Transcriptional changes in dendritic cells underlying allergen specific induced tolerance in a mouse model.

To investigate food allergy-tolerance mechanisms induced through allergen-specific immunotherapy we used RNA-Sequencing to measure gene expression in lymph-node-derived dendritic cells from Pru p 3-anaphylactic mice after immunotherapy with glycodendropeptides at 2 nM and 5 nM, leading to permanent tolerance and short-term desensitization, respectively. Gene expression was also measured in mice receiving no immunotherapy (anaphylaxis); and in which anaphylaxis could never occur (antigen-only). Compared to anaphylaxis, the antigen-only group showed the greatest number of expression-changes (411), followed by tolerant (186) and desensitized (119). Only 29 genes changed in all groups, including Il12b, Cebpb and Ifngr1. The desensitized group showed enrichment for genes related to chronic inflammatory response, secretory granule, and regulation of interleukin-12 production; the tolerant group showed genes related to cytokine receptor activity and glucocorticoid receptor binding, suggesting distinct pathways for similar outcomes. We identified genes and processes potentially involved in the restoration of long-term tolerance via allergen-specific immunotherapy, representing potential prognostic biomarkers.

Peptide Glycodendrimers as Potential Vaccines for Olive Pollen Allergy.

Olive pollen is one of the most important causes of respiratory allergy, with Ole e 1 being the most clinically relevant sensitizing allergen. Peptide-based vaccines represent promising therapeutic approaches, but the use of adjuvants is required to strengthen the weak immunogenicity of small peptides. We propose the use of dendrimeric scaffolds conjugated to the T cell immunodominant epitope of Ole e 1 (OE109-130) for the development of novel vaccines against olive pollen allergy. Four dendrimeric scaffolds containing an ester/ether with nine mannoses, an ester succinimidyl linker with nine N-acetyl-glucosamine units or nine ethylene glycol units conjugated to OE109-130 peptide were designed, and their cytotoxicity, internalization pattern, and immunomodulatory properties were analyzed in vitro. None of the dendrimers exhibited cytotoxicity in humanized rat basophil (RBL-2H3), human bronchial epithelial Calu-3, and human mast LAD2 cell lines. Confocal images indicated that mannosylated glycodendropeptides exhibited lower colocalization with a lysosomal marker. Moreover, mannosylated glycodendropeptides showed higher transport tendency through the epithelial barrier formed by Calu-3 cells cultured at the air-liquid interface. Finally, mannosylated glycodendropeptides promoted Treg and IL10+Treg proliferation and IL-10 secretion by peripheral blood mononuclear cells from allergic patients. Mannosylated dendrimers conjugated with OE109-130 peptide from Ole e 1 have been identified as suitable candidates for the development of novel vaccines of olive pollen allergy.

Psychometric variables of the EMUN-AR scale using Rasch analysis / Propiedades psicométricas de la escala EMUN-AR determinadas mediante el análisis de Rasch

Introduction: Self-report scales have been considered to be useful for evaluating and monitoring symptoms of manic-depressive illnesses. The EMUN-AR scale is one of such scales but it has not been validated. Objective: To validate the EMUN-AR scale using Rasch models. Materials and methods: The EMUN-AR scale measures 26 items to assess comprehensively symptoms of manic-depressive illnesses in three domains: Frequency, severity, and level of disturbance caused by the symptoms. To test the psychometric properties of this scale, we used the exploratory factorial and Rasch analyses. The Rasch analysis included unidimensionality, reliability, item fit, threshold ordering, and person-item maps. Results: The study included 267 hospitalized patients, most of them with a manic episode diagnosis (n=204, 76.4%), and receiving pharmacological treatment. The factor structure was summarized in four domains: Activation, inhibition, depressive ideation, and maladaptive behavior. The Rasch analysis supported unidimensionality of the EMUN-AR factors, satisfactory levels of reliability, and appropriate item fit, except for one of the items measuring death or suicidal thoughts. However, the scale did not measure adequately the mild forms of the illness given its redundant and unordered thresholds. Conclusion: The EMUN-AR was modified in two aspects: An item whose marginal indicators were poorly adjusted and the reduction in the number of categories. In its current form, the EMUN-AR is appropriate for measuring severe forms of the illnesses, but it does not adequately measure the mild forms of manic-depressive illnesses.

Introducción. Las escalas de autorreporte se han considerado útiles para evaluar y vigilar los síntomas de la enfermedad maníaco-depresiva. Uno de estos instrumentos, la escala de medición de la enfermedad maníaco-depresiva mediante autorreporte (EMUN-AR), no se ha validado aún. Objetivo. Validar la escala EMUN-AR usando el modelo de Rasch. Materiales y métodos. La escala EMUN-AR mide 26 ítems que evalúan por dimensiones los síntomas de la enfermedad maníaco-depresiva en tres categorías: frecuencia, intensidad y grado de molestia causada. Para evaluar las propiedades psicométricas de la escala, se efectuaron análisis factoriales exploratorios con el fin de tener una aproximación de su estructura latente, y se usaron modelos de Rasch que incluyeron la 'unidimensionalidad', la confiabilidad, el ajuste de ítems, el ordenamiento de umbrales, y los mapas de personas e ítems. Resultados. Se seleccionó una muestra de 267 pacientes hospitalizados, 204 de los cuales había sufrido un episodio maníaco (76,4 %) y estaba recibiendo tratamiento farmacológico. Se encontró una estructura factorial que puede resumirse en cuatro dominios: activación, inhibición, ideas depresivas e inadaptación. El análisis de Rasch evidenció la unidimensionalidad en los factores, adecuados valores de confiabilidad, buen ajuste de los 26 ítems en general (excepto en el ítem que mide las ideas de muerte o suicidio), un funcionamiento deficiente del sistema de calificación de los ítems y un cubrimiento limitado de los síntomas de la enfermedad correspondientes a las formas atenuadas. Conclusión. Se modificó la escala original en dos aspectos: se ajustó un ítem cuyos indicadores marginales tenían mal ajuste y se redujo el número de categorías. En su forma actual, el instrumento es apropiado para medir las formas graves de la enfermedad maníaco-depresiva, mas no así las atenuadas.

Propiedades psicométricas de la escala EMUN-AR determinadas mediante el análisis de Rasch / Psychometric variables of the EMUN-AR scale using Rasch analysis

Resumen Introducción. Las escalas de autorreporte se han considerado útiles para evaluar y vigilar los síntomas de la enfermedad maníaco-depresiva. Uno de estos instrumentos, la escala de medición de la enfermedad maníaco-depresiva mediante autorreporte (EMUN-AR), no se ha validado aún. Objetivo. Validar la escala EMUN-AR usando el modelo de Rasch. Materiales y métodos. La escala EMUN-AR mide 26 ítems que evalúan por dimensiones los síntomas de la enfermedad maníaco-depresiva en tres categorías: frecuencia, intensidad y grado de molestia causada. Para evaluar las propiedades psicométricas de la escala, se efectuaron análisis factoriales exploratorios con el fin de tener una aproximación de su estructura latente, y se usaron modelos de Rasch que incluyeron la 'unidimensionalidad', la confiabilidad, el ajuste de ítems, el ordenamiento de umbrales, y los mapas de personas e ítems. Resultados. Se seleccionó una muestra de 267 pacientes hospitalizados, 204 de los cuales había sufrido un episodio maníaco (76,4 %) y estaba recibiendo tratamiento farmacológico. Se encontró una estructura factorial que puede resumirse en cuatro dominios: activación, inhibición, ideas depresivas e inadaptación. El análisis de Rasch evidenció la unidimensionalidad en los factores, adecuados valores de confiabilidad, buen ajuste de los 26 ítems en general (excepto en el ítem que mide las ideas de muerte o suicidio), un funcionamiento deficiente del sistema de calificación de los ítems y un cubrimiento limitado de los síntomas de la enfermedad correspondientes a las formas atenuadas. Conclusión. Se modificó la escala original en dos aspectos: se ajustó un ítem cuyos indicadores marginales tenían mal ajuste y se redujo el número de categorías. En su forma actual, el instrumento es apropiado para medir las formas graves de la enfermedad maníaco-depresiva, mas no así las atenuadas.

Abstract Introduction: Self-report scales have been considered to be useful for evaluating and monitoring symptoms of manic-depressive illnesses. The EMUN-AR scale is one of such scales but it has not been validated. Objective: To validate the EMUN-AR scale using Rasch models. Materials and methods: The EMUN-AR scale measures 26 items to assess comprehensively symptoms of manic-depressive illnesses in three domains: Frequency, severity, and level of disturbance caused by the symptoms. To test the psychometric properties of this scale, we used the exploratory factorial and Rasch analyses. The Rasch analysis included unidimensionality, reliability, item fit, threshold ordering, and person-item maps. Results: The study included 267 hospitalized patients, most of them with a manic episode diagnosis (n=204, 76.4%), and receiving pharmacological treatment. The factor structure was summarized in four domains: Activation, inhibition, depressive ideation, and maladaptive behavior. The Rasch analysis supported unidimensionality of the EMUN-AR factors, satisfactory levels of reliability, and appropriate item fit, except for one of the items measuring death or suicidal thoughts. However, the scale did not measure adequately the mild forms of the illness given its redundant and unordered thresholds. Conclusion: The EMUN-AR was modified in two aspects: An item whose marginal indicators were poorly adjusted and the reduction in the number of categories. In its current form, the EMUN-AR is appropriate for measuring severe forms of the illnesses, but it does not adequately measure the mild forms of manic-depressive illnesses.

Supported and Unsupported Chiral Squaramides as Organocatalysts for Stereoselective Michael Additions: Synthesis of Enantiopure Chromenes and Spirochromanes.

Novel supported chiral bifunctional squaramides have been easily prepared starting from diamines derived from natural amino acids and commercially available aminoalkyl polystyrene resins. These squaramides behave as excellent stereoselective recoverable organocatalysts in different Michael additions, in neat conditions at room temperature. The reaction on 2-(2-nitrovinyl) phenol as electrophile lead, in excellent yields and enantioselectivities, to intermediates that can be easily transformed into 4H-chromenes, and spirochromanones.

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

Sensibilidad en el Reconocimiento de Emociones Faciales Como Endofenotipo de Esquizofrenia / Sensitivity in the Recognition of Facial Emotions as an Endophenotype for Schizophrenia / Sensibilidade no Reconhecimento de Emoções Faciais Como Endofenótipo de Esquizofrenia

Los endofenotipos son rasgos presentes antes de la aparición de un trastorno y podrían ser útiles para identificar genes de susceptibilidad. Se determinó si personas con esquizofrenia y sus familiares de primer grado no afectados tenían un desempeño menor que los controles en la Tarea de Multitransformación de Expresión Emocional, que mide reconocimiento de emociones faciales. Las personas con esquizofrenia y sus familiares mostraron menor sensibilidad o requirieron más intensidad para identificar emociones que los controles. La exactitud para identificar emociones fue similar entre familiares y controles, pero menor en aquellos con esquizofrenia. Esto sugiere que la sensibilidad para el reconocimiento de emociones faciales es un endofenotipo de la esquizofrenia.

Endophentoypes are the traits present before the appearance of a disorder and could be useful to identify susceptibility genes. The purpose of this study was to determine whether persons suffering from schizophrenia and their immediate relatives performed less well than controls in the Emotional Expression Multi-transformation Task, which measures recognition of facial expressions. Persons with schizophrenia and their relatives showed less sensitivity than controls or required greater intensity to identify emotions than controls did. Accuracy in the identification of emotions was similar in relatives and controls, but lower in individuals with schizophrenia. This suggests that sensitivity in the recognition of facial emotions is an endophenotype for schizophrenia.

Os endofenótipos são traços presentes antes do surgimento de um transtorno e poderiam ser úteis para identificar genes de suscetibilidade. Determinou-se se pessoas com esquizofrenia e seus familiares de primeiro grau não afetados tinham um desempenho menor que os controles na Tarefa de Multitransformação de Expressão Emocional, que mede reconhecimento de emoções faciais. As pessoas com esquizofrenia e seus familiares mostraram menor sensibilidade ou requereram mais intensidade para identificar emoções que os controles. A exatidão para identificar emoções foi similar entre familiares e controles, mas menor naqueles com esquizofrenia. Isso sugere que a sensibilidade para o reconhecimento de emoções faciais é um endofenótipo da esquizofrenia.

Desarrollo de una escala de auto-reporte para medición de síntomas maníacos / Development of a self-report scale to measure manic symptoms

Resumen Antecedentes. No existen instrumentos de auto-reporte en español para medir síntomas de trastorno bipolar. La perspectiva del paciente puede dar información complementaria de utilidad para el diagnóstico y manejo de la enfermedad. Objetivo. Desarrollar una escala de auto-reporte para medir síntomas maníacos, a partir de la escala EMUN. Materiales y métodos. Los ítems de la escala EMUN se transformaron a un lenguaje en primera persona por parte de dos psiquiatras. Esta versión preliminar en primera persona fue analizada en un estudio piloto y ajustada de acuerdo con los resultados de la evaluación. Se realizó un segundo estudio piloto con 20 pacientes con enfermedad bipolar, aplicando la versión ajustada. Resultados. Se generó una escala con 26 ítems que incorporan síntomas del episodio mixto. La escala mide tres dimensiones de importancia clínica en salud mental: frecuencia, intensidad y grado de desadaptación producido por los síntomas. Conclusión. El instrumento desarrollado puede ser de utilidad en áreas de investigación y en escenarios clínicos para intervenciones psicoeducativas y seguimiento del paciente.

Summary Background. In Spanish language, no self-report instruments have been specifically developed to measure symptoms of bipolar disorder. The patient's perspective provides valuable information useful to diagnose and treat the disorder. Objective. Develop a self-report scale for measuring manic symptoms making use of the EMUN scale. Materials and methods. The items of the EMUN scale were transformed into a first person language by two psychiatrists. This preliminary version was evaluated in a pilot testing and adjusted according to this evaluation. A second pilot study applying the adjusted version to 20 patients having bipolar disorder was performed. Results. A 26 items scale including symptoms of mixed episode was developed. This scale measures three clinical relevant dimensions in mental health: frequency, severity and maladaptive effect of symptoms. Conclusions. The instrument developed can be a useful tool for researchers and in clinical settings to support educational interventions and patient's follow-up.

Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms.

OBJECTIVE: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. METHODS: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for "negative symptoms" and "disorganization" was performed afterwards. RESULTS: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. CONCLUSION: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia.

Edad de inicio como marcador de subtipos de enfermedad maniacodepresiva / Age at onset as a marker of subtypes of manic-depressive illness

Introducción: En los trastornos bipolares, la edad de inicio se ha sugerido como una variable que puede asociarse con diferentes subtipos clínicos. Objetivo: Identificar patrones en la distribución de la edad de inicio de la enfermedad bipolar y determinar si la edad de inicio se asocia con características clínicas específicas. Métodos: Se usó análisis de distribuciones normales mezcladas para identificar subtipos de trastorno bipolar de acuerdo con la edad de inicio. Se aplicó la escala EMUN para evaluar las características clínicas y se estimaron componentes principales para evaluar la relación entre subtipos, según edad de inicio y síntomas en la fase aguda de la enfermedad, utilizando análisis multivariables. Resultados: De acuerdo con la edad de inicio, se encontraron tres distribuciones: inicio temprano: 17,7 años (S. D. 2,4); inicio intermedio: 23,9 años (S. D. 5,6); inicio tardío: 42,8 años (S. D. 12,1). El grupo de inicio tardío es asocial, con síntomas depresivos, trastornos del pensamiento y el lenguaje, y comportamientos socialmente peligrosos. Conclusión: En pacientes con enfermedad bipolar, la edad de inicio es asocial, con tres grupos que tienen características clínicas específicas…

Introduction: Age at onset of bipolar disorder has been reported as a variable that may be associated with different clinical subtypes. Objective: To identify patterns in the distribu-tions of age at onset of bipolar disease and to determine whether age at onset is associated with specific clinical characteristics. Methods: Admixture analysis was applied to identify bipolar disorder subtypes according to age at onset. The EMUN scale was used to evaluate clinical characteristics and principal components were estimated to evaluate the relationship between subtypes according to age at onset and symptoms in the acute in the acute phase, using multivariable analyses. Results: According to age at onset, three distributions have been found: early onset: 17.7 years (S.D. 2.4); intermediate-onset: 23.9 years (S.D. 5.6); late onset: 42.8 years (S.D. 12.1). The late-onset group is antisocial, with depressive symptoms, thinking and language disorders, and socially disruptive behaviors. Conclusions: In patients having bipolar disorder, age at onset is antisocial with three groups having specific clinical characteristics…

[Age at Onset as a Marker of Subtypes of Manic-Depressive Illness]. / Edad de inicio como marcador de subtipos de enfermedad maniacodepresiva.

INTRODUCTION: Age at onset of bipolar disorder has been reported as a variable that may be associated with different clinical subtypes. OBJECTIVE: To identify patterns in the distributions of age at onset of bipolar disease and to determine whether age at onset is associated with specific clinical characteristics. METHODS: Admixture analysis was applied to identify bipolar disorder subtypes according to age at onset. The EMUN scale was used to evaluate clinical characteristics and principal components were estimated to evaluate the relationship between subtypes according to age at onset and symptoms in the acute in the acute phase, using multivariable analyses. RESULTS: According to age at onset, three distributions have been found: early onset: 17.7 years (S.D. 2.4); intermediate-onset: 23.9 years (S.D. 5.6); late onset: 42.8 years (S.D. 12.1). The late-onset group is antisocial, with depressive symptoms, thinking and language disorders, and socially disruptive behaviors. CONCLUSIONS: In patients having bipolar disorder, age at onset is antisocial with three groups having specific clinical characteristics.

Sickle cell disease painful crisis and steady state differentiation by proton magnetic resonance.

The delay time of the Hb S polymerization process was investigated in 63 patients with sickle cell disease during steady state and 10 during painful crisis starting from spin-spin proton magnetic resonance (PMR) time behavior measured at 36 degrees C and during spontaneous deoxygenation. We found a significant decrease of delay time as a result of the crisis (36 +/- 10%) and two well-differentiated ranges of values for each state: 273-354 min for steady state and 166-229 min for crisis with an uncertainty region of 15%. It is possible to use PMR as an objective and quantitative method in order to differentiate both clinical conditions of the sickle cell patient, but a more clear differentiation can be established comparing the delay time (td) value of one patient during crisis with his own td value during steady state.

In vivo action of Vanillin on delay time determined by magnetic relaxation.

The antisickling action on polymerization of 4-hydroxy-3-metoxybenzaldehyde (Vanillin) was demonstrated in vivo in a double blind, placebo-controlled clinical therapeutic trial performed in 30 patients (11 belonging to the control group), through the increment of the delay time (td). The td was observed in the kinetic curve of the polymerization of the Hb S solution at 26 degrees C and pH 7.4. The kinetics of the Hb S aliquots was monitored by measuring the proton spin-spin magnetic relaxation time (T2) at 4 MHz. The kinetic curve families of the control group showed similarities and the td values remained constant during the 8 weeks of the study. This was not so for the patients treated with Vanillin, for which the td increased on average 1.6 times. On the other hand, the relative variation of drepanocytes observed by the Simple Test decreased 24.50% Both results indicate a decrease in the effectiveness of the polymerization process.

TOC en niños y adolescentes / OCD in children and adolescents

Utilizando la entrevista clínica y varias escalas de evaluación se realizó la caracterización de un grupo de 28 niños con TOC en la ciudad de Bogotá. Estos hallazgos fueron contrastados con lo reportado en la literatura mundial