Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3–4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.Supported in part with the grants PI10/01417 from Fondo de Investigaciones Sanitarias and RD12/0036/0029 from RTICC, Instituto de Salud Carlos III, 2014 SGR225(GRE), CERCA Program, Generalitat de Catalunya, Spain, and a funding from ‘La Caixa’ Foundation

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis

Izaña Atmospheric Research Center. Activity Report 2019-2020

Editors: Emilio Cuevas, Celia Milford and Oksana Tarasova.[EN]The Izaña Atmospheric Research Center (IARC), which is part of the State Meteorological Agency of Spain (AEMET), is a site of excellence in atmospheric science. It manages four observatories in Tenerife including the high altitude Izaña Atmospheric Observatory. The Izaña Atmospheric Observatory was inaugurated in 1916 and since that date has carried out uninterrupted meteorological and climatological observations, contributing towards a unique 100-year record in 2016. This reports are a summary of the many activities at the Izaña Atmospheric Research Center to the broader community. The combination of operational activities, research and development in state-of-the-art measurement techniques, calibration and validation and international cooperation encompass the vision of WMO to provide world leadership in expertise and international cooperation in weather, climate, hydrology and related environmental issues.[ES]El Centro de Investigación Atmosférica de Izaña (CIAI), que forma parte de la Agencia Estatal de Meteorología de España (AEMET), representa un centro de excelencia en ciencias atmosféricas. Gestiona cuatro observatorios en Tenerife, incluido el Observatorio de Izaña de gran altitud, inaugurado en 1916 y que desde entonces ha realizado observaciones meteorológicas y climatológicas ininterrumpidas y se ha convertido en una estación centenaria de la OMM. Estos informes resumen las múltiples actividades llevadas a cabo por el Centro de Investigación Atmosférica de Izaña. El liderazgo del Centro en materia de investigación y desarrollo con respecto a las técnicas de medición, calibración y validación de última generación, así como la cooperación internacional, le han otorgado una reputación sobresaliente en lo que se refiere al tiempo, el clima, la hidrología y otros temas ambientales afines

FMR1 premutation and full mutation molecular mechanisms related to autism

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism

Anales de Edafología y Agrobiología Tomo 47 Número 3-4

Suelos. Física. Resistencia del suelo y susceptibilidad a la compactación en terrenos a monte sometidos a pastoreo. Por R. Pérez Moreira y F. Diaz-Fierros Viqueira.-- La reserva de agua útil de los suelos de Galicia. l. Relación con la textura y el contenido de materia orgánica. Por A. M. Martinez Cortizas.-- Química Empleo de aminas alifáticas en el estudio de asociaciones haloisita-esmectita en suelos. Por F. J. Aragoneses, J. Casas, y J. L. Martin de Vidales.-- Quelación por EDDHA de micronutrientes en suelos calizos. Ecuación de límite máximo. Por M. Juárez, J. Sánchez-Andréu, L. Pla y J. Jorda.-- Quelación por EDDHA de micronutrientes en suelos calizos. Ecuación de orden "n ".Por J. Sánchez-Andréu, M. Juarez, L. Pla y J. Jordá.-- Génesis, Clasificación y Cartografía Caracterización de un podsol ferro - húmico en el Puerto de la Quesera (Sierra del Ayllón). Por R. Espejo Serrano, F. Guerrero López y A. Saa Requejo.-- Natrixerales en el Baix Segre (Lleida). Por J. Bech i Borrás, J. Garrigo i Reixach y J. R. Torrento i Marselles.-- Aspectos micromorfológicos del horizonte superior en suelos artificiales (Sorribas) de las Islas Canarias. Por A. Rodríguez Rodríguez y J. M. Ontañón Sánchez.-- Fertilidad Influencia de diferentes factores del suelo sobre su contenido en microelementos asimilables: Mn, Fe, Cu y Zn. Por B. C. Ortega, Ma C. Ortega y J. G. de las Heras.--Incidencia de la salinidad del agua de riego en la mineralización del nitrógeno orgánico en suelos calizos del sureste español. Por J. García-Serna, J. Sánchez Andréu, M. Juárez y J. Mataix.-- Biología Vegetal-Fisiología Efectos de la toxicidad del flúor sobre el ciclo biológico en especies herbáceas dicotiledoneas. Por M. Ibarra, F. López Belmonte y Ma A. Diez.-- Efectos de la toxicidad del flúor sobre el ciclo biológico de especies de monocotiledoneas. Por M. Ibarra, F. López-Belmonte y Mª A . Diez.-- Proteasas ácidas en uvas Vitis vinifera (variedad Macabeo). l. Actividad proteásica durante su maduración. Por J. Marín Expósito, C. Miguel Gordillo, J. l. Maynar Mariño y J. L. Mesias Iglesias.-- Agro biología Efectos de enmiendas calcáreas en suelos fijadores de fósforo. Por S. G. Ramos Hernández y N. Aguilera Herrera.-- III. Trabajo Recapitulativo. Una deriva hacia hemiparasftismo de los líquenes epifitos: Análisis fisiológico de las relaciones con sus fitoforos. Por C. VicentePeer reviewed2019-08.- CopyBook.- Libnova.- Biblioteca IC

Labile haemoglobin as a glycaemic biomarker for patient-specific monitoring of diabetes: mathematical modelling approach.

Diabetes mellitus constitutes a major health problem and its clinical presentation and progression may vary considerably. A number of standardized diagnostic and monitoring tests are currently used for diabetes. They are based on measuring either plasma glucose, glycated haemoglobin or both. Their main goal is to assess the average blood glucose concentration. There are several sources of interference that can lead to discordances between measured plasma glucose and glycated haemoglobin levels. These include haemoglobinopathies, conditions associated with increased red blood cell turnover or the administration of some therapies, to name a few. Therefore, there is a need to provide new diagnostic tools for diabetes that employ clinically accessible biomarkers which, at the same time, can offer additional information allowing us to detect possible conflicting cases and to yield more reliable evaluations of the average blood glucose level concentration. We put forward a biomathematical model to describe the kinetics of two patient-specific glycaemic biomarkers to track the emergence and evolution of diabetes: glycated haemoglobin and its labile fraction. Our method incorporates erythrocyte age distribution and utilizes a large cohort of clinical data from blood tests to support its usefulness for diabetes monitoring

Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency.

Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a promising therapeutic tool for many diseases, including aged tissues and organs at high risk of failure. However, the intrinsic self-renewal and pluripotency of ES and iPS cells make them tumorigenic, and hence, the risk of tumor development hinders their clinical application. Here, we present a novel approach to limit their tumorigenicity and increase their safety through increased copy number of tumor suppressors. iPS containing an extra copy of the p53 or Ink4a/ARF locus show normal pluripotency, as determined by in vitro and in vivo differentiation assays. Yet, while retaining full pluripotency, they also possess an improved engagement of the p53 pathway during teratocarcinoma formation, which leads to a reduced tumorigenic potential in various in vitro and in vivo assays. Furthermore, they show an improved response to anticancer drugs, which could aid in their elimination in case tumors arise with no adverse effects on cell function or aging. Our system provides a model for studying tumor suppressor pathways during reprogramming, differentiation, and cell therapy applications. This offers an improved understanding of the pathways involved in tumor growth from engrafted pluripotent stem cells, which could facilitate the use of ES and iPS cells in regenerative medicine

Failure of Intravenous Immunoglobulin to Prevent Congenital Heart Block Findings of a Multicenter, Prospective, Observational Study

OBJECTIVE: Congenital heart block (CHB) is presumed to be caused by transplacental passage of maternal immunoglobulin against Ro and La ribonucleoproteins. The recurrence rate in subsequent pregnancies following the birth of a child with CHB is approximately 19%. The purpose of this study was to determine whether intravenous immunoglobulin (IVIG) therapy could prevent the development of CHB in the fetuses of high-risk pregnant women. METHODS: A total of 24 pregnancies in 22 women who had a previous pregnancy in which CHB developed, were over the age of 18 years, were <12 weeks pregnant, and had anti-Ro, anti-La, or both antibodies were monitored in this multicenter, prospective, observational study. Fifteen patients received infusions of IVIG. The 9 pregnancies in the remaining 7 patients served as controls. IVIG was administered at a dose of 400 mg/kg at weeks 12, 15, 18, 21, and 24 of pregnancy. Echocardiograms were performed at least every 3 weeks from week 15 to week 30 of gestation. Electrocardiograms were obtained at birth. The outcome measure was the development of third-degree CHB detected by fetal echocardiogram. RESULTS: CHB developed in 3 babies among the 15 pregnancies in the treatment group (20%) and in 1 baby among the 9 pregnancies in the control group (11%). CHB was detected at weeks 18, 23, and 26, respectively, in the 3 babies in the treated group and at week 19 in the baby in the control group. Three of the affected pregnancies ended in termination; 2 for reasons related to the fetal disease and 1 for reasons related to both maternal (severe pulmonary hypertension) and fetal disease (at 21 weeks of gestation). CONCLUSION: IVIG at the dose and frequency used in this study was not effective as prophylactic therapy for CHB in high-risk mothers