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Louis Bolk Instituut maakte een inventarisatie van het aantal pendelende regenwormen in grasland op zandgrond met verschillende leemgehalten. Over het algemeen worden meer pendelaars gevonden naar- mate het leemgehalte van de zandbodem hoger is. Soms echter leven ook in leemarme zandbodems veel regenwormen. Meer factoren hebben invloed, waaronder de grondwaterstand.

Item does not contain fulltext, INTRODUCTION: A 6-month course of cyclophosphamide (CP) and steroids is effective in primary membranous nephropathy (MN), but unappealing because of long-term side effects. We evaluated efficacy of an "antibody-guided" treatment schedule. METHODS: Patients with phospholipase A2 receptor (PLA2R)-related MN and high risk of progression were treated with CP 1.5 mg/kg/d and steroids in cycles of 8 weeks. Anti-PLA2R antibodies were measured by indirect immunofluorescence (IIFT) at 8, 16, and 24 weeks, and a negative test resulted in withdrawal of CP, and rapid tapering of prednisone. In patients with persistent anti-PLA2R antibodies at 24 weeks, CP was switched to mycophenolate mofetil. Treatment was repeated in patients with a relapse. RESULTS: Our analysis included 65 patients (48 males, 17 females), age 61 ± 12 years, estimated glomerular filtration rate (eGFR) 46 ml/min per 1.73 m(2) (35-68), urine protein-to-creatinine ratio 7.7 grams/10 mmol creatinine (5.4-11.1) and serum albumin 20 g/l (16-26). Immunologic remission rate was 71% after 8 weeks, 86% after 16 weeks, 88% after 24 weeks, and 94% after 3 years. Twenty-seven patients (42%) had persistent clinical remission after only 8 weeks of therapy. Sixteen patients needed a second course of therapy because of immunologic or clinical relapse. Follow-up was 37 (26-58) months. Overall partial remission rate was 92%. One patient developed end-stage kidney disease. Antibody-guided therapy (ABG) was as effective as the standard 6-month course, whereas providing a lower cumulative dose of CP (11.1 [8.0-18.5] vs. 18.9 [14.2-23.6] grams). CONCLUSION: ABG is effective, and allows individualized therapy, with many patients responding to 8 weeks of CP-based therapy.

Contains fulltext : 299626.pdf (Publisher’s version ) (Open Access), OBJECTIVES: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. METHODS: We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results <38 g/L for the diagnosis of protein energy wasting. RESULTS: Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2 %, respectively vs. 66.7 % for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3 %) as opposed to BCP (0.7-1.5 %). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8 % vs. 0.7-1.5 % vs. 0.4-1.6 %). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. CONCLUSIONS: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BC

Radboud University, 19 september 2022, Promotor : Wetzels, J.F.M. Co-promotor : Hofstra, J.M., Contains fulltext : 252891.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 286835.pdf (Publisher’s version ) (Open Access), INTRODUCTION: COVID-19 vaccination has been associated with rare but severe complications characterized by thrombosis and thrombocytopenia. METHODS AND RESULTS: Here we present three patients who developed de novo or relapse atypical hemolytic uremic syndrome (aHUS) in native kidneys, a median of 3 days (range 2-15) after mRNA-based (Pfizer/BioNTech's, BNT162b2) or adenoviral (AstraZeneca, ChAdOx1 nCoV-19) COVID-19 vaccination. All three patients presented with evident hematological signs of TMA and AKI, and other aHUS triggering or explanatory events were absent. After eculizumab treatment, kidney function fully recovered in 2/3 patients. In addition, we describe two patients with dubious aHUS relapse after COVID-19 vaccination. To assess the risks of vaccination, we retrospectively evaluated 29 aHUS patients (n=8 with native kidneys) without complement-inhibitory treatment, who received a total of 73 COVID-19 vaccinations. None developed aHUS relapse after vaccination. CONCLUSION: In conclusion, aHUS should be included in the differential diagnosis of patients with vaccine-induced thrombocytopenia, especially if co-occuring with mechanical hemolytic anemia (MAHA) and acute kidney injury (AKI). Still, the overall risk is limited and we clearly advise continuation of COVID-19 vaccination in patients with a previous episode of aHUS, yet conditional upon clear patient instruction on how to recognize symptoms of recurrence. At last, we suggest monitoring serum creatinine (sCr), proteinuria, MAHA parameters, and blood pressure days after vaccination.

Contains fulltext : 251898.pdf (Publisher’s version ) (Open Access), BACKGROUND: In the general population with coronavirus disease 2019 (COVID-19), obesity is associated with an increased risk of mortality. Given the typically observed obesity paradox among patients on kidney function replacement therapy (KFRT), especially dialysis patients, we examined the association of obesity with mortality among dialysis patients or living with a kidney transplant with COVID-19. METHODS: Data from the European Renal Association COVID-19 Database (ERACODA) were used. KFRT patients diagnosed with COVID-19 between 1 February 2020 and 31 January 2021 were included. The association of Quetelet's body mass index (BMI) (kg/m(2)), divided into: <18.5 (lean), 18.5-24.9 (normal weight), 25-29.9 (overweight), 30-34.9 (obese I) and ≥35 (obese II/III), with 3-month mortality was investigated using Cox proportional-hazards regression analyses. RESULTS: In 3160 patients on KFRT (mean age: 65 years, male: 61%), 99 patients were lean, 1151 normal weight (reference), 1160 overweight, 525 obese I and 225 obese II/III. During follow-up of 3 months, 28, 20, 21, 23 and 27% of patients died in these categories, respectively. In the fully adjusted model, the hazard ratios (HRs) for 3-month mortality were 1.65 [95% confidence interval (CI): 1.10, 2.47], 1 (ref.), 1.07 (95% CI: 0.89, 1.28), 1.17 (95% CI: 0.93, 1.46) and 1.71 (95% CI: 1.27, 2.30), respectively. Results were similar among dialysis patients (N = 2343) and among those living with a kidney transplant (N = 817) (P(interaction) = 0.99), but differed by sex (P(interaction) = 0.019). In males, the HRs for the association of aforementioned BMI categories with 3-month mortality were 2.07 (95% CI: 1.22, 3.52), 1 (ref.), 0.97 (95% CI: 0.78. 1.21), 0.99 (95% CI: 0.74, 1.33) and 1.22 (95% CI: 0.78, 1.91), respectively, and in females corresponding HRs were 1.34 (95% CI: 0.70, 2.57), 1 (ref.), 1.31 (95% CI: 0.94, 1.85), 1.54 (95% CI: 1.05, 2.26) and 2.49 (95% CI: 1.62, 3.84), respectively. CONCLUSION: In KFRT patients

Item does not contain fulltext, Serum albumin is a widely used biomarker in clinical nephrology. Serum albumin cut-off values are used to define disease, to predict outcome and to guide patient care. The available commercial assays to measure serum albumin rely on different analytical principles, all with their own (analytical) specifications. This article provides an overview of the different clinical applications of serum albumin measurements in nephrology, the (dis)advantages of the available assays and the estimates of the effects of the measurement uncertainty between different assays in clinical decision making. This article concludes that harmonization of serum albumin assay results is needed.

Contains fulltext : 283477.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.

Contains fulltext : 237463.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy tha

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RNAs are key players in the cell, and to fulfil their functions, they are enzymatically modified. These modifications have been found to be dynamic and dependent on internal and external factors, such as stress. In this study we used nucleic acid isotope labeling coupled mass spectrometry (NAIL-MS) to address the question of which mechanisms allow the dynamic adaptation of RNA modifications during stress in the model organism S. cerevisiae. We found that both tRNA and rRNA transcription is stalled in yeast exposed to stressors such as H2O2, NaAsO2 or methyl methanesulfonate (MMS). From the absence of new transcripts, we concluded that most RNA modification profile changes observed to date are linked to changes happening on the pre-existing RNAs. We confirmed these changes, and we followed the fate of the pre-existing tRNAs and rRNAs during stress recovery. For MMS, we found previously described damage products in tRNA, and in addition, we found evidence for direct base methylation damage of 2′O-ribose methylated nucleosides in rRNA. While we found no evidence for increased RNA degradation after MMS exposure, we observed rapid loss of all methylation damages in all studied RNAs. With NAIL-MS we further established the modification speed in new tRNA and 18S and 25S rRNA from unstressed S. cerevisiae. During stress exposure, the placement of modifications was delayed overall. Only the tRNA modifications 1-methyladenosine and pseudouridine were incorporated as fast in stressed cells as in control cells. Similarly, 2′-O-methyladenosine in both 18S and 25S rRNA was unaffected by the stressor, but all other rRNA modifications were incorporated after a delay. In summary, we present mechanistic insights into stress-dependent RNA modification profiling in S. cerevisiae tRNA and rRNA.

De zomer van 2020 heeft wederom bevestigd dat verstandig watermanagement van aanzienlijk belang is. Hierin is een sleutelrol weggelegd voor bodembiodiversiteit. Neem nu de regenworm, het boegbeeld van het bodemleven. Ze bevolken onze bodems met miljoenen per hectare en verrichten daar cruciale processen voor ecosysteemdiensten zoals waterregulatie.

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Item does not contain fulltext, Differences between laboratory assays can have important clinical implications. For creatinine assays this became apparent soon after the introduction of the Modification of Diet in Renal Disease formula and resulted in international efforts towards standardization. Albumin in blood is measured by different assays, either chromogenic using Bromocresol green (BCG) or Bromocresol purple (BCP), or by an immunoassay. Since differences between these assays have received limited attention we evaluated bias and imprecision of BCG and BCP assays in comparison to the immunoassay using blood samples from patients with membranous nephropathy and nephrotic syndrome. For the BCG assay, the mean bias was high (6.2 g/l, with a standard deviation of 2.4 g/l) compared to a bias of 0.3 g/l (standard deviation 1.5 g/l) for the BCP assay. Importantly, we questioned clinical relevance by evaluating the accuracy of the decision toward the use of prophylactic anticoagulant therapy. Notably, nephrologists may reach inappropriate treatment decisions using the BGC assay in up to 59% of patients. Thus, our study should stimulate efforts towards standardization of the albumin assays.

Contains fulltext : 215542.pdf (publisher's version ) (Closed access), The discovery in 2009 of the M-type phospholipase A2 receptor (PLA2R) as the primary target in membranous nephropathy (MN) greatly advanced basic and clinical research. Primary MN is now considered a renal-limited autoimmune disease, with antibodies against PLA2R (aPLA2Rab) identified in 70-80 % of patients of various ethnic groups. Although the use of aPLA2Rab as a diagnostic and prognostic biomarker is now widely accepted, many questions related to the development of the auto-immune response, the role of IgG subclasses and antigenic epitopes, and the pathways to podocyte injury remain unresolved. PLA2R-associated MN most likely develops governed by factors such as genetic susceptibility, loss of tolerance, alterations in antigen expression with a role for environmental factors like air pollution, smoking, and infections. More detailed knowledge of genetic factors, the relevant B- and T-cell epitopes, and the mechanisms of podocyte injury is needed to identify patients at risk for disease progression and to develop optimized, targeted treatment strategies. In this review we highlight unresolved issues, addressing initiation of antibody formation, the timeline of antibody production, the role of IgG subclass, and the pathogenicity of the antibodies in concert with complement to produce glomerular pathology and proteinuria.

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In deze thesis wordt het oeuvre en kunstenaarschap van Willem Arondeus (1894-1943) geplaatst binnen het canon en de context van gaykunst, zoals deze wordt geschetst in James M. Saslows Pictures and Passions. A history of homosexuality in the visual arts uit 1999, Christopher Reeds Homosexuality in art. A history of ideas en James Smalls’ Homosexuality in art uit 2012. Deze drie overzichtswerken scheppen een canon en geven voorbeelden hoe kunst en homoseksualiteit door de eeuwen heen met elkaar verbonden zijn. Willem Arondeus is een redelijk onbekende kunstenaar die in de jaren twintig en dertig van de twintigste eeuw actief was en sinds 1914 als enige bekende Nederlandse kunstenaar openlijk uitkwam voor zijn homoseksualiteit. In deze thesis wordt ten eerste uitgelegd wat de theoretische ontwikkeling van homoseksualiteit is. Daarnaast wordt een overzicht gegeven van het homoseksuele leven in Europese steden als Berlijn en Londen in vergelijking met de Nederlandse situatie, zodat er een beeld geschetst kan worden van de maatschappelijke context waarin Arondeus zich voortbewoog. Vervolgens wordt een overzicht geschetst van de relatie tussen homoseksualiteit en kunst, zoals deze wordt beschreven in de boeken van Saslow, Reed en Smalls. Tot slot wordt er een verband gelegd met het kunstenaarschap en oeuvre van Arondeus.

Contains fulltext : 191656.pdf (publisher's version ) (Closed access)

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Contains fulltext : 152771.pdf (publisher's version ) (Open Access), TRIAL REGISTRATION: ClinicalTrials.gov NCT00694863.

Warhols digitale kunstwerken geplaatst binnen de ontwikkeling van digitale kunst en zijn eigen oeuvre om zo zijn vernieuwingen, originaliteit en pioniersschap te bepalen.

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1 september 2010, Contains fulltext : 89720.pdf (publisher's version ) (Closed access), BACKGROUND: In myotonic dystrophy type 1 (DM1), sleep disorders are common, with excessive daytime sleepiness (EDS) as a predominant feature. In myotonic dystrophy type 2 (DM2), the presence of sleep disturbances is unknown. OBJECTIVE: To investigate the frequency of EDS, poor sleep quality and fatigue in DM2. METHODS: 29 genetically proven DM2 patients were surveyed using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Checklist Individual Strength. The results were compared with 29 adult onset DM1 patients and 65 population controls, both matched for age and sex. RESULTS: Only 6.9% of DM2 patients had EDS compared with 44.8% of DM1 patients and 6.2% of population controls (DM2-DM1: p=0.001; DM2-controls: p=0.51). Sleep quality was poor (PSQI >5) in both DM2 and DM1 groups, and differed significantly from population controls (DM2 6.5+/-3.0; DM1 6.2+/-3.7; controls 4.3+/-3.0; DM2-controls: p=0.002). Poor sleep quality was not explained by depression or other comorbidity but was mainly due to sleep disturbances as a result of nocturnal pain. Comparable with the DM1 group, DM2 patients experienced severe fatigue (DM2 38.7+/-13.1; DM1 42.9+/-8.5; controls 21.1+/-11.1; DM2-controls: p<0.001). Results were not confounded by abnormal thyroid function or medication use. CONCLUSION: These results provide new insight into the phenotype of DM2 and have consequences for clinical treatment. In addition, the absence of EDS in DM2 is a new discriminative feature with adult onset DM1.

Contains fulltext : 81451.pdf (publisher's version ) (Closed access), BACKGROUND: Myotonic dystrophy type 2 (DM2) is a dominantly inherited multisystem disorder, characterised by progressive proximal weakness, myotonia, cataracts and cardiac conduction abnormalities. Our clinical impression of an association between DM2 and autoimmune diseases or autoantibody formation has not been published previously. OBJECTIVE: The aim of the present study was to investigate the frequency of autoimmune diseases and serum autoantibodies in patients with DM2 compared with patients with adult onset myotonic dystrophy type 1 (DM1). METHODS: 28 genetically proven Dutch DM2 patients participated in the study and were compared with 51 age and sex matched adult onset DM1 patients. As the primary outcome measure, the presence of an autoantibody or autoreactive T cell associated autoimmune disorder was assessed. As a secondary outcome measure, the presence of autoantibodies in serum (nuclear and non-nuclear antibodies) was assessed in all patients. RESULTS: The frequency of autoimmune diseases (21% vs 2%) and the frequency of autoantibodies (25% vs 2%) were both significantly (p<0.01) higher in DM2 patients compared with DM1 patients. Data on DM1 patients were comparable with the general population. Results were not confounded by smoking, medication use, familial clustering, age or sex. CONCLUSION: The results provide new insight into the clinical picture of DM2. In addition, possible explanations for the association between DM2 and autoimmune diseases are proposed.

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