Modelado computacional y pruebas experimentales de la orientación y transporte de nanoportadores guiados magnéticamente para aplicaciones en distribución localizada de fármacos

RESUMEN: El Alzheimer es una enfermedad fatal y progresiva del cerebro que. con el paso del tiempo, conlleva a un deterioro mental traducido en demencia. Los tratamientos tradicionales contra múltiples patologías como el Alzheimer o el Cáncer implican efectos secundarios, debido entre otras razones, a que las drogas alcanzan tejidos sanos durante su transporte en el cuerpo. Otra importante limitación es que, para alcanzar las células afectadas, en el caso particular de enfermedades neurodegenerativas, los medicamentos deberán atravesar la barrera hematoencefálica: membrana altamente selectiva al paso de sustancias hacia el cerebro. Los nanomateriales han surgido como una alternativa para superar las contravenciones de dichos tratamientos, debido principalmente a su capacidad para ser funcionalizados con macromoléculas biocompatibles, que a su vez pueden conjugarse con medicamentos. De esta forma se construyen nanoportadores de fármacos, cuyo transporte en el cuerpo es susceptible de ser direccionado para lograr la distribución localizada de medicamentos directamente sobre las células afectadas. Adicionalmente, debido a su tamaño, son excelentes candidatos para su translocación a través de la barrera hematoencefálica. Los ferrofluidos son suspensiones de nanopartículas magnéticas cuyo transporte puede ser direccionado por campos magnéticos externos continuos no uniformes, lo que los convierte en una alternativa de transporte en terapias que se benefician por la liberación localizada de fármacos. Sin embargo, este tipo de terapias no se han caracterizado lo suficiente para aplicarse in vivo y los ensayos in vitro son generalmente costosos, demandan tiempo e incluyen errores experimentales. El modelado computacional ha surgido como una alternativa para llevar a cabo ensayos in silico, ya que permite simular experimentos reales en un entorno computacional, eludiendo el error experimental y ahorrando tiempo y recursos. Este proyecto busca avanzar en el transporte y orientación magnética de nanopartículas funcionalizadas con medicamentos a través del cuerpo, en pro del desarrollo de tratamientos de liberación localizada de fármacos a nivel cerebral. Por lo tanto, el objetivo general de este proyecto es modelar y simular el transporte guiado de agentes terapéuticos para el tratamiento del Alzheimer, que se encuentran inmovilizados en nanopartículas magnéticas y confinados en microcanales que emulan en geometría y tortuosidad sistemas vasculares encontrados en proximidad al cerebro humano. Esto se pretende lograr mediante el ensamblaje in silico de dispositivos de microfluídica que permitan modelar y simular el transporte de nanopartículas de magnetita bajo el efecto de campos magnéticos externos continuos. Adicionalmente, se validaron los resultados del modelado computacional mediante el prototipado de un dispositivo de microfluídica con características topológicas y geométricas de sistemas fisiológicos para la posterior liberación y guía de nanopartículas de magnetita. De esta manera, se establecieron los criterios para el direccionamiento magnético de las partículas hacia sitios específicos del dispositivo de microfluídica. Se espera que los resultados del proyecto permitan elucidar los requerimientos para el desarrollo de instrumentación robusta que asegure el direccionamiento de nanopartículas magnéticas en aplicaciones in vivo a través de la manipulación de campos magnéticos

Brotes por Salmonella spp., Staphylococcus aureus y Listeria monocytogenes asociados al consumo de pollo

Introduction. Food borne diseases are a serious public health problem. Poultry are often associatedwith these outbreaks.Objective. A systematic review of the literature is provided concerning the distribution and frequencyof food borne outbreaks associated with consumption of chicken contaminated with Salmonella spp.,Listeria monocytogenes and Staphylococcus aureus.Materials and methods. The search for studies of outbreaks associated with Salmonella, S. aureusand L. monocytogenes was conducted in Medline, Pubmed, Science Direct, Scielo, Cochrane Library(CCRT), Virtual Health Library (VHL), Highwire, HINARI and MedicLatina. Data were obtained for thecalculation of odds ratio (OR) by preparing contingency tables using the RevMan5 program.Results. Seven articles met the inclusion criteria; however, no reports of L. monocytogenes wereobtained. The overall OR was 3.01 (95% CI: 2.37, 3.81); this was interpreted as a significant associationbetween the consumption of contaminated chicken and food poisoning. In the included studiesheterogeneity (p= 0.03) was presented, so it took a subgroup analysis of microorganisms, in the caseof Salmonella OR was 2.67 (95% CI: 2.09 -3.41). No analysis was made for S. aureus reported a singlearticle.Conclusions. The OR indicated a strong association between chicken consumption and acquisition ofsalmonellosis. The main risk factor for acquiring salmonellosis is the consumption of chicken from grillrestaurants.doi: http://dx.doi.org/10.7705/biomedica.v32i3.697Introducción. Las enfermedades transmitidas por alimentos son un serio problema de salud pública y,el pollo, uno de los alimentos asociados con ellas.Objetivo. Determinar la distribución y frecuencia de brotes alimentarios asociados al consumo de pollocontaminado por Salmonella spp., Listeria monocytogenes y Staphylococus aureus, mediante unarevisión sistemática de la literatura científica.Materiales y métodos. Se buscaron los estudios de brotes asociados a Salmonella spp., S. aureus y L.monocytogenes, en las bases de datos Medline, Pubmed, Science Direct, SciELO, Librería Cochrane(CCRT), Biblioteca Virtual en Salud (BVS), Highwire, HINARI y MedicLatina. Se obtuvieron los datospara el cálculo de odds ratios (OR) mediante la elaboración de tablas de contingencia en el programaRevMan5™.Resultados. Siete artículos cumplieron con los criterios de inclusión y no se encontraron reportesde L. monocytogenes. El OR global fue de 3,01 (IC95% 2,37-3,81), lo que se interpreta como unaasociación significativa entre el consumo de pollo contaminado y la infección alimentaria. Se presentó heterogeneidad en los estudios incluidos (p=0,03), por lo que fue necesario un análisis por subgruposde microorganismos; para el caso de Salmonella spp., el OR fue de 2,67 (IC95% 2,09-3,41). No se hizoanálisis para S. aureus por reportarse un solo artículo.Conclusiones. Se encontró un OR de 2,61, lo que indica que hay una fuerte asociación entre el consumode pollo y la adquisición de salmonelosis. El principal factor de riesgo para adquirir salmonelosis es elconsumo de pollo de asadero en los restaurantes. doi: http://dx.doi.org/10.7705/biomedica.v32i3.697

Proactive esophageal cooling protects against thermal insults during high-power short-duration radiofrequency cardiac ablation

[EN] Background Proactive cooling with a novel cooling device has been shown to reduce endoscopically identified thermal injury during radiofrequency (RF) ablation for the treatment of atrial fibrillation using medium power settings. We aimed to evaluate the effects of proactive cooling during high-power short-duration (HPSD) ablation. Methods A computer model accounting for the left atrium (1.5 mm thickness) and esophagus including the active cooling device was created. We used the Arrhenius equation to estimate the esophageal thermal damage during 50 W/ 10 s and 90 W/ 4 s RF ablations. Results With proactive esophageal cooling in place, temperatures in the esophageal tissue were significantly reduced from control conditions without cooling, and the resulting percentage of damage to the esophageal wall was reduced around 50%, restricting damage to the epi-esophageal region and consequently sparing the remainder of the esophageal tissue, including the mucosal surface. Lesions in the atrial wall remained transmural despite cooling, and maximum width barely changed (<0.8 mm). Conclusions Proactive esophageal cooling significantly reduces temperatures and the resulting fraction of damage in the esophagus during HPSD ablation. These findings offer a mechanistic rationale explaining the high degree of safety encountered to date using proactive esophageal cooling, and further underscore the fact that temperature monitoring is inadequate to avoid thermal damage to the esophagus.Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R44HL158375 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health) and by the Spanish Ministerio de Ciencia, Innovacion y Universidades/Agencia Estatal de Investigacion (MCIN/AEI/10.13039/501100011033 under grant RTI2018-094357-B-C21).Mercado Montoya, M.; Gomez Bustamante, T.; Berjano, E.; Mickelsen, SR.; Daniels, JD.; Hernández Arango, P.; Schieber, J.... (2022). Proactive esophageal cooling protects against thermal insults during high-power short-duration radiofrequency cardiac ablation. International Journal of Hyperthermia. 39(1):1202-1212. https://doi.org/10.1080/02656736.2022.21218601202121239

The Use of Core Warming as a Treatment for Coronavirus Disease 2019 (COVID-19): an Initial Mathematical Model

Background: Increasing data suggest that elevated body temperature may be helpful in resolving a variety of diseases, including sepsis, acute respiratory distress syndrome (ARDS), and viral illnesses. SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), may be more temperature sensitive than other coronaviruses, particularly with respect to the binding affinity of its viral entry via the ACE2 receptor. A mechanical provision of elevated temperature focused in a body region of high viral activity in patients undergoing mechanical ventilation may offer a therapeutic option that avoids arrhythmias seen with some pharmaceutical treatments.  We investigated the potential to actively provide core warming to the lungs of patients with a commercially available heat transfer device via mathematical modeling, and examine the influence of blood perfusion on temperature using this approach.  Methods: Using the software Comsol Multiphysics, we modeled and simulated heat transfer in the body from an intraesophageal warming device, taking into account the airflow from patient ventilation. The simulation was focused on heat transfer and warming of the lungs and performed on  a simplified geometry of an adult human body and airway from the pharynx to the lungs.  Results: The simulations were run over a range of values for blood perfusion rate, which was a parameter expected to have high influence in overall heat transfer, since the heat capacity and density remain almost constant. The simulation results show a temperature distribution which agrees with the expected clinical experience, with the skin surface at a lower temperature than the rest of the body due to convective cooling in a typical hospital environment.  The highest temperature in this case is the device warming water temperature, and that heat diffuses by conduction to the nearby tissues, including the air flowing in the airways. At the range of blood perfusion investigated, maximum lung temperature ranged from 37.6°C to 38.6°C. Conclusions: The provision of core warming via commercially available technology currently utilized in the intensive care unit, emergency department, and operating room can increase regional temperature of lung tissue and airway passages. This warming may offer an innovative approach to treating infectious diseases from viral illnesses such as COVID-19, while avoiding the arrhythmogenic complications of currently used pharmaceutical treatments.  

The Use of Core Warming as a Treatment for Coronavirus Disease 2019 (COVID-19): an Initial Mathematical Model

Background: Increasing data suggest that elevated body temperature may be helpful in resolving a variety of diseases, including sepsis, acute respiratory distress syndrome (ARDS), and viral illnesses. SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), may be more temperature sensitive than other coronaviruses, particularly with respect to the binding affinity of its viral entry via the ACE2 receptor. A mechanical provision of elevated temperature focused in a body region of high viral activity in patients undergoing mechanical ventilation may offer a therapeutic option that avoids arrhythmias seen with some pharmaceutical treatments.  We investigated the potential to actively provide core warming to the lungs of patients with a commercially available heat transfer device via mathematical modeling, and examine the influence of blood perfusion on temperature using this approach.  Methods: Using the software Comsol Multiphysics, we modeled and simulated heat transfer in the body from an intraesophageal warming device, taking into account the airflow from patient ventilation. The simulation was focused on heat transfer and warming of the lungs and performed on  a simplified geometry of an adult human body and airway from the pharynx to the lungs.  Results: The simulations were run over a range of values for blood perfusion rate, which was a parameter expected to have high influence in overall heat transfer, since the heat capacity and density remain almost constant. The simulation results show a temperature distribution which agrees with the expected clinical experience, with the skin surface at a lower temperature than the rest of the body due to convective cooling in a typical hospital environment.  The highest temperature in this case is the device warming water temperature, and that heat diffuses by conduction to the nearby tissues, including the air flowing in the airways. At the range of blood perfusion investigated, maximum lung temperature ranged from 37.6°C to 38.6°C. Conclusions: The provision of core warming via commercially available technology currently utilized in the intensive care unit, emergency department, and operating room can increase regional temperature of lung tissue and airway passages. This warming may offer an innovative approach to treating infectious diseases from viral illnesses such as COVID-19, while avoiding the arrhythmogenic complications of currently used pharmaceutical treatments.  

Gestión del conocimiento: perspectiva multidisciplinaria. Volumen 12

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 12, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro cuenta con el apoyo de los grupos de investigación: Universidad Sur del Lago “Jesús María Semprúm” (UNESUR), Zulia – Venezuela; Universidad Politécnica Territorial de Falcón Alonso Gamero (UPTAG), Falcón – Venezuela; Universidad Politécnica Territorial de Mérida Kleber Ramírez (UPTM), Mérida – Venezuela; Universidad Guanajuato (UG) - Campus Celaya - Salvatierra - Cuerpo Académico de Biodesarrollo y Bioeconomía en las Organizaciones y Políticas Públicas (C.A.B.B.O.P.P), Guanajuato – México; Centro de Altos Estudios de Venezuela (CEALEVE), Zulia – Venezuela, Centro Integral de Formación Educativa Especializada del Sur (CIFE - SUR) - Zulia - Venezuela, Centro de Investigaciones Internacionales SAS (CIN), Antioquia - Colombia.y diferentes grupos de investigación del ámbito nacional e internacional que hoy se unen para estrechar vínculos investigativos, para que sus aportes científicos formen parte de los libros que se publiquen en formatos digital e impreso

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 17

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 17 de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada, de acceso abierto a todas las áreas del conocimiento, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico. Con esta colección, se aspira contribuir con el cultivo, la comprensión, la recopilación y la apropiación social del conocimiento en cuanto a patrimonio intangible de la humanidad, con el propósito de hacer aportes con la transformación de las relaciones socioculturales que sustentan la construcción social de los saberes y su reconocimiento como bien público

Seroprevalence of anti-SARS-CoV-2 antibodies in Colombia, 2020: A population-based study

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause very high morbidity and mortality throughout Latin American countries. However, few population-based seroprevalence surveys have been conducted to quantify attack rates and characterize drivers of transmission.MethodsWe conducted a population-based cross-sectional study to assess the seroprevalence of antibodies against SARS-CoV-2 in ten cities in Colombia between September and December 2020. The study involved multi-stage cluster sampling at each city. Participants provided a serum sample and answered a demographic and risk factor questionnaire. Prior infection by SARS-CoV-2 was ascertained using the "SARS-CoV-2 Total (COV2T) Advia Centaur - Siemens" chemiluminescence assay.FindingsA total of 17863 participants from 7320 households participated in the study. Seroprevalence varied substantially between cities, ranging from 26% (95%CI 23-29 %) in Medellín to 68% (95%CI 62-74 %) in Guapi. There were no differences in seroprevalence by sex, but seropositivity was higher in certain ethnic groups. There was substantial heterogeneity in seroprevalence within cities, driven to a large extent by a strong association between socioeconomic stratum and seropositivity.InterpretationColombia has been one of the Latin American countries most affected by the COVID-19 pandemic. This study documented very high attack rates in several Colombian cities by the end of 2020 and identified key drivers of heterogeneities including ethnicity and socioeconomic stratum. Few studies of seroprevalence of SARS-CoV-2 have been conducted in Latin America, and therefore this study contributes to the fundamental understanding of the pandemic in the region.FundingThe study was sponsored by, Ministerio de Ciencia y Tecnología e Innovación -CT361/2020, Ministerio de Salud y Protección Social, Fundación Universitaria del Norte, Imperial College of London, Universidad Nacional de Colombia (Sede Medellín), Universidad de Córdoba, California University, Unidad Nacional de Gestión del Riesgo, Centro de Atención y Diagnóstico de Enfermedades Infecciosas -CDI-, Centro Internacional de Entrenamiento e Investigaciones Médicas -CIDEIM-, Departamento Administrativo Nacional de Estadística - DANE, Fondo Nacional de Turismo -FONTUR-, Secretarías de Salud Departamentales, Distritales y Municipales and Instituto Nacional de Salud