Expresión de KISS1 en embarazo ectópico

La implantación es el proceso por el que el embrión se orienta, adhiere y, finalmente, invade el endometrio materno, siendo un proceso clave para el éxito de la reproducción y desarrollo embrionario. Se requiere una estrecha regulación del proceso para prevenir una invasión patológica o excesiva. Existen grandes similitudes entre el proceso de invasión del citotrofoblasto (implantación) y la invasión de las células cancerígenas. Sin embargo, el proceso de implantación está regulado por una serie de procesos no del todo conocidos, que evitan una invasión celular descontrolada. Uno de los factores implicados en este proceso regulatorio es el gen KISS-1, que codifica una familia de neuropéptidos denominados kisspéptidos, los cuales actúan a través de un receptor, una proteína G llamada GPR54. La expresión del sistema KISS1-GPR54 ha sido demostrada en gran variedad de tejidos entre los que se encuentra la placenta, el hipotálamo, los ganglios basales, la medula espinal, el páncreas y el plasma. Las funciones descritas de los kisspéptidos son variadas, desde intervenir en el eje hipotálamo-hipófisis-gonadal en el desarrollo puberal a la supresión de metástasis en procesos oncológicos. Respecto a su papel en la regulación de la invasión del trofoblasto, considerando la localización de las células en el sinciotiotrofoblasto y su aumento progresivo en plasma durante la gestación, es posible que las kisspeptinas se encuentren implicadas en el mecanismo de regulación de la invasión trofoblástica. Parece ser que actuaría como supresora de este proceso, de forma que sus niveles aumentarían progresivamente durante el embarazo, siendo proporcionales al grado de una correcta implantación. Del mismo modo, gestaciones que cursen con alteraciones de la implantación podrían correlacionarse con una disregulación de este mecanismo, y por tanto con variaciones en los niveles de expresión de estas kisspeptinas, hecho que ya se ha mostrado en la literatura en gestaciones con preeclampsia, retrasos de crecimiento o que acabaron en abortos espontáneos. Dentro de estas alteraciones de la implantación, es de particular interés la gestación ectópica, embarazo que se desarrolla fuera de la cavidad uterina, con alto riesgo de morbimortalidad materna. Hasta el momento no ha sido estudiada la relación del eje KISS1-GPR54-kisspeptinas en este tipo de gestaciones, de demostrarse una desviación respecto a las gestaciones normoevolutivas podría abrirse un nuevo abanico de posibilidades en el diagnóstico y manejo de esta patología

A case report of switching from specific vendor-based to R-based pipelines for untargeted LC-MS metabolomics

Data pre-processing of the LC-MS data is a critical step in untargeted metabolomics studies in order to achieve correct biological interpretations. Several tools have been developed for pre-processing, and these can be classified into either commercial or open source software. This case report aims to compare two specific methodologies, Agilent Profinder vs. R pipeline, for a metabolomic study with a large number of samples. Specifically, 369 plasma samples were analyzed by HPLC-ESI-QTOF-MS. The collected data were pre-processed by both methodologies and later evaluated by several parameters (number of peaks, degree of missingness, quality of the peaks, degree of misalignments, and robustness in multivariate models). The vendor software was characterized by ease of use, friendly interface and good quality of the graphs. The open source methodology could more effectively correct the drifts due to between and within batch effects. In addition, the evaluated statistical methods achieved better classification results with higher parsimony for the open source methodology, indicating higher data quality. Although both methodologies have strengths and weaknesses, the open source methodology seems to be more appropriate for studies with a large number of samples mainly due to its higher capacity and versatility that allows combining different packages, functions, and methods in a single environment

The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications

[Abstract] BACKGROUND: Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. OBJECTIVE: The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and their underlaying molecular mechanisms and to ascertain the diagnostic implications of these changes. STUDY DESIGN: A total of 122 women with normal pregnancy who underwent voluntary termination of pregnancy and 84 patients who experienced tubal ectopic pregnancy were recruited. Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in ectopic pregnancy and voluntary termination of pregnancy control subjects during the early gestational window (<12 weeks). Putative microRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected microRNAs and validation of repressive interactions in vitro. Circulating levels of these microRNAs were also assayed in ectopic pregnancy vs voluntary termination of pregnancy. RESULTS: Circulating kisspeptins gradually increased during the first trimester of normal pregnancy but were reduced markedly in ectopic pregnancy. This profile correlated with the expression levels of KISS1 in human embryonic/placental tissue, which increased in voluntary termination of pregnancy but remained suppressed in ectopic pregnancy. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue at <12 weeks gestation, when expression of microRNAs was low in voluntary termination of pregnancy control subjects but significantly increased in ectopic pregnancy. Yet, a significant repressive interaction was documented only for miR-324-3p, occurring at the predicted 3'-UTR of KISS1. Interestingly, circulating levels of miR-324-3p, but not of miR-27b-3p, were suppressed distinctly in ectopic pregnancy, despite elevated tissue expression of the pre-microRNA. A decision-tree model that used kisspeptin and miR-324-3p levels was successful in discriminating ectopic pregnancy vs voluntary termination of pregnancy, with a receiver-operating characteristic area under the curve of 0.95±0.02 (95% confidence interval). CONCLUSION: Our results document a significant down-regulation of KISS1/kisspeptins in early stages of ectopic pregnancy via, at least partially, a repressive interaction with miR-324-3p. Our data identify circulating kisspeptins and miR-324-3p as putative biomarkers for accurate screening of ectopic pregnancy at early gestational ages.Ministerio de E$conomía y Competitividad (España); BFU2014-57581-PMinisterio de Economía y Competitividad ; BFU2017-83934-PInstituto de Salud Carlos III; PIE-00005Junta de Andalucía; P08-CVI-03788Junta de Andalucía; P12-FQM-0194

Validation of UVEDAI: An Index for Evaluating the Level of Inflammatory Activity in Uveitis

Introduction Uveitis is the inflammation of the middle layer of the eye, the uvea, and is a major cause of blindness. None of the instruments used in clinical practice are, in themselves, sufficient to evaluate the course of uveitis. Therefore, it is necessary to develop instruments enabling standardized measurement of inflammatory activity. We developed a composite disease activity index for patients with uveitis known as UVEDAI, which considers the overall activity of the eye. The objective of this study was to validate the composite index of ocular inflammation, UVEDAI. Methods A multicenter cross-sectional study involving eight Spanish tertiary hospitals. Sixty-two patients aged ≥ 18 years with acute uveitis were recruited. Participants gave informed consent before participating in the study. A full ophthalmological examination was performed by two ophthalmologists to determine inflammatory activity: one used the UVEDAI score and the other used clinical judgment. The ophthalmologists did not share their findings with each other to avoid introducing bias into the analysis. Construct validity was established by means of factor analysis. The criterion validity of the index was determined using an ordinal multivariate regression model, in which the dependent variable was the degree of uveal inflammation (mild, moderate, or high/severe). Cut-off points were determined for the UVEDAI and for the receiver operating characteristic (ROC) curves. Results Sixty-two patients were included. Total variance with the three components accounted for 80.32% of the construct validity. Each of the three components identified one type of eye involvement. The discriminatory capacity of UVEDAI was 0.867 (95% CI 0.778; 0.955 p < 0.001) for mild versus moderate–high and 0.946 (95% CI 0.879; 1.000 p < 0.001) for high versus mild–moderate. Conclusions The variables included in UVEDAI enable ocular inflammatory activity to be described with a high degree of accuracy. The index may be used to evaluate and classify this activity with considerable discriminatory power.We would like to acknowledge the support of Abbvie: this study was conducted with an unrestricted grant from Abbvie. The Spanish Society of Rheumatology is the sponser and funder of this study and the journal's Rapid Service Fee, and has participated in the study design; in the analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had full access to all study data and had final responsibility for the decision to submit the manuscript for publication

Dietary Intake of Advanced Glycation End Products (AGEs) and Mortality among Individuals with Colorectal Cancer

Funding [WCRF 2015/1391, PI: M. Jenab] was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de lEducation Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, the Catalan Institute of OncologyICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vaesterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). V. Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, P-interaction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, P-interaction = 0.003; all-cause, P-interaction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted.Wereld Kanker Onderzoek Fonds (WKOF), World Cancer Research Fund International grant program WCRF 2015/1391World Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDanish Cancer SocietyLigue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de lEducation Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany)Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR)Netherlands GovernmentWorld Cancer Research Fund International (WCRF)Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII)Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of OncologyICO (Spain)Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vaesterbotten (Sweden)Cancer Research UK 14136 C8221/A29017UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1 UK Research & Innovation (UKRI) Medical Research Council UK (MRC)European Commission MR/N003284/1 MC-UU_12015/1Cancer Research UK C864/A14136Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award RR20005

Recuperación de las mujeres en situación de violencia machista de pareja : descripción e instrumentación

Podeu consultar la versió en català de l'any 2013 a: http://hdl.handle.net/11703/91078Aquesta publicació presenta els resultats d'una recerca aplicada, patrocinada per l'Ajuntament de Barcelona, dirigida per la Universitat de Barcelona i realitzada amb la participació de l'Equip d'Atenció a les Dones de la Direcció del Programa de la Dona de l'Ajuntament de Barcelona i gestionat per la Fundació Salut i Comunitat

Wine tourism in La Rioja Alavesa

RESUMEN: Este Trabajo Final de Grado se realizará para la conclusión del Grado en Turismo de la Escuela Universitaria de Turismo Altamira de Santander, estudiará cómo el cultivo de la vid es una actividad tradicional que está estrechamente relacionada con la Comarca de La Rioja-Alavesa. El presente estudio realizará un análisis de la Ruta del Vino, con sus respectivas Denominaciones de Origen, como ha evolucionado este tipo de turismo a lo largo de la historia, las primeras personas que realizaron un viaje para ser conocedoras del vino. Dicho trabajo pretende comprobar si es un producto no estacional, es decir; se podría disfrutar durante todo el año de una amplia oferta de actividades relacionadas con el mundo del vino.ABSTRACT: This Final Degree Project will be carried out for the conclusion of the Degree in Tourism of the Altamira University School of Tourism of Santander, It will be studied how the cultivation of the vine is a traditional activity that is closely related to the Region of La Rioja Alavesa. The present study will carry out an analysis of the Wine Route, with their respective Denomination of Origin, how this type of tourism has evolved throughout history, the first people who made a trip to be wine connoisseurs. This project aims to verify if it is a non-seasonal product, that is, if you could enjoy a wide range of activities related to the world of wine throughout the year.Grado en Turism