Molecular Mechanisms and Clonal Evolution underlying the Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia: Genomic characterization by Next Generation Sequencing

[ES] Los Síndromes Mielodisplásicos (SMD) son un grupo heterogéneo de enfermedades clonales que afectan a las células madre hematopoyéticas los cuales presentan un curso clínico muy variable, por lo que su diagnóstico, pronóstico y toma de decisiones terapéuticas son todo un reto. En los últimos años, el uso de técnicas de alto rendimiento, como la secuenciación masiva, ha revolucionado la investigación genómica, aumentando nuestro conocimiento sobre las alteraciones moleculares subyacentes a la patogénesis del SMD y mejorando nuestra compresión acerca de los mecanismos implicados en la progresión de la enfermedad. Sin embargo, la ausencia de una combinación eficiente entre genética e información clínica ha limitado la interpretación de los datos de secuenciación y, por consiguiente, la implantación de la secuenciación masiva en la práctica clínica habitual. Por tanto, el objetivo principal de esta tesis es caracterizar los mecanismos moleculares y la evolución clonal que están implicados en la patogénesis del SMD y en la progresión de los SMD a Leucemia Aguda Mieloblástica secundaria (LAMs), tan bien como utilizar los datos moleculares para alcanzar un diagnóstico integrado más fiable y una estratificación pronóstica más precisa. Para ello, la tesis se ha centrado en 3 estudios: - Caracterización del perfil mutacional de los pacientes con SMD que evolucionan a LAMs. - Estudio de la relevancia de las mutaciones de las cohesinas en pacientes con SMD. - Estudio de la significancia del perfil mutacional de la vía de señalización de Ras en la patogénesis del SMD

Hydatidosis simulating a cardiac tumour with pulmonary metastases

AbstractBackgroundThe presence of multiple symptomatic pulmonary nodules and one cardiac tumour in a child requires urgent diagnosis and treatment. Until a few decades ago, the diagnosis of a cardiac tumour was difficult and was based on a high index of suspicion from indirect signs, and required angiocardiography for confirmation. Echocardiography and other imaging techniques have also helped in the detection of cardiac neoplasms. However, it is not always easy to make the correct diagnosis.Clinical caseThe case is presented of a 12-year-old boy with pulmonary symptoms, and diagnosed with a cardiac tumour with lung metastases. The presence of numerous pulmonary nodules was confirmed in our hospital. The echocardiogram detected a solid cardiac nodule in the right ventricle. Magnetic resonance imaging confirmed the findings and the diagnosis. Puncture-aspiration of a lung nodule gave the diagnosis of hydatidosis. He underwent open-heart surgery with cardiac cyst resection and treated with anthelmintics. The lung cysts were then excised, and he recovered uneventfully.DiscussionThis child had multiple pulmonary nodules and a solid cardiac nodule, and was suspected of having a cardiac tumour with pulmonary metastases. However, given the clinical history, background and morphology of pulmonary nodules, another possible aetiology for consideration is echinococcosis. The clinical picture of cardiac hydatidosis and its complications is highly variable. The clinical history is essential in these cases, as well as having a high index of suspicion.ConclusionHydatidosis should be included in the differential diagnosis of a solid, echogenic, cardiac nodule. The treatment for cardiopulmonary hydatid cysts is surgical, followed by anthelmintics

When do tourists really enjoy authentic and exotic food experiences? Product adaptation and tourists’ attitudes

Gastronomy is an essential component of the travel experience.The current paper analyses the extent to which the perceived authenticity in the local food, the degree of adaptation and the cultural contrast determine tourist memorable experiences. Moreover, it proposes the moderating effect of searching for authenticity and adaptation ability. Results from a sample of international tourists in Segovia who tasted a typical dish “cochinillo” (roasted suckling pig) support the positive effect of authenticity and cultural contrast in the perceived experience, whereas the product adaptation reduces the perception of authenticity and cultural contrast. Authenticity has a greater effect on the experience perception when the tourists search for it and individuals are less influenced by the cultural contrast when they are unable to adapt themselves to different cultures.La gastronomía es un componente esencial de la experiencia de los viajeros. El presente trabajo analiza el efecto de la autenticidad percibida y del contraste cultural en la experiencia gastronómica de los turistas. Además, se propone el efecto moderador de la búsqueda de autenticidad y la capacidad de adaptación del turista en dicha relación. Los resultados obtenidos con una muestra de turistas internacionales que han probado la gastronomía típica (cochinillo) de una ciudad con un claro posicionamiento gastronómico-cultural (Segovia) apoya el efecto positivo de la autenticidad y el contraste cultural sobre la experiencia percibida mientras que la adaptación del producto reduce la autenticidad y el contraste cultural. Además, se prueba que la autenticidad posee un efecto mayor sobre la experiencia percibida cuando los turistas realmente la buscan mientras que los individuos con mayor capacidad de adaptación son menos sensibles al contraste cultural de la experiencia

Experience Value or Satiety? The Effects of the Amount and Variety of Tourists’ Activities on Perceived Experience

Producción CientíficaIn recent years, destinations have moved from designing products to focusing on creating experiences that engage and involve the tourist. This study explores the role played by the value of tourist experience and of satiety as mediators between experience intensity and variety as well as future visitor behaviour. Although the intensity and variety of the experience leads tourists to feel their experience has been richer and to appraising it positively, it might also bring unwanted consequences such as a feeling of saturation. The empirical study reveals that the extensiveness of the experience improves the perceived experience value, whereas intensiveness reduces the value and causes satiety in the tourist. Moreover, while the experience value reinforces the intention to return, the intention to recommend and the intensification of the experience, the feeling of satiety, on the other hand, reduces the intention to return and even the intention to recommend the destination.Junta de Castilla y León (proyecto VA112P17)Junta de Castilla y León (proyecto VA085G18)Ministerio de Economía, Industria y competitividad (proyecto ECO 2017-85528-P

La participación de las mujeres en el desarrollo rural y el bienestar social

Women are frequently situated at a risky situation at the rural social environment. Social agents aware of this situation, have to design specific programs to them in order to improve her development and participation. They have to affront not only the economical decadency of their communities but the native culture resistance to social innovation and traditional gender roles change. But in our globalize world, welfare is not possible without taking into account personal wellbeing and human and social capital importance. This article deeps into these topics and suggests possible intervention strategies.La mujer en el entorno rural se encuentra en una situación de vulnerabilidad que obliga a los agentes sociales a la articulación de medidas específicas de desarrollo y participación. Al hecho de encontrarse en un enclave económicamente desprotegido se suele sumar una cultura compartida reticente al cambio y a la innovación en los roles de género. Pero el bienestar social y el desarrollo comunitario no son posibles en nuestro entorno globalizado sin contar con el bienestar individual y la importancia de su capital humano y social. El artículo reflexiona sobre estos temas y aporta posibles estrategias de intervención. 

Photochemical site-selective synthesis of [70]methanofullerenes

Methanofullerenes such as the well-known [70]PCBM are commonly synthesized under harsh conditions to obtain the product as a mixture of site-isomers (namely a, b and minor c) due to the D5h symmetry of the C70 cage. We report the first site-selective synthesis of [70]methanofullerenes under light irradiation and low temperatures, thus avoiding time-consuming and highly expensive HPLC separations. Pure major site-isomers a-[70]PCBM and a-[70]DPM have been thus efficiently prepared including the crystal structure of 5b. Photovoltaic preliminary results revealed a slightly beneficial performance for a-pure [70]PCBM site-isomer devices

Benefits for cardiovascular system, bone density, and quality of life of a long-term hormone therapy in hysterectomized women: a 20-year follow-up study

This study was supervised by Full Professor José Luis Cuadros López, MD, PhD, who directed the menopause unit at Hospital Universitario San Cecilio for more than 30 years. We would like to express our gratitude to all women in his care who trusted him. Sit tibi terra levis. We would like to acknowledge Natalia Aptsiauri, PhD, for reviewing the manuscript.Objective The safety, consequences, and dosage of long-term hormone therapy (HT) for postmenopausal women remain unclear. Our aim was to analyze the effects of HT after 20 years of therapy in women after hysterectomy, focusing on the symptoms of menopause, blood pressure, lipid profiles, and bone density. Methods A prospective observational longitudinal study was designed. The initial transdermal estradiol dose was reduced in half (0.025 mg/d) at 60 years of age. Different parameters including demographic, cardiovascular, bone density, and metabolic variables, as well as quality of life characteristics, were analyzed using bivariate analyses. Multivariate generalized estimating equations for longitudinal data were fitted for differences over time and between doses (<60 vs ≥60 y) using the R package geepack. Results After 20 years of HT, the mean age of 56 studied hysterectomized women was 67.1 years. The mean Kupperman index score decreased from 26.7 to 12.0 (P < 0.001). A trend with total and low-density lipoprotein cholesterol reduction and high-density lipoprotein cholesterol increase was observed over time. A decrease in very-low-density lipoprotein cholesterol (P = 0.05) and an increase in T score vertebral densitometry (P = 0.014) were detected after HT. No changes in health outcome were detected in women older than 60 years with the reduced dose of HT. Breast cancer was the reason for dropouts in 0.02% women. Conclusions HT for up to 20 years after hysterectomy may be beneficial for bone and cardiovascular health and for the overall quality of life. Our data suggest the importance of evaluating the dose and the timing of HT.Projects FEDER and A-BIO-470-UGR20 of University of GranadaFEDER and CAIXA2017/1 of “La Caixa” Foundatio

Does loneliness contribute to mild cognitive impairment and dementia? A systematic review and meta-analysis of longitudinal studies

There is growing evidence that loneliness is associated with mild cognitive impairment (MCI) and dementia. However, the extent of this association remains unclear. A systematic review and meta-analysis of longitudinal studies examining this association was conducted. Six electronic databases were searched from inception to November 15th 2018. A random-effects meta-analysis was performed to obtain pooled estimates and 95% CIs. Studies were also assessed for heterogeneity, methodological quality and publication bias. A total of 4270 hits were retrieved based on the initial search strategy and ten studies met the eligibility criteria involving 37339 individuals (mean age from 64.9 to 83.1 years). Variation between studies was present for the measurement of loneliness as well as for the case ascertainment of MCI and dementia. Loneliness was positively associated with increased risk of dementia (overall RR = 1.26; 95% CI = 1.14, 1.40; n = 8). Due to lack of sufficient data, we could not explore the association between loneliness and risk of MCI through a meta-analysis, but limited evidence suggests a potential effect of loneliness on MCI. A further understanding of the deleterious effects of loneliness on MCI and dementia may assist the design of environmental and psychological interventions to prevent or delay the onset of these neuropsychiatric condition

LABEXNET: un laboratorio de economía experimental en Internet

La Economía Experimental ha desarrollado diferentes experimentos que pueden ser aprovechados como una actividad docente en la enseñanza de la Economía. Su naturaleza activa y participativa motiva a los alumnos y estimula la reflexión y la mejor comprensión de algunos fenómenos económicos como el funcionamiento de los mercados, donde los resultados individuales dependen del conjunto de las decisiones de los agentes y de sus interacciones. Los experimentos económicos tienen ya una larga tradición, y han proporcionado resultados espectaculares y conclusiones ampliamente admitidas sobre la dinámica de mercados y el efecto de las instituciones económicas. Las nuevas tecnologías facilitan la realización y el análisis de estos experimentos. En este artículo presentamos LABEXNET, un programa informático para la realización de experimentos económicos por Internet puesto a libre disposición de la comunidad académica