Factores asociados a calidad de vida en pacientes de hemodi��lisis incidentes y prevalentes

Introducci��n: la insuficiencia renal cr��nica IRC ha aumentado su prevalencia en los ��ltimos a��os pasando de 44.7 pacientes por mill��n en 1993 a 538.46 pacientes por mill��n en 2010, los pacientes quienes reciben terapia de remplazo renal hemodi��lisis en Colombia cada vez tienen una mayor sobrevida. El incremento de los pacientes y el incremento de la sobrevida nos enfocan a mejorar la calidad de vida de los a��os de di��lisis. Metodolog��a: se compar�� la calidad de vida por medio del SF-36 en 154 pacientes con IRC estadio terminal en manejo con hemodi��lisis, 77 pacientes incidentes y 77 pacientes prevalentes, pertenecientes a una unidad renal en Bogot��, Colombia. Resultados: se encontr�� una disminuci��n de la calidad de vida en los componentes f��sicos (PCS) y metales (MCS) de los pacientes de hemodi��lisis en ambos grupos. En el modelo de regresi��n log��stica la incapacidad laboral (p=0.05), el uso de cat��ter (p= 0,000), el bajo ��ndice de masa corporal (p=0.021), la hipoalbuminemia (p=0,033) y la anemia (p=0,001) fueron factores determinantes en un 78,9% de baja calidad de vida de PCS en los pacientes incidentes con respecto a los prevalentes. En el MCS de los pacientes incidentes vs. Prevalentes se encontr�� la hipoalbuminemia (p=0.007), la anemia (p=0.001) y el acceso por cat��ter (p=0.001) como factores determinantes en un 70.6% de bajo MCS Conclusiones: la calidad de vida de los pacientes de di��lisis se encuentra afectada con mayor repercusi��n en el grupo de los pacientes incidentes, se debe mejorar los aspectos nutricionales, hematol��gicos y de acceso vascular en este grupo.

PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical subphenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.761029, OR = 1.40 (95% CI = 1.25���1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67���0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG .20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.761025, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71��10-34, OR = 1.43[1.26-1.60]) and rs1234317-T (P = 1.16��10-28, OR = 1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5��� region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5��� risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-��Bp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-��B interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. �� 2013 Manku et al.

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6��10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9��10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1��), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1�� (Pmeta = 3.2��10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5��10-4, OR = 1.14). These results suggested that the CFHR3-1�� deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.

MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus

We previously reported that the G allele of rs3853839 at 3���untranslated region (UTR) of Toll-like receptor 7 (TLR7) was associated with elevated transcript expression and increased risk for systemic lupus erythematosus (SLE) in 9,274 Eastern Asians [P = 6.5��10���10, odds ratio (OR) (95%CI) = 1.27 (1.17���1.36)]. Here, we conducted trans-ancestral fine-mapping in 13,339 subjects including European Americans, African Americans, and Amerindian/Hispanics and confirmed rs3853839 as the only variant within the TLR7-TLR8 region exhibiting consistent and independent association with SLE (Pmeta = 7.5��10���11, OR = 1.24 [1.18���1.34]). The risk G allele was associated with significantly increased levels of TLR7 mRNA and protein in peripheral blood mononuclear cells (PBMCs) and elevated luciferase activity of reporter gene in transfected cells. TLR7 3���UTR sequence bearing the non-risk C allele of rs3853839 matches a predicted binding site of microRNA-3148 (miR-3148), suggesting that this microRNA may regulate TLR7 expression. Indeed, miR-3148 levels were inversely correlated with TLR7 transcript levels in PBMCs from SLE patients and controls (R2 = 0.255, P = 0.001). Overexpression of miR-3148 in HEK-293 cells led to significant dose-dependent decrease in luciferase activity for construct driven by TLR7 3���UTR segment bearing the C allele (P = 0.0003). Compared with the G-allele construct, the C-allele construct showed greater than two-fold reduction of luciferase activity in the presence of miR-3148. Reduced modulation by miR-3148 conferred slower degradation of the risk G-allele containing TLR7 transcripts, resulting in elevated levels of gene products. These data establish rs3853839 of TLR7 as a shared risk variant of SLE in 22,613 subjects of Asian, EA, AA, and Amerindian/Hispanic ancestries (Pmeta = 2.0��10���19, OR = 1.25 [1.20���1.32]), which confers allelic effect on transcript turnover via differential binding to the epigenetic factor miR-3148.

Prevalencia de enfermedad celiaca en Latinoam��rica: revisi��n sistem��tica de la literatura y meta-an��lisis

Introducci��n: La enfermedad celiaca (EC) es una enfermedad autoinmune (EA) intestinal desencadenada por la ingesta de gluten. Por la falta de informaci��n de la presencia de EC en Latinoam��rica (LA), nosotros investigamos la prevalencia de la enfermedad en esta regi��n utilizando una revisi��n sistem��tica de la literatura y un meta-an��lisis. M��todos y resultados: Este trabajo fue realizado en dos fases: La primera, fue un estudio de corte transversal de 300 individuos Colombianos. La segunda, fue una revisi��n sistem��tica y una meta-regresi��n siguiendo las gu��as PRSIMA. Nuestros resultados ponen de manifiesto una falta de anti-transglutaminasa tisular (tTG) e IgA anti-endomisio (EMA) en la poblaci��n Colombiana. En la revisi��n sistem��tica, 72 art��culos cumpl��an con los criterios de selecci��n, la prevalencia estimada de EC en LA fue de 0,46% a 0,64%, mientras que la prevalencia en familiares de primer grado fue de 5,5 a 5,6%, y en los pacientes con diabetes mellitus tipo 1 fue de 4,6% a 8,7% Conclusi��n: Nuestro estudio muestra que la prevalencia de EC en pacientes sanos de LA es similar a la notificada en la poblaci��n europea.

Hallazgos radiol��gicos de la enfermedad pulmonar en pacientes Colombianos con esclerodermia

La esclerosis sist��mica (ES) es una enfermedad autoinmune multisist��mica que afecta principalmente la piel, los pulmones, el tracto gastrointestinal, el coraz��n y los ri��ones. La enfermedad pulmonar, presente en casi el 100% de los casos, es el factor con mayor influencia en la mortalidad. El prop��sito de este estudio es realizar un an��lisis detallado de la enfermedad pulmonar por tomograf��a computarizada de alta resoluci��n(TCAR) en pacientes Colombianos con ES, para lo cual se realiz�� un estudio de prevalencia anal��tica en 44 pacientes con ES valorados en el Hospital Universitario Mayor M��deri en los ��ltimos 7 a��os. Los resultados mostraron caracter��sticas demogr��ficas y cl��nicas similares a las previamente descritas. La prevalencia de enfermedad pulmonar intersticial fue alta, y los hallazgos de fibrosis pulmonar como vidrio esmerilado y panal de abejas se asociaron con la presencia del autoanticuerpo antiSCL70. La medida del di��metro esof��gico por TCAR fue mayor en los pacientes con disfagia, antiSCL 70 y linfopenia, los cuales son marcadores de mal pron��stico.

Actitudes hacia el VIH/SIDA, el c��ncer y la enfermedad de Alzheimer

Esta revisi��n de la literatura tuvo como objetivo describir las actitudes hacia el VIH/SIDA, el c��ncer y la Enfermedad de Alzheimer desde el modelo tripartito. Se revisaron 109 art��culos publicados entre 2005 y 2015 en algunas bases de datos especializadas y herramientas de an��lisis de impacto. Tambi��n se incluyeron fuentes secundarias ampli��ndose la b��squeda a los ��ltimos 20 a��os (1995-2015). Los resultados mostraron que la mayor��a de los estudios realizados sobre las actitudes hacia estas tres enfermedades son de tipo cuantitativo y la informaci��n se analiz�� con base en los componentes del modelo tripartito. Algunos aspectos sociodemogr��ficos como el sexo y la edad est��n asociados con las actitudes hacia las tres enfermedades y predominan las creencias err��neas sobre ellas respecto a sus causas, curso y tratamiento. Tambi��n predominan actitudes negativas hacia las tres enfermedades y las conductas e intenciones conductuales son diversas hacia cada una de ellas. No se hallaron antecedentes emp��ricos del estudio de la estructura de las actitudes propuesta por el modelo tripartito hacia las tres enfermedades. La Salud P��blica ha liderado la investigaci��n con base en el modelo de conocimientos, actitudes y pr��cticas propuesto por la OMS.

Implications for early interventionists: Cross-cultural and low-income family differences

This study examined the existing literature on current early intervention processes for children who are deaf or hard of hearing who are from low-income or minority families. The review of literature includes a framework of understanding the dynamics of low-income households and cultural differences among African Americans, Latin Americans, and American Indians.

Motivaciones econ��micas en la manumisi��n de esclavas: una comparaci��n entre ciudades de Am��rica Latina (Estudios)

La manumisi��n esclava fue una caracter��stica estructural de la sociedad colonial latinoamericana. Sin embargo, esto no quiere decir que todos, o que la mayor��a,de los esclavos consiguieran salir del cautiverio. Solo un peque��o porcentaje logr�� terminar sus d��as como libre. En ese porcentaje la mayor��a fueron mujeres. Desde las grandes regiones esclavistas hasta las perif��ricas, y desde el comienzo de la era colonial hasta la emancipaci��n total, siempre las mujeres se manumitieron proporcionalmente m��s que los hombres. Este art��culo propone como hip��tesis parcial de tal fen��meno que las esclavas se manumitieron m��s porque contaban con una exenci��n fiscal que no ten��an los hombres. Para demostrar tal cosa, se enfatiza en que la familia esclava era la que tomaba la decisi��n de a qui��n manumitir y que la libertad era m��s una estrategia que un objetivo.

��Eran cuidadanos los afrodescendientes libres en las sociedades esclavistas?: Cuba, Brasil y Estados Unidos en el siglo XIX (Estudios)

Se analiza el tema del estatus de los afrodescendientes libres en las sociedades esclavistas m��s pobladas de Am��rica, desde el punto de vista de los derechos pol��ticos y sociales de s��bditos y ciudadanos. Con la carta de libertad, los antiguos esclavos y sus descendientes libres adquirieron te��ricamente los mismos derechos y obligaciones que la poblaci��n blanca eurodescendiente. Sin embargo, por razones de ���seguridad p��blica��� y de ���mantenci��n del orden establecido���, en la pr��ctica, se establecieron restricciones y privilegios para mantener la distancia social entre blancos y afrodescendientes. Desde una perspectiva comparada se estudian Brasil, Cuba y los Estados Unidos, las tres sociedades esclavistas m��s notorias en Am��rica durante el siglo XIX, y se examina este proceso tomando como objetos de an��lisis los derechos de libre movimiento, el acceso a la ense��anza superior, el sufragio y la propiedad.

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 +/- A 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO(2 max)). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 +/- A 1 mu M) and G4 (14.2 +/- A 0.6 mu M) and between G2 (20.1 +/- A 1.7 mu M) and G4 (14.2 +/- A 0.6 mu M). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 +/- A 1.2 mu M) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients

A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R(2) value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm`s predictive power. We suggest that three other single-nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm`s predictive power was similar across the self-identified ""race/color"" subsets. ""Race/color"" was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 +/- 13 mg/week, n = 196) than in black patients (35 +/- 15 mg/week, n = 76).

Racial Conflict in the United States of America : A Deconstructive Perspective on Native Speaker by Changrae Lee

Written about the time of the Golden Venture incident, Chang-rae Lee���s Native Speaker makes a particular reference to that incident, whereby implying that particular immigrants, on the grounds of their racial identities, are mistreated and considered as aliens by some Americas. While some whites discriminate against immigrants, there is widespread ethnic tension between Korean Americans and African Americans. Significantly, racial conflict between Koreans and blacks and the racist attitude of some whites toward immigrants are mirrored in the relationship between the Korean-American protagonist Henry and his American wife Lelia. That is, due to their different racial identities they do not understand each other and they always argue. However, toward the end of the novel, Henry and Lelia come to understand each other. While ethnic conflict between Koreans and blacks and certain whites��� discriminatory attitudes toward immigrants is serious one, the novel suggests the unimportance of racial identity. In other words, the novel concludes that there is no discriminatory treatment of immigrants and, in fact, every one is a native Speaker in America. In the novel there is no message of how racial conflict could be resolved. However, this essay suggests that by investigating how the tension between Henry and Lelia is resolved, one could suggest a solution for the ethnicity problem in America and in real life.

Diabetes e estrutura ventricular esquerda em afro-americanos : quest��es metodol��gicas em esudos epidemiol��gicos e dados do estudo ERIC (The Atherosclerosis Risk in Communities

Hipertrofia ventricular esquerda �� um importante fator de risco em doen��a cardiovascular e pode ser respons��vel por parte do elevado risco cardiovascular associado a diabetes. Apesar de que o estresse hemodin��mico seja classicamente indicado como causa da inj��ria mioc��rdica que leva ao remodelamento, a inj��ria associada aos fatores neuro-humorais e a sinaliza����o celular atrav��s da ativa����o imuno-inflamat��ria tamb��m desempenham um papel, acompanhando os mecanismos recentemente descritos na s��ndrome metab��lica, particularmente na obesidade, onde a ativa����o do sistema imune inato leva a uma resposta inadequada cr��nica mediada por citocinas em diversos sistemas corp��reos. A ecocardiografia tem sido usada para identificar anormalidades da estrutura card��aca, por��m, varia����es metodol��gicas e os diversos ajustes para os determinantes da massa ventricular como idade, sexo, tamanho corporal e outros correlatos cl��nicos s��o motivo de debate, assim como a defini����o dos estados de anormalidade, tanto para hipertrofia ventricular esquerda, como para outras medidas da estrutura ventricular. Em uma amostra populacional de 1479 Afro- Americanos do Estudo ARIC, investigamos de forma estratificada e multivariada as associa����es independentes entre diabetes e as altera����es estruturais do ventr��culo esquerdo, definidas por hipertrofia ventricular, aumento da espessura relativa e padr��es geom��tricos anormais. Encontramos preval��ncias elevadas dea altera����es estruturais nos indiv��duos com diabetes. Diabetes associou-se com hipertrofia ventricular em ambos os sexos e com espessura parietal aumentada e padr��es geom��tricos anormais nas mulheres. Na maior parte dos modelos, as associa����es com diabetes foram minimizadas com os ajustes para obesidade, sugerindo que o impacto da obesidade sobre as altera����es estruturais vistas em diabetes pode ser mediado por fatores outros do que a hiperglicemia. Essas novas evid��ncias est��o em sintonia com o conhecimento contempor��neo descrito.