AKT and JUN are differentially activated in mesenchymal stem cells after infection with human and canine oncolytic adenoviruses

Factor de impacto: 5,987 Q1There is increasing evidence about the use of oncolytic adenoviruses (Ads) as promising immunotherapy agents. We have previously demonstrated the clinical efficiency of mesenchymal stem cells (MSCs) infected with oncolytic Ads as an antitumoral immunotherapy (called Celyvir) in human and canine patients, using ICOVIR-5 or ICOCAV17 as human and canine oncolytic Ads, respectively. Considering the better clinical outcomes of canine patients, in this study we searched for differences in cellular responses of human and canine MSCs to Ad infection that may help understand the mechanisms leading to higher antitumor immune response. We found that infection of human and canine MSCs with ICOVIR-5 or ICOCAV17 did not activate the NF-κB pathway or the interferon regulatory factors IRF3 and IRF7. However, we observed differences in the profile of cytokines secretion, as infection of canine MSCs with ICOCAV17 resulted in lower secretion of several cytokines. Moreover, we showed that infection of human MSCs with ICOVIR-5 increased the phosphorylation of a number of proteins, including AKT and c-JUN. Finally, we demonstrated that differences in regulation of AKT and c-JUN in human and canine MSCs by ICOVIR-5 or ICOCAV17 are intrinsic to each virus. Our findings suggest that ICOCAV17 induces a more limited host response in canine MSCs, which may be related to a better clinical outcome. This result opens the possibility to develop new human oncolytic Ads with these specific properties. In addition, this improvement could be imitated by selecting specific human MSC on the basis of a limited host response after Ad infection.This study was funded by Instituto de Salud Carlos III (PI14CIII/00005 and PI17CIII/00013 grants), Consejería de Educación, Juventud y Deporte of Comunidad de Madrid (P2017/BMD-3692 grant), Fundación Oncohematología Infantil, AFANION, and Asociación Pablo Ugarte, whose support we gratefully acknowledge.S

An integrated approach of AHP-DEMATEL methods applied for the selection of allied hospitals in outpatient service

Nowadays, the citizens are more aware of high-quality medical care than ever. They pay much attention to medical treatment safety, instructions from physicians, and the overall service quality performed by the hospital. To manage a hospital successfully, the important goals are to attract and then retain as many patients as possible by meeting potential demands of various kinds of the patients. In this context the decision making process is important in order to achieve a strategic decision and strategy. When the decision making problem occurs there is usually a limited number of possible alternatives but a large number of criteria according to which the optimal solution is selected. It is important to use an appropriate approach. This study presents a hybrid methodological approach based on the Decision Making Trial and Evaluation Laboratory (DEMATEL) method and Analytic Hierarchy process method to define the best allied hospital for an integrated network of outpatient service. The goal of this paper is to present a methodological approach and a practical application of hybrid method in a real case study

Play in Children with Neurodevelopmental Disorders: Psychometric Properties of a Parent Report Measure ‘My Child’s Play’

Play is essential in childhood, allowing for a positive trend in development and learning. Health professionals need useful tools to assess it, especially in the case of children with neurodevelopmental disorders. The aim of this study was to validate and cross-culturally adapt the My Child’s Play questionnaire and to find out if this instrument allows us to differentiate the play of children with neurodevelopmental disorders from the play of children with neurotypical development. A total of 594 parents completed the questionnaire. A confirmatory factor analysis was conducted, which showed a similar structure to the English version: (1) executive functions; (2) environmental context; (3) play characteristics; and (4) play preferences and interpersonal interactions. The reliability of the analysis was high, both for the whole questionnaire and for the factors it comprises. The results provide evidence of the potential usefulness of the My Child’s Play questionnaire for determining play needs and difficulties of children; moreover, this tool can also be used to plan intervention programs according to the needs of each child and family

Immunosuppressive and angiogenic cytokine profile associated with Bartonella bacilliformis infection in post-outbreak and endemic areas of Carrion's disease in Peru

Analysis of immune responses in Bartonella bacilliformis carriers are needed to understand acquisition of immunity to Carrion's disease and may allow identifying biomarkers associated with bacterial infection and disease phases. Serum samples from 144 healthy subjects from 5 villages in the North of Peru collected in 2014 were analyzed. Four villages had a Carrion's disease outbreak in 2013, and the other is a traditionally endemic area. Thirty cytokines, chemokines and growth factors were determined in sera by fluorescent bead-based quantitative suspension array technology, and analyzed in relation to available data on bacteremia quantified by RT-PCR, and IgM and IgG levels measured by ELISA against B. bacilliformis lysates. The presence of bacteremia was associated with low concentrations of HGF (p = 0.005), IL-15 (p = 0.002), IL-6 (p = 0.05), IP-10 (p = 0.008), MIG (p = 0.03) and MIP-1alpha (p = 0.03). In multi-marker analysis, the same and further TH1-related and pro-inflammatory biomarkers were inversely associated with infection, whereas angiogenic chemokines and IL-10 were positively associated. Only EGF and eotaxin showed a moderate positive correlation with bacteremia. IgM seropositivity, which reflects a recent acute infection, was associated with lower levels of eotaxin (p = 0.05), IL-6 (p = 0.001), and VEGF (p = 0.03). Only GM-CSF and IL-10 concentrations were positively associated with higher levels of IgM (p = 0.01 and p = 0.007). Additionally, IgG seropositivity and levels were associated with high levels of angiogenic markers VEGF (p = 0.047) and eotaxin (p = 0.006), respectively. Our findings suggest that B. bacilliformis infection causes immunosuppression, led in part by overproduction of IL-10. This immunosuppression probably contributes to the chronicity of asymptomatic infections favoring B. bacilliformis persistence in the host, allowing the subsequent transmission to the vector. In addition, angiogenic markers associated with bacteremia and IgG levels may be related to the induction of endothelial cell proliferation in cutaneous lesions during chronic infections, being possible candidate biomarkers of asymptomatic infections

Label-free optical biosensing with slot-waveguides.

We demonstrate label-free molecule detection by using an integrated biosensor based on a Si3N4 /SiO2 slotwaveguide microring resonator. Bovine serum albumin (BSA) and anti-BSA molecular binding events on the sensor surface are monitored through the measurement of resonant wavelength shifts with varying biomolecule concentrations. The biosensor exhibited sensitivities of 1.8 and 3.2 nm/ _ng/mm2_ for the detection of anti-BSA and BSA, respectively. The estimated detection limits are 28 and 16 pg/mm2 for anti-BSA and BSA, respectively, limited by wavelength resolutio

Biophotonic Sensing Cells (BICELLs) for label-free biosensing

Label free immunoassay sector is a ferment of activity, experiencing rapid growth as new technologies come forward and achieve acceptance. The landscape is changing in a “bottom up” approach, as individual companies promote individual technologies and find a market for them. Therefore, each of the companies operating in the label-free immunoassay sector offers a technology that is in some way unique and proprietary. However, no many technologies based on Label-free technology are currently in the market for PoC and High Throughput Screening (HTS), where mature labeled technologies have taken the market

La sabiduría en Tomás de Aquino. Inspiración y reflexión: perspectivas filosóficas y teológicas

¿Por qué escribir un libro sobre la sabiduría según la pensó santo Tomás? ¿Por qué hablar de aquello sobre lo que, en alguna medida, Tomás prefirió callar? Porque expresar a Dios con palabras humanas sigue siendo una tarea que hay que abordar; y explicar, a la luz de la fe, la naturaleza de la sabiduría es todavía una tarea necesaria. De allí que quienes transitamos en este valle de lágrimas sin haber experimentado las cumbres místicas de un santo Tomás, de un san Juan de la Cruz, de una santa Teresa, debemos conocer y amar mejor a Dios cultivando la sabiduría filosófica, la práctica y la teológica. Este libro lo hace reflexionando sobre la misma naturaleza de la sabiduría que cultiva. Y lo hace en espera del día en que sea posible callar definitivamente, por haber alcanzado, junto a un Buey Mudo que hoy solo contempla gozoso a su Amado, la sabiduría eterna en la visión de Dios. José Luis Widow Este trabajo es uno de los resultados de investigación del Proyecto Dewan en español (2008-) desarrollado por el grupo Lumen de la Escuela de Filosofía y Humanidades, Universidad Sergio Arboleda. El proyecto ha tenido como objetivo principal traducir, analizar y difundir en el ámbito de habla hispana, tanto la magistral obra del filósofo tomista canadiense Lawrence Dewan, O.P., como la de aquellos expertos del tomismo que desarrollan una línea de pensamiento afín a la de Dewan

Caracterización de la cimentación y suelo subyacente de la Giralda de Sevilla/España

The objective of this work is to investigate the Giralda's typology and composition of its foundation, as well as the characteristics of the underlying foundation soil, coincident with the celebration of the 800 th anniversary of completing the muslin tower. The results of the investigation show us some important aspects as foundation deep, around 5 meters from the actual pavement; the existence of a small overwide in it; its composition made of calcarenite bedstone; the preparation of the support... In relation to the soil it has been fixed its bearing capacity; the abasements along the different phases in the tower's building and its time evolution; the differential abasement that justify the very small heeling and other soil characteristics, that explain the stability of this Universal Monument.Este estudio se ha realizado con el objetivo de investigar la naturaleza, tipología y composición de la cimentación de la Giralda, así como las características del terreno subyacente que sirve de apoyo, coincidiendo con la celebración de los 800 años de la terminación de la torre musulmana. Los resultados obtenidos han puesto de manifiesto aspectos tan importantes como la profundidad de la cimentación, en tomo a 5 m desde la actual cota de acerado; la existencia de un pequeño sobreancho en la misma; su composición, a base de sillares de piedra calcarenita; la preparación del terreno de apoyo... Por lo que respecta al suelo, se ha determinado su capacidad portante; los asientos producidos en las diferentes fases de la construcción de la torre y su evolución en el tiempo; el asiento diferencial que justifica la muy ligera inclinación que presenta

Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2–positive advanced breast cancer: Final results from MARIANNE

n/