A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis

Background and aims: Little is known about specific genetic determinants of carotid-intima-media thickness (CIMT) and carotid plaque in subjects with rheumatoid arthritis (RA). We have used the Metabochip array to fine map and replicate loci that influence variation in these phenotypes in Mexican Americans (MAs) and European Americans (EAs). Methods: CIMT and plaque were measured using ultrasound from 700 MA and 415 EA patients with RA and we conducted association analyses with the Metabochip single nucleotide polymorphism (SNP) data using PLINK. Results: In MAs, 12 SNPs from 11 chromosomes and 6 SNPs from 6 chromosomes showed suggestive associations (p \u3c 1 × 10-4) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (β ± SE = -0.84 ± 0.18, p = 3.80 × 10-6). In EAs, 9 SNPs from 7 chromosomes and 7 SNPs from 7 chromosomes showed suggestive associations with CIMT and plaque, respectively. The top association for CIMT was observed with rs1867148 (PPCDC gene, β ± SE = -0.28 ± 0.06, p = 5.11 × 10-6). We also observed strong association between plaque and two novel loci: rs496916 from COL4A1 gene (OR = 0.51, p = 3.15 × 10-6) in MAs and rs515291 from SLCA13 gene (OR = 0.50, p = 3.09 × 10-5) in EAs. Conclusions: We identified novel associations between CIMT and variants in SLC17A2 and PPCDC genes, and between plaque and variants from COL4A1 and SLCA13 that may pinpoint new candidate risk loci for subclinical atherosclerosis associated with RA

Data on genetic associations of carotid atherosclerosis markers in Mexican American and European American rheumatoid arthritis subjects

Carotid Intima-media thickness (CIMT) and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA) patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA) and European Americans (EA) populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or nearest genes associated with CIMT in MAs and EAs with RA are presented. In addition, common susceptibility loci influencing CIMT and plaque in both MAs and EAs have been presented. Polygenic Risk Score (PRS) plots showing complementary evidence for the observed CIMT and plaque association signals are also shown in this article. For further interpretation and details, please see the research article titled A Genetic Association Study of Carotid Intima-Media Thickness (CIMT) and Plaque in Mexican Americans and European Americans with Rheumatoid Arthritis which is being published in Atherosclerosis (Arya et al., 2018) [1].(Arya et al., in press) Thus, common variants in several genes exhibited significant associations with CIMT and plaque in both MAs and EAs as presented in this article. These findings may help understand the genetic architecture of subclinical atherosclerosis in RA populations

Investigación en matemáticas, economía y ciencias sociales

El resultado de este libro que reune inquietudes académicas en torno a temas tan estudiados como los que están alrededor del maíz, del frijol o del café; y tan contemporáneos como las aplicaciones concretas de las ciencias ya citadas, al estudio de la adopción del comercio electrónico en empresas del sector agroindustrial o, el caso de la generación de biogas o energía eléctrica por medio de biodigestores. Al editar este texto e incorporarlo a la bibliografía de los temas de referencia, se enriquecen opciones de consulta para los estudiosos de esos temas en general; pero también para interesados en aspectos tan específicos como la cadena de suministro del mercado hortofrutícola en Texcoco

Embriopatia pelo vírus zika na Argentina: Características clínicas e diagnóstico em recém-nascidos

Introducción: La microcefalia y las anomalías cerebrales congénitas pueden deberse a múltiples etiologías, siendo uno de ellas la infección congénita por el virus Zika (ZIKV). Desde 2016 hasta hoy se han sucedido una serie de brotes del ZIKV en Argentina. Métodos: La Red Nacional de Anomalías Congénitas (RENAC) y el Instituto Nacional de Enfermedades Virales (INEVH), dependientes de la Administración Nacional de Laboratorios e Institutos de Salud “Carlos Malbrán” (ANLIS), realizan la vigilancia intensificada de recién nacidos con microcefalia y anomalías cerebrales. Este trabajo presenta las características clínicas y estudios de laboratorio de los pacientes con infección congénita por ZIKV detectados entre abril de 2016 a marzo 2018. Resultados: se detectaron 10 casos con embriopatía, seis fueron autóctonos y cuatro importados; en dos casos las madres fueron asintomática durante el embarazo; todos los casos presentaron microcefalia y desproporción cráneo facial, ventriculomegalia en siete casos y en seis calcificaciones cerebrales. El diagnóstico de infección congénita por Zika en el recién nacido se realizó por estudios serológicos inmunoglobulina M antígeno específica (MAC-ELISA) y prueba de neutralización por reducción de placas (PRNT90). La PCR fue negativa en todos los casos. Conclusión: Los pacientes presentaron características clínicas coincidentes con las reportadas en otros países Se enfatiza la necesidad de estudios serológicos que permitan la confirmación, descartando la reactividad cruzada con otros FlavivirusIntroduction: Microcephaly and brain abnormalities may be due to multiple etiologies, one of them is the congenital infection by Zika virus (ZIKV). From 2016 to the present, there has been a series of ZIKV outbreaks in Argentina. Method: National Network of Congenital Anomalies (RENAC) and the National Institute of Viral Diseases (INEVH), under the National Administration of Laboratories and Health Institutes “Carlos Malbrán” (ANLIS), carry out the intensified surveillance of newborns with microcephaly and brain abnormalities. This article presents the clinical characteristics and laboratory test of patients detected with congenital infection by ZIKV between April 2016 to March 2018, Results: 10 cases with embryopathy were detected, six autochthonous and four imported; in two cases, the mothers were asymptomatic during pregnancy; all the cases presented microcephaly and cranial facial disproportion, ventriculomegaly in seven cases and in six cerebral calcifications. The diagnosis of congenital infection by Zika in the newborn was made by antigen-specific Immunoglobulin M (MAC-ELISA) and plaque-reduction neutralization test (PRNT90). PCR was negative in all cases. Conclusion: the patients presented clinical features that were consistent with those reported in other countries. The need for serological studies that allow confirmation is emphasized, ruling out crossreactivity with other Flaviviruses.Introdução: Microcefalia e anormalidades cerebrais congênitas podem ser causadas por múltiplas etiologias, sendo uma delas infecção congênita pelo vírus Zika (ZIKV). De 2016 a hoje, houve uma série de surtos de ZIKV na Argentina. Métodos: A Rede Nacional de Anomalias Congênitas (RENAC) e o Instituto Nacional de Doenças Virais (INEVH), da Administração Nacional de Laboratórios e Institutos de Saúde "Carlos Malbrán" (ANLIS), realizam a vigilância intensiva de recém-nascidos com microcefalia e anormalidades cerebrais. Este trabalho apresenta as características clínicas e estudos laboratoriais de pacientes com infecção congênita pelo ZIKV detectados entre abril de 2016 e março de 2018. Resultados: 10 casos com embriopatia foram detectados, seis nativos e quatro importados; em dois casos as mães eram assintomáticas durante a gravidez; Todos os casos apresentaram desproporção de microcefalia e crânio facial, ventriculomegalia em sete casos e em seis calcificações cerebrais. O diagnóstico de infecção congênita por zika no recém-nascido foi realizado por estudos sorológicos de antígeno específico da imunoglobulina M (MAC-ELISA) e teste de neutralização da redução de placa (PRNT90). A PCR foi negativa em todos os casos. Conclusão: Os pacientes apresentaram características clínicas coincidentes com as relatadas em outros países, enfatizando a necessidade de estudos sorológicos que permitam a confirmação, descartando a reatividade cruzada com outros flavivírus.Fil: Tellechea, Ana Laura. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Bidondo, Maria Paz. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Luppo, Victoria. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Baricalla, Agustin Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Liascovich, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Fabbri, Cintia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Morales, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Groisman, Boris. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Silva, María. Hospital Velez Sarsfield; ArgentinaFil: Masi, Patricia. Hospital Velez Sarsfield; ArgentinaFil: Israilev, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Rocha, Marcela. Gobierno de la Provincia de Tucumán. Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes; ArgentinaFil: Quaglia, Marcela. Hospital Materno Neonatal; ArgentinaFil: Escalante, Beatriz. Gobierno de la Provincia de Salta. Hospital Juan Domingo Perón; ArgentinaFil: Villarreal, Alexandra. Gobierno de la Provincia de Salta. Hospital San Vicente de Paul; ArgentinaFil: Antinori, Marilena. Gobierno de la Provincia de Formosa. Hospital de la Madre y El Niño; ArgentinaFil: Barbero, Pablo Miguel. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentin

Thermodynamically controlled chemoselectivity in lipase-catalyzed aza-Michael additions

Chemoselective synthesis of N-protected beta-amino esters involving lipase-catalyzed aza-Michael additions and alpha,beta-unsaturated precursors is mainly hampered by the two electrophilic sites present on these compounds. In order to control the chemoselectivity a solvent engineering strategy based on the thermodynamic behaviour of products in media of different polarity was designed. This strategy allowed to obtain aza-Michael adducts from benzylamine and different acrylates with high selectivity. In almost all reactions carried out in n-hexane, a non-polar solvent, aminolysis was avoided while the corresponding Michael adducts were exclusively synthesized in 53-78% yields. On the contrary, in reactions carried out in a polar solvent such as 2-methyl-2-butanol the aminolysis products were favoured. Thermodynamic analyses of these processes using the COSMO-RS method helped to understand some of the key factors affecting chemoselectivity and confirmed that a reliable estimation of the thermodynamic interactions of solutes and solvents allows an adequate selection of a reaction media that may lead to chemoselectivity

Anormalidad de la unión al ADN de Oct-1 en las células T de pacientes con síndrome de Sjogren

Primary Sjögren's syndrome (SS) is an autoimmune rheumatic disease characterized by T cell hypoactivity. To understand the diminished T cell response to activation signals, we measured nucleoprotein DNA?binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay. Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an octomer sequence (Oct?1). This Oct?1?binding phenotype remained stable in culture for up to 3 days prior to activation. This abnormality was not seen in resting T cells nor T cells from patients with systemic lupus erythematosus, rheumatoid arthritis (RA), or SS accompanied by RA. The SS Oct?1 DNA?binding abnormality correlated significantly with an inability of cells to exit the G0/G1 cell cycle phase when stimulated in vitro . Importantly, nucleoprotein extracts showing decreased DNA?binding activity had normal amounts of Oct?1 proteins as determined by immunoprecipitation, implying a functional defect in the Oct?1 protein. Moreover, defective DNA binding was corrected by treatment with acid phosphatase