Eosinophils: old players in a new game

Eosinophils are terminal polymorphonuclear cells with a high number of cytoplasmic granules that originate in bone marrow. Some are exosomes, which contain multiple molecules, such as specific eosinophilic proteins, cytokines, chemokines, enzymes, and lipid mediators that contribute to the effector role of these cells. Moreover, exosomes present a large number of receptors that allow them to interact with multiple cell types. Eosinophils play an important role in defense against infestations and are a key element in asthma and allergic diseases. Eosinophils are recruited to the inflamed area in response to stimuli, modulating the immune response through the release to the extracellular medium of their granule-derived content. Various mechanisms of degranulation have been identified. Polymorphonuclear leukocytes contain multivesicular bodies that generate exosomes that are secreted into the extracellular environment. Eosinophilic exosomes participate in multiple processes and mechanisms. Eosinophils participa e actively in asthma and are hallmarks of the disease. The cells migrate to the inflammatory focus and contribute to epithelial damage and airway remodeling. Given their relevance in this pathology, new therapeutic tools have been developed that target mainly eosinophils and their receptors. In this manuscript, we provide a global, updated vision of the biology of eosinophils and the role of eosinophils in respiratory diseases, particularly asthma. We also summarize asthma treatments linked to eosinophils and new therapeutic strategies based on biological products in which eosinophils and their receptors are the main targets

Los eosinófilos son células polimorfonucleares terminales originadas en la médula ósea con un número importante de gránulos citoplasmáticos, algunos de los cuales son exosomas, que contienen múltiples moléculas como proteínas eosinofílicas específicas, citocinas, quimiocinas, enzimas y mediadores lipídicos que contribuyen al papel efector de estas células. Además, presentan una gran cantidad de receptores que les permiten interactuar con múltiples tipos celulares. Los eosinófilos desempeñan un papel importante en la defensa contra las infestaciones y son un elemento clave en el asma y las enfermedades alérgicas. Los eosinófilos se reclutan hacia el área de inflamación en respuesta a varios estímulos, modulando la respuesta inmune a través de la liberación al medio extracelular del contenido derivado de sus gránulos, existiendo diferentes mecanismos de degranulación. Estos leucocitos polimorfonucleares contienen cuerpos multivesiculares que generan exosomas que se secretan al ambiente extracelular. Estos exosomas eosinofílicos participan en múltiples procesos y mecanismos. En relación con la enfermedad asmática, los eosinófilos participan activamente en los elementos distintivos de esta patología. Estas células migran al foco inflamatorio y contribuyen al daño del epitelio y a la remodelación de las vías respiratorias. Debido a su relevancia en esta patología, se han desarrollado nuevas herramientas terapéuticas, siendo los eosinófilos y sus receptores sus objetivos principales. En este manuscrito, proporcionamos una visión global y actualizada sobre la biología de los eosinófilos, su papel en las enfermedades respiratorias, centrando nuestra atención en la patología asmática, así como un resumen de los tratamientos y nuevas estrategias terapéuticas basadas en tratamientos biológicos en los que los eosinófilos y sus receptores son los principales objetivos

Número óptimo de ovocitos: modelo de predicción para fertilización in vitro / Optimal number of oocytes: In vitro fertilization predictive model

Resumen OBJETIVO: desarrollar un modelo de predicción para conseguir un recién nacido vivo con el menor número de ovocitos capturados. MATERIALES Y MÉTODOS: estudio observacional, longitudinal y retrolectivo, efectuado en el Instituto Nacional de Perinatología entre 2011 y 2016 en ciclos de FIV en fresco. Criterios de inclusión: pacientes mayores de 18 años de edad, con diagnóstico de infertilidad, a quienes se realizó fertilización in vitro con transferencia de embriones en fresco (FIV-TE). Las variables de estudio fueron: edad, IMC, concentración basal de FSH, tipo de infertilidad, tiempo de infertilidad y número de ovocitos capturados. Se elaboró un árbol de decisión tipo CHAID y un modelo binario de regresión logística. Para el análisis estadístico se utilizó el programa Statistic Package for Social Sciences (SPSS). Se consideró significativa la probabilidad de error alfa < 5%. RESULTADOS: se registraron 673 ciclos, de los que se obtuvieron 5,910 óvulos. El número óptimo de ovocitos recuperados fue mayor de 12 (independientemente de la edad), con RM = 4.666, IC95%: 2.676-8.137, p = <0.01. Las mujeres menores de 37 años de edad, con concentración basal de FSH <4.2 mUI/mL y recuperación de hasta 5 ovocitos tuvieron mayor posibilidad (28%) de obtener un recién nacido vivo (χ2 = 7.797; gl = 1, p = <0.047); por su parte, las pacientes entre 38 y 40 años de edad (RM = 0.338, IC95%: 0.147-0.776, p = <0.011) y tiempo de infertilidad de 10 a 12 años de evolución (RM = 0.394, IC95%: 0.181-0.858, p = 0.019) tuvieron menor posibilidad de obtener un recién nacido vivo. CONCLUSION: el número óptimo de ovocitos a recuperar es mayor de 12 (independientemente de la edad). Las mujeres menores de 37 años de edad, con concentración basal de FSH <4.2 mUI/mL y captura de hasta 5 ovocitos tienen mayor posibilidad de tener un recién nacido vivo.

Abstract OBJECTIVE: Develop a model to optimize the reproductive outcome (live birth rate). Identify the minimal number of oocytes to capture. MAERIALS AND METHODS: Observational, longitudinal, and retrolective study was made. In fresh IVF cycles, performed at INPer between 2011-2016. A logistic regression model was fitted with a CHAID, and performed a decision tree to predict live birth (LBR). Inclusion criteria: patients over 18 years of age, diagnosed with infertility, who underwent in vitro fertilization with fresh embryo transfer (FIV-TE). The study variables were: age, BMI, basal FSH concentration, type of infertility, time of infertility and number of oocytes captured. A decision tree type CHAID and a binary logistic regression model were performed. Statistical Package for Social Sciences (SPSS) was used for the statistical analysis. The probability of error alpha <5% was considered significant. RESULTS: A total of 673 cycles were studied. The optimal number was >12 oocytes (OR = 4.666, 95% CI: 2.676-8.137, p=<0.01). The highest chance to have LB (28%), was in women <37 years old, with FSH <4.2 mIU / mL and <5 oocytes; χ2 = 7.797 (df = 1, p = <0.047). The lowest chance was in 38-40 years (OR = 0.338, 95% CI: 0.147-0.776, p = <0.011) with a longer lapse of infertility; 10-12 years (OR = 0.394, 95% CI: 0.181-0.858, p = 0.019). CONCLUSION: Our data suggest that in the >12 oocytes may be the optimal number to obtain, independent of the age. On the other hand the best chance to have a live birth is with an age <37, FSH <4.2 mIU/mL and <5 oocytes. Fewer oocytes than previously deemed optimal, because the probability of having a euploid embryo in this group of people is much bigger.

Características clínico-bioquímicas de la insuficiencia ovárica primaria. Experiencia institucional de 12 años / Clinical-biochemical characteristics of the primary ovarian failure. An institutional experience of 12 years

Resumen Objetivo: Evaluar las características clínicas y bioquímicas de las pacientes con insuficiencia ovárica primaria. Materiales y métodos: Estudio observacional, ambispectivo y analítico, efectuado en pacientes atendidas entre los años 2005 a 2017 en el Instituto Nacional de Perinatología Isidro Espinosa de los Reyes con diagnóstico de insuficiencia ovárica primaria. Las pacientes se clasificaron en grupos según el origen del padecimiento. Se utilizó la prueba de ANOVA con corrección de Bonferroni para identificar diferencias en las variables cuantitativas en los cuatro grupos de estudio. Se realizó un modelo no lineal de tipo CHAID (X2 automatic interaction detector), con la finalidad de predecir la edad al inicio de la terapia hormonal, según el origen de la insuficiencia ovárica. Resultados: Se estudiaron 98 pacientes; 70 de ellas (71%) se clasificaron idiopáticas; 16 (17%) cromosómicas y 12 (12%) autoinmunitarias órgano-específicas. En las características clínicas se observó que las pacientes con etiología cromosómica tuvieron menopausia espontánea antes de los 30 años (80%); en las de causa quirúrgica fue después de los 30 años (53.8%). En relación con la densidad mineral ósea las mujeres con insuficiencia ovárica primaria de origen cromosómico resultaron con menos masa ósea al momento del diagnóstico en comparación con las demás causas; la columna lumbar (L1 a L4) resultó la más afectada. Conclusión: La principal causa de la insuficiencia ovárica primaria espontánea en la muestra estudiada fue idiopática, seguida de la cromosómica y autoinmunitaria órgano-especifica. El 12% tenía antecedente familiar, en primer grado, de insuficiencia ovárica primaria. Es obvia la necesidad de la asesoría genética.

Abstract Objective: Evaluate the clinical and biochemical characteristics of patients with primary ovarian failure. Materials and Methods: An observational, cross-sectional and ambispective study carried out in patients treated between 2005 and 2017 in the National Institute of Perinatology with a diagnosis of primary ovarian failure. The patients were classified into groups according to the origin of the condition. The ANOVA test with Bonferroni correction was used to identify differences in the quantitative variables in the four study groups. A nonlinear model of CHAID type (X2 automatic interaction detector) was performed, with the purpose of predicting the age at the beginning of the hormonal therapy according to the origin of the ovarian insufficiency. Results: 98 patients were studied; 70 of them (71%) were classified idiopathic; 16 (17%) chromosomal and 12 (12%) autoimmune organ-specific. In the clinical characteristics, it was observed that patients with chromosomal etiology had spontaneous menopause before the age of 30 (80%); in those of surgical origin it was after 30 years (53.8%). In relation to bone mineral density, women with primary ovarian insufficiency of chromosomal origin were found to have less bone mass at the time of diagnosis compared to the other causes; the lumbar spine (L1 to L4) was the most affected. Conclusion: The main cause of spontaneous primary ovarian failure in the sample studied was idiopathic, followed by chromosomal and organ-specific autoimmune. 12% had a family history, in first grade, of primary ovarian failure. The need for genetic counseling is obvious.

White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults.

Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (n=2009; n'=3501); Hypothesis 2 (n=2081; n'=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=-0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were linked to depressive symptoms, mostly among women. Further longitudinal studies are needed to replicate this sex-specific association.