Clinical and demographic factors in endometrial and ovary carcinoma: Synchronous carcinoma vs stage IIIA endometrial carcinoma

Objective: To compare pre-surgical demographic and clinical factors and preoperative serum tumor marker values of patients with endometrial and ovarian synchronous carcinoma with those diagnosed with endometrial carcinoma with metastatic ovarian involvement (FIGO stage IIIA). Methods: A retrospective observational study including patients with endometrial and ovarian malignant tumors that were treated at Miguel Servet University Hospital, Zaragoza, Spain, since January 2000 to June 2020. All pathologic specimens were reviewed by two pathologists specialized in gynecological oncology. Results: Overall, 51 patients were included. 24 cases of them, were endometrial and ovarian synchronous primary carcinomas and the remaining 27 cases were endometrial tumors with adnexa. Parity, personal and family oncological history, arterial hypertension, diabetes, dyslipidemia, obesity and the prior use of hormone replacement therapy did not show significant differences between both groups. Age (p = 0.002), menopausal status (p = 0.029), abnormal uterine bleeding (p = 0.001), Ca 12.5 preoperative serum level (p = 0.038) and Ca 19.9 preoperative serum level (0.028) were factors with significant differences between both groups. In multivariate analysis, only abnormal uterine bleeding and Ca 19.9 values were independents factors. Conclusions: The presence of abnormal uterine bleeding and Ca 19.9 preoperative serum level could guide the clinician in the preoperative differential diagnosis between endometrial cancer with ovarian involvement and endometrial and ovarian synchronous carcinoma. © 2021 The Author(s)

El aprendizaje del Derecho Procesal en los estudios de Grado

El presente trabajo refleja los resultados obtenidos en la red docente titulada “El Aprendizaje del Derecho Procesal en los Estudios de Grado”. En esta Red docente profesoras de Derecho Procesal de la Universidad de Alicante analizan el empleo de una serie de herramientas del Campus Virtual en la enseñanza de diferentes asignaturas de grado y de licenciatura con el objetivo de estudiar las distintas experiencias que generan en los alumnos. Con ello se pretende optimizar las herramientas docentes que funcionan con los alumnos en los procesos de enseñanza-aprendizaje y descartar aquellas otras de las que no se deriven un resultado adecuado. En definitiva, se pretende reflexionar sobre esta materia apuntada con el objetivo de mejorar el sistema de aprendizaje, potenciar el aprendizaje autónomo del alumno, elaborar instrumentos de evaluación de conocimientos, destrezas y habilidades y detectar las posibles deficiencias que presentan las herramientas docentes del Campus Virtual, realizando en relación con este último extremo una serie de propuestas que permitan mejorarlas en beneficio de toda la comunidad universitaria

Alberta Stroke Program Early CT Score applied to CT angiography source images is a strong predictor of futile recanalization in acute ischemic stroke

The final publication is available at Springer via http://dx.doi.org/10.1007/s00234-016-1652-7Introduction Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization. Methods Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, timelapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability). Results Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT+MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3–0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5–1.2). A score ≤5 in CTA-SIASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %). Conclusions CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapie

Identification of EP300 as a Key Gene Involved in Antipsychotic-Induced Metabolic Dysregulation Based on Integrative Bioinformatics Analysis of Multi-Tissue Gene Expression Data

Antipsychotics (APs) are associated with weight gain and other metabolic abnormalities such as hyperglycemia, dyslipidemia and metabolic syndrome. This translational study aimed to uncover the underlying molecular mechanisms and identify the key genes involved in AP-induced metabolic effects. An integrative gene expression analysis was performed in four different mouse tissues (striatum, liver, pancreas and adipose) after risperidone or olanzapine treatment. The analytical approach combined the identification of the gene co-expression modules related to AP treatment, gene set enrichment analysis and protein-protein interaction network construction. We found several co-expression modules of genes involved in glucose and lipid homeostasis, hormone regulation and other processes related to metabolic impairment. Among these genes, EP300, which encodes an acetyltransferase involved in transcriptional regulation, was identified as the most important hub gene overlapping the networks of both APs. Then, we explored the genetically predicted EP300 expression levels in a cohort of 226 patients with first-episode psychosis who were being treated with APs to further assess the association of this gene with metabolic alterations. The EP300 expression levels were significantly associated with increases in body weight, body mass index, total cholesterol levels, low-density lipoprotein cholesterol levels and triglyceride concentrations after 6 months of AP treatment. Taken together, our analysis identified EP300 as a key gene in AP-induced metabolic abnormalities, indicating that the dysregulation of EP300 function could be important in the development of these side effects. However, more studies are needed to disentangle the role of this gene in the mechanism of action of APs. Keywords: EP300; antipsychotics; gene; gene expression; metabolic syndrome; microarray; pharmacogenetics; weight gain

Genome-wide phenotypic RNAi screen in the Drosophila wing: Global parameters

We have screened a collection of UAS-RNAi lines targeting 10,920 Drosophila protein-coding genes for phenotypes in the adult wing. We identified 3653 genes (33%) whose knockdown causes either larval/pupal lethality or a mutant phenotype affecting the formation of a normal wing. The most frequent phenotypes consist of changes in wing size, vein differentiation, and patterning, defects in the wing margin and in the apposition of the dorsal and ventral wing surfaces. We also defined 16 functional categories encompassing the most relevant aspect of each protein function and assigned each Drosophila gene to one of these functional groups. This allowed us to identify which mutant phenotypes are enriched within each functional group. Finally, we used previously published gene expression datasets to determine which genes are or are not expressed in the wing disc. Integrating expression, phenotypic and molecular information offers considerable precision to identify the relevant genes affecting wing formation and the biological processes regulated by the

Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics

In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality 'in silico' of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original

Desarrollo de una App para el Grado de Publicidad y Relaciones Públicas como Sistema de Evaluación y Mejora Continua de la Calidad

Elaboración de una aplicación informática para conseguir mayor interacción con los alumnos y su opinión sobre la calidad del plan docente del grado de Publicidad y Relaciones Públicas

Metodología para tutorización y elaboración de trabajos de fin de grado en las líneas de Derecho procesal propuestas en las titulaciones-EEES de la UA

Se presenta a la Comunidad Universitaria una reflexión sobre el impacto práctico que desde el pasado curso académico 2014-2015 ha supuesto la implementación de la asignatura Trabajo de Fin de Grado en las líneas de Derecho Procesal propuestas en las titulaciones EEES de la Universidad de Alicante de Grado en Derecho, Grado en Criminología, Grado en Derecho y Administración de Empresas, y Grado en Gestión y Administración Pública. El estudio pone de manifiesto una serie de deficiencias formales y materiales que se conocen tras la puesta en común de la casuística experimentada por las investigadoras, en calidad de tutoras individuales de los/las alumnos/as que han cursado dicha asignatura; además, se concluye con una propuesta concreta de modelo de tutorización, basada, de un lado en una motivación del/la alumno/a desde la docencia cooperativa, y de otro lado, en la colaboración entre tutores

Abacavir increases purinergic P2X7 receptor activation by ATP: does a pro-inflammatory synergism underlie its cardiovascular toxicity?

16 p.-9 fig.-1 tab.The cardiovascular toxicity of Abacavir is related to its purinergic structure. Purinergic P2X7-receptors (P2X7R), characterized by activation by high concentrations of ATP and with high plasticity, seem implicated. We appraise the nature of the interplay between Abacavir and P2X7R in generating vascular inflammation. The effects of Abacavir on leukocyte-endothelium interactions were compared with those of its metabolite carbovir triphosphate (CBV-TP) or ATP in the presence of apyrase (ATP-ase) or A804598 (P2X7R-antagonist). CBV-TP and ATP levels were evaluated by HPLC, while binding of Abacavir, CBV-TP and ATP to P2X7R was assessed by radioligand and docking studies. Hypersensitivity studies explored a potential allosteric action of Abacavir. Clinical concentrations of Abacavir (20 µmol/L) induced leukocyte-endothelial cell interactions by specifically activating P2X7R, but the drug did not show affinity for the P2X7R ATP-binding site (site 1). CBV-TP levels were undetectable in Abacavir-treated cells, while those of ATP were unaltered. The effects of Abacavir were Apyrase-dependent, implying dependence on endogenous ATP. Exogenous ATP induced a profile of proinflammatory actions similar to Abacavir, but was not entirely P2X7R-dependent. Docking calculations suggested ATP-binding to sites 1 and 2, and Abacavir-binding only to allosteric site 2. A combination of concentrations of Abacavir (1 µmol/L) and ATP (0.1 µmol/L) that had no effect when administered separately induced leukocyte-endothelium interactions mediated by P2X7R and involving Connexin43 channels. Therefore, Abacavir acts as a positive allosteric modulator of P2X7R, turning low concentrations of endogenous ATP themselves incapable of stimulating P2X7R into a functional proinflammatory agonist of the receptor.This work was supported by Ministerio de Economía y Competitividad and the European Regional Development fund of the European Union (FEDER) (SAF2015–67678-R, RTI2018-094436-B-I00 and CTQ2017-88353-R), Ministerio de Sanidad y Consumo (CB06/04/0071, CIBERehd) and Generalitat Valenciana (PROMETEOII/2014/035 and PROMETEO 2018/141), along with an unrestricted grant from GILEAD S.L. VCD and ASL were funded by VALI + D program from Generalitat Valenciana (grants number ACIF/2015/316 and ACIF/2016/119, respectively) and PGM by FPU program from Ministerio de Educación, Cultura y Deporte (grant number FPU16/06064) and MABR by FPU program from Ministerio de Ciencia, Innovación y Universidades (grant number FPU17/04249).Peer reviewe

The polygenic basis of relapse after a first episode of schizophrenia

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11–0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse