Structural implications of the DFD-in domain in computer-aided molecular design of MAP kinase interacting kinase 2 inhibitors.

Protein translation is a key process on cell development and proliferation that is often deregulated in cancer. MAP kinase interacting kinases 1 and 2(Mnk1/2) play a pivotal role in regulating the capdependent translation through phosphorylation ofeIF4E transcription factor. Thus, Mnk1/2 targeting have been proposed as a novel therapeutic strategy that would minimize side-effects in contrast to other therapies. For this reason, there is a growing interestin designing in silico new Mnk1/2 inhibitors which demands from reliable structural models. Interestingly,the catalytic domain of Mnk proteins are characterized by a DFD motif instead of the characteristicDFG motif of other kinases. However, Mnk2 structural models described in literature are DFG mutated and do not contain the activation loop. Molecular design techniques have been applied to obtain a structural model of the full wild type Mnk2 protein including the activation loop. The effect of the loop on the interaction mechanism of well-known ligands has been evaluated. Obtained results suggest that the presence of the activation loop is determinant for the correct prediction of the active site and it is essential for the design of new inhibitors

Lipoma of the Uterine Corpus: Exceptional Eventuality Combined with an Ovarian Thecoma

Uterine lipomas are very uncommon with symptoms that are similar to leiomyomas. Their diagnosis is always histological although some radiological methods may suggest their existence prior to surgery. They are sometimes associated with endometrial pathology, but there are no previous reported cases related to ovarian thecoma. Their prognosis is excellent. Clinical, radiological, morphologic, and immunohistochemical findings are shown which correspond to uterine lipoma associated with endometrial polyps and ovarian thecoma

Role of transport performance on neuron cell morphology

The compartmental model is a basic tool for studying signal propagation in neurons, and, if the model parameters are adequately defined, it can also be of help in the study of electrical or fluid transport. Here we show that the input resistance, in different networks which simulate the passive properties of neurons, is the result of an interplay between the relevant conductances, morphology and size. These results suggest that neurons must grow in such a way that facilitates the current flow. We propose that power consumption is an important factor by which neurons attain their final morphological appearance.Comment: 9 pages with 3 figures, submitted to Neuroscience Letter

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future

COVID-19; Bioseguretat; PatologiaCOVID-19; Bioseguridad; PatologíaCOVID-19; Biosafety; PathologyBackground: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. Materials and methods: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. Results: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. Conclusions: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

Neuroglia at the crossroads of homoeostasis, metabolism and signalling: evolution of the concept

Ever since Rudolf Virchow in 1858 publicly announced his apprehension of neuroglia being a true connective substance, this concept has been evolving to encompass a heterogeneous population of cells with various forms and functions. We briefly compare the 19th–20th century perspectives on neuroglia with the up-to-date view of these cells as an integral, and possibly integrating, component of brain metabolism and signalling in heath and disease. We conclude that the unifying property of otherwise diverse functions of various neuroglial cell sub-types is to maintain brain homoeostasis at different levels, from whole organ to molecular

Update of the recommendations for the determination of biomarkers in colorectal carcinoma: National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology

In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplifcation of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly diferentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future

Comparación entre las técnicas de cribado de patología cervical y las conizaciones de tres hospitales en españa

Objetivo: Analizar las características poblacionales y los métodos diagnósticos de patología cervical para la prevención del cáncer de cérvix de tres hospitales españoles para mejorar y unificar los programas de cribado y prevención. Material y métodos: Estudio retrospectivo de las características demográficas y clínicas de 408 mujeres con patología cervical uterina diagnosticadas en 3 hospitales españoles. Se comparan los factores de riesgo, el proceso diagnóstico y la indicación de tratamiento de dos grupos: las que requirieron conización cervical (n=222) y las que no precisaron tratamiento quirúrgico (n=186). También se analizan las recomendaciones vacunales y su grado de cumplimiento. Resultados: Las mujeres conizadas usaron más anticoncepción hormonal y tienen un mayor hábito tabáquico mientras que el número de compañeros sexuales es mayor en pacientes no conizadas. Más del 50% de pacientes con biopsia cervical positiva presentaron un resultado igual o más grave en la anatomía patológica de la pieza quirúrgica. Existen diferencias significativas en sensibilidad y valor predictivo positivo de la citología y de la determinación de HPV entre hospitales. La recomendación de vacunación en ambos grupos fue similar, el porcentaje de mujeres que no la cumplieron fue elevado y significativamente mayor entre pacientes conizadas. Conclusión: En nuestro medio las mujeres conizadas tienen características clínicas y epidemiológicas diferentes a las no conizadas, existen diferencias entre las técnicas diagnósticas de distintos hospitales y sin embargo la concordancia entre biopsia y resultado del cono es elevada. Sigue siendo necesaria una correcta educación sanitaria en relación con la vacunación en mujeres con patología cervical. Background: To analyse the characteristics of the population and diagnostic methods related to the cervical cancer prevention program in three different-level hospitals of a Spanish region in order to improve and unify the screening program. Methods: We retrospectively studied demographic and clinical characteristics of 408 women with cervical lesions diagnosed in three hospitals in Aragon (Spain). Correlation between risk factors, diagnosis process and conisation indication was analysed divided in two groups: conisation required (n=222) or non-conisation (n=186). We also assessed the number of vaccine recommendations made to the patients and the degree of compliance. Results: Conisaited women more frequently used a combined hormonal contraceptive method and are more smokers, while the sexual partners are more in women without conisation. More than 50% of women con positive biopsy was confirmed after surgical treatment. There are significant differences between sensibility and positive predictive value of pap-smear and HPV determination in different hospitals. The recombinant vaccine was recommended to both groups at a similar rate. The percentage of women who were recommended to receive the vaccine but chose not to do it, was high in both groups but significantly higher in the Conisation group. Conclusion: In our environment conisaited women have different clinical and epidemiological profiles, there are differences between diagnosis techniques in different hospitals, however, the concordance between biopsy and definitive result is high. A good sanitary education is necessary in relation with the vaccination of women with cervical pathology