Herramienta para el diagnóstico de la resistencia al cambio durante el desarrollo de proyectos mayores.

A partir de un arqueo exhaustivo delos estudios y propuestas de diversos autores en torno al concepto de gerencia del cambio, nos percatamos dela importancia de un adecuado manejo de la resistencia que los individuos pueden presentar ante iniciativas de cambio de naturaleza diversa. Por ello consideramos de utilidad el diseño de una herramienta de diagnóstico de los niveles y causas de resistencia o flexibilidad de los individuos frente al desarrollo de proyectos mayores (procesos de cambio planificados).Esta propuesta incluye insertar los procesos de gerencia del cambio como una de las áreas del conocimiento de la gerencia de proyectos. En líneas generales, con propuestas como la derivada de este estudio esperamos contribuir con el desarrollo de herramientas que permitan que más y más proyectos que se inician, finalicen en forma exitosa. Se ofrecen los instrumentos y estrategias necesarios para la recolección, procesamiento, análisis y presentación de la información; probablemente el mayor atractivo está en la conjunción de las propuestas de diversos autores en torno a un enfoque particular.

Bisphenol A at the reference level counteracts doxorubicin transcriptional effects on cancer related genes in HT29 cells

Human exposure to Bisphenol A (BPA) results mainly from ingestion of food and beverages. Information regarding BPA effects on colon cancer, one of the major causes of death in developed countries, is still scarce. Likewise, little is known about BPA drug interactions although its potential role in doxorubicin (DOX) chemoresistance has been suggested. This study aims to assess potential interactions between BPA and DOX on HT29 colon cancer cells. HT29 cell response was evaluated after exposure to BPA, DOX, or co-exposure to both chemicals. Transcriptional analysis of several cancer-associated genes (c-fos, AURKA, p21, bcl-xl and CLU) shows that BPA exposure induces slight up-regulation exclusively of bcl-xl without affecting cell viability. On the other hand, a sub-therapeutic DOX concentration (40 nM) results in highly altered c-fos, bcl-xl, and CLU transcript levels, and this is not affected by co-exposure with BPA. Conversely, DOX at a therapeutic concentration (4 μM) results in distinct and very severe transcriptional alterations of c-fos, AURKA, p21 and CLU that are counteracted by co-exposure with BPA resulting in transcript levels similar to those of control. Co-exposure with BPA slightly decreases apoptosis in relation to DOX 4 μM alone without affecting DOX-induced loss of cell viability. These results suggest that BPA exposure can influence chemotherapy outcomes and therefore emphasize the necessity of a better understanding of BPA interactions with chemotherapeutic agents in the context of risk assessment.

Diagnóstico de suelos en cultivos de café (Coffea arabica L.), maíz (Zea mays L.) y frijol (Phaseolus vulgaris L.), comunidad de Santa Julia, El Crucero, Managua

Uno de los parámetros de mayor importancia en la agricultura es el estado nutricional del suelo, así como el manejo de parte de los agricultores. En 2014, a través del programa para el Desarrollo Participativo Integral Rural (DEPARTIR)se efectuó un muestreo de suelos a profundidad de 25 cm en 34 lotes productivos de 17 unidades de producción, dedicadas a la producción de café (Coffea arabica), maíz ( Zea mays L.) y frijol (Phaseolusvulgaris L.) en la comunidad Santa Julia, El Crucero, Managua. Se analizaron los factores que condicionan el uso del suelo, a través de análisis de correlación, ANDEVA y análisis de correspondencia en N, P,K, Mg, Ca, MO, CO y pH. El N total,y altitudfueron correlacionadas. El 95% de las áreas presentaron 10.5 hectáreas, con predominancia decultivo de café. Lafertilización químicaes unapráctica común en las unidades productivasy cultivos estudiados. Los muestreos efectuados en las parcelas de maíz fueron homogéneos a lo interno y externo de las unidades productivas; no así en el cultivo de café. Las áreas de siembra, destino de la producción y la aplicación de fertilizantes químicos, presentaron una alta relación.

Novel pharmacogenomic markers of irinotecan-induced severe toxicity in metastatic colorectal cancer patients

L’irinotécan est un agent de chimiothérapie largement utilisé pour le traitement de tumeurs solides, particulièrement pour le cancer colorectal métastatique (mCRC). Fréquemment, le traitement par l’irinotécan conduit à la neutropénie et la diarrhée, des effets secondaires sévères qui peuvent limiter la poursuite du traitement et la qualité de vie des patients. Plusieurs études pharmacogénomiques ont évalué les risques associés à la chimiothérapie à base d’irinotécan, en particulier en lien avec le gène UGT1A, alors que peu d’études ont examiné l’impact des gènes codant pour des transporteurs. Par exemple, le marqueur UGT1A1*28 a été associé à une augmentation de 2 fois du risque de neutropénie, mais ce marqueur ne permet pas de prédire la toxicité gastrointestinale ou l’issue clinique. L’objectif de cette étude était de découvrir de nouveaux marqueurs génétiques associés au risque de toxicité induite par l’irinotécan, en utilisant une stratégie d’haplotype/SNP-étiquette permettant de maximiser la couverture des loci génétiques ciblés. Nous avons analysé les associations génétiques des loci UGT1 et sept gènes codants pour des transporteurs ABC impliqués dans la pharmacocinétique de l’irinotécan, soient ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2 ainsi que SLCO1B1. Les profils de 167 patients canadiens atteints de mCRC sous traitement FOLFIRI (à base d’irinotécan) ont été examinés et les marqueurs significatifs ont par la suite été validés dans une cohorte indépendante de 250 patients italiens. Nous avons découvert dans la région intergénique en aval du gène UGT1, un nouveau marqueur (rs11563250G) associé à un moindre risque de neutropénie sévère (rapport des cotes (RC)=0.21; p=0.043 chez les canadiens, RC=0.27; p=0.036 chez les italiens, et RC=0.31 p=0.001 pour les deux cohortes combinées). De plus, le RC est demeuré significatif après correction pour multiples comparaisons (p=0.041). Par ailleurs, pour l’haplotype défini par les marqueurs rs11563250G et UGT1A1*1 (rs8175347 TA6), le RC était de 0.17 (p=0.0004). Un test génétique évaluant ces marqueurs permettrait d’identifier les patients susceptibles de bénéficier d’une augmentation de dose d’irinotécan. En revanche, une autre combinaison de marqueurs, ABCC5 rs3749438 et rs10937158 (T–C), a prédit un risque plus faible de diarrhée sévère dans les deux cohortes (RC = 0.43; p=0.001). La coexistence des marqueurs ABCG1 rs225440T et ABCC5 rs2292997A a prédit un risque accru de neutropénie (RC=5.93; p=0.0002), alors qu’une prédiction encore plus significative a été obtenue lorsque ces marqueurs sont combinés au marqueur de risque bien établi UGT1A1*28 rs8175347 (RC=7.68; p<0.0001). Enfin, les porteurs de l’allèle de protection UGT1 rs11563250G en absence d’allèles de risque, ont montré une incidence réduite de neutropénie sévère (8.2% vs. 34.0%; p<0.0001). Nous concluons que ces nouveaux marqueurs génétiques prédictifs pourraient permettre d’améliorer l’évaluation du risque de toxicité et personnaliser le traitement à base d’irinotécan pour les patients atteints du cancer colorectal métastatique.

The Role of PME-1 in Cancer: Therapeutic Implication

Protein phosphatase 2A (PP2A) plays a major role in maintaining cellular signaling homeostasis in human cells by reversibly affecting the phosphorylation of a variety of proteins. Protein phosphatase methylesterase-1 (PME-1) negatively regulates PP2A activity by reversible demethylation and active site binding. Thus far, it is known that overexpression of PME-1 in human gliomas contributes to ERK pathway signaling, cell proliferation, and malignant progression. Whether PME-1-mediated PP2A inhibition promotes therapy resistance in gliomas is unknown. Specific PP2A targets regulated by PME-1 in cancers also remain elusive. Additionally, whether oncogenic function of PME-1 can be generalized to various human cancers needs to be investigated. This study demonstrated that PME-1 expression promotes kinase inhibitor resistance in glioblastoma (GBM). PME-1 silencing sensitized GBM cells to a group of clinically used indolocarbazole multikinase inhibitors (MKIs). To facilitate the quantitative evaluation of MKIs by cancer-cell specific colony formation assay, Image-J software-plugin ‘ColonyArea’ was developed. PME-1-silencing was found to reactivate specific PP2A complexes and affect PP2A-target histone deacetylase HDAC4 activity. The HDAC4 inhibition induced synthetic lethality with MKIs similar to PME-1 depletion. However, synthetic lethality by both approaches required co-expression of a pro-apoptotic protein BAD. In gliomas, PME-1 and HDAC4 expression was associated with malignant progression. Using tumor PME-1, HDAC4 and BAD expression based stratification signatures this study defined patient subgroups that are likely to respond to MKI alone or in combination with HDAC4 inhibitor therapies. In contrast to the oncogenic role of PME-1 in certain cancer types, this study established that colorectal cancer (CRC) patients with high tumor PME-1 expression display favorable prognosis. Interestingly, PME-1 regulated survival signaling did not operate in CRC cells. Summarily, this study potentiates the candidacy of PME-1 as a therapy target in gliomas, but argues against generalization of these findings to other cancers, especially CRC.

Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer

Monocarboxylate Transporter 2 (MCT2) is a major pyruvate transporter encoded by the SLC16A7 gene. Recent studies pointed to a consistent overexpression of MCT2 in prostate cancer (PCa) suggesting MCT2 as a putative biomarker and molecular target. Despite the importance of this observation the mechanisms involved in MCT2 regulation are unknown. Through an integrative analysis we have discovered that selective demethylation of an internal SLC16A7/MCT2 promoter is a recurrent event in independent PCa cohorts. This demethylation is associated with expression of isoforms differing only in 5'-UTR translational control motifs, providing one contributing mechanism for MCT2 protein overexpression in PCa. Genes co-expressed with SLC16A7/MCT2 also clustered in oncogenic-related pathways and effectors of these signalling pathways were found to bind at the SLC16A7/MCT2 gene locus. Finally, MCT2 knock-down attenuated the growth of PCa cells. The present study unveils an unexpected epigenetic regulation of SLC16A7/MCT2 isoforms and identifies a link between SLC16A7/MCT2, Androgen Receptor (AR), ETS-related gene (ERG) and other oncogenic pathways in PCa. These results underscore the importance of combining data from epigenetic, transcriptomic and protein level changes to allow more comprehensive insights into the mechanisms underlying protein expression, that in our case provide additional weight to MCT2 as a candidate biomarker and molecular target in PCa.

CAREGIVING FOR A FAMILY MEMBER WITH HEAD AND NECK CANCER

Objective: To know the perception of informal caregivers regarding the care for a family member with head and neck cancer. Methods: Qualitative study conducted between March and May 2014 in the radiotherapy outpatient center of the Centro de Alta Complexidade em Oncologia – CACON (Oncology High Complexity Center) of the Hospital Universitário de Brasília – HUB (University Hospital of Brasília) using semi-structured interviews with nine caregivers about the experience of caring for family members. Data underwent Content Analysis and four units of meaning were identified: “Representation of cancer in the Family”, “The care as debt, individual reward or reconstruction of family ties”, “Repercussions of cancer on the caregiver’s personal life” and “Social support and network used by caregivers”. Results: Feelings of sadness and surprise at the moment of diagnosis were attributed to cancer, as well as the idea of punishment. The care was seen as personal satisfaction, accomplishment and opportunity for family rapprochement. Work overload and change in routine were altered functions. Religiosity, exchange of experience in the waiting room and institutional support appeared as coping strategies. Conclusion: The experience of caring for family members with head and neck cancer directly interferes in the lives of caregivers. Pointing out the institutional embracement as a strategy within the social network reinforces the importance of integrating the caregivers as a significant part of the health care plan developed by the health team.

Radiative Behaviour of Gd2O3:Er/Yb nanoparticles under near infrared illumination

Upconverting nanoparticles have attracted much attention in science recently, specifically in view of medical and biological applications such as live imaging of cell temperatures or cancer treatment. The previously studied system of gadolinium oxide nanorods co-doped with erbium and ytterbium and decorated with different number densities of gold nanoparticles has been studied. So far, these particles have been proven as efficient nanothermometers in a temperature range from 300 up to 2000 K. In this work, a more detailed study on the morphological and radiative behaviour of these particles has been conducted. It was found that the laser power threshold for the onset of the black body radiation decreases strongly with the increase in the gold concentration. The temperature of the onset itself seems to remain approximately constant. The heating efficiency was determined to increase significantly with the gold concentration. The morphological study revealed that the temperature at the black body radiation threshold was not enough to induce any significant transformation in neither the nanorods nor the gold nanoparticles, as was expected from comparison with literature. However, significant changes in radiative properties and the morphology were detected for powders that underwent strong laser heating until the emission of brightly visible black body radiation.

Qualidade de vida no trabalho da Emater-RN: validação de um instrumento síntese de pesquisa e diagnóstico

The theoretical recital of the present study it is initiated of the evidence that the work occupies an important space in the man s life in way that the majority of the people works and passes great part of its time inside organizati ons. However, it is verified that the relation between man and work is becoming increasingly disagreement a time that the employees had started to complain work s routines, stress, not use all their potential and inadequate work s conditions. It can be observed by the way of Dejours (1994) studies. Thus, as contribution for the quality of work life s (QWL) studies the research developed here objectified to characterize the public employees quality of work life at EMATER -RN taking as reference an instrumen t of research synthesized from the typical academic literature of the subject. The synthesis of an ampler instrument is a necessity not taken care to the literature that treats on the subject but already perceived by some studies like Moraes et al (1990); Rodrigues (1989); Siqueira & Coleta (1989); Moraes et al (1992); Carvalho & Souza (2003); El -Aouar & Souza (2003) and Mourão, Kilimnick & Fernandes (2005); Adorno, Marques & Borges (2005) amongst others. These studies point out weak points of the existing models in the QWL s literature, as well as they recommend the elaboration of a model more flexible, that contemplates Brazilian cultural characteristics, and that contemplates the entire variable studied in the main existing models. For reach this objectiv e the adopted methodology was characterized as a case study with collected data in qualitative and quantitative way. Questionnaires and comments had been used as sources of evidences. These evidences had been tabulated through of statistical package SPSS ( Statistical Package for Social Science), in which the main technique of multivariate analysis used were the factorial analysis. As for the gotten results, it was verified the grouping of the quality of work life s indicators in 11 factors which are: Work s execution, Individual accomplishment, Work s equity, Relation individual and organization, Work s organization, Adequacy of the remuneration, Relation between head and subordinate, Effectiveness of the communication and the learning, Relation between work and personal life, Participation and Effectiveness of the work processes. Whatever to the characterization of the EMATER -RN s quality of work life it was clearly that to the measure that the satisfaction s evaluation with the QWL in the organization walks to intrinsic factors for extrinsic factors this level of satisfaction goes diminishing what points to the importance to improve these extrinsic factors in the institution. In summary it is possible to conclude that the organization studied has offered a significant set of referring variable to the quality of work life of the individual

Co-occurrence of Helicobacter pylori with faecal bacteria in Nairobi river basin: public health implications.

Introduction: Overwhelming evidence implicates Helicobacter pylori (H. pylori) as an etiologic agent of gastrointestinal diseases including gastric cancer. The mode of transmission of this pathogen remains poorly understood. Objective: This investigation is to establish the presence of H. pylori in the waters of the Nairobi river basin and the predictive value the presence of fecal indicator bacteria would have for H. pylori. Methodology: Physical, chemical and biological assessment of water quality of rivers in Nairobi were carried out using standard methods. H. pylori DNA in water was detected using highly specific primers of glmM gene (294pb). Results: There was high presence of faecal bacteria in the waters sampled. H. pylori DNA was detected in two domestic wells and one river. The wells were located in two different regions of the water basin but influenced by similar human activities. Conclusion: The high presence of faecal bacteria in the waters sampled did not parallel the H. pylori detection in the same waters. H. pylori was detected in the Nairobi river basin, but there was no relationship between the numerical levels of fecal bacteria and H. pylori.

Endometrial tuberculosis simulating an ovarian cancer

Female genital tuberculosis remains a major health problem in developing countries and is an important cause of infertility. As symptoms, laboratory data and physical fndings are non-specifc, its diagnosis can be diffcult. We describe a case of a 39-year-old woman suffering from peri-umbilical pain and increased abdominal size for one year, anorexia, asthenia, weight loss, occasionally dysuria and dyspareunia, and four months amenorrhea. Laboratory data revealed cancer antigen 125 (CA-125) level of 132.3 U/mL, erythrocyte sedimentation rate of 42 mm/h, and gamma-globulins of 2.66 g/dL. Computer Tomography scan showed loculated ascites. It was initially suspected a carcinomatous origin, but ascites evaluation was negative for malignant cells. Magnetic Resonance Imaging from another hospital showed endometrial heterogeneity. Therefore, an endometrial biopsy was performed demonstrating an infammatory infltrate with giant cells of type Langhans and bacteriological culture identifed Mycobacterium tuberculosis

Introducción. El diagnóstico de una política pública: un ejercicio entre la teoría y la práctica

Este libro se constituye en un esfuerzo para ayudar a que más personas diferencien el campo específico de las políticas públicas, buscando también que estos razonamientos y lenguajes se vuelvan de uso más común. En otras palabras, se ofrece un conjunto relativamente amplio de herramientas de las políticas públicas aplicadas a un área de política colombiana, con el fin de que nuestros “hacedores”2 de políticas cuenten con ellas para un mejor diagnóstico y con un ejemplo práctico de cómo utilizarlas. Cabe advertir que, además del público interesado en el área de juventud, se procura apelar a un público general que busca incorporar en su quehacer las herramientas del llamado análisis de políticas (policy analysis) para el diagnóstico de problemas.

Un diagnóstico de los instrumentos de gobierno de una política pública

En esta sección se analizan el uso y la aplicación de los instrumentos de gobierno en algunos programas de juventud. El objetivo de este análisis es entender, con mayor profundidad, las herramientas que son utilizadas para intervenir los problemas que ha identificado el Estado en una población o sector específico. En primer lugar, se presenta un marco teórico para comprender las discusiones principales sobre este tema y poder contar con una visión general sobre los instrumentos de gobierno, es decir, las herramientas de las cuales se sirve el gobierno local para ejecutar una acción pública. Este marco teórico se complementa con otra literatura que indica la manera como deben ser seleccionados dichos instrumentos y sobre las formas para evaluarlos cuando se está haciendo un análisis de implementación. Una vez construido el marco teórico, se analizan los programas de juventud de acuerdo con el uso de los instrumentos de gobierno. El análisis, entonces, se hace a partir de la información recolectada en las entrevistas realizadas a los operadores de los programas, así como con algunas secretarías encargadas de ejecutar los programas de manera directa. Además, se analiza la información de acuerdo con tres niveles de acción: el primero, que se compone de los programas de política universal, es decir, de programas dirigidos a toda la población; el segundo nivel contiene programas para población vulnerable y se denomina políticas de protección; y el tercer nivel de acción, dirigido a población vulnerada, pretende atender a los jóvenes que no han sido cobijados por las políticas del primer o segundo nivel y, por lo tanto, deben ser formuladas como políticas de recuperación. Esto, con el fin de sensibilizar el análisis a las condiciones de exclusión estructural.

Calidad del agua. Evaluación y diagnóstico

Este libro recoge los aspectos más importantes relacionados con la calidad del agua en ambientes lóticos (ríos y corrientes superficiales) y lénticos (lagos y embalses). De una manera práctica e integrada, el texto recopila los conceptos básicos de diferentes ciencias como la estadística, la química del agua, las evaluaciones ambientales y la modelación, y los aplica para que el lector pueda diagnosticar y evaluar la calidad del agua, proponer medidas de mitigación a los problemas y establecer criterios, usos y objetivos de calidad del agua. Los temas están presentados recurriendo a la discusión teórica y presentando ejemplos prácticos de cada aspecto contemplado. Con base en lo anterior, el libro está dirigido a que sea utilizado en programas de pregrado y posgrado en ingeniería en los cursos de calidad del agua, tratamiento de aguas, contaminación de recursos hídricos, evaluaciones ambientales, etc. También, puede ser una herramienta muy importante en la planeación, ordenamiento y conservación de cuencas para las autoridades ambientales y empresas prestadoras de servicios públicos.

Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma

International audience