CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys

How does Brazil measure up? Comparing rankings through the lenses of nation brand indexes

A considerable amount of literature has been published on nation brand and yet not much regarding measurement. The purpose of this paper is to examine nation brand indexes and explore the unbalanced outcomes of a country’s position in these recognized instruments. Although research has been carried out on nation brand, no single study exists comparing a country in four diverse nation brand indexes, which are the reputable ones by Anholt (2007), Fetscherin (2010), Fombrun (2014) and Anholt and Govers (2014). This paper also reflects on the critical studies perspective of the place branding research domain, discussed by Lucarelli and Berg (2011). After a qualitative approach applied to Brazil, it is believed that these indexes mutually support and complement each other - even though they use different approaches, methodologies, samples, and data. Moreover, each of them has their own strengths and weaknesses in terms of accuracy and rationality. Findings from this paper’s evaluation may guide nation brand managers, governments, and researchers to recognize that indexes should be taken into account when analysing a nation brand and its complex image. Therefore, this paper contributes to existing knowledge on the critical studies perspective of the contemporary theoretical structure of the place branding research domain by providing a comparative study based on real data-based rankings of nation brand indexes

Kinematics of the distal tibiofibular syndesmosis - Radiostereometry in 11 normal ankles

In 11 healthy volunteers, the normal kinematics of the tibiofibular syndesmosis of the ankle during weight bearing and external rotation stress were compared to a nonweight-bearing neutral position by radiostereometry. We found very small rotations and displacements in this "normal" group, which indicated that the fibula is closely attached to the tibia, thereby preventing larger movements at the level of the ankle. We found no common kinematic pattern during weight bearing in the neutral position. Application of a 7.5 Nm external rotation moment on the foot caused external rotation of the fibula between 2 and 5 degrees, medial translation between 0 and 2.5 mm and posterior displacement between 1.0 and 3.1 mm. These data can be used as normal reference values for studies of patients with suspected syndesmotic injuries

Liquid chromatography with triple-quadrupole and quadrupole-time-of-flight mass spectrometry for the determination of micro-constituents - a comparison

The potential of liquid chromatography with triple-quadrupole mass spectrometry (LC-QqQ MS) was compared to that of quadrupole time-of-flight mass spectrometry (LC-Q-ToF MS) for the determination of microconstituents. Three applications were studied: (1) the ng/l quantification of five human drugs in surface water and waste-water effluents; (2) the quantification and confirmation of three corticosteroids in bovine urine at concentrations of 1-100 μg/l, and; (3) the confirmation of nicotine in rat plasma. In all cases, the criteria of the EU Commission Decision 2002/657/EC were followed (for confirmation analysis two MS/MS ions were monitored, and the ratio of their abundances were calculated and compared with those of standards). With both techniques fully satisfactory results were obtained in almost all instances. That is, unequivocal confirmation according to the most stringent EU criteria, those for "illegal compounds", was possible. One main advantage of LC-Q-ToF MS is that for identification and confirmation purposes, full MS/MS spectra are available after a single injection: no second injection, as required with QqQ MS, is needed. As well as the increased efficiency, the enhanced selectivity due to the impressive mass selectivity of LC-Q-ToF MS must be emphasized, which allows accurate masses of fragment ions to be calculated. Method characteristics such as linear dynamic range and repeatability were found to be essentially the same for both techniques, but LC-QqQ MS has the advantage that its detection limits are somewhat lower. © Springer-Verlag 2004