Caracterización de BCAS1 como marcador de una subpoblación de oligodendrocitos premielinizantes en el cerebro humano y su potencial trascendencia

Treball Final de Grau en Medicina. Codi: MD1158. Curs acadèmic: 2020/2021Los oligodendrocitos son células gliales presentes en el sistema nervioso central cuya principal función es la mielinización axonal. Además, en el cerebro adulto existe una población celular relativamente abundante que corresponde a células precursoras de oligodendrocitos (OPC), que se mantiene en un estado indiferenciado. Recientemente se ha descrito un nuevo marcador molecular, BCAS1, de función desconocida en el cerebro, que se expresa en una subpoblación oligodendroglial circunscrita a estadios intermedios de maduración. El interés de dicho marcador radica, principalmente, a que es expresado por OPC premielinizantes, siendo relevante en el estudio de procesos como la remodelación de la mielina y la remielinización ante situaciones patológicas. Nuestro trabajo pretende llevar a cabo una caracterización descriptiva de la población celular definida por la expresión del marcador BCAS1 en el cerebro humano en etapas infantiles y adultas, tanto en tejido sano como de pacientes de esclerosis múltiple. Hipotetizamos que BCAS1 podría definir una subpoblación oligodendroglial presente desde etapas posnatales hasta en el cerebro adulto, actuando como reservorio de OPC capaces de responder a necesidades de remodelado mielínico. Para abordar dicha hipótesis realizamos estudios de inmunofluorescencia, microscopía electrónica y cuantificación de la densidad celular de la población BCAS1-positiva en muestras de tejido cerebral de donantes en edad pediátrica y adulta. Nuestros resultados sugieren que la proteína BCAS1 se expresa en el cerebro humano en estadios madurativos intermedios del linaje oligodendroglial, sin diferencias ultraestructurales, moleculares, ni en cuanto a densidad celular entre los estratos infantil y adulto comparados.Oligodendrocytes are glial cells present in the central nervous system whose main function is axonal myelination. In addition, in the adult brain there is a relatively abundant cell population corresponding to oligodendrocyte precursor cells (OPC), which is maintained in an undifferentiated state. It has been recently described that a novel molecular marker of unknown function in the brain, namely BCAS1, is expressed by an oligodendroglial subpopulation circumscribed to intermediate stages of maturation. The interest of this marker lies mainly in the fact that it is expressed by premyelinating OPCs, being relevant in the study of processes such as myelin remodeling and remyelination in pathological processes. Our work aims to perform a descriptive characterization of the cell population defined by the expression of the BCAS1 marker in the human brain during childhood and adult stages, both in healthy tissue and that from multiple sclerosis patients. We hypothesized that BCAS1 could define an oligodendroglial subpopulation present from postnatal stages to the adult brain, acting as a reservoir of OPCs capable of responding to myelin remodeling needs. To address this hypothesis, we conducted immunofluorescence studies, electron microscopy and quantification of the cell density of BCAS1-positive cells in brain tissue samples from pediatric and adult donors. Our results suggest that BCAS1 protein is expressed in intermediate maturation stages of the oligodendroglial lineage in the human brain, without evident ultrastructural, molecular, or cell density differences between the compared child and adult groups

Application of liquid chromatography/mass spectrometry in assessment of potential use of azadirachtins (TreeAzin ™ ) against Asian longhorned beetle

Azadirachtins are natural triterpenoid compounds derived from Neem tree extracts with potential for use as systemic insecticides against invasive wood-boring insect pests. In this work, a sensitive and selective analytical method has been developed for the simultaneous determination of azadirachtin A and azadirachtin B (3-tigloylazadirachtol) in foliage and twigs of various tree species. Samples were mixed with C18 and primary-secondary amine (PSA), and extracted with acetonitrile. Then, an aliquot of the raw extract was 10-fold diluted with water and directly analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The method was validated in foliage and twig matrices of four different tree species (London Plane Tree, Red/Freemani Maple, Norway Maple and Sugar Maple) that are known hosts of the exotic invasive insect pest – Asian Longhorn Beetle (ALB). Analytical results for replicate (N = 5) samples, fortified at 0.01, 0.1 and 1 mg kg , showed good recoveries (86 – 119%) and precision (<20% RSD). The methodology was successfully applied to the analysis of 200 samples taken from a field experiment designed to investigate uptake, translocation and expression of azadirachtins in representative high-value urban trees followed by stem injection with TreeAzinTM

Sponyloarthritis features forecasting the presence of HLA-B27 or sacroiliitis on magnetic resonance imaging in patients with suspected axial spondyloarthritis: Results from a cross-sectional study in the ESPeranza Cohort

Introduction: Chronic back pain (CBP) is frequently the presenting symptom in patients with suspected axial spondyloarthritis (axSpA). Presence of sacroiliitis on magnetic-resonance-imaging (MRI) or HLA-B27 adds to diagnostic certainty. However, these costly tests cannot be applied in all patients with CBP. This study aims to investigate which SpA features increase the likelihood of a positive HLA-B27 or positive MRI of the sacroiliac-joints (MRI-SI) in patients with suspected axSpA. Methods: Data from 665 patients with CBP within the ESPeranza Programme were analysed. Diagnostic utility measures (LR+, LR−) for a positive MRI-SI or HLA-B27 were calculated for various definitions of inflammatory back pain (IBP), their separate items and for other SpA features. Results: Pretest probabilityies of a positive result was 41 % for MRI-SI and 40 % for HLA-B27. For a positive MRI-SI result the most useful IBP characteristic was alternating buttock pain (LR + =2.6). Among the IBP-criteria, fulfillment of the ‘ASAS criteria’ (LR + =2.1) was most contributory. Interestingly, the addition of alternating buttock pain to the Calin/ASAS-IBP criteria (LR + =6.0 and 5.5, respectively) or the addition of awakening at second half of night to the Calin-IBP criteria (LR + =5.5) increased the pre-test probability of MRI-sacroiliitis from 41 % to 79–80 %. Dactylitis (LR + =4.1) and inflammatory bowel disease (IBD) (LR + =6.4) increased this probability to 73 % and 81 %, respectively. To forecast HLA-B27 positivity, awakening at the second half of the night, fulfillment of the ASAS-IBP definition and uveitis were the most useful, but only marginally predictive (LR + = 1.3, 1,6 and 2.6, respectively). Conclusions: If patients with suspected axial SpA have either 1) IBP according to Calin/ASAS definition plus alternating buttock pain, or 2) IBP according to Calin definition plus awakening at night, or 3) dactylitis or 4) IBD, the probability of finding a positive MRI-SI increases significantlyVNC received one of the ASAS research grants on call 2013 to perform this study. The Spanish Foundation of Rheumatology received funding from Pfizer to develop the Esperanza Programme. Nowadays, the programme is supported by a restricted grant of the Institute Carlos III (FIS PI13/02034)

Use of microperimetry to evaluate hydroxychloroquine and chloroquine retinal toxicity

To check the ability of microperimetry to detect early retinal damage in patients with rheumatism taking hydroxychloroquine (HCQ), chloroquine (CQ), or both, and to describe the microperimetric alterations attributable to these drugs and their correlation with some clinical variables

Detección de Patotipos de Cepas de Escherichia coli Causantes de Diarrea Infantil de Establecimientos de Salud de la Región Lambayeque-Perú, 2018

Objetive. To identify pathotypes of virulence genes of Escherichia coli from diarrheal samples of children under five years of age in the Lambayeque Region, in the period April-September 2018. The study: Descriptive and cross-sectional study. 75 E. coli strains from diarrheogenic samples were analyzed using real-time Multiplex PCR and primers for E. coli pathotype genes: daaD, aggR, eaeA, stx, ipaH and st. Findings: 34.66% (26/75) of virulence genes were detected from the total isolates. The enterotoxigenic E. coli pathotype presented the highest frequency, 18.67% (14/75) of the total isolates. It was also detected that the enterotoxigenic E. coli pathotype appeared in 53.86% (14/26) of the total positive strains. Also, in 11.54% of positive strains (3/26) they presented more than one pathotype. Conclusion: Molecular epidemiology will help a better, adequate and timely diagnosis of childhood diarrhea in this vulnerable population.Objetivo: Identificar patotipos de genes de virulencia de Escherichia coli de muestras diarreicas de niños menores de cinco años de la Región Lambayeque, en el periodo abril–setiembre 2018. El estudio: Estudio descriptivo y transversal. Se analizaron 75 cepas de E. coli de muestras diarreogénicas usando PCR Multiplex en tiempo real y primers para genes de patotipos de E. coli: daaD, aggR, eaeA, stx, ipaH y st. Hallazgos: Se detectó 34,66 % (26/75) de genes de virulencia del total de cepas aisladas. El patotipo de E. coli Enterotoxigénica presentó mayor frecuencia, 18,67% (14/75) del total de cepas aisladas. También se detectó que el patotipo E. coli Enterotoxigénica se presentó en 53,86% (14/26) del total de cepas positivas. También en un 11,54% de cepas positivas (3/26) presentaron más de un patotipo. Conclusión: La epidemiologia molecular ayudará a un mejor diagnóstico adecuado y oportuno de las diarreas infantiles en esta población vulnerable

Estímulo del trabajo autónomo en el aprendizaje práctico de la Histología: una experiencia transversal en Ciencias de la salud

El estudio microscópico de tejidos y órganos constituye un aspecto muy importante del aprendizaje de la histología, pero no siempre se dispone de suficientes colecciones de muestras, sobre todo humanas, para que el alumnado pueda disponer de ellas de forma presencial durante las prácticas. Por ello, el portal virtual digital slidebox (DSB) permite al profesorado generar una colección de preparaciones histológicas virtuales, de manera que los estudiantes tienen acceso "online" a estas muestras y pueden visualizarlas a la misma escala que ofrece la observación directa del microscopio óptico, e incluso mayor. Para la realización de cada práctica en sus horas presenciales el alumno dispone previamente de un guión con los objetivos que debe cumplir al realizar la observación de cada preparación histológica. Al final de cada práctica presencial los objetivos son explicados por el alumno, y evaluados por el profesor, realizando una puesta en común. Una vez realizada la práctica, y en horario no presencial, el alumnado tiene la posibilidad de completar este trabajo usando el portal virtual DSB. Con las imágenes digitales captadas el alumno realiza su portafolio de prácticas incorporando dichas imágenes y rotulándolas. Al final del curso se realiza un examen práctico global y la evaluación final del portafolio

Long-term etanercept survival in patients with psoriatic arthritis: a multicenter retrospective analysis in daily clinical practice in Spain

Although several randomized clinical trials and observational studies have evaluated the effectiveness, safety and drug survival of etanercept (ETN) in the treatment of psoriatic arthritis (PsA), long-term data regarding these aspects are currently scarce. For this reason, we sought to investigate the long-term survival and safety of ETN in PsA patients in 4 tertiary care Spanish hospitals over a 13-year observation period (from 2004 to 2017). The records of 85 PsA patients were reviewed. ETN showed an excellent survival profile, with rates of treatment discontinuation at 1, 3, 5 and 10 years of 15, 37, 46 and 59%, respectively. In our cohort, a trend toward longer drug survival in patients with shorter disease duration and those who were treated with ETN as their first biologic agent was observed. On the other hand, combination therapy with conventional disease-modifying antirheumatic drugs did not provide greater improvement on the long-term drug survival. Only 12% of the patients reported adverse events (AEs) during therapy, being most of them of mild to moderate intensity, and in only 7% AEs led to drug discontinuation. To the best of our knowledge, the present study shows the largest follow-up period of ETN-treated population analyzed in a real-life setting, and these results demonstrate the positive safety profile and long-term effectiveness of this biologic agent in the management of PsA patients

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Municipios de Popayán, Pasto, Cúcuta, Santander de Quilichao y Offenburg.

Este informe presenta el relato cinco relacionado con el caso de “Carlos Arturo Bravo”, un chico de 14 años, quien es víctima de la violencia y del conflicto armado en Colombia, a causa de una explosión de una granada de fusil dejada por las FARC, y quien sufrió lesiones en distintas regiones de su cuerpo, afectándolo física y emocionalmente para toda su vida; las secuelas y el impacto son muy altos para él y su familia; para complementar el análisis del comportamiento y posibles sucesos psicosociales a nivel traumático vinculados a la experiencia de Carlos Arturo Bravo, se construyen 9 preguntas: 3 circulares, 3 reflexivas y 3 estratégicas. También se tiene presente, el análisis del caso de “Peñas Coloradas”, una población conformada por habitantes de regiones como “Huila, Tolima, Cauca y Valle de Santander”, quienes huyen de la violencia y son víctimas del conflicto Armado, este grupo de colonos ha sido desconocido y desplazado por parte del Gobierno, se plantean estrategias a nivel psicosocial que contribuirán con una mirada en la solución de la problemática. Finalmente, se presenta el informe analítico del trabajo de la foto voz, en el cual se reflexiona acerca de cinco voces, en cinco de escenarios de violencia de diferentes municipios y comunidades dentro y fuera del país, narrados desde la subjetividad por parte de los participantes del grupo. Las historias y relatos son sucesos que representan acontecimientos de violencia, y permiten desde un sentir, descubrir la esencia del dolor y tristeza de la guerra, como también la resiliencia y afrontamiento para superar los daños psicológicos y emocionales, levantarse y continuar viviendo por la esperanza y un mejor provenir para todos.This report presents story five related to the case of “Carlos Arturo Bravo”, a 14-year-old boy, who is a victim of violence and the armed conflict in Colombia, due to an explosion of a rifle grenade left by the FARC, and who suffered injuries in different regions of his body, affecting him physically and emotionally for his entire life; the aftermath and the impact are very high for him and his family; To complement the analysis of behavior and possible psychosocial events at a traumatic level linked to the experience of Carlos Arturo Bravo, 9 questions are constructed: 3 circular, 3 reflective and 3 strategic. The analysis of the case of "Peñas Coloradas" is also taken into account, a population made up of inhabitants of regions such as "Huila, Tolima, Cauca and Valle de Santander", who are fleeing violence and are victims of the armed conflict, settlers have been unknown and displaced by the Government, strategies are proposed at a psychosocial level that will contribute with a look at the solution of the problem. Finally, the analytical report of the work of the photo voice is presented, in which it is reflected on five voices, in five scenarios of violence of different municipalities and communities inside and outside the country, narrated from the subjectivity by the participants of the group. The stories are events that represent violent events, and allow from a feeling, to discover the essence of the pain and sadness of the war, as well as the resilience and coping to overcome the psychological and emotional damages, get up and continue living by hope and a better future for all

Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain

Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10&lt;sup&gt;−8&lt;/sup&gt;, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10&lt;sup&gt;−7&lt;/sup&gt;, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10&lt;sup&gt;−20&lt;/sup&gt;, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10&lt;sup&gt;−22&lt;/sup&gt;, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10&lt;sup&gt;−4&lt;/sup&gt;), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific