, ya tienen un training que les capacita para sacar adelante un trabajo colaborativo, un proyecto y además les forma en las competencias profesionales necesarias para el trabajo en equipo. Además, el proyecto incluye la creación de una web y un laboratorio audiovisual (que ya está en marcha) para la difusión de los trabajos presentados y como herramienta para ampliar la proyección profesional y académica de los alumnos. El reto es poner Internet al servicio de la capacidad creativa y técnica de los estudiantes como fórmula para descubrir el nuevo talento, para poder experimentar con un nuevo medio al alcance de todos, y para conseguir una muy amplia difusión. Internet, lo interactivo, lo virtual y lo on-line serían las grandes herramientas para la realización de este proyecto. Es una experiencia de trabajo en el que varias asignaturas se unen y en el que la planificación y la nota final de cada una de las asignaturas se consolidan un proyecto real para dar a conocer el funcionamiento del mundo laboral. Es un proyecto de integración de varias asignaturas que suman un conjunto de experiencias en los que la innovación es la primera premisa

El practicum como espacio de aprendizaje profesional para docentes en formación del Grado de Maestro en Educación Infantil y Educación Primaria

Memoria ID-0189. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017