Volumen y vascularización angio-power doppler tridimensional de la placenta en relación con la PAPP-A

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Obstetricia y Ginecología. Fecha de lectura: 18-05-2017Esta tesis tiene embargado el acceso al texto completo hasta el 18-11-201

Modeling Cancer Using Zebrafish Xenografts: Drawbacks for Mimicking the Human Microenvironment

The first steps towards establishing xenografts in zebrafish embryos were performed by Lee et al., 2005 and Haldi et al., 2006, paving the way for studying human cancers using this animal species. Since then, the xenograft technique has been improved in different ways, ranging from optimizing the best temperature for xenografted embryo incubation, testing different sites for injection of human tumor cells, and even developing tools to study how the host interacts with the injected cells. Nonetheless, a standard protocol for performing xenografts has not been adopted across laboratories, and further research on the temperature, microenvironment of the tumor or the cell–host interactions inside of the embryo during xenografting is still needed. As a consequence, current non-uniform conditions could be affecting experimental results in terms of cell proliferation, invasion, or metastasis; or even overestimating the effects of some chemotherapeutic drugs on xenografted cells. In this review, we highlight and raise awareness regarding the different aspects of xenografting that need to be improved in order to mimic, in a more efficient way, the human tumor microenvironment, resulting in more robust and accurate in vivo resultsConsellería de Educación, Universidade e Formación Profesional (ED431C 2018/28)S

Multifractal fluctuations of the precipitation in Spain (1960–2019)

Datos de investigación disponibles en: http://www.aemet.es/es/datos_abiertos/AEMET_OpenDataIn this work, an analysis of multifractal parameters of daily precipitation series over the Iberian Peninsula was performed in two 30-year periods to explore whether these properties follow any pattern. Fluctuations of precipitation series show three different scaling regions. Only two distinct regimes for small and large timescales can be confirmed, while intermediate scales are part of a transition region. It is also observed a certain degree of multifractality, which is higher for small timescales. At these scales, there is a high persistence which follows the spatial gradient of the annual precipitation. Moreover, multifractal parameters of the precipitation are modified according to complex spatial and temporal patterns. Only persistence uniformly decreases in the last period. Other relevant findings are the changes in the asymmetry of multifractal spectra in the eastern belt at larger timescales, which might be related to the change in the behavior of the Mediterranean cyclones.Datos de investigación disponibles en: http://www.aemet.es/es/datos_abiertos/AEMET_OpenDaDatos de investigación disponibles en: http://www.aemet.es/es/datos_abiertos/AEMET_OpenD

Analysis of Air Mean Temperature Anomalies by Using Horizontal Visibility Graphs

The last decades have been successively warmer at the Earth’s surface. An increasing interest in climate variability is appearing, and many research works have investigated the main effects on different climate variables. Some of them apply complex networks approaches to explore the spatial relation between distinct grid points or stations. In this work, the authors investigate whether topological properties change over several years. To this aim, we explore the application of the horizontal visibility graph (HVG) approach which maps a time series into a complex network. Data used in this study include a 60-year period of daily mean temperature anomalies in several stations over the Iberian Peninsula (Spain). Average degree, degree distribution exponent, and global clustering coefficient were analyzed. Interestingly, results show that they agree on a lack of significant trends, unlike annual mean values of anomalies, which present a characteristic upward trend. The main conclusions obtained are that complex networks structures and nonlinear features, such as weak correlations, appear not to be affected by rising temperatures derived from global climate conditions. Furthermore, different locations present a similar behavior and the intrinsic nature of these signals seems to be well described by network parameters

Choledocal fasciolasis by Fasciola hepatica in surgery of chronic calculous cholecistitis

Resumen Se reporta un caso de Fasciola hepatica en una mujer de 50 años de edad, natural de Huaral, procedente de un asentamiento humano del distrito de Ate en Lima, con un tiempo de enfermedad de siete días caracterizado al inicio por dolor abdominal tipo cólico de curso progresivo en el epigastrio, dolor que se irradia a hipocondrio derecho. Luego presentó luego náuseas y vómitos en cuatro oportunidades, de contenido alimenticio y bilioso, por lo que se decide su hospitalización previa atención por emergencia. Al examen físico se encontró conjuntivas oculares levemente ictéricas, abdomen balonado, blando, depresible, no visceromegalia, Murphy positivo, ruidos hidroaéreos presentes, tórax y pulmones sin alteraciones. Posteriormente a los exámenes auxiliares, se diagnosticó colecistitis calculosa aguda y fascioliasis coledociana. En el acto quirúrgico se extrajo tres especímenes identificados como Fasciola hepatica. La paciente después de recibir el triclabendazol, concurrió al Hospital para la evaluación y control, habiendo logrado mejoría y bienestar.We report a case of Fasciola hepatica in a 50 year-old woman born in Huaral, Lima, and living in Ate Vitarte, district of Lima, Peru, who was admitted because of seven days of disease characterized by progressive abdominal pain. She visited Ate’s Hospital because of right hipocondrial and epigastric cramping abdominal pain in the morning accompanied by nausea and vomiting in four opportunities. Conjunctives were slightly icteric, abdomen was distended and depressible, there was no visceromegaly, Murphy’s sign was positive, and thorax and lungs showed no alterations. At cholecistectomy three specimens identified as Fasciola hepatica were extracted. Following treatment with triclabendazole, clinical course was uneventful

The Immunomodulatory Properties of Extracellular Vesicles Derived from Probiotics: A Novel Approach for the Management of Gastrointestinal Diseases

Probiotics, included in functional foods, nutritional supplements, or nutraceuticals, exhibit different beneficial effects on gut function. They are extensively used to improve the digestive processes as well as reduce the symptoms and progression of different diseases. Probiotics have shown to improve dysbiosis and modulate the immune response of the host by interacting with different cell types. Probiotics and the host can interact in a direct way, but it is becoming apparent that communication occurs also through extracellular vesicles (EVs) derived from probiotics. EVs are key for bacteria–bacteria and bacteria–host interactions, since they carry a wide variety of components that can modulate different signaling pathways, including those involved in the immune response. Interestingly, EVs are recently starting to be considered as an alternative to probiotics in those cases for which the use of live bacteria could be dangerous, such as immunocompromised individuals or situations where the intestinal barrier is impaired. EVs can spread through the mucus layer and interact with the host, avoiding the risk of sepsis. This review summarizes the existing knowledge about EVs from different probiotic strains, their properties, and their potential use for the prevention or treatment of different gastrointestinal diseases.This work was supported by Junta de Andalucia (Spain) (research grants CTS 164 and PI-0206-2016) and the Spanish Ministry of Economy and Competitiveness (research grant AGL2015-67995-C3-3-R) and cofinanced by the Fondo Europeo de Desarollo Regional (FEDER) from the European Union. JA-MT is a Ph.D. student from the Postgraduate Program Nutricion y Ciencias de los Alimentos at the University of Granada (Spain). The CIBER-EHD is funded by the Instituto de Salud Carlos III

Improving zebrafish embryo xenotransplantation conditions by increasing incubation temperature and establishing a proliferation index with ZFtool

Background Zebrafish (Danio rerio) is a model organism that has emerged as a tool for cancer research, cancer being the second most common cause of death after cardiovascular disease for humans in the developed world. Zebrafish is a useful model for xenotransplantation of human cancer cells and toxicity studies of different chemotherapeutic compounds in vivo. Compared to the murine model, the zebrafish model is faster, can be screened using high-throughput methods and has a lower maintenance cost, making it possible and affordable to create personalized therapies. While several methods for cell proliferation determination based on image acquisition and quantification have been developed, some drawbacks still remain. In the xenotransplantation technique, quantification of cellular proliferation in vivo is critical to standardize the process for future preclinical applications of the model. Methods This study improved the conditions of the xenotransplantation technique – quantification of cellular proliferation in vivo was performed through image processing with our ZFtool software and optimization of temperature in order to standardize the process for a future preclinical applications. ZFtool was developed to establish a base threshold that eliminates embryo auto-fluorescence and measures the area of marked cells (GFP) and the intensity of those cells to define a ‘proliferation index’. Results The analysis of tumor cell proliferation at different temperatures (34 °C and 36 °C) in comparison to in vitro cell proliferation provides of a better proliferation rate, achieved as expected at 36°, a maintenance temperature not demonstrated up to now. The mortality of the embryos remained between 5% and 15%. 5- Fluorouracil was tested for 2 days, dissolved in the incubation medium, in order to quantify the reduction of the tumor mass injected. In almost all of the embryos incubated at 36 °C and incubated with 5-Fluorouracil, there was a significant tumor cell reduction compared with the control group. This was not the case at 34 °C. Conclusions Our results demonstrate that the proliferation of the injected cells is better at 36 °C and that this temperature is the most suitable for testing chemotherapeutic drugs like the 5-FluorouracilThis research was funded by the Fondo de Investigación Sanitaria (Instituto Carlos III) - FIS project (PI13/01388). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing of this manuscriptS

The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition

Critically ill patients have an alteration in the microbiome in which it becomes a disease-promoting pathobiome. It is characterized by lower bacterial diversity, loss of commensal phyla, like Firmicutes and Bacteroidetes, and a domination of pathogens belonging to the Proteobacteria phylum. Although these alterations are multicausal, many of the treatments administered to these patients, like antibiotics, play a significant role. Critically ill patients also have a hyperpermeable gut barrier and dysregulation of the inflammatory response that favor the development of the pathobiome, translocation of pathogens, and facilitate the emergence of sepsis. In order to restore the homeostasis of the microbiome, several nutritional strategies have been evaluated with the aim to improve the management of critically ill patients. Importantly, enteral nutrition has proven to be more efficient in promoting the homeostasis of the gut microbiome compared to parenteral nutrition. Several nutritional therapies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, are currently being used, showing variable results, possibly due to the unevenness of clinical trial conditions and the fact that the beneficial effects of probiotics are specific to particular species or even strains. Thus, it is of great importance to better understand the mechanisms by which nutrition and supplement therapies can heal the microbiome in critically ill patients in order to finally implement them in clinical practice with optimal safety and efficacy.This work was supported by Junta de Andalucía (Spain) (research grants CTS 164 and PI-0206-2016) and cofinanced by the Fondo Europeo de Desarollo Regional (FEDER) from the European Union. RM has a Río Hortega contract (CM17/00237) and PA has a Nicolás Monardes contract (C-0013-2018)

Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer

Background: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell plasticity characteristics to better understand the biology of these cells. Methods: CTCs isolation was carried out in 38 patients with advanced high-grade serous ovarian cancer using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize these cells. Results: Epithelial CTCs were found in 21% of patients, being their presence higher in patients with extraperitoneal metastasis. Importantly, this population was characterized by the expression of epithelial markers as MUC1 and CK19, but also by genes associated with mesenchymal and more malignant features as TIMP1, CXCR4 and the stem markers CD24 and CD44. In addition, we evidenced the relevance of TIMP1 expression to promote tumor proliferation, suggesting its interest as a therapeutic target. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM+ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1Part of this research was supported by CIBERONC funds (CB16/12/00328)S

Beneficial Effects of Limosilactobacillus fermentum in the DCA Experimental Model of Irritable Bowel Syndrome in Rats

Limosilactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, has reported beneficial effects on different gastrointestinal disorders. Moreover, it has shown its ability to restore altered immune responses, in association with microbiome modulation in different pathological conditions. Therefore, our aim was to assess the effects of a Limosilacbacillus fermentum CECT5716 in a rat experimental model of irritable bowel syndrome (IBS) that resembles human IBS. The experimental IBS was induced by deoxycholic acid (DCA) in rats and then, Limosilactobacillus fermentum CECT5716 (109 CFU/day/rat) was administered. Behavioral studies, hyperalgesia and intestinal hypersensitivity determinations were performed and the impact of the probiotic on the inflammatory and intestinal barrier integrity was evaluated. Additionally, the gut microbiota composition was analyzed. Limosilactobacillus fermentum CECT5716 attenuated the anxiety-like behavior as well as the visceral hypersensitivity and referred pain. Moreover, this probiotic ameliorated the gut inflammatory status, re-establishing the altered intestinal permeability, reducing the mast cell degranulation and re-establishing the gut dysbiosis in experimental IBS. Therefore, our results suggest a potential use of Limosilactobacillus fermentum CECT5716 in clinical practice for the management of IBS patients.Junta de Andalucia A-CTS-447-UGR18 CTS 164Instituto de Salud Carlos IIIEuropean Commission PI19/01058 PI20/0144