DNA damage and its association with early-life exposome: Gene-environment analysis in Colombian children under five years old.

Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.

Artificial intelligence, applications and challenges in simulation-based education

The rapid advancement of Artificial Intelligence (AI) has taken the world by "surprise" due to the lack of regulation over this technological innovation which, while promising application opportunities in different fields of knowledge, including education, simultaneously generates concern, rejection and even fear. In the field of Health Sciences Education, clinical simulation has transformed educational practice; however, its formal insertion is still heterogeneous, and we are now facing a new technological revolution where AI has the potential to transform the way we conceive its application.

El rápido avance de la inteligencia artificial (IA) ha tomado al mundo por "sorpresa" debido a la falta de regulación sobre esta innovación tecnológica, que si bien promete oportunidades de aplicación en diferentes campos del conocimiento, incluido el educativo, también genera preocupación e incluso miedo y rechazo. En el campo de la Educación en Ciencias de la Salud la Simulación Clínica ha transformado la práctica educativa; sin embargo, aún es heterogénea su inserción formal, y ahora nos enfrentamos a una nueva revolución tecnológica, en la que las IA tienen el potencial de transformar la manera en que concebimos su aplicación.

Detección de anticuerpos contra Neospora caninum en caninos del área urbana y rural de Cumaral, Meta-Colombia

RESUMEN Objetivo. Estimar la seroprevalencia a Neospora caninum en caninos del área urbana y rural de Cumaral, Meta y determinar algunos factores de riesgo asociados a la seropositividad. Materiales y métodos. Se efectuó un estudio transversal en 222 perros (112 perros del área urbana y 110 del área rural). El tamaño de la muestra fue calculado en el programa Epidat v. 3.1. Los sueros sanguíneos fueron analizados mediante la técnica de Inmunofluorescencia Indirecta para IgG con un kit comercial. Los análisis de frecuencias, chi-cuadrado, fueron realizados mediante el paquete estadístico SPSS v. 25.0 Resultados. La seroprevalencia general fue 36.9% (IC95%: 30.9-43.5 %). La seropositividad entre los grupos fue: urbana (38.4 %) y rural (35.5%) (p>0.05), machos (36.9%) y hembras (36.9%) (p >0.05); en cachorros (32.7%), jóvenes (40.0%) y adultos (37.4%) (p>0.05), en contacto con predios pecuarios (40.7%) y sin contacto (35.2%) (p>0.05). Conclusiones. La seroprevalencia observada fue alta en las dos poblaciones analizadas y sugiere que los caninos han estado en contacto con el parásito, posiblemente por diferentes fuentes de infección que requieren ser estudiadas posteriormente.

ABSTRACT Objective. To estimate the seroprevalence to Neospora caninum in canines of the urban and rural area of Cumaral, Meta and determine some risk factors associated with seropositivity. Materials and methods. A cross-sectional study was carried out in 222 dogs (112 dogs from the urban area and 110 dogs from the rural area), the sample size was calculated by using Epidat v program. 3.1. The sera were analyzed using the Indirect Immunofluorescence technique for IgG with a commercial kit. Frequency analyzes by chi-square of independence were performed in SPSS v. 25.0 Results. The general seroprevalence was 36.9% (95% CI: 30.9-43.5%). The seropositivity between the groups was: urban (38.4%) and rural (35.5%) (p>0.05), males (36.9%) and females (36.9%) (p>0.05); in puppies (32.7%), youth (40.0%) and adults (37.4%) (p>0.05), in contact with livestock farms (40.7%) and without contact (35.2 %) (p>0.05), Conclusions. The seroprevalence observed was high in the two populations analyzed and suggests that the canines have been in contact with the parasite, possibly due to different sources of infection that need to be studied later.

Glucosylceramides From Lomentospora prolificans Induce a Differential Production of Cytokines and Increases the Microbicidal Activity of Macrophages.

Lomentospora prolificans is an emerging opportunistic fungus with a high resistance to antifungal agents and it can cause localized infections in immunocompetent patients and disseminated infections with a high mortality rate in immunosuppressed patients. Glucosylceramides (GlcCer) are synthetized in the majority of known fungal pathogens. They are bioactive molecules presenting different functions, such as involvement in fungal growth and morphological transitions in several fungi. The elucidation of the primary structure of the fungal surface glycoconjugates could contribute for the understanding of the mechanisms of pathogenicity. In this work, GlcCer species were isolated from mycelium and conidia forms of L. prolificans and their chemical structures were elucidated by mass spectrometry (ESI-MS). GlcCer purified from both forms presented a major species at m/z 750 that corresponds to N-2-hydroxyhexadecanoyl-1-ß-D-glucopyranosyl-9-methyl-4,8-sphingadienine. Monoclonal antibodies against GlcCer could recognize L. prolificans GlcCer species from mycelium and conidia, suggesting a conserved epitope in fungal GlcCer. In addition, in vivo assays showed that purified GlcCer species from both forms was able to induce a high secretion of pro-inflammatory cytokines by splenocytes. GlcCer species also promote the recruitment of polymorphonuclear, eosinophils, small peritoneal macrophage (SPM) and mononuclear cells to the peritoneal cavity. GlcCer species were also able to induce the oxidative burst by peritoneal macrophages with NO and superoxide radicals production, and to increase the killing of L. prolificans conidia by peritoneal macrophages. These results indicate that GlcCer species from L. prolificans are a potent immune response activator.

Validación externa del modelo HUSI para la predicción de coledocolitiasis en pacientes con colelitiasis-colecistitis / External validation of the HUSI model for prediction of choledocholithiasis in patients with cholelithiasis-cholecystitis

Introducción. La probabilidad de que los pacientes con colelitiasis cursen con coledocolitiasis y determinar si realmente el cálculo se encuentra en la vía biliar, siguen siendo un reto para el cirujano. La toma de decisiones puede generar costos elevados, por lo que se requiere evaluar con exactitud la probabilidad de cálculos en la vía biliar y la utilidad de las escalas de probabilidad. Objetivo. Validar externamente el modelo de predicción de coledocolitiasis desarrollado por Domínguez, et al., en el Hospital Universitario de San Ignacio, haciendo una evaluación preoperatoria de la coledocolitiasis en pacientes con colelitiasis-colecistitis en Medellín. Material y métodos. Se revisaron de manera retrospectiva 2.122 historias clínicas de pacientes con diagnóstico de colelitiasis-colecistitis en el Hospital Pablo Tobón Uribe, de las cuales 201 fueron incluidas en este estudio. Se usó la escala propuesta de predicción de coledocolitiasis, evaluando los costos directos del modelo de uso de recursos diagnósticos. Resultados. Se incluyeron 201 pacientes (117 mujeres y 84 hombres), con edad media de 54 años. El riesgo de coledocolitiasis en la población evaluada fue de 19,9 %, distribuido por grupos, así: población normal, 0 %; con bajo riesgo, 5,26 %; con riesgo intermedio, 52,6 %, y con riesgo alto, 93,7 %. El área bajo la curva ROC para el modelo predictivo fue de 0,95 (IC95% 0,92-0,98). Según el análisis de los costos por grupos de riesgo, en los pacientes con riesgo normal, se obtuvo un sobrecosto de COP$ 7'010.000 y, en aquellos con riesgo bajo, uno de COP$ 44'013.500; en el grupo con riesgo medio, contrario a los demás grupos, se obtuvo una disminución de COP$ 26'829.000, mientras en el grupo de riesgo alto el sobrecosto fue de COP$ 977.500. Conclusiones. El modelo ofrece un buen rendimiento para predecir el riesgo de coledocolitiasis en la población estudiada. Si la escala se usa correctamente y se sigue el protocolo establecido con los pacientes, se disminuyen los estudios innecesarios y los costos, y se hace un uso racional de los recursos

Introduction. To determine the probability of choledocholithiasis in patients with cholelithiasis and to predict if the biliary stones are located at the common bile duct is a challenge for surgeons. Decision making can increase costs, so it is necessary to define the utility of predictive scores in these cases. Objective. To validate the score to predict coledocolitiasis in patients with cholelithiasis developed by Domínguez, et al., in an external cohort in Medellín. Material y methods. 2122 clinical records of patients with diagnosis of cholecystitis/ cholelithiasis were reviewed at the Hospital Pablo Tobón Uribe. The Dominguez score was used to predict probability of choledocholithiasis and we calculated the use of resources and costs. Area under ROC curve was calculated. Results. 201 patients (117 women and 84 men), with a mean age of 54 years were included. The frequency of choledocholithiasis was 19,9 %, distributed by risk groups: no risk, 0 %; low risk, 5,26 %; intermediate risk, 52,6 %, and high risk, 93,7 %. Area under ROC curve was 0,95 (IC95% 0,92-0,98). Regarding costs, overrun was: COP$ 7'010.000 in patients without risk, COP$ 44'013.500 in those with low risk and COP$ 977.500 in the high-risk group. In the intermediate risk group there was a saving of COP$ 26'829.000. Conclusions. The Dominguez score offer good performance to predict choledocholithiasis. If the score is used according to recommendations, unnecessary costs decrease and more rational use of resources is achieved

Paracoccidioides brasiliensis vaccine formulations based on the gp43-derived P10 sequence and the Salmonella enterica FliC flagellin.

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. Anti-PCM vaccine formulations based on the secreted fungal cell wall protein (gp43) or the derived P10 sequence containing a CD4(+) T-cell-specific epitope have shown promising results. In the present study, we evaluated new anti-PCM vaccine formulations based on the intranasal administration of P. brasiliensis gp43 or the P10 peptide in combination with the Salmonella enterica FliC flagellin, an innate immunity agonist binding specifically to the Toll-like receptor 5, in a murine model. BALB/c mice immunized with gp43 developed high-specific-serum immunoglobulin G1 responses and enhanced interleukin-4 (IL-4) and IL-10 levels. On the other hand, mice immunized with recombinant purified flagellins genetically fused with P10 at the central hypervariable domain, either flanked or not by two lysine residues, or the synthetic P10 peptide admixed with purified FliC elicited a prevailing Th1-type immune response based on lung cell-secreted type 1 cytokines. Mice immunized with gp43 and FliC and intratracheally challenged with P. brasiliensis yeast cells had increased fungal proliferation and lung tissue damage. In contrast, mice immunized with the chimeric flagellins and particularly those immunized with P10 admixed with FliC reduced P. brasiliensis growth and lung damage. Altogether, these results indicate that S. enterica FliC flagellin modulates the immune response to P. brasiliensis P10 antigen and represents a promising alternative for the generation of anti-PCM vaccines.