Fluorescence imaging contrast in guided surgery on nerves measured in rats in vivo

An appropriate identification of the tissue type that is in front of the excision surgical tool is critical, for either tumoral tissue removal, or even accessory healthy tissues whose destruction could cause severe collateral damage. Healthy tissue distinction is an unsolved task in real surgical praxis, due for instance to alterations or hemorrhages. Many approaches have tried to solve the problem of healthy tissue discrimination, such as spectroscopy. Diffuse Reflectance Spectroscopy (DRS), an easy to implement and reliable optical diagnostic technique, has shown great potential in tumoral tissue discrimination, as long as in healthy tissue distinction. However, the identification of nerve tissue in particular is challenging. What is more, nerve tissue distinction is critical in surgical interventions, due to the severe irreversible dysfunctions in patient mobility that collateral damage could cause. Fluorescence is an optical technique that could be of relevance for nerve identification. The need of specific fluorophores that tend to accumulate preferentially on nerve tissue is essential for this task. Image quality requires also an analysis of the optical source, filters employed, fluorophore concentration or inoculation method. Together with those aspects, additional open questions include incubation time or cytotoxicity, critical for clinical translation. In this work, fluorescence imaging for nerve identification is applied on in vivo rats. The approach uses several fluorophore concentrations, based on Oxazine, and combines topical and intravascular inoculation. Optical irradiance is considered for image contrast. The results show an appreciable nerve contrast for optimized parameters.This work has been partially supported by the project “High-pressure driven plasmonic and luminescence properties ofnaked and core/shell metal-oxide nanocomposites” (PGC2018-101464-B-I00) of the Spanish Ministry of Science, Research and Universities, cofunded by FEDER funds, and by the San Cándido Foundation

Comparación del entorno IBM Websphere BPM y sus equivalentes funcionales en código fuente abierto

BPM (Business Process Management) se encarga de la gestión de procesos de negocio en el marco empresarial. Es un enfoque integral en el cual se modelan las características y restricciones de los procesos en todas las etapas de su ciclo de vida, apuntando fundamentalmente a automatizar la mayor cantidad de tareas de manera de lograr un control integral que permita dar soporte, simular, modelar y monitorear en forma controlada las actividades del proceso. Este trabajo tiene como finalidad analizar el entorno IBM Websphere BPM haciendo hincapié en las etapas del ciclo de vida de los procesos que este cubre, como así también las capacidades de desarrollo e integración para la interacción de los procesos con aplicaciones reales. Por otro lado, observar las alternativas que ofrece el mercado en herramientas BPM de licenciamiento de código fuente abierto, intentando lograr un grado de integración y cohesión similar al logrado por la herramienta de IBM.Eje: ingeniería de softwareRed de Universidades con Carreras en Informátic

Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: Modulation of inflammatory pathways

Major Depression is a severe psychiatric condition with a still poorly understood etiology. In the last years, evidence supporting the neuroinflammatory hypothesis of depression has increased. In the current clinical scenario, in which the available treatments for depression is far from optimal, there is an urgent need to develop fast-acting drugs with fewer side effects. In this regard, recent pieces of evidence suggest that cannabidiol (CBD), the major non-psychotropic component of Cannabis sativa with anti-inflammatory properties, appears as a drug with antidepressant properties. In this work, CBD 30 mg/kg was administered systemically to mice 30 min before lipopolysaccharide (LPS; 0.83 mg/kg) administration as a neuroinflammatory model, and behavioral tests for depressive-, anhedonic- and anxious-like behavior were performed. NF-?B, I?B? and PPAR? levels were analyzed by western blot in nuclear and cytosolic fractions of cortical samples. IL-6 and TNF? levels were determined in plasma and prefrontal cortex using ELISA and qPCR techniques, respectively. The precursor tryptophan (TRP), and its metabolites kynurenine (KYN) and serotonin (5-HT) were measured in hippocampus and cortex by HPLC. The ratios KYN/TRP and KYN/5-HT were used to estimate indoleamine 2,3-dioxygenase (IDO) activity and the balance of both metabolic pathways, respectively. CBD reduced the immobility time in the tail suspension test and increased sucrose preference in the LPS model, without affecting locomotion and central activity in the open-field test. CBD diminished cortical NF-?B activation, IL-6 levels in plasma and brain, and the increased KYN/TRP and KYN/5-HT ratios in hippocampus and cortex in the LPS model. Our results demonstrate that CBD produced antidepressant-like effects in the LPS neuroinflammatory model, associated to a reduction in the kynurenine pathway activation, IL-6 levels and NF-?B activation. As CBD stands out as a promising antidepressant drug, more research is needed to completely understand its mechanisms of action in depression linked to inflammation.FUNDING AND ACKNOWLEDGMENTS: This research was supported by the Ministerio de Economía y Competitividad (SAF2015-67457-R MINECO/FEDER), the Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00), the Instituto de Salud Carlos III (PI19/00170), and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). E F-Z was supported by a predoctoral fellowship from the Universidad de Cantabria (Spain). We acknowledge the technical assistance of Annamaria Architravo and Deborah Vasturzo, and Dr Rebeca Vidal for her scientific advice

Sistema basado en BPM para el seguimiento del proceso licitario y la ejecución de proyectos del programa PMGM-UEC : Ministerio del Interior y Transporte de la Nación Argentina

Desde el punto de vista de las organizaciones, los procesos de negocio son esenciales para comprender cómo operan las mismas y descubrir en qué medida los objetivos del negocio se alinean con los objetivos de la organización. BPM es una estrategia para gestionar y mejorar el rendimiento de un negocio optimizando sus procesos a través de la modelización, ejecución y medida de rendimiento dentro de un ciclo de mejora continua. El presente trabajo describe la experiencia de implementación de un sistema basado en BPM para el seguimiento del proceso licitatorio en una organización pública y muestra las mejoras obtenidas como consecuencia de dicha implementación.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Sistema basado en BPM para el seguimiento del proceso licitario y la ejecución de proyectos del programa PMGM-UEC : Ministerio del Interior y Transporte de la Nación Argentina

Desde el punto de vista de las organizaciones, los procesos de negocio son esenciales para comprender cómo operan las mismas y descubrir en qué medida los objetivos del negocio se alinean con los objetivos de la organización. BPM es una estrategia para gestionar y mejorar el rendimiento de un negocio optimizando sus procesos a través de la modelización, ejecución y medida de rendimiento dentro de un ciclo de mejora continua. El presente trabajo describe la experiencia de implementación de un sistema basado en BPM para el seguimiento del proceso licitatorio en una organización pública y muestra las mejoras obtenidas como consecuencia de dicha implementación.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Sistema basado en BPM para el seguimiento del proceso licitario y la ejecución de proyectos del programa PMGM-UEC : Ministerio del Interior y Transporte de la Nación Argentina

Desde el punto de vista de las organizaciones, los procesos de negocio son esenciales para comprender cómo operan las mismas y descubrir en qué medida los objetivos del negocio se alinean con los objetivos de la organización. BPM es una estrategia para gestionar y mejorar el rendimiento de un negocio optimizando sus procesos a través de la modelización, ejecución y medida de rendimiento dentro de un ciclo de mejora continua. El presente trabajo describe la experiencia de implementación de un sistema basado en BPM para el seguimiento del proceso licitatorio en una organización pública y muestra las mejoras obtenidas como consecuencia de dicha implementación.Sociedad Argentina de Informática e Investigación Operativa (SADIO

mTOR knockdown in the infralimbic cortex evokes a depressive-like state in mouse

Fast and sustained antidepressant effects of ketamine identified the mammalian target of rapamycin (mTOR) signaling pathway as the main modulator of its antidepressive effects. Thus, mTOR signaling has become integral for the preclinical evaluation of novel compounds to treat depression. However, causality between mTOR and depression has yet to be determined. To address this, we knocked down mTOR expression in mice using an acute intracerebral infusion of small interfering RNAs (siRNA) in the infralimbic (IL) or prelimbic (PrL) cortices of the medial prefrontal cortex (mPFC), and evaluated depressive- and anxious-like behaviors. mTOR knockdown in IL, but not PrL, cortex produced a robust depressive-like phenotype in mice, as assessed in the forced swimming test (FST) and the tail suspension test (TST). This phenotype was associated with significant reductions of mTOR mRNA and protein levels 48 h post-infusion. In parallel, decreased brain-derived neurotrophic factor (BDNF) expression was found bilaterally in both IL and PrL cortices along with a dysregulation of serotonin (5-HT) and glutamate (Glu) release in the dorsal raphe nucleus (DRN). Overall, our results demonstrate causality between mTOR expression in the IL cortex and depressive-like behaviors, but not in anxiety.Funding: This research was funded by grants of the Ministerio de Economía y Competitividad (SAF2011-25020 and SAF2015-67457-R MINECO); Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00); Ministerio de Ciencia e Innovación (PID2019-105136RB-100); and the European Regional Development Fund (ERDF), UE; Instituto de Salud Carlos III (PI19/00170), and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)

Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study

Ketamine has rapid and robust antidepressant effects. However, unwanted psychotomimetic effects limit its widespread use. Hence, several studies examined whether GluN2B-subunit selective NMDA antagonists would exhibit a better therapeutic profile. Although preclinical work has revealed some of the mechanisms of action of ketamine at cellular and molecular levels, the impact on brain circuitry is poorly understood. Several neuroimaging studies have examined the functional changes in the brain induced by acute administration of ketamine and Ro 25-6981 (a GluN2B-subunit selective antagonist), but the changes in the microstructure of gray and white matter have received less attention. Here, the effects of ketamine and Ro 25-6981 on gray and white matter integrity in male Sprague-Dawley rats were determined using diffusion-weighted magnetic resonance imaging (DWI). In addition, DWI-based structural brain networks were estimated and connectivity metrics were computed at the regional level. Immunohistochemical analyses were also performed to determine whether changes in myelin basic protein (MBP) and neurofilament heavy-chain protein (NF200) may underlie connectivity changes. In general, ketamine and Ro 25-6981 showed some opposite structural alterations, but both compounds coincided only in increasing the fractional anisotropy in infralimbic prefrontal cortex and dorsal raphe nucleus. These changes were associated with increments of NF200 in deep layers of the infralimbic cortex (together with increased MBP) and the dorsal raphe nucleus. Our results suggest that the synthesis of NF200 and MBP may contribute to the formation of new dendritic spines and myelination, respectively. We also suggest that the increase of fractional anisotropy of the infralimbic and dorsal raphe nucleus areas could represent a biomarker of a rapid antidepressant response.Funding: Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from the Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación (PI13/00038, PI16/00217 and PI19/00170 to A.A.) that were co-funded by the European Regional Development Fund (‘A way to build Europe’); Generalitat Valenciana, Conselleria d’ Educació, Investigació, Cultura i Esport (GV/2018/049 to A.B-S.); Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00 to F.P.-C.). Funding from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III is also acknowledged

Dopamine-induced arrestin recruitment and desensitization of the dopamine D4 receptor is regulated by G protein-coupled receptor kinase-2

The dopamine D4 receptor (D4R) is expressed in the retina, prefrontal cortex, and autonomic nervous system and has been implicated in attention deficit hyperactivity disorder (ADHD), substance use disorders, and erectile dysfunction. D4R has also been investigated as a target for antipsychotics due to its high affinity for clozapine. As opposed to the closely related dopamine D2 receptor (D2R), dopamine-induced arrestin recruitment and desensitization at the D4R have not been studied in detail. Indeed, some earlier investigations could not detect arrestin recruitment and desensitization of this receptor upon its activation by agonist. Here, we used a novel nanoluciferase complementation assay to study dopamine-induced recruitment of β-arrestin2 (βarr2; also known as arrestin3) and G protein-coupled receptor kinase-2 (GRK2) to the D4R in HEK293T cells. We also studied desensitization of D4R-evoked G protein-coupled inward rectifier potassium (GIRK; also known as Kir3) current responses in Xenopus oocytes. Furthermore, the effect of coexpression of GRK2 on βarr2 recruitment and GIRK response desensitization was examined. The results suggest that coexpression of GRK2 enhanced the potency of dopamine to induce βarr2 recruitment to the D4R and accelerated the rate of desensitization of D4R-evoked GIRK responses. The present study reveals new details about the regulation of arrestin recruitment to the D4R and thus increases our understanding of the signaling and desensitization of this receptor

Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation

Postsynaptic 5-HT1A receptors (5-HT1AR) play an important role in anxiety and stress, although their contribution is still controversial. Previous studies report that mice overexpressing postsynaptic 5-HT1ARs show no changes in basal anxiety, though the influence of stress conditions has not been addressed yet. In this study, we used this animal model to evaluate the role of 5-HT1ARs in anxiety response after pre-exposure to an acute stressor. Under basal conditions, 5-HT1AR overexpressing animals presented high corticosterone levels and a lower mineralocorticoid/ glucocorticoid receptor ratio. After pre-exposure to a single stressor, they showed a high anxiety-like response, associated with a blunted increase in corticosterone levels and higher c-Fos activation in the prefrontal cortex. Moreover, these mice also presented a lack of downregulation of hippocampal long-term potentiation after stress exposure. Therefore, higher postsynaptic 5-HT1AR activation might predispose to a high anxious phenotype and an impaired stress coping behavior.Funding sources: This research was supported by Spanish Ministry of Economy and Competitiveness (SAF2011-25020 and SAF2015-67457-R), Instituto de Salud Carlos III (FIS Grant PI13-00038) co-funded by the European Regional Development Fund (‘A way to buildEurope’) and Centro de Investigacion Biomedica en Red de Salud Mental(CIBERSAM)