Search

Apolipoprotein-CIII (apo-CIII) is involved in triglyceride-rich lipoprotein metabolism and linked to beta-cell damage, insulin resistance, and cardiovascular disease. Apo-CIII exists in four main proteoforms: non-glycosylated (apo-CIII0a), and glycosylated apo-CIII with zero, one, or two sialic acids (apo-CIII0c, apo-CIII1 and apo-CIII2). Our objective is to determine how apo-CIII glycosylation affects lipid traits and type 2 diabetes prevalence, and to investigate the genetic basis of these relations with a genome-wide association study (GWAS) on apo-CIII glycosylation. We conducted GWAS on the four apo-CIII proteoforms in the DiaGene study in people with and without type 2 diabetes (n = 2318). We investigated the relations of the identified genetic loci and apo-CIII glycosylation with lipids and type 2 diabetes. The associations of the genetic variants with lipids were replicated in the Diabetes Care System (n = 5409). Rs4846913-A, in the GALNT2-gene, was associated with decreased apo-CIII0a. This variant was associated with increased high-density lipoprotein cholesterol and decreased triglycerides, while high apo-CIII0a was associated with raised high-density lipoprotein-cholesterol and triglycerides. Rs67086575-G, located in the IFT172-gene, was associated with decreased apo-CIII2 and with hypertriglyceridemia. In line, apo-CIII2 was associated with low triglycerides. On a genome-wide scale, we confirmed that the GALNT2-gene plays a major role i O-glycosylation of apolipoprotein-CIII, with subsequent associations with lipid parameters. We newly identified the IFT172/NRBP1 region, in the literature previously associated with hypertriglyceridemia, as involved in apolipoprotein-CIII sialylation and hypertriglyceridemia. These results link genomics, glycosylation, and lipid metabolism, and represent a key step towards unravelling the importance of O-glycosylation in health and

Vine copulas have become the standard tool for modelling complex probabilistic dependence. It has been shown that the number of regular vines grows extremely quickly with the number of nodes. Chimera is the first attempt to map the vast space of regular vines. Software for operating with regular vines is available for R, matlab and Python. However, no dataset containing all regular vines is available. Our atlas of regular vines, Chimera, comprises all 24 4 × 4 matrices representing regular vines on 4 nodes, 480 5 × 5 matrices representing regular vines on 5 nodes, 23,040 6 × 6 matrices representing regular vines on 6 nodes, 2,580,480 7 × 7 matrices representing regular vines on 7 nodes and 660,602,880 8 × 8 matrices representing regular vines on 8 nodes. Regular vines in Chimera are classified according to their tree-equivalence class. We fit all regular vines to synthetic data to demonstrate the potential of Chimera. Chimera provides thus a tool for researchers to navigate this vast space in an orderly fashion., Hydraulic Structures and Flood Risk

Aging Western populations are confronted with an increasing prevalence of chronic inflammatory and degenerative diseases for which adequate treatments are lacking. One of the major hurdles in therapy development is the poor translation of disease concepts, often developed in rodent disease models, into effective treatments for the patient. Reasons for the high failure rate of promising drug candidates are unforeseen toxicity and lack of efficacy. Essential elements of human disease are apparently lacking in the current preclinically used animal models. Results obtained in a generic nonhuman primate model of human autoimmunity, the marmoset experimental autoimmune encephalomyelitis (EAE) model, are discussed to emphasize the claim that primates are essential complementary models that can help to bridge the wide translational gap between mouse and man.

Introduction: In fast-track metabolic surgery, the window to identify complications is narrow. Postoperative checklists can be useful tools in the decision-making of safe early discharge. The aim of this study was to evaluate the predictive value of a checklist used in metabolic surgery. Methods: Retrospective data from June 2018 to January 2021 was collected on all patients that underwent metabolic surgery in a high-volume bariatric hospital in the Netherlands. Patients without an available checklist were excluded. The primary outcome was major complications and the secondary outcomes were minor complications, readmission, and unplanned hospital visits within 30 days postoperatively.Results: Major complications within 30 days postoperatively occurred in 62/1589 (3.9%) of the total included patients. An advise against early discharge was significantly more seen in patients with major complications compared to those without major complications (90.3% versus 48.1%, P < 0.001, respectively), and a negative checklist (advice for discharge) had a negative predictive value of 99.2%. The area under the curve for the total checklist was 0.80 (P < 0.001). Using a cut-off value of ≥3 positive points, the sensitivity and specificity were 65% and 82%, respectively. Individual parameters from the checklist: oral intake, mobilization, calf pain, willingness for discharge, heart rate, drain (>30 ml/24 h), hemoglobin, and leukocytes count were also significantly different between groups. Conclusion: This checklist is a valuable tool to decide whether patients can be safely discharged early. Heart rate appeared to be the most predictive parameter for the development of major complications. Future studies should conduct prediction models to identify patients at risk for major complications. Graphical Abstract: [Figure not available: see fulltext.].

Aims/Hypothesis:Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes. Methods: In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors. Results: IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex. Conclusions: We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.

Introduction: In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the risk of hemorrhage in patients undergoing laparoscopic sleeve gastrectomy (SG). Methods: In this double-blind randomized controlled trial, patients undergoing primary SG in a high-volume bariatric hospital were randomized (1:1) to receive 1500-mg TXA or placebo peroperatively. Primary outcome measure was peroperative staple line reinforcement using hemostatic clips. Secondary outcome measures were peroperative fibrin sealant use and blood loss, postoperative hemoglobin, heart rate, pain, major and minor complications, length of hospital stay (LOS), side effects of TXA (i.e., venous thrombotic event (VTE)) and mortality. Results:In total, 101 patients were analyzed and received TXA (n = 49) or placebo (n = 52). There was no statistically significant difference in hemostatic clip devices used in both groups (69% versus 83%, p = 0.161). TXA administration showed significant positive changes in hemoglobin levels (millimoles per Liter; 0.55 versus 0.80, p = 0.013), in heart rate (beats per minute; -4.6 versus 2.5; p = 0.013), in minor complications (Clavien–Dindo ≤ 2, 2.0% versus 17.3%, p = 0.016), and in mean LOS (hours; 30.8 versus 36.7, p = 0.013). One patient in the placebo-group underwent radiological intervention for postoperative hemorrhage. No VTE or mortality was reported. Conclusion: This study did not demonstrate a statistically significant difference in use of hemostatic clip devices and major complications after peroperative administration of TXA. However, TXA seems to have positive effects on clinical parameters, minor complications, and LOS in patients undergoing SG, without increasing the risk of VTE. Larger studies are needed to investigate the effect of TXA on postoperative major complications.

As big strides were being made in many science fields in the 1970s and 80s, faster computation for solving problems in molecular biology, semiconductor technology, aeronautics, particle physics, etc., was at the forefront of research. Parallel and super-computers were introduced, which enabled problems of a higher level of complexity to be solved. At about the same time, Nobel-laureate physicist Richard Feynman launched what seemed at the time a wild idea; to build a computer based on quantum physics concepts such as superposition and entanglement [1]. The outrageousness of his ideas is documented in the book 'Surely, You're Joking, Mr. Feynman' [2]., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., QCD/Vandersypen Lab, QCD/Sebastiano Lab, Quantum Circuit Architectures and Technology

Crosstalk between glomerular endothelial cells and glomerular epithelial cells (podocytes) is increasingly becoming apparent as a crucial mechanism to maintain the integrity of the glomerular filtration barrier. However, in vitro studies directly investigating the effect of this crosstalk on the glomerular filtration barrier are scarce because of the lack of suitable experimental models. Therefore, we developed a custom-made glomerulus-on-a-chip model recapitulating the glomerular filtration barrier, in which we investigated the effects of co-culture of glomerular endothelial cells and podocytes on filtration barrier function and the phenotype of these respective cell types. The custom-made glomerulus-on-a-chip model was designed using soft lithography. The chip consisted of two parallel microfluidic channels separated by a semi-permeable polycarbonate membrane. The glycocalyx was visualized by wheat germ agglutinin staining and the barrier integrity of the glomerulus-on-a-chip model was determined by measuring the transport rate of fluorescently labelled dextran from the top to the bottom channel. The effect of crosstalk on the transcriptome of glomerular endothelial cells and podocytes was investigated via RNA-sequencing. Glomerular endothelial cells and podocytes were successfully cultured on opposite sides of the membrane in our glomerulus-on-a-chip model using a polydopamine and collagen A double coating. Barrier integrity of the chip model was significantly improved when glomerular endothelial cells were co-cultured with podocytes compared to monocultures of either glomerular endothelial cells or podocytes. Co-culture enlarged the surface area of podocyte foot processes and increased the thickness of the glycocalyx. RNA-sequencing analysis revealed the regulation of cellular pathways involved in cellular differentiation and cellular adhesion as a result of the interaction between glomerular endothelial cells and podocytes. We present a novel custom-made glo

Background: Obesity is becoming more prevalent in the end-stage renal disease population. Bariatric surgery (BS) is increasingly considered as an approach to become eligible for kidney transplant (KT) or reduce obesity-related morbidities. Objectives: To assess the short- and long-term outcomes of patients who underwent both BS and KT and to determine the optimal timing of BS. Methods: Patients who underwent both KT and BS between January 2000 and December 2020 were included and stratified according to the sequence of the 2 operations. The primary outcomes were patient and graft survival. The secondary outcomes were postoperative complications and efficacy of weight loss. Results: Twenty-two patients were included in the KT first group and 34 in the BS first group. Death-uncensored graft survival in the KT first group was significantly higher than in the BS first group (90.9% versus 71.4%, P = .009), without significant difference in patient survival and death-censored graft survival (100% versus 90.5%, P = .082; 90.9% versus 81.0%, P = .058). There was no significant difference in 1-year total weight loss (1-yr TWL: median [interquartile range {IQR}], 36.0 [28.0–42.0] kg versus 29.6 [21.5–40.6] kg, P = .424), 1-year percentage of excess weight loss (1-yr %EWL: median [IQR], 74.9 [54.1–99.0] versus 57.9 [47.5–79.4], P = .155), and the incidence of postoperative complications (36.4% versus 50.0%, P = .316) between the KT first and BS first groups. Conclusion: Both pre- and posttransplant BS are effective and safe. Different conditions of each transplant candidate should be considered in detail to determine the optimal timing of BS.

Many fuels are currently considered for reducing the emissions in shipping; Methanol, LNG, Ammonia, Nuclear, Biodiesel, etc. However, Bio-ethanol is not considered at all.This research looked into all aspects of ethanol in a comparison with its most closely related alternative methanol. Using a similar approach as found in earlier comparisons. Though updating the data as well as the application ot vessels relevant for the Dutch ship owners. This research identified that 2nd generation bio-ethanol would in price be close to 2nd generation bio-methanol, but with several technical advantages. Furthermore the bio-ethanol production capacity is far larger than that of any of the other alternative fuels for shipping and with the ongoing electrification of cars, this capacity will most likely be looking for a new market in the future, putting pressure on the price. Hence the report calls for further investigations and reconsiderations of bio-ethanol as a marine fuel., Ship Design, Production and Operations

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.

RIVM rapport:Er worden veel stoffen aan sigaretten en e-sigaretten toegevoegd die schadelijk of verslavend zijn. Of ze maken roken en vapen aantrekkelijker. Europese regels voor tabaksproducten moeten ervoor zorgen dat sigaretten en e-sigaretten minder schadelijk, verslavend en aantrekkelijk zijn. De Europese richtlijn geeft aan welke stoffen er wel en niet in tabaksproducten en e-sigaretten mogen zitten. De richtlijn is vrij algemeen en noemt, behalve cafeïne en taurine, geen concrete stoffen. Er staat bijvoorbeeld in dat er geen stoffen in tabaksproducten en e-sigaretten mogen zitten die de gebruiker het idee geven dat roken of vapen voordelen heeft voor de gezondheid, zoals vitaminen. Ook mogen er geen kankerverwekkende stoffen aan het product worden toegevoegd. Daarbij geldt voor e-sigaretten dat er geen stoffen in de vloeistof of damp mogen zitten die gevaarlijk zijn voor de gezondheid. In opdracht van het ministerie van VWS(Ministerie van Volksgezondheid, Welzijn en Sport ) heeft het RIVM een concrete lijst gemaakt van stoffen die volgens de richtlijn niet aan tabaksproducten of e-sigaretten mogen worden toegevoegd. Op dit moment staan er 149 stoffen en stofgroepen op deze lijst. Deze lijst is een advies voor het ministerie van VWS, dat over een verbod gaat beslissen. De lijst is bedoeld om de richtlijn te verduidelijken. De lijst helpt ook om te controleren of deze stoffen in tabaksproducten en e-sigaretten zitten, nu en in de toekomst. Het RIVM adviseert om de lijst regelmatig uit te breiden als er nieuwe stoffen in beeld komen die onder de Europese regels vallen. De basis voor de lijst zijn de stoffen van de lijsten die Duitsland en België al hebben gemaakt van verboden toevoegingen aan tabaksproducten en e-sigaretten. Het RIVM is het meestal eens met hun onderbouwing voor een verbod. Een paar stoffen zijn niet opgenomen omdat het RIVM de onderbouwing niet sterk genoeg vond. Het RIVM heeft ook drie stoffen toegevoegd: nicotinezouten, vitamine E acetaat en titaniumdioxid, A large number of substances are added to cigarettes and e-cigarettes that are harmful or addictive or that make smoking and vaping more attractive. European rules on tobacco products must ensure that cigarettes and e-cigarettes are less harmful, addictive and attractive. The European directive sets out which substances may or may be contained in tobacco products and e-cigarettes. The directive is fairly general in nature and, apart from caffeine and taurine, does not refer to any specific substances. For example, the directive states that tobacco products and e-cigarettes must not contain substances that may give the user the idea that smoking or vaping has health benefits, such as vitamins. Nor may any carcinogenic substance be added to the product. In addition, e-cigarettes must not contain any substances in the liquid or vapour that pose a risk to human health. On behalf of the Ministry of Health, Welfare and Sport, RIVM has drawn up a specific list of substances that, under the directive, may not be added to tobacco products or e-cigarettes. That list currently includes 149 substances and substance groups. The list is compiled to serve as a recommendation for the Ministry of Health, Welfare and Sport, which will be deciding on a ban. The list is intended as a means to clarify the directive. It also helps in checking whether these substances are present in tobacco products and e-cigarettes – both now and in the future. RIVM recommends regularly expanding the list if new substances come into the picture that fall under European rules. The Dutch list is based on lists of prohibited additives in tobacco products and e-cigarettes previously drawn up by Germany and Belgium. In general, RIVM concurred with their reasons to ban a particular substance. A number of substances were not included due to the fact that RIVM did not consider the relevant substantiation to be robust enough. RIVM has also added three substances: nicotine salts, vitamin E acetate and titanium dio

In this article we introduce the notion of imaginaries as a conceptual entry to study and better understand how and why commons re-create and transform. We do so by first exploring imaginaries as assemblages, and second by analytically dividing imaginaries in dominant and alternative imaginaries. While the former refer to how people imagine and live their social existence around built expectations and their underlying notions, the latter refers to imaginaries that critique instituted society and through it create ‘germs’ that can lead to transformation. Through this lens we analyze contestations that have emerged around the introduction of drip irrigation in two irrigation communities in the Valencia Region of Spain. These two case studies (Carcaixent and Potries) show how, among the commons, alternative imaginaries are challenging the dominant imaginaries of drip irrigation. We show how these alternative imaginaries result from a different way of assembling irrigation and the social, cultural, material, and economic relations around it. These insights, we argue, open up avenues that allow us to better understand the imaginary creations that reproduce a specific existing order, as well as the germ(s) that can lead to transformations and change