Interleukin-10 Promoter Polymorphisms and Susceptibility to Skin Squamous Cell Carcinoma After Renal Transplantation

After organ transplantation, susceptibility to cancer is multifactorial, especially for skin carcinomas. Risk factors may include genetic susceptibilities, such as the control of cytokine production. Interleukin-10 is a cytokine that is implicated in tumorigenesis, and it has been shown that polymorphisms in its gene promoter correlate with differential amounts of production. The aim of this study was to investigate a possible association between interleukin-10 gene promoter polymorphisms and the occurrence of skin carcinomas after renal transplantation. Seventy kidney transplant recipients who developed a squamous cell carcinoma or a basal cell carcinoma were examined for polymorphisms in the interleukin-10 gene promoter using polymerase chain reaction based methods. Single base pair mutations were studied at positions –1082, –819, and –592. These patients were compared to 70 healthy controls and to 70 matched renal transplant recipients without cancer. The interleukin-10 secretion capability was tested in a subgroup of 40 of these patients by in vitro stimulation of peripheral mononuclear cells. Interleukin-10 genotypes and haplotypes were differently distributed in kidney transplant recipients who developed a skin carcinoma, but especially a squamous cell carcinoma, with an increased frequency of the GCC haplotype and a decreased frequency of the ATA haplotype. Subsequently, we found a shift in the predicted phenotypes from the low production phenotype to the high production phenotype. Secretion of interleukin-10 was strongly correlated to the production predicted phenotype, and tended to be higher in patients who developed a squamous cell carcinoma than in the others. These results indicate that interleukin-10 gene polymorphisms and interleukin-10 production capability may contribute to the development of skin squamous cell carcinomas after renal transplantation

Doctoral graduates’ transition to industry: networks as a mechanism?:Cases from Norway, Sweden and the UK

Increased public investment in PhD education to drive innovation has led to a recent rapid growth in the number of PhD graduates. Academic labour markets have not developed at the same pace. An ever-larger share of the graduates is finding employment in industry. The transition from academia to industry is not always easy. The present study aims to provide insights into the role played by PhDs networks in the job search after graduation. Our data comprise interviews with industry-employed doctoral graduates in STEM disciplines from Sweden, Norway and the UK. Our findings show that PhDs autonomously built personal networks can help match their specific scientific expertise with labour market demands. We distinguish country-specific patterns and characteristics of the transition, in which regional career paths are more (Scandinavia) or less (the UK) noticeable. The study has practical implications, in particular for PhD students and graduates, related to their career orientation.Funding Agencies|European UnionEuropean Union (EU) [722295]</p

Assessing renal graft function in clinical trials: Can tests predicting glomerular filtration rate substitute for a reference method?

Assessing renal graft function in clinical trials: Can tests predicting glomerular filtration rate substitute for a reference method?BackgroundIn clinical trials, comparison of renal graft function needs a rigorous determination of glomerular filtration rate (GFR). Since reference methods to measure GFR cannot be easily implemented, a number of tests predicting GFR are usually used. However, little is known about their validity in renal transplant patients. We aimed to compare the performances of six GFR tests with inulin clearance in this population.MethodsFive hundred consecutive inulin clearances performed in 294 renal transplant recipients with stable renal function were retrospectively selected. For each of them, we computed six estimates: the 24-hour creatinine clearance, the Cockcroft-Gault, Walser, Jelliffe, Nankivell, and Levey formulas. Their respective performance was assessed by correlation (simple linear regression), accuracy (dispersion of true error), and agreement (Bland and Altman method).ResultsEach GFR test closely correlated with inulin clearance (P < 0.0001). Comparisons between pairs of GFR tests did not show any significant difference in accuracy between the Levey, Jelliffe, and Walser formulas. Conversely, each of these formulas demonstrated a significant lower dispersion (P < 0.005) than the others. Nevertheless, all GFR tests displayed considerable lack of agreement with limits of agreement over 40mL/min/1.73m2 apart. The proportion of predicted GFR differing from inulin clearance by ± 10mL/min/1.73m2, ranged from 34% for the Jelliffe formula to 53% for the Nankivell's one.ConclusionNone of these formulas seems to be able to safely substitute for inulin clearance. In clinical trials, renal graft function should be preferably assessed using a reference method of GFR measurement

Reconnecting the University to the Region of Twente : Findings from the RUNIN-Design Lab Think Tank

The RUNIN project's Design Lab Think Tank took place on 28th June 2018. Its aim was to discuss the topic of universities' engagement with society, specifically in their region. It used a world café format that brought together regional stakeholders to discuss how the University of Twente (UT) can incorporate societal questions in its core activities and, through this, create regional benefits. This report provides a description of the event, a summation of the initiatives proposed and an analysis of the discussion that was prompted by the sub-questions around the subject of universities' societal engagement

Is It Possible to Predict the Evolution of IgAN? Validation of the IgA Nephropathy Progression Calculator and Its Relationship With MEST-C Score in Our Population

Introducción: La nefropatía IgA es la enfermedad glomerular más frecuente y heterogénea. Hay estrategias histológicas y clínicas para determinar la progresión a ESRD. Valoramos el significado pronóstico de la clasificación de Oxford/MEST-C y la calculadora de progresión de la NIgA (IgANPC) en nuestra población y relacionamos ambas herramientas. Material y métodos: Realizamos un estudio retrospectivo de biopsias NIgA de 1990 hasta 2015. Se realizó el MEST de las biopsias y se calculó el riesgo de progresión con IgANPC. Se relaciona con la evolución clínica. Resultados: Se analizaron 48 biopsias, 83% varones de 45 an? os de media.La correlación entre el MEST-C y el IgANPC score a la biopsia mostró una concordancia entre pacientes con un score IgANPC alto y E1 (p = 0,021). La correlación de Pearson para el porcentaje de semilunas y el IgAPC es estadísticamente significativo (p = 0,014) con r: 0,357. El 100% de los pacientes clasificados en el grupo 1 de IgANPC mantienen un FGe > 30 ml/min a 10 an? os, mientras que ninguno de los del grupo 3 presenta un FGe > 30 ml/min a 10 an? os (p = 0,001). La comparación de log rank para variables del MEST-C score presenta resultados estadísticamente significativos entre E (0,036) y S (0,022), y el tiempo a FGe < 30 ml/min. También se observa una relación estadísticamente significativa entre T1 y FGe < 30 ml/min. El análisis multivariante con la regresión de Cox para IgANPC y FGe< 30 ml/min muestra una fuerte correlación (p = 0,016) entre el grupo de riesgo y FGe < 30 ml/min. Conclusión: IgANP predice el tiempo hasta FGe < 30 ml/min y an? ade información independiente del MEST. La clasificación de MEST-C score y el IgANPC score son útiles e independientes para la predicción pronóstica; queda validar su uso en la población general.Introduction: IgA nephropathy (IgAN) is the most common and heterogeneous glomerular nephropathy. Several strategies have been used to determine the risk of progression to ESRD. We evaluate the prognostic significance and correlate the IgAN progression calculator (IgANPC) and the Oxford/MEST-C score in our population. Material and methods: We performed a retrospective study of biopsied patients with diagnosis of IgA nephropathy from 1990 to 2015. We classified the biopsies using MEST-C score and we correlated the score to clinical evolution. We also calculated the risk of progression with the online IgANPC at the time of the biopsy. Results: We analysed 48 biopsies, 83% of which were men with a mean age of 45 years at the time of the biopsy. Patients with a biopsy E1 according to MEST-C score had a higher IgANPC score than those with E0 (P=.021). The Pearson's correlation for the percentage of crescents and the IgANPC risk score was statistically significant (P=.014) with r=0.357. The percentage of patients with eGFR above 30 ml/min at 10 years was 100% for the low-risk group (group 1 of IgANPC), and 0% for the high-risk group (group 3), log rank P=0.001. The log rank comparison for variables of the MEST-C score, presented statistically significant results between E (0.036) and S (0.022) and the eGFR time<30 ml/min. A statistically significant relationship was also observed between T1 and eGFR<30 ml/min. The multivariate Cox regression analysis for IgANPC and eGFR<30 ml/min demonstrated a strong correlation (P=.016) between the risk group and eGFR <30 ml/min. Conclusion: In our study population, the IgANPC predicts the time to eGFR<30 ml/min, and adds information independent of the MEST. The MEST-C classification and IgANPC are useful and independent ÿolos for prognostic prediction, but more studies are needed to validate its use in the general population

A scoring system to predict renal outcome in IgA nephropathy: a nationwide 10-year prospective cohort study

Background. Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis, and a substantial number of patients succumb to end-stage renal disease (ESRD). However, prediction of the renal outcome in individual patients remains difficult. We have already published a scoring system using the data in a prospective cohort of IgAN patients followed up from 1995 to 2002

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease