Cáncer de ovario: cambios en el manejo y en el pronóstico debido a las nuevas clasificaciones FIGO y OMS y análisis de genes reparadores de DNA

[ES]1.Antecedentes El cáncer de ovario (CO) es el más mortal de todos los cánceres ginecológicos. En los últimos años, se han revisado las clasificaciones de la Federación Internacional de Ginecología y Obstetricia (FIGO) y la Organización Mundial de la Salud (OMS). Del mismo modo, en los últimos años, varios estudios moleculares, histopatológicos e inmunológicos han modificado la comprensión de la biología tumoral del cáncer de ovario. En nuestro trabajo hemos comparado los cambios principales entre las clasificaciones y examinado los efectos sobre el tratamiento y el pronóstico del cáncer de ovario, trompas de Falopio y peritoneo en nuestra serie de acuerdo con ambas clasificaciones. Por otro lado, hemos analizado y comparamos polimorfismos de genes reparadores de DNA en pacientes con cáncer de ovario y población sana de la comunidad de Castilla y León, con el fin de comprobar si modifican la susceptibilidad a padecer este tipo de tumor. 2. Materiales y métodos Hemos realizado un estudio observacional descriptivo de 210 pacientes a los que se les diagnosticó un tumor ovárico maligno entre los años 2010 a 2016. Se registraron las clasificaciones aceptadas de la FIGO y la OMS en cada momento. Reclasificamos ambos datos, obteniendo ambas clasificaciones para cada paciente. Se examinaron los cambios en el manejo terapéutico y pronóstico. En la segunda parte de nuestro estudio, realizamos un estudio de asociación en línea germinal de 10 SNPs en genes con importante implicación en vías de carcinogénesis. Incluimos 185 pacientes con cáncer de ovario, seleccionados al azar del Servicio de Ginecología del Complejo Asistencial Universitario de Salamanca - CAUSA y de la consulta de Consejo Genético del Centro de Investigación del Cáncer, que es referencia para pacientes de las provincias de la comunidad de Castilla y León provenientes de León, Zamora, Ávila y Salamanca, entre enero de 2012 y junio de 2018. Incluimos 129 personas de sexo femenino sin cáncer de ovario ni ningún otro tipo de cáncer de la población de Salamanca, como cohorte control. 3. Resultados En ambas clasificaciones de FIGO de nuestra serie de casos, la mayoría de los pacientes con cáncer de ovario se encontraban en el estadio III de FIGO. Encontramos que el 4.2% de las pacientes en el antiguo estadio IIIC han cambiado a estadio IIIA2 o estadio IIIB, con mejor pronóstico y mayor tasa de supervivencia. En la clasificación de 1973 de la OMS, el principal cambio, en nuestra serie de casos, fue el aumento en el porcentaje de carcinoma seroso de alto grado. Según las recomendaciones actuales, observamos un 7,56% más de pacientes en estadios iniciales de cáncer de ovario tratados con platino y taxano. Tanto en el grupo de cáncer de ovario en estadios iniciales como en el avanzado, predominaron los tumores de carcinoma seroso de alto grado. Con respecto al estudio de polimorfismos de los genes de reparación de DNA, el genotipo GA del gen XRCC1 (rs1799782), el genotipo CC del gen TP53 (rs1042522) y el genotipo GG del gen MLH1 (rs1800734) se asociaron con mayor susceptibilidad de cáncer de ovario. En el análisis de haplotipos del gen XRCC1, hemos encontrado que las pacientes portadoras de los haplotipos AGTT, AGCC, AGCT, GGTT, GGCC y GGCT son más susceptibles de presentar CO. En relación al gen XRCC1 (rs1799782), el genotipo GA se asoció a mayor susceptibilidad de cáncer de ovario en pacientes jóvenes, en pacientes mayores y en pacientes con CO hereditario, familiar o esporádico. El genotipo GA del gen XRCC1 también se asocia a mayor riesgo de recidiva en pacientes con CO. En relación al gen APEX1 (rs1130409), el genotipo TT se asoció a una aparición más tardia de la enfermedad y CO hereditario y el genotipo GT se asoció a un aumento del riesgo en CO hereditario, familiar y esporádico. En relación al gen XRCC3 (rs1799794), el genotipo TT se asoció a mayor susceptibilidad de CO en pacientes mayores y pacientes con CO familiar. En relación al gen MLH1 (rs1800734), el genotipo GG se asoció a mayor susceptibilidad de CO en pacientes mayores y en pacientes con CO hereditario. El SNP rs1799977 del gen MLH1 se asoció con un mayor riesgo de recurrencia de la enfermedad. 4. Conclusiones Las nuevas clasificaciones de la OMS y de la FIGO han mejorado la capacidad de predecir el pronóstico y, en consecuencia, cambiar el tratamiento terapéutico de los pacientes con cáncer de ovario. Nuestros resultados ponen de manifiesto que variantes polimorfas de genes reparadores del DNA, diferentes de BRCA1 y 2, modifican el riesgo de padecer cáncer de ovario. Dada la importancia de estos datos en futuras investigaciones sobre la prevención del CO, es esencial analizar si estos resultados se confirman en un estudio más amplio de nuestra población

Nanocrystalline Anatase Tio2/reduced Graphene Oxide Composite Films As Photoanodes For Photoelectrochemical Water Splitting Studies: The Role Of Reduced Graphene Oxide.

Nanocrystalline TiO2 and reduced graphene oxide (TiO2/RGO) composite films were prepared by combining a sol-gel method with hydrothermal treatment, employing titanium isopropoxide (Ti(O(i)Pr)4) and graphene oxide (GO) as starting materials. Although several reports in the literature have explored the benefits of RGO addition in titania films for photocatalysis and water splitting reactions, the role of RGO in the composite is always described as that of a material that is able to act as an electron acceptor and transport electrons more efficiently. However, in most of these reports, no clear evidence for this role is presented, and the main focus is deviated to the improved efficiency and not to the reasons for said efficiency. In this study, we employed several techniques to definitively present our understanding of the role of RGO in titania composite films. The TiO2/RGO composite films were characterized by X ray diffraction, Raman spectroscopy, microscopy and electrochemical techniques. In photoelectrochemical water splitting studies, the TiO2/RGO(0.1%) photoelectrodes showed the highest photocurrent density values (0.20 mA cm(-2) at 1.23 VRHE) compared to other electrodes, with an increase of 78% in relation to pristine TiO2 film (0.11 mA cm(-2) at 1.23 VRHE). The transient absorption spectroscopy (TAS) results indicated increases in the lifetime and yield of both the photogenerated holes and electrons. Interestingly, the TiO2/RGO(0.1%) film exhibited the best charge generation upon excitation, corroborating the photoelectrochemical data. We proposed that in films with lower concentrations (<0.1 wt%), the RGO sheets are electron acceptors, and a decrease in the charge recombination processes is the immediate consequence. Thus, both holes and electrons live longer and contribute more effectively to the photocurrent density.182608-261

Proteome Analysis of Leptospira interrogans Virulent Strain

Leptospirosis is a worldwide zoonotic infection of human and veterinary concern. Caused by pathogenic spirochetes of the genus Leptospira, the disease presents greater incidence in tropical and subtropical regions. The identification of proteins that could be involved in the bacteria host interactions may facilitate the search for immune protective antigens. We report the proteomic analysis of Leptospira interrogans serovar Pomona virulent strain LPF cultured from kidney and liver of infected hamsters. Total protein extracts were separated by two-dimensional gel electrophoresis (2-DE), 895 spots were analyzed by MALDI-TOF mass spectrometry (MS), and 286 were identified as leptospiral proteins, corresponding to 108 distinct proteins. These proteins are allocated in all the bacterial cell compartments and are distributed in every functional category. Furthermore, the previously described, known outer membrane proteins, OmpL1, LipL21, LipL31, LipL32/Hap-1, LipL41, LipL45, LipL46, LruA/LipL71, and OmpA-like protein Loa22 were all recognized. Most importantly, this research work identified 27 novel leptospiral proteins annotated as hypothetical open reading frames (ORFs). We report for the first time an array of proteins of the Leptospira expressed by virulent, low-passage strain. We believe that our studies, together with the genome data will enlighten our understanding of the disease

PROJETO DE EDUCAÇÃO AMBIENTAL COM OS PROPRIETÁRIOS RURAIS CONFRONTANTES COM O PARQUE NACIONAL DO CAPARAÓ

Este projeto, através da extensão florestal, transmite informações básicas sobre a importância da manutenção dos recursos naturais renováveis para os proprietários rurais confrontantes com o Parque Nacional do Caparaó, referente ao estado do Espírito Santo. O projeto inicia-se com o trabalho de envolvimento dos órgãos de assistência técnica rural, prefeituras municipais e IBAMA (Instituto Brasileiro de Meio Ambiente e Recursos Naturais Renováveis) na comemoração de eventos ecológicos. Este envolvimento institucional torna- se necessário, provocando mudanças na política institucional destes órgãos

The Fractal-Lattice Hubbard Model

Here, we investigate the fractal-lattice Hubbard model using various numerical methods: exact diagonalization, the self-consistent diagonalization of a (mean-field) Hartree-Fock Hamiltonian and state-of-the-art Auxiliary-Field Quantum Monte Carlo. We focus on the Sierpinski triangle with Hausdorff dimension $1.58$ and consider several generations. In the tight-binding limit, we find compact localised states, which are also explained in terms of symmetry and linked to the formation of a ferrimagnetic phase at weak interaction. Simulations at half-filling revealed the persistence of this type of magnetic order for every value of interaction strength and a Mott transition for U/t $\sim$ 4.5. In addition, we found a remarkable dependence on the Hausdorff dimension regarding $i)$ the number of compact localised states in different generations, $ii)$ the scaling of the total many-body ground-state energy in the tight-binding limit, and $iii)$ the density of the states at the corners of the lattice for specific values of electronic filling. Moreover, in the presence of an intrinsic spin-orbit coupling, the zero-energy compact localized states become entangled and give rise to inner and outer corner modes

A novel leptospiral protein increases ICAM-1 and E-selectin expression in human umbilical vein endothelial cells

It has been reported previously that activation of vascular endothelium by outer membrane proteins of the spirochetes Borrelia sp. and Treponema sp. resulted in enhanced expression of endothelial cell adhesion molecules. To investigate the role of leptospiral proteins in this process, a predicted lipoprotein encoded by the gene LIC10365 was selected, which belongs to a paralogous family that presents a domain of unknown function, DUF1565. The LIC10365 gene was cloned and the protein expressed in Escherichia coli C43 (DE3) strain using the vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and was used to assess its ability to activate cultured human umbilical vein endothelial cells. The rLIC10365 activated endothelium in such a manner that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose-dependent fashion. The LIC10365-encoded protein was identified in vivo in the renal tubules of animal during experimental infection with Leptospira interrogans. Collectively, these results implicate the LIC10365-coding protein of L. interrogans as a potential effector molecule in the promotion of a host inflammatory response. This is the first report of a leptospiral protein capable of up-regulating the expression of endothelial cell adhesion molecules ICAM-1 and E-selectin.Instituto de Biotecnologia y Biologia Molecula

Telehealth in the Amazon Region in Latin America: an Overview

Purpose: This paper describes the current status of telehealth in the Latin American Amazon and displays the result of a distance course on malaria, focused on physicians and healthcare professionals from nine countries of the Amazon region. Methods: Data were collected on telehealth implementation and course participation for the following countries in the Amazon region: Brazil, Colombia, Ecuador, Peru, Venezuela and Bolivia. Results: There are 808 Municipalities in the Amazon region. Over half (51.9%) of the Municipalities have implemented or are implementing telehealth projects in the region. Among these 6 countries, Brazil has the highest percentage of municipalities with telehealth projects implemented (498 of 808, 61,6%;), Venezuela  (38 of 91, 41.7%) and  following by Bolívia  (5 of 39; 12,8%). Participation in the distance course on malaria has included 868 students: Brazil, 291 participants (33.5%); Bolivia, 28 (3.2%); Colombia, 104 (12.0%); Ecuador, 52 (6.0%); Guyana, 2 (0.2%); Paraguay 1 (0.1%), 270 Peru (31,1%); 102 Venezuela (11.8%) and others (2.1%). Nearly all (99.1%) of learners would recommend the course to colleagues. Conclusion: Shared action between countries is an important framework that can lead to incorporation of telehealth resources and training for a common, remote setting, as exemplified by international activities in the Amazon region

A novel leptospiral protein increases ICAM-1 and E-selectin expression in human umbilical vein endothelial cells

It has been reported previously that activation of vascular endothelium by outer membrane proteins of the spirochetes Borrelia sp. and Treponema sp. resulted in enhanced expression of endothelial cell adhesion molecules. To investigate the role of leptospiral proteins in this process, a predicted lipoprotein encoded by the gene LIC10365 was selected, which belongs to a paralogous family that presents a domain of unknown function, DUF1565. The LIC10365 gene was cloned and the protein expressed in Escherichia coli C43 (DE3) strain using the vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and was used to assess its ability to activate cultured human umbilical vein endothelial cells. The rLIC10365 activated endothelium in such a manner that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose-dependent fashion. The LIC10365-encoded protein was identified in vivo in the renal tubules of animal during experimental infection with Leptospira interrogans. Collectively, these results implicate the LIC10365-coding protein of L. interrogans as a potential effector molecule in the promotion of a host inflammatory response. This is the first report of a leptospiral protein capable of up-regulating the expression of endothelial cell adhesion molecules ICAM-1 and E-selectin.Instituto de Biotecnologia y Biologia Molecula