Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency

Objective: Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood. Methods: We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B-cell, CD8+ T-cell and CD4+ T-cell subsets, sequence analysis of IGA and IGG transcripts, in vitro B-cell activation and blood cytokine measurements. Results: All patients had significantly decreased numbers of T-cell-dependent (TD; CD27+) and T-cell-independent (TI; CD27−) IgA memory B cells and increased CD21low B-cell numbers. IgM+IgD− memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B-cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF-β1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers. Conclusion: Impaired IgA memory formation in sIgAD patients is not due to a B-cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF-β1 might reflect disturbed regulation of IgA responses in vivo. These insights into B-cell extrinsic immune defects suggest the need for a broader immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD

Prevalencia de esofagitis eosinofílica: estudio multicéntrico en población pediátrica evaluada en 36 centros de gastroenterología de América Latina

Introducción y objetivo: La esofagitis eosinofílica es una enfermedad crónica, mediada inmunológicamente, descrita en series y publicaciones alrededor del mundo. En los últimos 20 años diversos estudios han intentado evaluar la incidencia y prevalencia de la enfermedad. El objetivo del presente trabajo es estimar la prevalencia de esofagitis eosinofílica en un grupo de niños atendidos en 36 centros de gastroenterología pediátrica de 10 países latinoamericanos. Materiales y métodos: A través de un protocolo multicéntrico, observacional y transversal se estimó la prevalencia de período de esofagitis eosinofílica entre los niños atendidos en consulta externa y sometidos a endoscopia superior diagnóstica por cualquier motivo en 36 centros de 10 países latinoamericanos durante un período de 3 meses. Resultados: Entre abril y junio de 2016 108 casos de esofagitis eosinofílica fueron evaluados. Asimismo, un promedio de 29,253 consultas ambulatorias y 4,152 endoscopias superiores de carácter diagnóstico fueron realizadas en los 36 centros participantes. La tasa de prevalencia de esofagitis eosinofílica en la población estudiada (n = 29,253) fue de 3,69 casos × 1,000 (IC 95%: 3.04 a 4.44) y entre los niños sometidos a endoscopia superior de rutina (n = 4,152) fue de 26 x 1,000 (IC 95%: 22.6 a 29.4). Conclusión: La tasa general de prevalencia de período de esofagitis eosinofílica en un grupo de niños evaluados en 36 centros latinoamericanos de gastroenterología pediátrica resultó de 3,69 × 1,000, y entre aquellos sometidos a endoscopia fue de 26 × 1,000. La prevalencia mostró una importante variabilidad entre los países y centros participantes. Este es el primer estudio de prevalencia de esofagitis eosinofílica pediátrica en Latinoamérica. Abstract: Introduction and objective: Eosinophilic esophagitis is a chronic, immune-mediated disease described in case series and publications worldwide. Over the past twenty years, the authors of different studies have attempted to evaluate its incidence and prevalence. The objetive of the present study was to estimate the prevalence of eosinophilic esophagitis in a group of children seen at 36 pediatric gastroenterology centers in ten Latin American countries. Materials and methods: A multicenter, observational, and cross-sectional study was conducted that estimated the period prevalence of eosinophilic esophagitis in children seen at outpatient consultation and that underwent diagnostic upper gastrointestinal endoscopy for any indication at 36 centers in 10 Latin American countries, within a 3-month time frame. Results: Between April and June 2016, 108 cases of eosinophilic esophagitis were evaluated. Likewise, an average of 29,253 outpatient consultations and 4,152 diagnostic upper gastrointestinal endoscopies were carried out at the 36 participating centers. The period prevalence of eosinophilic esophagitis in the population studied (n = 29,253) was 3.69 cases × 1,000 (95% CI: 3.04 to 4.44), and among the children that underwent routine upper gastrointestinal endoscopy (n = 4,152), it was 26 x 1,000 (95% CI: 22.6 to 29.4). Conclusions: The general period prevalence of eosinophilic esophagitis in a group of children evaluated at 36 Latin American pediatric gastroenterology centers was 3.69 × 1,000, and in the children that underwent endoscopy, it was 26 × 1,000. There was important prevalence variability between the participating countries and centers. The present analysis is the first study conducted on the prevalence of pediatric eosinophilic esophagitis in Latin America. Palabras clave: Esofagitis, Eosinofílica, Niños, Prevalencia, Latinoamérica, Keywords: Esophagitis, Eosinophilic, Children, Prevalence, Latin Americ

Modelling the potential impacts of climate change on the hydrology of the Aipe river basin in Huila, Colombia

[EN] The dynamics of a global world, and humans performing as a new geological force, require that an effort is undertaken to make robust decisions in order to devise strategies for the management and adaptation to climate change. This study aims to investigate the potential impact of climate change on the hydrology of the Aipe river basin in Huila, Colombia. The abcd Thomas model (four parameters) was calibrated and validated for the stream flows of the Aipe catchment (1992¿2012). The sensitivity and identifiability of the parameters were evaluated using the Monte Carlo Analysis Toolbox (MCAT). The results show the ability of the model to simulate the monthly stream flow (Nash¿Sutcliffe efficiency coefficient of 0,89). The most influential parameters are: a (water storage in the soil) and c (contribution to the aquifer). From the simulated scenarios, the baseline (1992¿2012) was estimated to be an average flow of 15,44 m3s¿1; the trend extrapolation scenario estimated a rate 13,79 m3s¿1 (¿10,64%); while for the multi-model assembly scenario it was 9,34 m3s¿1 (¿39,47%) and for the A2 scenario it was 5,74 m3s¿1 (¿62,60%). Lastly, we propose a set of strategies for adaptation to climate change that are committed to the integral management of water resources.[ES] La dinámica de un mundo global y el hombre como nueva fuerza geológica plantean la necesidad de tomar decisiones robustas, diseñar estrategias de manejo y de adaptarse al cambio climático. Este estudio investiga la respuesta hidrológica de la cuenca hidrográfica del río Aipe (688.9 km2 ), en Huila, Colombia, en acorde con los escenarios de cambio climático desde 2011 a 2040. El modelo hidrológico abcd de Thomas (4 parámetros) fue calibrado y validado comparando el caudal simulado y lo observado en el punto de cierre de la cuenca (en la estación Puente Carretera), usando series históricas mensuales (1992¿2012). Realizamos la evaluación de la sensibilidad e identificabilidad de los parámetros con la herramienta `Monte Carlo Analysis Toolbox¿ (MCAT). Los resultados muestran que el modelo es capaz de representar adecuadamente los caudales mensuales observados en el punto de desagüe de la cuenca, al encontrarse un índice de eficiencia de Nash¿Sutcliffe (NSE) de 0,89. Los parámetros más influyentes son a (almacenamiento del agua en el suelo) y c (aporte al acuífero). Con respecto a la simulación de los escenarios, la línea base (1992¿2012) estimó un caudal medio de 15,44 m3 s ¿1 ; el escenario de extrapolación de tendencias estimó un caudal de 13,79 m3 s ¿1 (¿10,64%); el escenario de ensamble multi-modelo de 9,34 m3 s ¿1 (¿39,47%) y el escenario A2 de 5,74 m3 s ¿1 (¿62,60%). Proponemos una batería de medidas de adaptación al cambio climático que buscan la gestión integral del recurso hídrico.Romero-Cuellar, J.; Buitrago-Vargas, A.; Quintero-Ruiz, T.; Francés, F. (2018). Simulación hidrológica de los impactos potenciales del cambio climático en la cuenca hidrográfica del río Aipe, en Huila, Colombia. RIBAGUA - Revista Iberoamericana del Agua. 5(1):63-78. https://doi.org/10.1080/23863781.2018.1454574S63785

Advanced Antenna Technology for Wireless Communications in Indoor Environments

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Fotemustine in patients with advanced gastric cancer, a phase II trial from the EORTC-GITCGG (European Organization for research and treatment of cancer, gastrointestinal tract cancer cooperative group)

Contains fulltext : 23912___.PDF (publisher's version ) (Open Access

LOCALLY ADMINISTERED ADIPOSE DERIVED MESENCHYMAL STEM CELLS REINFORCE THEIR ANTI-INFLAMMATORY EFFECT THROUGH IL-1 beta MEDIATED ATTRACTION OF NEUTROPHILS INTO KNEE JOINTS WITH EXPERIMENTAL OSTEOARTHRITIS

Contains fulltext : 149106.pdf (Publisher’s version ) (Closed access

Childhood Adiposity Associated With Expanded Effector Memory CD8(+) and V delta 2(+)V gamma 9(+)T Cells

Context: Adult obesity is associated with chronic low-grade inflammation and may give rise to future chronic disease. However, it is unclear whether adiposity-related inflammation is already apparent in childhood.Objective: To study associations between child adiposity measures with circulating monocytes and naive and memory subsets in CD4, CD8, and gamma delta T cell lineages.Methods: Ten-year-old children (n = 890) from the Generation R Cohort underwent dual-energy x-ray absorptiometry and magnetic resonance imaging for body composition (body mass index [BMI], fat mass index [FMI], android-to-gynoid fat mass ratio, visceral fat index, liver fat fraction). Blood samples were taken for detailed immunophenotyping of leukocytes by 11-color flow cytometry.Results: Several statistically significant associations were observed. A 1-SD increase in total FMI was associated with +8.4% (95% CI 2.0, 15.2) V delta 2(+)V gamma 9(+) and +7.4% (95% CI 2.4, 12.5) CD8(TEMRO)(+) cell numbers. A 1-SD increase in visceral fat index was associated with +10.7% (95% CI 3.3, 18.7) V delta 2(+)V gamma 9(+) and +8.3% (95% CI 2.6, 14.4) CD8(TEMRO)(+) cell numbers. Higher android-to-gynoid fat mass ratio was only associated with higher V delta 2(+)V gamma 9(+) T cells. Liver fat was associated with higher CD8(TEMRO)(+) cells but not with V delta 2(+)V gamma 9(+) T cells. Only liver fat was associated with lower Th17 cell numbers: a 1-SD increase was associated with -8.9% (95% CI -13.7, -3.7) Th17 cells. No associations for total CD8(+), CD4(+) T cells, or monocytes were observed. BMI was not associated with immune cells.Conclusion: Higher V delta 2(+)V gamma 9(+) and CD8(TEMRO)(+) cell numbers in children with higher visceral fat index could reflect presence of adiposity-related inflammation in children with adiposity of a general population.Public Health and primary carePrevention, Population and Disease management (PrePoD