Dynamics of intracellular metabolite pools in MDCK suspension cells during growth and influenza virus infection

Influenza virus infections are responsible for millions of flu cases with hundred thousands of deaths worldwide [1]. Additionally, pandemic outbreaks of aggressive influenza virus strains are very dangerous both for livestock and human population. Seasonal vaccination campaigns are in place to reduce infections, especially among young, old or immunodeficient individuals, generating a huge demand of 500 million (2015) vaccine doses every year [2]. Besides egg-based vaccine manufacturing, production platforms based on animal cell culture increasingly contribute to an overall growing market. Thus, the use of suspension MDCK cells (MDCKsus) cultivated in chemically defined medium emerges as a modern vaccine manufacturing platform. In order to improve overall productivity and reduce costs, process analysis, process optimization, and process intensification strategies are necessary. In particular, a better understanding of the effect of virus replication on cell growth, cell morphology and cell metabolism is crucial for developing production processes. In this study, the effect of a synchronous influenza A virus infection on cell growth and central carbon metabolism was investigated. Additionally, intracellular virus replication dynamics of influenza were analyzed and correlated to metabolic pool dynamics. For analysis of intracellular metabolites, an established HPLC-MS method was used to identify and quantify extracted metabolites [3]. A mathematical model, established for adherent MDCK cells, was modified to describe cell growth, consumption and production of main extracellular metabolites [4] as well as dynamics of intracellular metabolite pools of glycolysis and TCA. Our results showed fast infection (\u3c 2 h) of the whole MDCKsus population under the used infection conditions. Intracellular infection was very similar to the already reported dynamics in adherent MDCK cells [5]. Virus particles were released six hours post infection (hpi) for 30 h, with an overall yield of 10,000 virus particles per cell. Despite massively impaired cell growth at 6 hpi, the concentrations of extracellular metabolites did not differ significantly from mock-infected cells used as a control. The majority of intracellular TCA metabolites also followed a similar dynamics. For glycolysis, however, metabolite pools of lower glycolysis decreased rapidly after infection, whereas glucose-6-P and fructose-6-P pools where maintained at a similar level as controls. Overall it seems that influenza infected MDCK cells show primarily an alteration in the glycolysis pathway, channeling metabolites not to the lower part of glycolysis but to the pentose phosphate pathway. Energy metabolism (ATP pools and energy charge) and TCA pools seemed not be affected by virus infection. Quantitative data for mock-infected cells are described by the mathematical model. Work is in progress to explain the dynamics observed in infected cells. [1] Influenza (seasonal) fact sheet (Nov 2016). WHO [online] www.who.int/mediacentre/factsheets/fs211/en/ [2] Palache A. et al., Vaccine 35 (2017): 4681–4686. doi: 10.1016/j.vaccine.2017.07.053 [3] Ritter J.B. et al., Journal of Chrom B, 843 (2006): 216–226. doi: 10.1016/j.jchromb.2006.06.004 [4] Rehberg M. et al., PLoS Comput Biol 10.10 (2014): e1003885. doi: 10.1371/journal.pcbi.1003885 [5] Frensing T. et al., Appl Microbiol Biotechnol 100 (2016): 7181–7192. doi: 10.1007/s00253-016-7542-

Complicaciones de la terapia de inducción a remisión en niños con leucemia linfoblástica aguda en el Servicio de Hematología del HNPNP “LNS” (enero 2002 – diciembre 2012)

Publicación a texto completo no autorizada por el autorEstablece las complicaciones presentadas en los niños con Leucemia Linfoblastica Aguda en la fase de inducción a remisión, en el servicio de Hematología Clínica del Hospital Nacional PNP Luis N. Sáenz entre 2002 – 2012. Se seleccionaron 29 niños con LLA que presentaron complicaciones durante el tratamiento de inducción a remisión, distribuyéndose en dos grupos: Grupo Casos, 19 niños con LLA, fallecidos y Grupo Control, 10 niños con LLA, no fallecidos. La edad promedio globalmente fue de 9.52 ± 4.6 años, predominó el sexo masculino. La L-1 fue la LLA más frecuente (79.3%). Las complicaciones más frecuentes fueron: choque séptico en 13 casos (44.80%), neutropenia y fiebre (24.15%), anemia grave (5.90%), hemorragia en 4 casos (13.80%). Las complicaciones fueron más frecuentes en la fase de inducción (62.40%). El choque séptico y la neutropenia profunda se relacionaron con mayor riesgo de mortalidad (pm= 0.05 y p = 0.004). Las características de la atención médica por complicación presentada se aporta a la literatura de Leucemia Linfoblastica Aguda en niños y de acuerdo a la GCCOG. Las complicaciones infecciosas son las más frecuentes. El análisis de las características clínicas de los pacientes con choque séptico y con neutropenia y fiebre muestran que la confirmación de la fiebre al ingreso al hospital, así como la neutropenia profunda son los indicadores de mayor riesgo de mortalidad. Dentro de la atención de estos niños, las acciones que aparentemente contribuyen a la mortalidad son el retraso en la administración de la primera dosis de antibióticos y la falta de adherencia a la GCCOG en cuanto a las decisiones de cambio de los mismos. En las complicaciones hematológicas, observamos que los valores de hemoglobina o plaquetas no significan una diferencia en cuanto a mortalidad. Así mismo, no hay algún proceso de atención que afecte significativamente. También notamos que existen deficiencias en cuanto a la toma de cultivos en los niños infectados y en la documentación de los procesos de transfusión de hemoderivados. Hay pacientes que mueren de complicaciones posiblemente evitables y por lo tanto existen áreas de oportunidad, relacionados por la falta de apego a las guías de atención de las complicaciones influye en la mortalidad.Trabajo académic

Trabajo remoto y rendimiento laboral en los docentes del área de EPT del Centro Educativo María Inmaculada Huancayo – 2021

La presente investigación, se ha planteado como problema ¿Cuál es la relación que se da entre el trabajo remoto y el rendimiento laboral en los docentes de EPT del Centro Educativo María inmaculada Huancayo - 2021?, por lo que se planteó como objetivo general “Identificar la relación entre la variable trabajo remoto y la variable rendimiento laboral en los docentes de EPT del Centro Educativo María Inmaculada Huancayo - 2021”. Se ha empleado la metodología científica con enfoque cuantitativo, de tipo aplicada con diseño No experimental. Transaccional y correlacional, se realizó una encuesta con la escala de Likert a partir de una muestra de 45 docentes nombrados y contratados del área de educación para el trabajo, lo cual para su validez fue sometido al juicio de expertos y al estadístico del Alfa de Cronbach, el procesamiento de los resultados se hizo a través del programa SPSS v26, estadística descriptiva frecuencia y porcentajes. a través de la prueba no paramétrica de Rho de Spearman se obtuvo como resultado el nivel de significancia de (alfa) α =5% = 0,05 que existe relación positiva fuerte (0,912) entre trabajo remoto y rendimiento laboral, por lo que se concluye: que, a mayor eficiencia en el trabajo remoto, mayor será el rendimiento laboral en los docentes de EPT del Centro Educativo María Inmaculada Huancayo en el año 2021. Por tanto, se recomienda a los directivos implementar estrategias de mejora en la gestión de personal. Palabras Clave. Trabajo Remoto / Rendimiento Labora

Implementación de un proceso de mejora en el programa de rutas para optimizar la productividad en la entrega de pedidos del operador logístico Yobel SCM del distrito de Los Olivos, 2018

RESUMEN La presente investigación tiene como objetivo implementar una solución para optimizar la entrega de pedidos de Yobel SCM, dedicada al almacenamiento y distribución de pedidos para diferentes clientes. El cliente en el que se centró la investigación fue Entel. Se procurará optimizar el proceso de entrega de pedidos, calcular las rutas óptimas de entrega, reducir el tiempo promedio de entrega, incrementar el número de pedidos entregados a tiempo, incrementar la satisfacción de los vendedores y aumentar el nivel de satisfacción del cliente Entel. La investigación inició con el análisis de la situación inicial del proceso de entrega de pedidos, detallando la problemática de los procesos y considerando las reglas de negocio para determinar los requerimientos y los acuerdos de nivel de servicio deseados. Asimismo, se analizaron las tendencias tecnológicas existentes en el mercado que coadyuven a incrementar la eficiencia del sistema de entrega. Como resultado, se determinó que la aplicación de un sistema computarizado permitirá mejorar la gestión del sistema de pedidos de Yobel SCM, para su cliente Entel, logrando los objetivos de reducción de tiempos y costos, sobre la base de calcular rutas óptimas de entrega. Los resultados obtenidos permitieron concluir que la solución es viable y especialmente atractiva

Adaptation reconceptualized: "retrofitting" ongoing organizational activities with essential elements of evidence-based interventions

http://deepblue.lib.umich.edu/bitstream/2027.42/134544/1/13012_2015_Article_948.pd

PROCESSING SPEED DIFFERENCES BETWEEN SCHIZOPHRENIA AND SCHIZOAFFECTIVE DISORDER: A PILOT STUDY

We aimed to compare processing speed (PS) and its subcomponents in schizophrenia (SC) and schizoaffective disorder (SA). Thirty-five patients were divided into two groups (SC=18; SA=17). PS tasks from the MATRICS Consensus Cognitive Battery Central/South America version were used. Additional PS subcomponents were analyzed (i.e., behavioral execution, response processing, and accuracy). SA obtained significant higher scores than SC in response processing, verbal fluency and the PS general domain. Our results indicate that PS is a potential cognitive marker to differentiate between SC and SA. Further research with larger samples must be conducted

The Influence of Setting on Care Coordination for Childhood Asthma

Asthma affects 7.1 million children in the United States, disproportionately burdening African American and Latino children. Barriers to asthma control include insufficient patient education and fragmented care. Care coordination represents a compelling approach to improve quality of care and address disparities in asthma. The sites of The Merck Childhood Asthma Network Care Coordination Programs implemented different models of care coordination to suit specific settings—school district, clinic or health care system, and community—and organizational structures. A variety of qualitative data sources were analyzed to determine the role setting played in the manifestation of care coordination at each site. There were inherent strengths and challenges of implementing care coordination in each of the settings, and each site used unique strategies to deliver their programs. The relationship between the lead implementing unit and entities that provided (1) access to the priority population and (2) clinical services to program participants played a critical role in the structure of the programs. The level of support and infrastructure provided by these entities to the lead implementing unit influenced how participants were identified and how asthma care coordinators were integrated into the clinical care team.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/1/MCAN_Settings_Manuscript_20150708.docxhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/3/MCAN_Settings_Manuscript_20150708.pdfDescription of MCAN_Settings_Manuscript_20150708.docx : Main ArticleDescription of MCAN_Settings_Manuscript_20150708.pdf : Main Article with Title Page and Abstrac

Immunogenicity and protection against Mycobacterium caprae challenge in goats vaccinated with BCG and revaccinated after one year

Vaccination has been proposed as a supplementary tool for the control of tuberculosis in livestock. The long-term immunogenicity elicited by bacillus Calmette-Guerin (BCG) and the efficacy of revaccination were investigated in thirty goat kids distributed into three groups: unvaccinated controls, BCG (vaccinated at week 0) and BCG-BCG (vaccinated at weeks 0 and 56). Sixty-four weeks after the first vaccination, all animals were challenged with Mycobacterium caprae and examined post-mortem (pathology and bacterial load) at week 73. Antigen-specific interferon-gamma (IFN-γ) release was measured throughout the experiment. At week 59, peripheral blood mononuclear cells were stained for CD4, CD45RO and IFN-γ to determine the presence of antigen-specific cells secreting IFN-γ. The BCG-BCG group showed reductions in rectal temperatures, M. caprae DNA load in pulmonary lymph nodes (LN), the volume of lesions in pulmonary LN, mineralization in lungs, and higher weight gains compared to unvaccinated controls. IFN-γ responses were undetectable from 32 weeks after primary vaccination until revaccination, when the BCG-BCG group showed detectable IFN-γ production and a greater percentage of antigen-specific CD4+CD45RO+IFNγ+ and CD4-CD45RO+IFNγ+ cells compared to the BCG and control groups, which may be an indicator of the mechanisms of protection. Thus, re-vaccination of goats with BCG appears to prolong protection against infection with M. caprae.info:eu-repo/semantics/publishedVersio

Immunogenicity and protection against Mycobacterium caprae challenge in goats vaccinated with BCG and revaccinated after one year

Vaccination has been proposed as a supplementary tool for the control of tuberculosis in livestock. The long-term immunogenicity elicited by bacillus Calmette-Guerin (BCG) and the efficacy of revaccination were investigated in thirty goat kids distributed into three groups: unvaccinated controls, BCG (vaccinated at week 0) and BCG-BCG (vaccinated at weeks 0 and 56). Sixty-four weeks after the first vaccination, all animals were challenged with Mycobacterium caprae and examined post-mortem (pathology and bacterial load) at week 73. Antigen-specific interferon-gamma (IFN-γ) release was measured throughout the experiment. At week 59, peripheral blood mononuclear cells were stained for CD4, CD45RO and IFN-γ to determine the presence of antigen-specific cells secreting IFN-γ. The BCG-BCG group showed reductions in rectal temperatures, M. caprae DNA load in pulmonary lymph nodes (LN), the volume of lesions in pulmonary LN, mineralization in lungs, and higher weight gains compared to unvaccinated controls. IFN-γ responses were undetectable from 32 weeks after primary vaccination until revaccination, when the BCG-BCG group showed detectable IFN-γ production and a greater percentage of antigen-specific CD4+CD45RO+IFNγ+ and CD4-CD45RO+IFNγ+ cells compared to the BCG and control groups, which may be an indicator of the mechanisms of protection. Thus, re-vaccination of goats with BCG appears to prolong protection against infection with M. caprae.info:eu-repo/semantics/publishedVersio