185 research outputs found

    Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial.

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    There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53-74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4-13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12-45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D3 for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.This work was supported by Fundación Universidad Alfonso X el Sabio (FUAX, Madrid, Spain; ID Project: 1.012.010; ID Project EQA: 925.280); the Coordinated Research Activities at the National Center of Microbiology (Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr. Inmaculada Casas (WHO National Influenza Center of the CNM); a generous donation provided by Chiesi España, S.A.U. (Barcelona, Spain). The work of Montserrat Torres was financed by the Coordinated Research Activities at the CNM (Instituto de Salud Carlos III) (COV20_00679). The work of Lorena Vigón was supported by a pre-doctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER). The work of Sara Rodríguez-Mora was financed by NIH grant R01AI143567.S

    A New Automatic Method to Identify Galaxy Mergers I. Description and Application to the STAGES Survey

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    We present an automatic method to identify galaxy mergers using the morphological information contained in the residual images of galaxies after the subtraction of a Sersic model. The removal of the bulk signal from the host galaxy light is done with the aim of detecting the fainter minor mergers. The specific morphological parameters that are used in the merger diagnostic suggested here are the Residual Flux Fraction and the asymmetry of the residuals. The new diagnostic has been calibrated and optimized so that the resulting merger sample is very complete. However, the contamination by non-mergers is also high. If the same optimization method is adopted for combinations of other structural parameters such as the CAS system, the merger indicator we introduce yields merger samples of equal or higher statistical quality than the samples obtained through the use of other structural parameters. We explore the ability of the method presented here to select minor mergers by identifying a sample of visually classified mergers that would not have been picked up by the use of the CAS system, when using its usual limits. Given the low prevalence of mergers among the general population of galaxies and the optimization used here, we find that the merger diagnostic introduced in this work is best used as a negative merger test, i.e., it is very effective at selecting non-merging galaxies. As with all the currently available automatic methods, the sample of merger candidates selected is contaminated by non-mergers, and further steps are needed to produce a clean sample. This merger diagnostic has been developed using the HST/ACS F606W images of the A901/02 cluster (z=0.165) obtained by the STAGES team. In particular, we have focused on a mass and magnitude limited sample (log M/M_{O}>9.0, R_{Vega}<23.5mag)) which includes 905 cluster galaxies and 655 field galaxies of all morphological types.Comment: 25 pages, 14 figures, 4 tables. To appear in MNRA

    Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry

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    Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease with autosomal dominant inheritance. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in more than 90% of cases submitted to molecular diagnosis. Methods: We used data from the RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry to describe genetic variants and to assess their genotype-phenotype correlation among HHT patients in Spain. Results: By May 2019, 215 patients were included in the RiHHTa registry with a mean age of 52.5 ± 16.5 years and 136 (63.3%) were women. Definitive HHT diagnosis defined by the Curaçao criteria were met by 172 (80%) patients. Among 113 patients with genetic test, 77 (68.1%) showed a genetic variant in ACVRL1 and 36 (31.8%) in ENG gene. The identified genetic variants in ACVRL1 and ENG genes and their clinical significance are provided. ACVRL1 mutations were more frequently nonsense (50%) while ENG mutations were more frequently, frameshift (39.1%). ENG patients were significantly younger at diagnosis (36.9 vs 45.7 years) and had pulmonary arteriovenous malformations (AVMs) (71.4% vs 24.4%) and cerebral AVMs (17.6% vs 2%) more often than patients with ACVRL1 variants. Patients with ACVRL1 variants had a higher cardiac index (2.62 vs 3.46), higher levels of hepatic functional blood tests, and anemia (28.5% vs 56.7%) more often than ENG patients. Conclusions: ACVRL1 variants are more frequent than ENG in Spain. ACVRL1 patients developed symptomatic liver disease and anemia more often than ENG patients. Compared to ACVRL1, those with ENG variants are younger at diagnosis and show pulmonary and cerebral AVMs more frequently

    Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D

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    Main cause of severe illness and death in COVID-19 patients appears to be an excessive but ineffectual inflammatory immune response that may cause severe acute respiratory distress syndrome (ARDS). Vitamin D may favour an anti-inflammatory environment and improve cytotoxic response against some infectious diseases. A multicenter, single-blind, prospective, randomized clinical trial was approved in patients with COVID-19 pneumonia and levels of 25-hydroxyvitamin D (25(OH)D) of 14.8 ng/ml (SD: 6.18) to test antiviral efficacy, tolerance and safety of 10,000 IU/day of cholecalciferol (vitamin D3) for 14 days, in comparison with 2000 IU/day. After supplementation, mean serum 25(OH)D levels increased to 19 ng/ml on average in 2000 IU/day versus 29 ng/ml in 10,000 IU/day group (p < 0.0001). Although levels of inflammatory cytokines were not modified by treatment with 10,000 IU/day, there was an increase of anti-inflammatory cytokine IL-10 and higher levels of CD4+ T cells, with predominance of T central memory subpopulation. Cytotoxic response against pseudotyped SARS-CoV-2 infected cells was increased more than 4-fold in patients who received 10,000 IU/day. Moreover, levels of IFNγ were significantly higher in this group. Beneficial effect of supplementation with 10,000 IU/day was also observed in participants who developed ARDS and stayed at the hospital for 8.0 days, whereas those who received 2000 IU/day stayed for 29.2 days (p = 0.0381). Administration of high doses of vitamin D3 as adjuvant of the standard care treatment during hospitalization for COVID-19 may improve the inflammatory environment and cytotoxic response against pseudotyped SARS-CoV-2 infected cells, shortening the hospital stay and, possibly, improving the prognosis.We greatly appreciate all the patients for their participation in this study. We thank the excellent secretarial assistance of Mrs Olga Palao at the Centro Nacional de Microbiología (CNM, Instituto de Salud Carlos III). The authors also acknowledge María C. de la Cruz at Unidad Central de Apoyo a la Investigación Clínica y Ensayos Clínicos (Instituto de Investigación Sanitaria Gregorio Marañon; IiSGM) for her advice and assistance related to the clinical research with medicines. This work was supported by the Coordinated Research Activities at CNM (Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr Inmaculada Casas (WHO National Influenza Center of the CNM); the Spanish Ministry of Science and Innovation (PID2019–110275RB-I00); the Spanish AIDS Research Network RD16CIII/0002/0001 that is included in Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2016–2020, Instituto de Salud Carlos III, European Region Development Fund (ERDF) and Fundación Universidad Alfonso X el Sabio (FUAX, Madrid, Spain; Reference 1012010). The work of Montserrat Torres is financed by the Coordinated Research Activities at the CNM (Instituto de Salud Carlos III) (COV20_00679). The work of María Rosa López-Huertas and Sara Rodríguez-Mora is financed by NIH grant R01AI143567. The work of Lorena Vigón is supported by a pre-doctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER). The work of Fernando Ramos Martín is financed by the Spanish Ministry of Science and Innovation (PID2019–110275RB-I00). Drug Cholecalciferol (vitamin D) used in the study was donated by Italfarmaco Group (Cholecalciferol 25,000IU/2,5 ml oral solution). Italfarmaco Group had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or the preparation, review, or approval of the manuscript.S

    Self-assessment of quality of life and aging of Alzheimer development risk adults

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    ABSTRACT: middle-age adult carriers and non-carriers of mutation E280A in gene Presenilin 1 for Early Onset Familial Alzheimer’s Disease and of elderly adults in Antioquia-Colombia. Study conducted from January 2005 to June 2007. Methodology: descriptive transversal study in which 162 asymptomatic people at risk of developing Alzheimer’s disease as a genetic consequence or as a consequence of the process of aging. They were subdivided into three groups: 27 carriers of the mutation, 39 non-carriers and 96 elderly adults. The study was conducted at the Neuroscience Group in Medellín (Antioquia) and at a gerontology center in Envigado (Antioquia) named Atardecer. Social-demographic characteristics were analyzed and quality of life and overall aging selfassessment tests were applied, which included the World Health Organization Quality of Life, and the Nürnberg -Self-Evaluation-List respectively. Statistic Analysis: The groups were described and they were compared to the variables of the study using Kruskall Wallis non-parametric ANOVA and Mann-Whitney’s U-test. Results: the mean scores of the instruments to assess quality of life and overall aging of three groups of participants were above 50 points and below 55 points respectively. Conclusions: elderly adults assessed themselves as having a lower quality of life than carriers and non-carriers, especially in the physical health area, and in their perception of aging, in spite of carriers’ conditions, although in general the scores were good in all the groups.RESUMEN: Describir la autovaloración de calidad de vida y del envejecimiento de tres grupos: adultos portadores y no portadores de la mutación E280A en el gen de la Presenilina 1 para Enfermedad de Alzheimer Familiar Precoz, y adultos mayores, en Antioquia-Colombia, estudio realizado entre enero de 2005 y junio de 2007. Metodología: estudio descriptivo transversal donde participaron 162 personas asintomáticas en riesgo de desarrollar Enfermedad de Alzheimer como consecuencia genética o del proceso de envejecimiento, quienes se subdividieron en tres grupos: 27 portadores, 39 no portadores y 96 adultos mayores. Investigación realizada en el Grupo de Neurociencias de la Universidad de Antioquia (Medellín) y en el Centro Gerontológico Atardecer (Envigado). Se analizaron las características sociodemográficas, y se aplicaron pruebas para la autovaloración de la calidad de vida global del envejecimiento: World Health Organization Quality of Life y la Nürnberg -Self-Evaluation-List respectivamente. Análisis estadístico: Se describieron los grupos y se compararon frente a las variables de estudio utilizando el análisis de varianza no paramétrico de Kruskall Wallis y la prueba U de Mann-Whitney. Resultados: las calificaciones medias de los instrumentos para la autovaloración de calidad de vida y global del envejecimiento en los tres grupos de participantes, fueron superiores a 50 puntos e inferiores a 55 puntos respectivamente. Conclusiones: los adultos mayores se autovaloran con menor calidad de vida que los portadores y los no portadores, especialmente en el área de salud física, al igual que en la percepción del envejecimiento, a pesar de las condiciones de los portadores, aunque, en general, todos los grupos las puntuaron bien

    Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry

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    Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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