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

A 3D Sensor Based on a Profilometrical Approach

An improved method which considers the use of Fourier and wavelet transform based analysis to infer and extract 3D information from an object by fringe projection on it is presented. This method requires a single image which contains a sinusoidal white light fringe pattern projected on it, and this pattern has a known spatial frequency and its information is used to avoid any discontinuities in the fringes with high frequency. Several computer simulations and experiments have been carried out to verify the analysis. The comparison between numerical simulations and experiments has proved the validity of this proposed method

Complications and treatment of dens in dente: case report

Dens in dente is an anomaly of dental development characterized by focal or multifocal invaginations of the enamel in the dental papilla before its mineralization, it can result in additional layers of enamel, cementum, dentin or pulp tissue, it is also known as invaginated tooth or invaginated odontoma. The clinical case of an 18-year-old female patient is presented, she comes to the clinic for referring halitosis and purulent exudate for 1 month, a clinical and radiographic examination of tooth 22 was performed, a radiopaque invagination line was observed that penetrates the portion radicular in the cervical third, wide radiolucent area in the apical third, sinuous course and purulent exudate. Root canal treatment was performed with a flexible rotary system and canal obturation with a lateral technique and vertical compaction, restored with resin

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

Mutational Landscape of CEBPA in Mexican Pediatric Acute Myeloid Leukemia Patients: Prognostic Implications

BackgroundIn Mexico, the incidence of acute myeloid leukemia (AML) has increased in the last few years. Mortality is higher than in developed countries, even though the same chemotherapy protocols are used. CCAAT Enhancer Binding Protein Alpha (CEBPA) mutations are recurrent in AML, influence prognosis, and help to define treatment strategies. CEBPA mutational profiles and their clinical implications have not been evaluated in Mexican pediatric AML patients.Aim of the StudyTo identify the mutational landscape of the CEBPA gene in pediatric patients with de novo AML and assess its influence on clinical features and overall survival (OS).Materials and MethodsDNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing of CEBPA was performed in 80 patients.ResultsCEBPA was mutated in 12.5% (10/80) of patients. Frameshifts at the N-terminal region were the most common mutations 57.14% (8/14). CEBPA biallelic (CEBPABI) mutations were identified in five patients. M2 subtype was the most common in CEBPA positive patients (CEBPAPOS) (p = 0.009); 50% of the CEBPAPOS patients had a WBC count &gt; 100,000 at diagnosis (p = 0.004). OS &gt; 1 year was significantly better in CEBPA negative (CEBPANEG) patients (p = 0.0001). CEBPAPOS patients (either bi- or monoallelic) had a significantly lower OS (p = 0.002). Concurrent mutations in FLT3, CSF3R, and WT1 genes were found in CEBPAPOS individuals. Their contribution to poor OS cannot be ruled out.ConclusionCEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of CEBPAPOS was in the range reported for pediatric AML (4.5–15%). CEBPA mutations showed a negative impact on OS as opposed to the results of other studies

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.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe