Estudio del receptor 2 de la dopamina en ovario humano y efecto de su modulación sobre el Síndrome de Hiperestimulación Ovárica

El síndrome de hiperestimulación ovárica (SHO) es una complicación iatrogénica derivada del uso de gonadotropinas exógenas para la inducción de la ovulación que cursa durante la fase lútea o el embarazo, pudiendo causar graves efectos sobre la salud e incluso la muerte. El uso de agonistas del receptor 2 de la dopamina (DrD2) se ha visto efectivo en el tratamiento de SHO, sin embargo tan solo se obtienen resultados beneficiosos en el 50% de los casos de SHO temprano, mientras que es totalmente inefectivo en los casos de SHO tardío. Para tratar de establecer los mecanismos moleculares que dan lugar a esta situación, se ha llevado a cabo una descripción a nivel histológico de la expresión del DrD2 en ovario humano a lo largo del ciclo y a su vez un estudio in Vitro de la modulación del sistema dopaminérgico sobre las células de la granulosa humanas. Los resultados obtenidos nos han proporcionado evidencias de que los agonistas dopaminérgicos a través de DrD2 son capaces de inhibir la secreción de VEGF por parte de las células de la granulosa en cultivo, mientras que la expresión de DrD2 en ovario humano varía a lo largo del ciclo ovárico, existiendo una disminución de tal expresión en el cuerpo lúteo tardío. Todos estos hallazgos podrían justificar las diferentes respuestas observadas en el tratamiento del SHO con agonistas dopaminérgicos.The Ovarian Hyperstimulation Syndrome (OHSS) is an iatrogenic complication raised after exogenous administration of gonadotrophins for ovulation induction in assisted reproduction techniques. The syndrome appears during luteal phase or pregnancy and can result in serious life threatening or even lethal complications. Dopamine D2 receptor (DrD2) agonists have been reported as an effective treatment for OHSS but only in 50% of early OHSS cases and non effective in late form of the syndrome. In order to establish the molecular mechanism responsible for this differential effectiveness, we have performed the histological description of DrD2 expression in human ovary through the menstrual cycle as well as the in vitro modulation of dopaminergic system of human granulosa cells. Results obtained give us the evidence of dopamine agonists inhibits the hCG-mediated VEGF secretion in human granulosa cells through DrD2 activation, while histological ovarian DrD2 expression fluctuates throughout menstrual cycle decreasing in the late corpus luteum. All these findings could explain the different responses to DrD2 agonists observed among patients treated for OHSS

Material principles and economic relations underlying Neolithic axe circulation in Western Europe

Neolithic societies produced and circulated axeheads made out of different rock types over substantial distances. These tools were indispensable to their economic reproduction, but they also demanded considerable manufacturing efforts. The material properties of the raw materials chosen to produce axeheads had a direct effect on the grinding and polishing processes, as well as on the use life of these tools. However, surprisingly little is known about the criteria followed by these societies when it came to choosing adequate raw materials, or why certain rocks were exploited in greater volumes and circulated over larger distances than others. In order to determine the material parameters ruling axe production, circulation, and use, a range of different rock types was submitted to mechanical tests. For the first time, comparative values relating to the resistance to friction and to breakage are presented for some of the most important rock types used for the manufacture of axeheads by the Neolithic communities of Western Europe. These mechanical parameters allow us to approach hypothetical production and use values, which are then correlated with the distances travelled and the volumes of rock in circulation. This combination of petrographic, mechanical, and paleo-economic information leads to new understandings of the principles ruling Neolithic supply and distribution networks and the economic rationale behind them. It reveals how deeply the economic and symbolic meanings of these outstanding Neolithic artefacts were rooted in their production and use values.Peer ReviewedPostprint (author's final draft

SORL1 polymorphisms in Mexican patients with Alzheimer\u27s disease

The present study evaluated the risk effect of 12 Single Nucleotide Polymorphisms in the SORL1 gene in the Mexican population using Late-Onset Alzheimer\u27s Disease (LOAD) and control subjects. Considering APOE as the strongest genetic risk factor for LOAD, we conducted interaction analyses between single nucleotide polymorphisms (SNPs) and the APOE genotype. METHODS: Patients were interviewed during their scheduled visits at neurologic and geriatric clinics from different institutions. The LOAD diagnosis included neurological, geriatric, and psychiatric examinations, as well as the medical history and neuroimaging. Polymorphisms in RESULTS: The A/A genotype in rs1784933 might be associated with an increased LOAD risk. Two blocks with high degree linkage disequilibrium (LD) were identified. The first block composed by the genetic variants rs668387, rs689021 and rs641120 showed a positive interaction (mainly the rs689021) with rs1784933 polymorphism. Moreover, we found a significant association between the CONCLUSION: The rs1784933 polymorphism is associated with LOAD in Mexican patients. In addition, the presence o

Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells

During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC

A collaboratively derived environmental research agenda for Galapagos

Galápagos is one of the most pristine archipelagos in the world and its conservation relies upon research and sensible management. In recent decades both the interest in, and the needs of, the islands have increased, yet the funds and capacity for necessary research have remained limited. It has become, therefore, increasingly important to identify areas of priority research to assist decision-making in Galápagos conservation. This study identified 50 questions considered priorities for future research and management. The exercise involved the collaboration of policy makers, practitioners and researchers from more than 30 different organisations. Initially, 360 people were consulted to generate 781 questions. An established process of preworkshop voting and three rounds to reduce and reword the questions, followed by a two-day workshop, was used to produce the final 50 questions. The most common issues raised by this list of questions were human population growth, climate change and the impact of invasive alien species. These results have already been used by a range of organisations and politicians and are expected to provide the basis for future research on the islands so that its sustainability may be enhanced. </jats:p

La sustancia de la representación: esencia y significado

Catálogo de la exposición colectiva celebrada en la sala de exposiciones de la Facultad de Bellas Artes de la Universidad Complutense de Madrid entre el 5 y el 20 de marzo de 2018. La exposición denominada “LA SUSTANCIA DE LA REPRESENTACIÓN. ESENCIA Y SIGNIFICADO” tiene como objetivo mostrar las obras más relevantes y personales de treinta y tres artistas pertenecientes a la facultad de Bellas Artes de la Universidad Complutense de Madrid. Comisariada por Mauro Hernández, Sandra Malvar y Rodrigo Moreno

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.