Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR)

In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup's whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation. Five substances, chosen based on evidence provided in the literature, were screened in vitro in neurospheres from untreated rabbits: Docosahexaenoic acid (DHA), melatonin (MEL), zinc, 3,3',5-Triiodo-L-thyronine (T3), and lactoferrin (LF) or its metabolite sialic acid (SA). DHA, MEL and LF were further selected for in vivo administration and subsequent evaluation in the Neurosphere Assay. In the IUGR culture, we observed a significantly reduced percentage of oligodendrocytes (OLs) which correlated with clinical findings indicating white matter injury in IUGR infants. We identified DHA and MEL as the most effective therapies. In all cases, our in vitro rabbit neurosphere assay predicted the outcome of the in vivo administration of the therapies and confirmed the reliability of the model, making it a powerful and consistent tool to select new neuroprotective therapies

Development of customized bioinks for 3D printed dynamic cancer models.

238 p.Esta tesis se ha centrado en el desarrollo de biomateriales basados en matriz extracelular descelularizada (en inglés, dECM) de tejidos porcinos y humanos, para su uso como biotintas en la impresión 3D de modelos dinámicos de cáncer. Debido a la necesidad de modelos alternativos a los animales de experimentación, el desarrollo y la aplicación de alternativas in vitro ha experimentado un crecimiento exponencial. El campo de los modelos de cáncer es particularmente activo debido a la prevalencia y variabilidad de esta enfermedad. Esta tesis se centró principalmente en el melanoma y el cáncer de mama, debido a su creciente incidencia en cáncer metastásico, teniendo como objetivo principal el desarrollo y la validación de biotintas derivadas de dECM para la modelización de tumores sólidos tridimensionales. En concreto, dicha investigación se llevó a cabo mediante el desarrollo de biotintas basadas en tejidos descelularizados; incorporación de nanopartículas para marcar diferentes poblaciones celulares; impresión de modelos tridimensionales de diferentes tumores; y prueba de medicamentos anticancerígenos en los modelos 3D

Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR)

In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup’s whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation. Five substances, chosen based on evidence provided in the literature, were screened in vitro in neurospheres from untreated rabbits: Docosahexaenoic acid (DHA), melatonin (MEL), zinc, 3,3′,5-Triiodo-L-thyronine (T3), and lactoferrin (LF) or its metabolite sialic acid (SA). DHA, MEL and LF were further selected for in vivo administration and subsequent evaluation in the Neurosphere Assay. In the IUGR culture, we observed a significantly reduced percentage of oligodendrocytes (OLs) which correlated with clinical findings indicating white matter injury in IUGR infants. We identified DHA and MEL as the most effective therapies. In all cases, our in vitro rabbit neurosphere assay predicted the outcome of the in vivo administration of the therapies and confirmed the reliability of the model, making it a powerful and consistent tool to select new neuroprotective therapies

The golden hour: Sustainability and clinical outcomes of adequate time to antibiotic administration in children with cancer and febrile neutropenia in northwestern mexico

PURPOSE Time to antibiotic administration (TTA) is a commonly used standard of care in pediatric cancer settings in high-income countries. Effective interventions to improve outcomes in cancer patients with febrile neutropenia (FN) often address timely and appropriate antibiotic administration. We assessed the effectiveness of a locally adapted multimodal strategy in decreasing TTA in a resource-constrained pediatric cancer center in Mexico. METHODS We conducted a prospective observational study between January 2014 and April 2019. A threephase (phase I: Execution, phase II: Consolidation, phase III: Sustainability) multimodal improvement strategy that combined system change, FN guideline development, education, auditing and monitoring, mentoring, and dissemination was implemented to decrease TTA in inpatient and ambulatory areas. Sustainability factors were measured by using a validated tool during phases I and III. RESULTS Our population included 105 children with cancer with 204 FN events. The baseline assessment revealed that only 50% of patients received antibiotics within 60 minutes of prescription (median time: Inpatient, 75 minutes; ambulatory, 65 minutes). After implementing our improvement strategy, the percentage of patients receiving antibiotics within 60 minutes of prescription increased to 88%. We significantly decreased median TTA in both clinical areas during the three phases of the study. In phase III (sustainability), the median TTA was 40 minutes (P = .023) in the inpatient area and 30 minutes (P = .012) in the ambulatory area. The proportion of patients with sepsis decreased from 30% (baseline) to 5% (phase III) (P = .001). CONCLUSION Our results demonstrate that locally adapted multimodal interventions can reduce TTA in resourceconstrained settings. Mentoring and dissemination were novel components of the multimodal strategy to improve FN-associated clinical outcomes. Improving local infrastructure, ongoing monitoring systems, and leadership engagement have been key factors to achieving sustainability during the 5-year period

Guía de Práctica Clínica basada en la evidencia científica para la atención de la infección por VIH en niñas y niños menores de 13 años de edad. Guía completa

El Ministerio de Salud y Protección Social y el Fondo de Población de Naciones Unidas – UNFPA, a través del convenio de cooperación N° 036 de 2012, ha encargado a la Asociación Colombiana de Infectología (ACIN) el desarrollo de una guía de práctica clínica sobre el diagnóstico, tratamiento antirretroviral de primera y segunda línea de niñas y niños menores de 13 años de edad con diagnóstico y/o exposición a VIH/Sida. La guía proporcionará recomendaciones en los tópicos mencionados, basadas en la mejor evidencia disponible y la evaluación económica de una recomendación clave en el proceso, según la recomendación de la Guía metodológica para el desarrollo de guías de práctica clínica de Colombia. Esta guía será material de consulta y referencia para la práctica clínica en los diferentes niveles de atención del Sistema General de Seguridad Social en Salud, basada en recomendaciones extraídas de evidencia de alta calidad y el concurso de expertos en la materia, tanto desde el punto de vista clínico como epidemiológico y metodológico.Guía de práctica clínica1-61