[Reproducibilidad clínica de reacciones de hipersensibilidad a fármacos en pruebas de exposición controlada].

Objective: To assess the reproducibility of symptoms in drug challenge tests. Methods: The study included patients with positive cutaneous or challenge test throughout 2019. For each patient, clinical suspicion according to Karch-Lasagna algorithm was registered. Primary outcome was the reproducibility of symptoms in the provocation tests using a paired analysis of data with McNemar test. Results: Eighty-nine patients were included, 16 of them presented more than one positive test. Thirty were skin tests positive and 75 reacted to provocation tests. Eighty nine percent of patients who reacted in challenge test were probably or possibly reactors according to Karch-Lasagna scale. Symptoms of initial reaction did not differ from those triggered in challenge tests. Conclusions: Karch-Lasagna scale is useful in predicting the response to drug provocation tests. In most of the positive studies, results were suggested by clinical history and no differences were found between symptoms triggered in challenge test and that referred to in the previous reaction.

Objetivo: Evaluar la reproducibilidad de los síntomas en pruebas de exposición con fármacos. Métodos: Estudio retrospectivo, efectuado en pacientes con prueba cutánea o exposición positiva, atendidos en 2019. De cada paciente se registró la sospecha clínica según el algoritmo de Karch-Lasagna. El resultado principal fue la reproducibilidad de síntomas en las pruebas de exposición, mediante el análisis de datos emparejado con prueba de McNemar. Resultados: Se incluyeron 89 pacientes, y de estos 16 reportaron varias pruebas positivas. Se obtuvieron 30 pruebas cutáneas y 75 de exposición positivas. En el 89% de las pruebas de exposición positivas, las reacciones iniciales se clasificaron en probables o posibles, según la escala de Karch-Lasagna. Los síntomas reportados en la reacción inicial no difirieron de los de las pruebas de exposición. Conclusiones: La escala de Karch-Lasagna es un método útil para predecir la respuesta en las pruebas de exposición con fármacos. En la mayor parte de las pruebas positivas, los resultados fueron sugeridos por la historia clínica, sin diferencias entre la manifestación de síntomas en la prueba de exposición versus los referidos en la reacción inicial.

A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

Basophil activation test as alternative method to CAP-inhibition in patients with double sensitization to vespid venoms.

Most patients with Hymenoptera venom allergy (HVA) to vespid venoms present double sensitization by specific IgE (sIgE)-mediated cross-reactivity. Thus, it is mandatory could discriminate between a true double and primary sensitization to implement an accurate venom-specific immunotherapy (VIT). To date, CAP-inhibition is the reference method in the diagnosis of cross-reactivity in double sensitized patients to vespid venoms, being the results obtained with the component resolved diagnostics (CRD) conflicting. For this, we have studied in a cohort of double sensitized patients to Vespula vulgaris (VV) and Polistes dominulus (PD) venoms (n = 40) the diagnostic accuracy of CRD using the CAP-inhibition as reference method, as well as to investigate whether basophil activation test (BAT) is an alternative method for inconclusive results obtained by CAP-inhibition. CAP-inhibition showed a sensitivity of 59.46 % in view of the indeterminate results; most patients had true double sensitization (54.5 %), followed by single sensitization to PD (27.27 %) and VV (18.18 %) venoms. CRD based on rVes v 5/rPol d 5 (or vice versa) ratio as well as whole extracts I3/I77 (or vice versa) ratio (specific IgE-I3 to VV/specific IgE-I77 to PD) showed a low diagnostic accuracy (AUC = 0.504, p = 0.974; AUC = 0.35, p = 0.235; respectively). BAT was determined in parallel with CAP-inhibition in 12 patients, presented higher sensitivity than CAP-inhibition (p = 0.021) and a positive agreement of 71.43 %. Likewise it was able to identify 100% of inconclusive results, showing a specificity of 83.3 %. Therefore, CRD is not a suitable method to distinguish monosensitization and BAT appears to be an appropriate method resolving indeterminate results from the gold standard method.

Epigenetic control of the EWS­FLI1 promoter in Ewing's sarcoma.

Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra­osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS­FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS­FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS­FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS­FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter. The EWS­FLI1 fusion gene was evaluated in two patients with ES using conventional cytogenetic, fluorescence in situ hybridization and nested PCR assays, which revealed that the aberrant expression of the EWS­FLI1 gene is accompanied by enrichment of H3K4Me3, H3K9ac and H3K27ac at the promoter region.

Ex Vivo and In Vivo Biocompatibility Assessment (Blood and Tissue) of Three-Dimensional Bacterial Nanocellulose Biomaterials for Soft Tissue Implants.

Bacterial nanocellulose (BNC) is a promising biomedical material. However, the haemocompatibility (haemolysis and thrombogenicity) and acute and sub-chronic immune responses to three-dimensional (3D) BNC biomaterials have not been evaluated. Accordingly, this manuscript focused on the effect of 3D microporosity on BNC haemocompatibility and a comparison with 2D BNC architecture, followed by the evaluation of the immune response to 3D BNC. Blood ex vivo studies indicated that compared with other 2D and 3D BNC architectures, never-dried 2D BNC presented antihemolytic and antithrombogenic effects. Nevertheless, in vivo studies indicated that 3D BNC did not interfere with wound haemostasis and elicited a mild acute inflammatory response, not a foreign body or chronic inflammatory response. Moreover, compared with the polyethylene controls, the implant design with micropores ca. 60 µm in diameter showed a high level of collagen, neovascularization and low fibrosis. Cell/tissue infiltration increased to 91% after 12 weeks and was characterized by fibroblastic, capillary and extracellular matrix infiltration. Accordingly, 3D BNC biomaterials can be considered a potential implantable biomaterial for soft tissue augmentation or replacement.

[Postanoxic encaphalopathy after and episode of resuscitated sudden death. Minimizing sequelae]. / Encefalopatía postanóxica tras episodio de muerte súbita reanimada. Cómo minimizar los daños.

Sudden death in young people while performing intense physical activity has a very low prevalence but a significant burden in terms of loss of years of life in society and a strong social impact. We present the case of a 19-year-old man who had a cardiac arrest while playing a football match, with prolonged resuscitation, and multiple subsequent complications (acute renal failure, coagulopathy, digestive bleeding, ischaemic colitis, and need for implantable cardioverter-defibrillator placement and hemicolectomy). The onset of intensive early rehabilitation in a specialised centre minimised the sequels, improving the Rankin score from 4 to 2 and Barthel index from 0 to 95 points, allowing the patient to lead an almost autonomous life.

Mercury levels in blood, urine and hair in a nation-wide sample of Spanish adults.

Mercury (Hg) is among the top 10 environmental chemicals of major public health concern (WHO). The Minamata Convention on Mercury (United Nations Environment Program, 2017), commits signing countries to control anthropogenic mercury emissions and reduce human exposure. Human biomonitoring (HBM) programs, are the most straight-forward approaches to get information on the actual exposure levels in the population and assess over time. We report here the results of a HBM study in a nationwide cross-section of Spanish adults (18-65y) as baseline values obtained before the Minamata Convention entered into force. Subsequent follow-ups will show if the Convention has been successful. The study includes 1880 blood samples, 1704 urine samples and 577 hair samples from all Spanish regions collected and analysed under a strictly quality controlled and quality assured protocol. The EU-DEMOCOPHES project demonstrated that fish and seafood are the major sources of mercury exposure and that the Spanish as well as the Portuguese populations have higher levels than other European countries. The data from the present study confirms this pattern at national level and that inhabitants in coastal regions have higher values than from inland regions. The geometric mean (GM) for blood is 6.35 µg Hg/l, in urine is 1.11 µg Hg/l and for hair is 1.91 µg Hg/g. In an international comparison these values are not exceptional. Spanish concentrations fall into the group of Easter Mediterranean populations. Although information on gender, age, occupational sector, geographical area, sampling period and frequency of fish consumption is reported in the tables, the purpose of this paper has not been to analyse the determinants of exposure in detail but to provide baseline data for future assessments and for regional authorities.

Colonización por Pneumocystis jirovecii en la enfermedad pulmonar obstructiva crónica / Colonization by Pneumocystis jirovecii in Chronic Obstructive Pulmonary Disease

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad prevalente en la población colombiana, que característicamente tiene un deterioro progresivo y altera la calidad de vida de los pacientes. Solo del 15% al 20% de los pacientes con antecedente de tabaquismo desarrollan la enfermedad, por lo que factores ambientales y genéticos adicionales influyen en su progresión. De las causas infecciosas que han tomado importancia, el Pneumocystis jiroveái, un hongo ubicuo que entra en contacto con la vía aérea de los humanos desde la infancia, es causa de neumonía en pacientes inmunosuprimidos. Se han descrito tasas elevadas de colonización en pacientes con EPOC, que aumentan con la severidad de la enfermedad. EPOC e infección por P jiroveái parecen compartir una respuesta inmunológica similar; lo cual podría explicar el papel de la colonización por el hongo en su progresión y gravedad.

Chronic obstructive pulmonary disease (COPD) is a prevalent disease in our population, which characteristically has a Progressive deterioration and alters the quality of Iife of patients. Only 15-20% of patients with a history of smoking develop the disease, so there are additional environmental and genetic factors that influence the progression of the disease. Of the infectious causes that have taken importance is Pneumocystis jiroveái, this is a ubiquitous fungus that comes into contact with the airway of humans since childhood and is a cause of pneumonía in immunosuppressed patients. In addition, high rates of colonization have been reported in patients with COPD, which increase with the severity of the disease. COPD and P jiroveái infection appear to share a similar immune response, which may explain the role of fungal colonization in the progression and severity of the disease.

Modelación y parámetros genéticos de curvas de lactancia en bovinos Holstein en Colombia / Modeling and genetic parameters of lactation curves in Holstein bovine breed in Colombia

Objetivo. Evaluar diferentes modelos matemáticos aplicados a las curvas de lactancia, establecer cuál de ellos presenta el mejor ajuste y estimar los parámetros genéticos para las características derivadas del mejor modelo. Materiales y métodos. Se empleó la información de 426797 registros de control lechero mensual de 49108 vacas Holstein de 470 hatos de los departamentos de Cundinamarca, Antioquia, Valle, Boyacá, Nariño y Cauca. Fueron evaluados los modelos matemáticos no lineales propuestos por Wood, Brody, Wilmink y Papajcsik y Bodero. Luego de seleccionar el modelo que mejor ajustó las curvas de lactancia, se estimaron los parámetros genéticos para las características (βo), producción de leche al pico (y max), tiempo al pico (t pico) y producción total a los 305 días (P305) donde se emplearon los efectos fijos de zona, parto y grupo contemporáneo. Resultados. El modelo de Wood presentó valores altos de PAIC y PBIC y valores altos de R². En las características bo, y max, t pico y P305, derivadas del modelo de Wood, el valor promedio fue de 16.64±6.34 lt, 27.39±6.85 lt, 44.55 ± 13.19 días y 6212 ± 1690 lt, respectivamente. Las características βo y t pico presentaron una heredabilidad baja (0.02) y las características y max y P305 presentaron una heredabilidad de baja a media (0.15 y 0.17, respectivamente). Conclusiones. El modelo que mejor ajusta las curvas de lactancia en bovinos Holstein es el modelo de Wood. Las heredabilidades medias y la alta correlación genética entre y max y P305, indican que es posible incluirlas en programas de selección.

Objective. Evaluate different mathematical models applied to lactation curves, determine which of them represent the best fit and estimate genetic parameters for the characteristics derived from the best model. Materials and methods. Information from 426797 monthly milk control records was used from 49108 Holstein cows coming from 470 dairy herds located in Cundinamarca, Antioquia, Valle, Boyacá, Nariño and Cauca. Nonlinear mathematical models proposed by Wood, Brody, Wilmink and Papajcsik and Bodero were evaluated. After selecting the model that best adjusted the lactation curves, genetic parameters were estimated for the characteristics (βo), peak milk production (y max), time to peak (t pico) and total production at 305 days (P305) where the fixed area effects, delivery and contemporary group were used. Results. Wood's model showed high values of PAIC and PBIC and high values of R². In relation to bo, y max, t pico y P305 characteristics, derived from the Wood model, the average value was 16.64 ± 6.34 lt, 27.39 lt ± 6.85, 44.55 ± 13.19 days and 6212 ± 1690 lt, respectively. βo y t pico characteristics presented a low heritability (0.02) and the y max and P305 showed a low to medium heritability (0.15 and 0.17, respectively). Conclusions. The model that best fit lactation curves in Holstein bovines is the Wood model. The average heritability and high genetic correlation between e y max and P305 indicate that it is possible to include them in breeding programs.

Parámetros genéticos de características de tipo y producción en ganado Holstein del departamento de Antioquia / Genetic parameters of type traits and production in Holstein cattle from the Department of Antioquia

Objetivo. Estimar heredabilidades, correlaciones fenotípicas y genotípicas entre 24 características de tipo y producción de leche en vacas Holstein del departamento de Antioquia. Materiales y métodos. Se analizaron un total de 2395 registros de vacas Holstein. Se estimaron componentes de varianza mediante el procedimiento de máxima verosimilitud restricta con modelos animales bi-característicos. Para las características de tipo, el modelo incluyó los efectos fijos de finca, año de nacimiento y país de origen del padre de la vaca, el grupo contemporáneo (año-mes-clasificador) y la covariable edad a la clasificación. Para la producción de leche el modelo incluyó los efectos fijos de finca, año de parto, país y año de nacimiento del padre. Resultados. Las heredabilidades encontradas para las características de tipo variaron de 0.04 a 0.44 y para producción de leche fue de 0.22, los errores estándar de la heredabilidad fueron inferiores a 0.06. Las correlaciones genéticas de producción de leche con las características profundidad de la ubre (-0.72) fue alta, mientras las correlaciones más altas entre las características de tipo fueron entre extremo anterior y tamaño (0.90), ángulo de la pezuña y profundidad del talón (0.98), profundidad del talón y uniformidad de pezuñas (0.85); y ligamento suspensorio medio y colocación de pezones posteriores (0.76). Conclusiónes. Se encontró una considerable variación genética en características de tipo dentro de la población Holstein de Antioquia. Las correlaciones genéticas entre algunas características de tipo fueron altas e indican la posibilidad de reducir el número de características evaluadas en cada animal.

Engineering platforms for directed evolution of Laccase from Pycnoporus cinnabarinus.

While the Pycnoporus cinnabarinus laccase (PcL) is one of the most promising high-redox-potential enzymes for environmental biocatalysis, its practical use has to date remained limited due to the lack of directed evolution platforms with which to improve its features. Here, we describe the construction of a PcL fusion gene and the optimization of conditions to induce its functional expression in Saccharomyces cerevisiae, facilitating its directed evolution and semirational engineering. The native PcL signal peptide was replaced by the α-factor preproleader, and this construct was subjected to six rounds of evolution coupled to a multiscreening assay based on the oxidation of natural and synthetic redox mediators at more neutral pHs. The laccase total activity was enhanced 8,000-fold: the evolved α-factor preproleader improved secretion levels 40-fold, and several mutations in mature laccase provided a 13.7-fold increase in k(cat). While the pH activity profile was shifted to more neutral values, the thermostability and the broad substrate specificity of PcL were retained. Evolved variants were highly secreted by Aspergillus niger (∼23 mg/liter), which addresses the potential use of this combined-expression system for protein engineering. The mapping of mutations onto the PcL crystal structure shed new light on the oxidation of phenolic and nonphenolic substrates. Furthermore, some mutations arising in the evolved preproleader highlighted its potential for heterologous expression of fungal laccases in yeast (S. cerevisiae).

Modelación de curvas de lactancia para producción de leche, grasa y proteína en bovinos Holstein en Antioquia, Colombia / Modeling the lactation curves for milk, fat and protein yield of Holstein cattle in Antioquia, Colombia

Objetivo. Modelar curvas de lactancia para producción de leche y para los porcentajes de grasa y proteína y determinar los principales factores que influyen en la curva de lactancia. Materiales y métodos. Fueron empleados los datos de control lechero de 1532 animales de raza Holstein pertenecientes a 19 haciendas ubicadas en el departamento de Antioquia, Colombia, donde se compararon los modelos matemáticos no lineales propuestos por Wood, Brody, Papajcsik y Bodero y Wilmink. En el modelo que presentó los mejores ajustes se determinó el efecto del parto, la época de parto y el año de parto. Resultados. Las curvas de lactancia para producción de leche y porcentaje de grasa y proteína, estimadas por el modelo de Wood, presentaron los mejores valores en los criterios de comparación empleados. Los efectos de año y número de parto fueron significativos para los parámetros estimados en el modelo de Wood. Conclusiones. El modelo de Wood mostró el mejor ajuste en curvas de lactancia para producción de leche y para los porcentajes de grasa y proteína. La curva de lactancia para el porcentaje de proteína se caracterizó por ser muy consistente y no presentar mayores fluctuaciones durante toda la lactancia.

Relación entre características de tipo y producción de leche en vacas Holstein de Antioquia, Colombia / Relationship between type traits and milk production in Holstein cows from Antioquia, Colombia

Objetivo. Evaluar la relación entre las características de tipo agrupadas por factores con la producción de leche en ganado Holstein de Antioquia, Colombia. Materiales y métodos. Se utilizaron datos de 24 características lineales y producción de leche de 3102 vacas de la raza Holstein del departamento de Antioquia en control lechero oficial. Se realizó un análisis por factores (AF) con el método de componentes principales y se retuvieron los factores que mostraron valores propios mayores que 1.0. Posteriormente se realizó un análisis de varianza para la variable producción de leche, donde se tuvieron en cuenta los efectos fijos de finca, mes de parto y año de clasificación y se estimaron los coeficientes de regresión lineal para cada uno de los factores retenidos. Resultados. El AF mostró que sólo siete factores fueron retenidos y agruparon cerca del 64% del total de la varianza de todas las características de tipo analizadas. El primer factor reunió las variables relacionadas con la estructura general de la vaca y tuvo un valor propio de 3.85. El análisis de varianza mostró que los factores se relacionaron con producción de leche Conclusiones. Para producción de leche en Antioquia, Colombia, sobresalen las vacas grandes, anchas de pecho, altas y profundas del cuerpo, con pezuñas uniformes, angulosas y talones profundos, un sistema mamario caracterizado por ubres de textura suave, buen ligamento medio, un buen carácter lechero y ubres profundas.

Estimación de parámetros genéticos para peso al destete en ganado blanco orejinegro (bon) en el noroccidente colombiano / Estimation of genetic parameters for weaning weight in white orejinegro cattle in the colombian northwest

Objetivo. Estimar los componentes de varianza genético aditivo directo y materno para peso al destete en ganado criollo Blanco Orejinegro (BON). Materiales y métodos. Se utilizaron 356 registros entre los años 1988 al 2007, del núcleo de animales BON puro de la hacienda Vegas de la Clara de la Universidad de Antioquia. El análisis fue realizado utilizando un modelo animal incluyendo los efectos fijos de sexo y época de destete, y como covariable la edad al destete y los efectos aleatorios genético directo, genético materno, ambiente permanente y residual. Resultados. El peso promedio al destete fue de 196.3 ± 31.4 kg, a una edad promedio de 271.8 ± 13.5 días. Se encontraron 21 animales endogámicos con un coeficiente de endogamia de 24.5%. La heredabilidad directa y materna fueron de 0.63 ± 0.36 y 0.22 ± 0.19 con una correlación entre el efecto directo y el materno de -0.78 ± 0.21. Conclusión. De acuerdo a los resultados, existe variabilidad genética en el núcleo BON para esta característica.

[Dementia secondary to thalamic infarct: a case report]. / Demencia secundaria a infarto talamico: comunicacion de un caso.

INTRODUCTION: The term dementia refers to the deterioration of the intellectual or cognitive functions, with little or no alteration of consciousness, which is capable of interfering with the activities of daily living and the ability to cope by oneself. One infrequent cause of dementia is its being secondary to a thalamic lesion and is normally due to the involvement of both thalami. CASE REPORT: We report a case of sudden onset dementia caused by lesions affecting only the left thalamus. A 64 year old right handed female patient with chronic arterial hypertension for which she received regular treatment. The patient visited because of difficulty in speaking without any alterations to consciousness, and amnesia of recent anterograde and retrograde events. A CAT scan of the brain revealed a superlacuna in the left thalamus. From then on, the patient presented memory disorders, the most typical being loss of retention memory. CONCLUSIONS: Thalamus injuries that are accompanied by dementia are commonly bilateral and are preferably located in the anterior and medial nuclei. There have been cases of memory disorders secondary to unilateral infarcts of the thalamus and these are related to a thalamocortical deafferentiation. Our case is one of sudden onset thalamic dementia secondary to an infarct affecting only the left thalamus.

Experimental heterotopic heart transplantation: an easier technique.

AIM: The use of heterotopic heart transplantation (HHT) in experimental surgery is an extended method to evaluate cardiac graft viability. To study endothelial injury after ischemia-reperfusion, the technique described by Matsui et al. in 1988 for HHT was chosen. A modification, which consists of replacing the atrium-to-atrium anastomosis for the tip of a 30-Fr venous cannula, was developed with the purpose of using this technique in small pigs. Both techniques were compared. METHODS: Twenty-seven consecutive HHTs in 17- to 20-kg pigs using Matsui's original technique and the modified technique were performed. Ischemia time, bleeding volume, mean gradient and anastomosis complications were measured to compare both techniques. RESULTS: Statistically significant decreases in ischemia time, bleeding volume and mean gradient with the modified technique were found. Furthermore, there were two cases of suture dehiscence with the original technique. CONCLUSIONS: The replacement of the atrium-to-atrium anastomosis for the venous cannula is a modification that statistically decreases the ischemia time, blood loss and avoids suture complications. This modification makes Matsui's technique easier, faster and safer in small pigs and it may be used in bigger animals and in any kind of non-permanent anastomosis.