The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR. We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set—the Kidney Solid Organ Response Test (kSORT)—was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91–0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88–1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86–0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials. The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants

Antimicrobial resistance and genotyping of Salmonella Typhimurium strains isolated from guinea pigs (Cavia porcellus) from intensive production farms of the city of Lima, Peru

El objetivo del estudio fue caracterizar 20 cepas de Salmonella enterica a nivel molecular y de resistencia antimicrobiana. De estas, 15 fueron obtenidas de cuyes infectados y cinco de cuyes clínicamente sanos, procedentes de dos centros de producción intensiva ubicados en Lima, Perú. Mediante una técnica de PCR múltiple se detectaron los genes invA, prot6E y fliC, correspondientes al género Salmonella y serovares Enteritidis y Typhimurium, respectivamente. Se detectó la variabilidad genética mediante la técnica BOX-PCR utilizando el primer BOXA1R. La resistencia fue evaluada utilizando la técnica de Kirby Bauer en base a eritromicina, nitrofurantoína, estreptomicina, penicilina, enrofloxacina, fosfomicina, amoxicilina con ácido clavulánico, sulfatrimetoprim y ciprofloxacina. Se determinó la serovariedad Typhimurium en el 100% de los aislados. La evaluación de los perfiles electroforéticos obtenidos por la técnica de BOX-PCR demostró alta homogeneidad, con patrones de bandas de ADN similares. Se detectaron cepas resistentes a eritromicina 60% (12/20), nitrofurantoína 40% (8/20), estreptomicina 30% (6/ 20), penicilina 25% (5/20), y enrofloxacina 10% (2/20). La detección de cepas resistentes puede ocasionar problemas en el tratamiento de salmonelosis en cuyes y la presencia de un solo grupo genético sugiere una dispersión clonal.The aim of this study was to characterize 20 strains of Salmonella enterica at molecular level and antimicrobial resistance. Of these, 15 strains were obtained from infected guinea pigs and five from clinically healthy guinea pigs from two intensive production centers located in Lima, Peru. The invA, prot6E and fliC genes corresponding to the genus Salmonella and serovars Enteritidis and Typhimurium, respectively, were detected by a multiple PCR technique. Genetic variability was detected using the BOX-PCR technique using the first BOXA1R. Resistance was evaluated using the Kirby Bauer technique based on erythromycin, nitrofurantoin, streptomycin, penicillin, enrofloxacin, fosfomycin, amoxicillin with clavulanic acid, sulfatrimetoprim and ciprofloxacin. Serotype Typhimurium was determined in 100% of the isolates. The evaluation of the electrophoretic profiles obtained by the BOX-PCR technique demonstrated high homogeneity, with similar DNA bands patterns. Strains resistant to erythromycin 60% (12/20), nitrofurantoin 40% (8/20), streptomycin 30% (6/20), penicillin 25% (5/20), and enrofloxacin 10% (2/20) were detected. The detection of resistant strains may cause problems in the treatment of salmonellosis in guinea pigs and the presence of only a genetic group suggests a clonal dispersion

A Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93759/1/j.1600-6143.2012.04253.x.pd

Promised Land? Immigration, Religiosity, and Space in Southern California

This article looks at how immigrants and their supporters appropriate and use religious space and other public spaces for religious and socio-political purposes in Southern California. While the everyday living conditions of many immigrants, particularly the unauthorized Latino immigrants, force unto them an embodied disciplinarity that maintains spatialities of restricted citizenship, the public appropriations of space for and through religious practices allow for them -even if only momentarily -to express an embodied transgression. This practice in public space helps realize spaces of freedom and hope, however ephemerally. Potentially, these rehearsing exercises can help revert internalized disempowering subjectivities and create social empowerment. Negative stereotypes about immigrants held by the larger public can also be challenged through these spatial practices, as the public demonstrations make visible the invisible. We focus on “Posadas Without Borders” and “the New Sanctuary Movement,” considering both the role of progressive civic and religious institutions in supporting immigrants and the agency of the immigrants themselves. The theoretical analysis builds on concepts drawn from a conversation between geography and religious and theological studies. We use a triangulated methodological approach that includes observation and participant observation, content-analysis of multimedia, interviews, and intellectual advocacy for the immigrant movement. The cases discussed here show that progressive religious groups and coalitions can be important allies to progressive planners, geographers, and policy makers in advancing social and environmental justice for the disenfranchised. They also show that the theological underpinnings of such groups share a lot in common with planning epistemologies for the just city

SPARC (secreted protein acidic and rich in cysteine) knockdown protects mice from acute liver injury by reducing vascular endothelial cell damage

Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC−/−) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC−/− mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC−/− mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC−/− mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC−/− mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury

Congenital nephrotic syndrome

Congenital nephrotic syndrome (CNS) is a rare kidney disorder characterized by heavy proteinuria, hypoproteinemia, and edema starting soon after birth. The majority of cases are caused by genetic defects in the components of the glomerular filtration barrier, especially nephrin and podocin. CNS may also be a part of a more generalized syndrome or caused by a perinatal infection. Immunosuppressive medication is not helpful in the genetic forms of CNS, and kidney transplantation is the only curative therapy. Before the operation, management of these infants largely depends on the magnitude of proteinuria. In severe cases, daily albumin infusions are required to prevent life-threatening edema. The therapy also includes hypercaloric diet, thyroxin and mineral substitution, prevention of thrombotic episodes, and prompt management of infectious complications. The outcome of CNS patients without major extrarenal manifestations is comparable with other patient groups after kidney transplantation