Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells

Altres ajuts: La Fundació Marató de TV3Purpose. TRPV1 is a multimodal channel mainly expressed in sensory neurons. We aimed to explore the pharmacodynamics of the TRPV1 agonists, capsaicin, natural capsaicinoids, and piperine in an in vitro bioassay using human PC-3 cells and to examine desensitization and the effect of the specific antagonist SB366791. Methods. PC-3 cells expressing TRPV1 were incubated with Fluo-4. Fluorescence emission changes following exposition to agonists with and without preincubation with antagonists were assessed and referred to maximal fluorescence following the addition of ionomycin. Concentration-response curves were fitted to the Hill equation. Results. Capsaicin and piperine had similar pharmacodynamics (E 204.8 ± 184.3% piperine versus 176.6 ± 35.83% capsaicin, P = 0.8814, Hill coefficient 0.70 ± 0.50 piperine versus 1.59 ± 0.86 capsaicin, P = 0.3752). In contrast, capsaicinoids had lower E (40.99 ± 6.14% capsaicinoids versus 176.6 ± 35.83% capsaicin, P < 0.001). All the TRPV1 agonists showed significant desensitization after the second exposition and their effects were strongly inhibited by SB366791. Conclusion. TRPV1 receptor is successfully stimulated by capsaicin, piperine, and natural capsaicinoids. These agonists present desensitization and their effect is significantly reduced by a TRPV1-specific antagonist. In addition, PC-3 cell bioassays proved useful in the study of TRPV1 pharmacodynamics

Natural history of swallow function during the three-month period after stroke

Oropharyngeal dysphagia is a prevalent complication following stroke (PS-OD), and one that is sometimes spontaneously recovered. This study describes the natural history of PS-OD between admission and three months post-stroke, and the factors associated with its prevalence and development. PS-OD was assessed with the volume- iscosity swallow test (V-VST) in all stroke patients on admission and at the three-month follow-up. We analyzed clinical, demographic, and neuroanatomical factors of 247 older post-stroke patients (National Institute of Health Stroke Scale (NIHSS) = 3.5 ± 3.8), comparing among those with PS-OD the ones with and without spontaneous recovery. PS-OD prevalence on admission was 39.7% (34.0% impaired safety; 30.8%, efficacy) and 41.7% (19.4% impaired safety; 39.3%, efficacy) at three months. Spontaneous swallow recovery occurred in 42.4% of patients with unsafe and in 29.9% with ineffective swallow, associated with younger age and optimal functional status. However, 26% of post-stroke patients developed new signs/symptoms of ineffective swallow related to poor functional, nutritional and health status, and institutionalization. PS-OD prevalence on admission and at the three-month follow-up was very high in the study population. PS-OD is a dynamic condition with some spontaneous recovery in patients with optimal functional status, but also new signs/symptoms can appear due to poor functionality. Regular PS-OD monitoring is needed to identify patients at risk of nutritional and respiratory complications

Methodology for selecting atmospheric monitoring sitesin urban areas affected by emissions from mobile sources

El monitoreo atmosférico es una de las etapas fundamentales en la identificación de estrategias para minimizar, prevenir y controlar los impactos de la dispersión de contaminantes en el aire, sobre la salud pública y el ambiente. Por tanto, el objetivo principal de este articulo consiste en proponer una metodología para la selección de &nbsp;sitios de monitoreo atmosférico en zonas urbanas afectadas por las emisiones de fuentes móviles. Primeramente se identificaron los sitios que presentaban mayor flujo vehicular y se priorizaron teniendo presente&nbsp; los siguientes &nbsp;criterios&nbsp; de selección: seguridad, influencia de otras fuentes, facilidad del montaje de los equipos,&nbsp; accesibilidad al sitio, identificación de barreras y obstáculos,&nbsp; registro histórico de datos &nbsp;y grado de concentración &nbsp;usando el software CALINE 3.La modelación agrupo datos característicos de las vías, meteorológicos y de flujo vehicular de un año típico de la zona en estudio.&nbsp; &nbsp;A cada uno de estos parámetros le es asignada una valoración cuantitativa, la cual define los sitios donde se realizará el monitoreo. Como resultados se desarrolló una guía para seleccionar los lugares en donde se puedan desarrollar campañas de monitoreo atmosférico asociadas a fuentes móviles. La metodología fue aplicada en la ciudad de Cartagena de Indias haciendo uso del modelo de calidad del aire CALINE3.Atmospheric monitoring is one of the fundamental steps in identifying strategies to minimize, prevent and control the impact of the dispersion of pollutants in the air, on public health and the environment. Therefore, the main objective of this article is to propose a methodology for selecting air monitoring sites in urban areas affected by emissions from mobile sources. First, the places with the highest vehicular flow were identified and prioritized according to the following selection criteria: safety, influence of other sources, ease of assembly of equipment, accessibility to the site, identification of barriers and obstacles, historical record of data and degree concentration of the pollutant: in this case carbon monoxide, using CALINE 3 software. The modeling grouped characteristic data related with roads, meteorology and vehicular flow of a typical year of the zone under study. A quantitative assessment is assigned to each of these parameters, which defines the sites where the monitoring will be performed. As a result, it was developed a guide to select those places where atmospheric monitoring campaigns related with mobile sources can be held. This methodology was applied in the city of Cartagena de Indias by using air quality model for assessment, CALINE

Methodology for selecting atmospheric monitoring sitesin urban areas affected by emissions from mobile sources

El monitoreo atmosférico es una de las etapas fundamentales en la identificación de estrategias para minimizar, prevenir y controlar los impactos de la dispersión de contaminantes en el aire, sobre la salud pública y el ambiente. Por tanto, el objetivo principal de este articulo consiste en proponer una metodología para la selección de &nbsp;sitios de monitoreo atmosférico en zonas urbanas afectadas por las emisiones de fuentes móviles. Primeramente se identificaron los sitios que presentaban mayor flujo vehicular y se priorizaron teniendo presente&nbsp; los siguientes &nbsp;criterios&nbsp; de selección: seguridad, influencia de otras fuentes, facilidad del montaje de los equipos,&nbsp; accesibilidad al sitio, identificación de barreras y obstáculos,&nbsp; registro histórico de datos &nbsp;y grado de concentración &nbsp;usando el software CALINE 3.La modelación agrupo datos característicos de las vías, meteorológicos y de flujo vehicular de un año típico de la zona en estudio.&nbsp; &nbsp;A cada uno de estos parámetros le es asignada una valoración cuantitativa, la cual define los sitios donde se realizará el monitoreo. Como resultados se desarrolló una guía para seleccionar los lugares en donde se puedan desarrollar campañas de monitoreo atmosférico asociadas a fuentes móviles. La metodología fue aplicada en la ciudad de Cartagena de Indias haciendo uso del modelo de calidad del aire CALINE3.Atmospheric monitoring is one of the fundamental steps in identifying strategies to minimize, prevent and control the impact of the dispersion of pollutants in the air, on public health and the environment. Therefore, the main objective of this article is to propose a methodology for selecting air monitoring sites in urban areas affected by emissions from mobile sources. First, the places with the highest vehicular flow were identified and prioritized according to the following selection criteria: safety, influence of other sources, ease of assembly of equipment, accessibility to the site, identification of barriers and obstacles, historical record of data and degree concentration of the pollutant: in this case carbon monoxide, using CALINE 3 software. The modeling grouped characteristic data related with roads, meteorology and vehicular flow of a typical year of the zone under study. A quantitative assessment is assigned to each of these parameters, which defines the sites where the monitoring will be performed. As a result, it was developed a guide to select those places where atmospheric monitoring campaigns related with mobile sources can be held. This methodology was applied in the city of Cartagena de Indias by using air quality model for assessment, CALINE

Targeting patient recovery priorities in degenerative cervical myelopathy: Design and rationale for the RECEDE-Myelopathy trial - Study protocol

Introduction: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. Methods and analysis RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. Study design Clinical trial protocol V.2.2 October 2020. Ethics and dissemination Ethical approval has been obtained from HRA - Wales.The results will be presented at an international and national scientific conferences and in a peer-reviewed journals

Targeting patient recovery priorities in degenerative cervical myelopathy:design and rationale for the RECEDE-Myelopathy trial-study protocol

Introduction: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. Methods and analysis: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. Study design: Clinical trial protocol V.2.2 October 2020. Ethics and dissemination: Ethical approval has been obtained from HRA - Wales. The results will be presented at an international and national scientific conferences and in a peer-reviewed journals.Trial registration number: ISRCTN Number: ISRCTN16682024.</p

Exploring the capacity for anaerobic biodegradation of polycyclic aromatic hydrocarbons and naphthenic acids by microbes from oil-sands-process-affected waters

Both polycyclic aromatic hydrocarbons (PAHs) and naphthenic acids (NAs) are natural components of fossil fuels, but they are also widespread toxic and environmentally persistent pollutants. They are the major cause of environmental toxicity in oil-sands-process waters (OSPW). This study aimed to investigate the anaerobic biodegradation of the PAHs pyrene and 2-methylnaphthalene, and the NAs adamantane-1-carboxylic acid and a "natural" NA mixture (i.e., acid-extractable NAs from OSPW) under sulfate-reducing and methanogenic conditions by a microbial community derived from an oil sands tailings pond. Using gas-chromatography mass spectrometry (GC-MS), the rate of biodegradation was measured in relation to changes in bacterial community composition. Only 2-methylnaphthalene was significantly degraded after 260 days, with significantly more degradation under sulfate-reducing (40%) than methanogenic conditions (25%). During 2-methylnaphthalene biodegradation, a major metabolite was produced and tentatively identified as 2-naphthoic acid. Denaturing gradient gel electrophoresis (DGGE) demonstrated an increase in intensity of bands during the anaerobic biodegradation of 2-methylnaphalene, which derived from species of the genera Fusibacter, Alkaliphilus, Desulfobacterium, Variovorax, Thaurea, and Hydrogenophaga. Despite the biodegradation of 2-methylnaphthalene, this study demonstrates that, under anaerobic conditions, NAs and high-molecular-weight PAHs are the predominant molecules likely to persist in OSPW. Therefore alternative remediation strategies are required

Targeting patient recovery priorities in degenerative cervical myelopathy: design and rationale for the RECEDE-Myelopathy trial-study protocol.

INTRODUCTION: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. METHODS AND ANALYSIS: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. STUDY DESIGN: Clinical trial protocol V.2.2 October 2020. ETHICS AND DISSEMINATION: Ethical approval has been obtained from HRA-Wales.The results will be presented at an international and national scientific conferences and in a peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN Number: ISRCTN16682024

Procesos de aplicación conceptual y práctico de la normatividad tributaria en contextos investigativos procedimentales tributarios para el fortalecimiento de las competencias disciplinares y profesionales

La presente investigación planteó como objetivo realizar las memorias con las temáticas investigativas que se desarrollaron en el Seminario de Investigación Aplicada, con el fin de actualizar en los participantes y fortalecer sus conocimientos específicos en materia tributaria con base en los temas investigativos dispuestos y orientados por cada docente desde su inicio, elaboración, construcción y presentación ante los docentes evaluadores. Los trabajos cumplen su fin primordial con es fortalecer con los desarrollos temático de cada módulo visto en el SIA sus capacidades y competencias profesionales especialmente en el contexto tributario, en cumplimiento al requerimiento para otorgar al título de Especialistas en Gerencia Tributaria. Luego las memorias compiladas son el resultado de los trabajos presentados y evaluados oportunamente por cada docente comprometido con la calidad en cuanto a las temáticas investigativas, calidad de los contenidos, talleres teóricos prácticos, elementos metodológicos y de más lineamentos institucionales y del programa. La importancia de las memorias radica en su contenido el cual desglosa definiciones, conceptos, desarrollos teóricos prácticos, constituyéndose en un ejemplar de consulta investigativa en áreas de conocimiento fiscal y tributario en el marco de la Ley 1819 de 2016 y sus decretos reglamentarios, en síntesis al interior encontraremos fundamentos teóricos prácticos, procedimentales y resolutivos de casos especiales de Gravamen a los Movimientos Financieros, Monotributo, Renta Personas Naturales, Renta Personas Jurídicas, Procedimiento Tributario, Impuestos Distritales, Normas internacionales de Información Financiera Pymes, entre otros temas

Positive feedbacks and alternative stable states in forest leaf types

The emergence of alternative stable states in forest systems has significant implications for the functioning and structure of the terrestrial biosphere, yet empirical evidence remains scarce. Here, we combine global forest biodiversity observations and simulations to test for alternative stable states in the presence of evergreen and deciduous forest types. We reveal a bimodal distribution of forest leaf types across temperate regions of the Northern Hemisphere that cannot be explained by the environment alone, suggesting signatures of alternative forest states. Moreover, we empirically demonstrate the existence of positive feedbacks in tree growth, recruitment and mortality, with trees having 4–43% higher growth rates, 14–17% higher survival rates and 4–7 times higher recruitment rates when they are surrounded by trees of their own leaf type. Simulations show that the observed positive feedbacks are necessary and sufficient to generate alternative forest states, which also lead to dependency on history (hysteresis) during ecosystem transition from evergreen to deciduous forests and vice versa. We identify hotspots of bistable forest types in evergreen-deciduous ecotones, which are likely driven by soil-related positive feedbacks. These findings are integral to predicting the distribution of forest biomes, and aid to our understanding of biodiversity, carbon turnover, and terrestrial climate feedbacks