Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Protest eller ideologi? Vänsterpopulism och väljarbeteende i Europaparlamentsval

Populist parties on both sides of the political spectrum continue to gain support in the European union. Their electoral support is often referred to as a symptom of the decline in political trust that is widespread across nation-states. Earlier research has mainly been focusing on the radical right despite the fact that left-wing populist parties are becoming more prominent in party-systems all over Europe. By focusing on electoral behaviour regarding the supporters of the populist left in the elections to the European parliament, where protest voting is a fairly common phenomenon, my purpose is to broaden our understanding for how political discontent and ideology affect voting behaviour regarding populism. The results from my logistic regression analysis indicate that protest voting is a far better explanatory factor than ideological voting regarding why citizens choose to support left-wing populist parties - regardless of socio-demographical factors. Nevertheless, ideology still proves to be a significant factor, which suggests that a vote for a left-wing populist party should not solely be regarded as a protest vote

Convergent or Unresponsive? : The effect of austerity and mainstream party positioning on the electoral success of left-wing populist parties in Western Europe

While several populist parties with ties to the left side of the ideological scale have become more prominent in the electoral arenas across Western Europe, the literature on populism still has a disproportionate focus on the right. To enhance the existing research on explanatory factors to the electoral fortunes of left-wing populist parties, this study tests two competing theories using multivariate regression analysis. The first theory concerns the effect of mainstream party convergence, and the second, the increased tension between governing parties’ responsive role towards the electorate and their responsible role as national leaders, here operationalized as the implementation of fiscal consolidation. The results show that austerity is conducive to left-wing populist success, and correspondingly supports the theory of the tension between governing parties’ responsibility and responsiveness. However, the effect is weaker when controlling for economic factors, which might be an indication of a partly spurious relationship or the included variables being endogenous. Despite a flexible operationalization, the convergence theory receives marginal to no support and the direction is opposite to what is expected in two of the models, rendering the results even more ambiguous and difficult to analyze. Whereas a lack of variation in the data denotes that the findings should be interpreted with caution, there is hence an indication that existing theories concerning the success of the populist left should not be taken for granted as long as empirical research is limited

Convergent or Unresponsive? : The effect of austerity and mainstream party positioning on the electoral success of left-wing populist parties in Western Europe

While several populist parties with ties to the left side of the ideological scale have become more prominent in the electoral arenas across Western Europe, the literature on populism still has a disproportionate focus on the right. To enhance the existing research on explanatory factors to the electoral fortunes of left-wing populist parties, this study tests two competing theories using multivariate regression analysis. The first theory concerns the effect of mainstream party convergence, and the second, the increased tension between governing parties’ responsive role towards the electorate and their responsible role as national leaders, here operationalized as the implementation of fiscal consolidation. The results show that austerity is conducive to left-wing populist success, and correspondingly supports the theory of the tension between governing parties’ responsibility and responsiveness. However, the effect is weaker when controlling for economic factors, which might be an indication of a partly spurious relationship or the included variables being endogenous. Despite a flexible operationalization, the convergence theory receives marginal to no support and the direction is opposite to what is expected in two of the models, rendering the results even more ambiguous and difficult to analyze. Whereas a lack of variation in the data denotes that the findings should be interpreted with caution, there is hence an indication that existing theories concerning the success of the populist left should not be taken for granted as long as empirical research is limited

Convergent or Unresponsive? : The effect of austerity and mainstream party positioning on the electoral success of left-wing populist parties in Western Europe

While several populist parties with ties to the left side of the ideological scale have become more prominent in the electoral arenas across Western Europe, the literature on populism still has a disproportionate focus on the right. To enhance the existing research on explanatory factors to the electoral fortunes of left-wing populist parties, this study tests two competing theories using multivariate regression analysis. The first theory concerns the effect of mainstream party convergence, and the second, the increased tension between governing parties’ responsive role towards the electorate and their responsible role as national leaders, here operationalized as the implementation of fiscal consolidation. The results show that austerity is conducive to left-wing populist success, and correspondingly supports the theory of the tension between governing parties’ responsibility and responsiveness. However, the effect is weaker when controlling for economic factors, which might be an indication of a partly spurious relationship or the included variables being endogenous. Despite a flexible operationalization, the convergence theory receives marginal to no support and the direction is opposite to what is expected in two of the models, rendering the results even more ambiguous and difficult to analyze. Whereas a lack of variation in the data denotes that the findings should be interpreted with caution, there is hence an indication that existing theories concerning the success of the populist left should not be taken for granted as long as empirical research is limited

North Portland Greenway Trail Strategic Plan

Grow Willamette Greenway was initiated through a partnership between npGreenway and Willamette Planning Studio, a group of six Portland State University graduate students in the Masters of Urban and Regional Planning program. Through a four month collaborative process of community engagement and analysis, including health impacts, economic development, and traffic demand modeling, a series of findings and recommendations were developed. The process built upon previous work undertaken by npGreenway, Metro, Portland Bureau of Transportation (PBOT), Portland Parks and Recreation (PP&R), and other government agencies and community organizations to present a strategic action plan for npGreenway to pursue what moves the greenway trail forward. This project was conducted under the supervision of Sy Adler, Marisa Zapata, Susan Hartnet