Análisis de la incidencia de la formulación e implementación de la ley 608 del 2000 (ley Quimbaya) en el departamento del Quindío (periodo 2000 – 2005) bajo el enfoque de las políticas públicas

La presente monografía intenta mostrar la incidencia del uso del enfoque de política pública (PP) en los resultados obtenidos tras la formación de la Ley 608 de 2000, principal instrumento para la reconstrucción del Departamento del Quindío después del terremoto del 25 de enero de 1999. Se identifican dos grandes enfoques de formación política para clasificar el caso: representativo-positivista y participativo-constructivista. La hipótesis inicial versa acerca de la implementación de la Ley que permitió la recuperación económica del Departamento, pero ella fue insuficiente. Así, la aplicación de los enfoques de PP permiten identificar las fallas y falencias durante el proceso de formación de la Ley estudiada.

Formación de periodistas de la ciencia en Bogotá

El propósito de este artículo periodístico es a partir de la descripción de la situación actual de la formación de periodistas científicos en Bogotá, identificar las dinámicas que se pueden implantar en esta ciudad para mejorar la formación de periodistas científicos. El corpus del artículo está dividido en dos partes. En primer lugar, se realizará un contexto de la situación actual del periodismo científico (PEC) y una investigación que incluye los diferentes actores involucrados en éste. El segundo capìtulo planteará las recomendaciones y consideraciones frente al objeto de estudio. En este orden de ideas, se analiza la nula oferta de educación de calidad para programas de profundización en la rama del periodismo científico. Se concluye dando unas posibles soluciones a la problemática de formación de periodistas científicos en Bogotá, siendo éstas identificadas a partir de la investigación realizada.

Asociación entre psoriasis y el control de diabetes mellitus tipo 2

La psoriasis es una enfermedad que se caracteriza por un proceso inflamatorio crónico y exagerado local y sistémico. Se ha encontrado en la literatura una relación entre la psoriasis y el desarrollo de patologías como diabetes mellitus tipo 2 y el mal control de estas patologías, lo cual aumenta la morbimortalidad de estos pacientes. El presente estudio mostró que no se encontró asociación entre psoriasis y el control de la DM2 , y que la variable mas significativa sobre el control es la adherencia al tratamiento hipoglicemiante.

Caso sospechoso de envenenamiento por araña reclusa (loxosceles) y revisión de la literatura

El Loxoscelismo en una enfermedad causada por la picadura de una araña del género Loxosceles, que se puede manifestar con compromiso cutáneo y/o sistémico e incluso llevar a la muerte. La distribución geográfica de la araña es mundial, con mayor incidencia en países como Perú, Chile y Brasil, y en algunos lugares de Norte América. En Colombia, se ha identificado este tipo de arácnido, sin embargo no se ha reportado ningún caso, se cree que probablemente exista subregistro. El cuadro clínico puede ir desde pacientes asintomáticos hasta dermonecrosis severa, con gran riesgo de secuelas e incapacidad funcional. Cuando hay compromiso sistémico, cursa con falla renal, hemólisis, coagulación intravascular diseminada y alto riesgo de muerte. El diagnóstico es clínico y epidemiológico, pues no hay pruebas serológicas confirmatorias disponibles. A pesar de que se han descrito múltiples opciones terapéuticas, no hay un consenso que permita hacer recomendaciones, por la escasa evidencia científica que existe al respecto. Este artículo presenta el caso de un varón de 11 años, con antecedente de picadura por animal desconocido, con evolución clínica sugestiva de loxoscelismo cutáneo y sistémico, que recibió manejo con suero antiarácnido, oxígeno hiperbárico, inhibidor de polimorfonucleares y reconstrucción quirúrgica. Se revisa la literatura y la situación de la enfermedad en Colombia, con el fin de llamar la atención sobre una enfermedad poco conocida y favorecer la sospecha diagnóstica y el enfoque adecuado.

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.

Herramientas estatales para el desarrollo sostenible de Colombia el caso del Rio grande de Magdalena

La columna vertebral de esta monografía es determinar cuál y cómo ha sido la función del Río Grande de la Magdalena, foco de inexplorado y desconocido potencial para el progreso del país. A través de diferentes herramientas que el Estado ha estructurado para darle de nuevo valor y preponderancia social, productiva y ambiental a la principal pero subutilizada vía fluvial de Colombia; visto desde un enfoque sistémico enmarcado en la estrategia de desarrollo sostenible, siendo el principal objetivo y desafío de la actualidad para un Estado social de derecho como es el Colombiano

Cardiovascular disease in latin american patients with systemic lupus erythematosus: a cross-sectional study and a systematic review

Objective. This study was performed to determine the prevalence of and associated risk factors for cardiovascular disease (CVD) in Latin American (LA) patients with systemic lupus erythematosus (SLE). Methods. First, a cross-sectional analytical study was conducted in 310 Colombian patients with SLE in whom CVD was assessed. Associated factors were examined by multivariate regression analyses. Second, a systematic review of the literature on CVD in SLE in LA was performed. Results. There were 133 (36.5%) Colombian SLE patients with CVD. Dyslipidemia, smoking, coffee consumption, and pleural effusion were positively associated with CVD. An independent effect of coffee consumption and cigarette on CVD was found regardless of gender and duration of disease. In the systematic review, 60 articles fulfilling the eligibility criteria were included. A wide range of CVD prevalence was found (4%–79.5%). Several studies reported ancestry, genetic factors, and polyautoimmunity as novel risk factors for such a condition.Conclusions. A high rate of CVD is observed in LA patients with SLE. Awareness of the observed risk factors should encourage preventive population strategies for CVD in patients with SLE aimed at facilitating the suppression of cigarette smoking and coffee consumption as well as at the tight control of dyslipidemia and other modifiable risk factors.

Systemic Lupus Erythematosus 2014

Systemic lupus erythematosus (SLE, lupus) is the prototype of systemic autoimmune disease (AD). Immune system activation in SLE is characterized by exaggerated B-cell and T-cell responses and loss of immune tolerance against selfantigens. Production and defective elimination of antibodies, circulation and tissue deposition of immune complexes, and complement and cytokine activation contribute to clinical manifestations that range from fatigue and joint pain to severe, life-threatening organ damage

Immunosenescence, Aging, and Systemic Lupus Erythematous

Senescence is a normal biological process that occurs in all organisms and involves a decline in cell functions. This process is caused by molecular regulatory machinery alterations, and it is closely related to telomere erosion in chromosomes. In the context of the immune system, this phenomenon is known as immunosenescence and refers to the immune function deregulation. Therefore, functions of several cells involved in the innate and adaptive immune responses are severely compromised with age progression (e.g., changes in lymphocyte subsets, decreased proliferative responses, chronic inflammatory states, etc.). These alterations make elderly individuals prone to not only infectious diseases but also to malignancy and autoimmunity. This review will explore the molecular aspects of processes related to cell aging, their importance in the context of the immune system, and their participation in elderly SLE patients

Lupus nephritis: an overview of recent findings

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. In susceptible individuals suffering of SLE, in situ formation and deposit of immune complexes (ICs) from apoptotic bodies occur in the kidneys as a result of an amplified epitope immunological response. IC glomerular deposits generate release of proinflammatory cytokines and cell adhesion molecules causing inflammation. This leads to monocytes and polymorphonuclear cells chemotaxis. Subsequent release of proteases generates endothelial injury and mesangial proliferation. Presence of ICs promotes adaptive immune response and causes dendritic cells to release type I interferon. This induces maturation and activation of infiltrating T cells, and amplification of Th2, Th1 and Th17 lymphocytes. Each of them, amplify B cells and activates macrophages to release more proinflammatory molecules, generating effector cells that cannot be modulated promoting kidney epithelial proliferation and fibrosis. Herein immunopathological findings of LN are reviewed.

Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.

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 (CFHR3-1Δ), 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 CFHR3-1Δ (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 CFHR3-1Δ 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.

Lupus nephritis in colombians: Contrasts and comparisons with other populations

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. The purpose of this study was to examine the clinical and immunological characteristics associated with LN development during the course of SLE in Colombians. Therefore, patients with SLE followed at five different referral centers in Medellin, Bogota, and Cali were included in this cross-sectional and multicenter study. Factors influencing LN were assessed by conditional logistic regression analysis, adjusting by gender, age at onset, duration of disease, and city of origin. The entire sample population included 467 patients, of whom 51% presented with LN. The presence of anti-dsDNA antibodies (adjusted odds ratio (AOR), 2.06; 95% confidence interval (CI), 1.16–3.65), pleuritis (AOR, 3.82; 95% CI, 1.38–10.54), and hypertension (AOR, 2.63; 95% CI, 1.23–5.62) were positively associated with LN, whereas the presence of anti-La antibodies was a protective factor against LN development (AOR, 0.4; 95% CI, 0.19–0.85). A review of literature on LN in different populations is made. The identified clinical- and laboratory-associated factors would assist earlier diagnosis and guide decisions on therapeutic interventions on this critical and frequent complication of SLE.

How do autoimmune diseases cluster in families? A systematic review and meta-analysis

Background: A primary characteristic of complex genetic diseases is that affected individuals tend to cluster in families (that is, familial aggregation). Aggregation of the same autoimmune condition, also referred to as familial autoimmune disease, has been extensively evaluated. However, aggregation of diverse autoimmune diseases, also known as familial autoimmunity, has been overlooked. Therefore, a systematic review and meta-analysis were performed aimed at gathering evidence about this topic. Methods: Familial autoimmunity was investigated in five major autoimmune diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis and type 1 diabetes mellitus. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Articles were searched in Pubmed and Embase databases. Results: Out of a total of 61 articles, 44 were selected for final analysis. Familial autoimmunity was found in all the autoimmune diseases investigated. Aggregation of autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, was the most encountered. Conclusions: Familial autoimmunity is a frequently seen condition. Further study of familial autoimmunity will help to decipher the common mechanisms of autoimmunity.

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.