Nabootsing chronische leukemie in nieuw muismodel

​Pallavi Sontakke: Extrinsic and intrinsic cues involved in BRC-ABL induced leukemogenesis Pallavi Sontakke ontwikkelde een nieuw muismodel om een …

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Beschadigd SETD2-gen draagt mogelijk bij aan ontstaan niercelkanker

​Jun Li: SETD2 and PBRM1 inactivation in the development of clear cell renal cell carcinoma Normale niercellen kunnen niet lang gekweekt worden, maar …

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Energiedrankjes geven geen vleugels

​Jana Holubcikova: Eating habits, body image and health and behavioural problems of adolescents Anders dan de reclames willen doen geloven, hangt het …

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Zwangerschapsvergiftiging verstoort regulatie doorbloeding hersenen

​Teelkien van Veen: Cerebral hemodynamics in normal and complicated pregnancy Bij vrouwen met zwangerschapsvergiftiging blijkt sprake te zijn van een …

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Onderzoek naar verstoorde emotieregulatie bij patiënten met psychiatrische aandoening

​Liwen Zhang: Emotion, self and psychopathology. Neural correlates of emotion regulation and self-reflection in mood disorder and schizophrenia Een …

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Het effect van 3D-beeldvorming op chirurgische prestaties tijdens endonasale endoscopische sinuschirurgie

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ABSTRACT
Introduction: The aim of this study was to determine whether the use of 3D-HD-endoscopy would lead to faster and more efficient performance on endoscopic tasks in the sinonasal area, compared to the use of 2D-HD-endoscopy.
Methods: Thirty endoscopically naïve subjects were randomly divided into two groups. Prior experience with endoscopic procedures, other possible relevant experience and demographic data were collected using questionnaires. All subjects carried out five endoscopic tasks in the nose and paranasal sinuses of a human body, during two consecutive rounds,. Subjects of one group started using 2D-endoscopy and switched to using 3D-endoscopy before starting the second round. The reversed order was used by the other group. Time to complete each part of a task, errors made, distance travelled, average velocity and subjective experience were registered. Statistical tests for paired data were used to compare results between both endoscopes and between the results of both rounds.
Results: No statistically significant difference was found in time score, errors made, distance travelled or average velocity between the use of 2D- and the use of 3D-endoscopy. Depth perception and image quality of the 3D-endoscope were rated significantly better. The use of 3D-endoscopy in the first round resulted in significantly poorer results compared to the use of 2D-endoscopy. In contrast, the results using 3D-endoscopy in the second round were superior to both the results using 3D-endoscopy in the first round and the results using 2D-endoscopy in either the first or second round. Statistically significant, positive correlations were found between endoscopic experience and the ability to locate anatomical structures and targets in the nose faster. Videogame-experience showed significant positive correlation with better performance during the second round of tasks.
Discussion: The use of 3D-endoscopy did not lead to significantly better results compared to the use of 2D-endoscopy. The superior results in the second round using 3D-endoscopy were neutralized by the poor results during the first round. This could be explained by the limitations of 3D-endoscopy when used in narrow spaces, together with the limited experience of the subjects in this study. Furthermore the type of endoscope used during the first round seemed to be of influence on the size and direction of the learning effect. As did videogame-experience seem to reinforce the learning effect, while prior knowledge of the anatomy of the sinonasal area led to faster identification of anatomical landmarks and targets in the nose.
Conclusion: Based on the results of this study, the use of 3D-endoscopy did not lead to significantly better performance on various endoscopic tasks compared to the use of 2D-endoscopy, when used by subjects with little to non prior experience in endoscopic procedures, in the narrow area of the nose and paranasal sinuses.

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Epidemiology of Functional Gastrointestinal Disorders among Antillean Adolescents and the Influence of Biopsychosocial Factors

BACKGROUND Functional gastrointestinal disorders are common among children and adolescents, but prevalence numbers from different parts of the world are lacking. Knowledge regarding the pathophysiological mechanisms is unclear. AIM To determine the prevalence of FGIDs in adolescents on Curacao and to assess the influence of biopsychosocial factors on the prevalence of abdominal pain-related functional gastrointestinal disorders (AP-FGIDs). METHODS We studied the epidemiology of functional gastrointestinal disorders in 782 Antillean adolescents, aged 11-18 years, of 6 different high schools who completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III version (QPGS-III) between May and September 2015. RESULTS Out of 946 questionnaires, 782 were included for further analysis. The mean age of the adolescents was 14.8 ± 1.8 years with 62% being female. FGIDs were present in 265 adolescents with a prevalence of 33.1%. AP-FGIDs were the biggest subgroup, with 121 adolescents suffering from (one of the) AP-FGIDs. In total, 77 patients met criteria for IBS (9.7%), 19 for AM (2.4%), 19 for FAP(S) (2.4%) and 9 for FD (1.1%). AP-FGIDs were more common in females (OR 2.33, CI 1.48 – 3.37, p<0.001). After multiple regression and correction for sex, somatic symptoms such as nausea, loss of appetite and photophobia remained significantly associated with the presence of an AP-FGID. Certain stressful events were also associated (p<0.05) with AP-FGIDs: an alcohol drinking parent, domestic violence, emotional abuse and stress as defined by the adolescent. CONCLUSIONS AP-FGIDs are common in adolescents in Curacao. Somatic symptoms and stressful related events are associated with the prevalence of AP-FGIDs.

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Stability of vasopressin and copeptin ex-vivo

Abstract
Background Arginine vasopressin (AVP) is a promising marker to predict renal disease
progression. However, limited ex-vivo stability has been suggested, which in combination
with a laborious assay led to the introduction of copeptin, an easy to measure surrogate
marker for AVP. Literature states better ex-vivo stability of copeptin in comparison to AVP,
although no study has formally investigated this issue. Therefore, we aimed to assess the
effects of pre-analytic sample handling procedures on stability of AVP and copeptin.
Methods Blood of ten healthy volunteers was collected in EDTA tubes. The effect of various
pre-analytic sample handling procedures was investigated: immediate centrifugation at 800g,
2000g and 5000g, storage of whole blood and plasma at 25°C and 4°C for 2, 6 and 24 hours
(h), prolonged frozen storage at -20°C, -80°C and -150°C, and lastly, the effect of repeated
freeze-thaw cycles (1, 2 and 4 cycles). The maximal percentage change that can be explained
by assay variability, i.e., the Acceptable Change Limit (ACL), was used as cut-off to
determine relevant changes in AVP and copeptin.
Results ACL was 25% and 19% for AVP and copeptin, respectively. Higher centrifugation
speed resulted in lower AVP levels, whereas it did not affect copeptin levels. In whole blood,
AVP was stable for 2h at 25°C and for 6h at 4°C, whereas in plasma, AVP was stable for 6h
at 25°C. When stored at 4°C, AVP in plasma did not change for at least 24 hours. In contrast,
copeptin levels were not affected at all by storage of whole blood and plasma at 4°C as well
as 25°C for the total study duration. Both AVP and copeptin were stable up to at least one
month when stored frozen at -20°C, -80°C or -150°C. AVP concentration decreased after 4
freeze-thaw cycles, whereas copeptin concentration was unaffected by repeated freeze-thaw
cycles.
Conclusion Pre-analytic sample handling conditions influenced AVP concentration
considerably, while copeptin levels were not affected. Therefore, measuring copeptin as
surrogate for AVP is an attractive alternative. In case measurement of AVP is chosen, a strict
sample processing protocol for AVP is recommended.

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2D strain echocardiography of the right atrium in patients with paroxysmal or persistent atrial fibrillation

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia. It has a prevalence of 1-2% in the European population. AF is accompanied with atrial remodeling e.g. fibrosis and dilatation which affect the atrial functions. These can be divided in a reservoir, conduit and contraction phase. Using ‘Speckle Tracking Echocardiography’ (STE) it is possible to measure atrial function by performing strain analysis. Left atrial (LA) strain is extensively studied but there is a lack of data for the right atrium, especially in patients with AF. The purpose of this study is to measure right atrial (RA) strain and compare/relate this to LA strain. Also RA strain will be related to different clinical parameters and AF progression after 1 year.
Method/results: Strain and volumetric measurements were performed on 350 baseline echoes from the AF-RISK population. These patients were included having short-lasting symptomatic AF. RA strain in respectively the reservoir, conduit and contraction phase was 44.6±11.8%, 24.4±9.1% and 19.8±6.6%. RA strain values agreed with the healthy population in the literature while LA strain was decreased. The sensitivity of atrial volume index predicting low strain was 93.8% for right and 96.5 % for left. Best predictors for RA reservoir strain were ‘right atrial volume index’ (RAVI) and Mean e’. For contraction strain these were age, TAPSE, LA contraction strain and RAVI.
Conclusion: In a population of 350 patients with short-lasting symptomatic AF, LA strain is decreased while RA strain is preserved. Atrial dilatation is associated with low strain. Our findings suggest for a process in which functional changes precede structural changes and left atrial function is earlier affected compared to right atrial function.

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Effects of inhaled corticosteroids on eosinophils and neutrophils in blood, sputum, airway wall biopsies and BAL and their association with clinical characteristics in COPD patients.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is defined as an incompletely reversible and mainly progressive airflow limitation. Neutrophilic airway inflammation is considered a distinctive feature of COPD, while an increase in eosinophils is observed in 15-40% of stable COPD patients and has been associated with a better inhaled corticosteroid (ICS) response with respect to preventing exacerbations. Notwithstanding this, the value of neutrophils and eosinophils as biomarkers of ICS response in blood, sputum, airway wall biopsies or bronchoalveolar lavage (BAL) has not been extensively studied, and even less is known about the association of these cells between these four different bodily compartments.
Materials & methods: This study is a prospective, two-centre, double blind, longitudinal, randomized trial on the effects of ICS on pulmonary outcomes in COPD. From 2000 till 2007, 114 steroid-naïve current or former smokers with COPD were included with an intended follow-up period of 30 months receiving ICS treatment (with or without a Long-acting β2-agonist) or placebo. At baseline, 6 months and 30 months of follow-up, cell counts (primary outcome) in blood, sputum, airway wall biopsies and BAL were obtained, as well as the Clinical COPD Questionnaire (CCQ) and lung function measurements. This lung function consists of the forced expiratory volume in one second (FEV1) and, as marker of hyperinflation, residual volume (RV) as percentage of total lung capacity (TLC). We investigated cross-sectional and longitudinal associations between eosinophils and neutrophils in the four compartments, and their predictive value for changes in respiratory symptoms and lung function with ICS treatment.
Results: At baseline, higher blood eosinophil levels were positively significantly correlated with higher eosinophil levels in sputum, biopsies and BAL. The positive correlation of eosinophils between blood and sputum as found at baseline, remained significant during 6- and 30-month ICS treatment. Importantly, baseline eosinophils and neutrophils did not predict longitudinal changes in FEV1 in whichever compartment measured. Finally, higher eosinophils in biopsies at baseline were associated with fewer symptoms and with deterioration of symptoms during 6- and 30-month ICS treatment.
Conclusion: Measuring blood eosinophils gives a good reflection of their presence in sputum, biopsies and BAL, a finding that, when measuring blood and sputum associations, is independent of ICS treatment. This may open avenues for monitoring instable COPD patients despite ICS treatment and for investigation of novel treatments able to reduce eosinophils with clinical benefit to patients. Eosinophils and neutrophils are, however, both not good predictors of ICS response in the short- and long-term with respect to the lung function. An interesting finding that needs further study is the observation that eosinophils in biopsies predict less respiratory symptoms at baseline, but predict deterioration after short- and long-term ICS treatment.

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A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts.

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts.

J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):896-905.e6

Authors: Middeldorp CM, Hammerschlag AR, Ouwens KG, Groen-Blokhuis MM, St Pourcain B, Greven CU, Pappa I, Tiesler CM, Ang W, Nolte IM, Vilor-Tejedor N, Bacelis J, Ebejer JL, Zhao H, Davies GE, Ehli EA, Evans DM, Fedko IO, Guxens M, Hottenga JJ, Hudziak JJ, Jugessur A, Kemp JP, Krapohl E, Martin NG, Murcia M, Myhre R, Ormel J, Ring SM, Standl M, Stergiakouli E, Stoltenberg C, Thiering E, Timpson NJ, Trzaskowski M, van der Most PJ, Wang C, EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium, Psychiatric Genomics Consortium ADHD Working Group, Nyholt DR, Medland SE, Neale B, Jacobsson B, Sunyer J, Hartman CA, Whitehouse AJ, Pennell CE, Heinrich J, Plomin R, Davey Smith G, Tiemeier H, Posthuma D, Boomsma DI

Abstract
OBJECTIVE: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis.
METHOD: Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated.
RESULTS: SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10(-6) and 2.66 × 10(-6)). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96.
CONCLUSION: The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants.

PMID: 27663945 [PubMed – in process]

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Beste behandeling voor vasculitis met minste bijwerkingen

​Anoek de Joode: Improving clinical management in ANCA-associated vasculitis Ten minste achttien maanden, zo lang kan het medicijn azathioprine …

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Reflectie in plaats van discussie over diagnose schizofrenie

​Annerieke de Vos: Insight in psychosis. Metacognitive processes and treatment Meer dan de helft van alle mensen met schizofrenie heeft beperkt …

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Design en materiaal kunstlens beïnvloedt lichtverstrooiingsniveau

​Marie Huibert van der Mooren: Retinal stray light originating from intraocular lenses and its effect on visual performance Tijdens een staaroperatie …

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Transient Receptor Potential Channels and Inflammatory Breast Cancer : A novel approach to understand metastasis.

Inflammatory breast cancer (IBC) is known as an aggressive type of cancer and is
characterized by invasion of tumor emboli in the lymphatic system. Despite the severe
multimodal treatment strategy, this disease carries a 5- and 10-year disease-free
survival rate as low as 43% and 10%, respectively. Therefore, increasing
understanding of the behavior of this cancer and discovery of targeted therapy is
highly desirable. Transient Receptor Potential (TRP) channels are widely expressed
non-selective cation channels, which play an important role in the calcium
homeostasis of both excitable and non-excitable cells. In cancer, TRP channels show
an increase or decrease in expression and are very likely involved in processes of
tumor initiation and progression. However, TRP channels have yet to be studied in
IBC. The aim of this study is to determine of TRP channel expression in IBC, and the
involvement of these channels in tumor emboli formation and adhesion using
selective and non-selective inhibitors and activators. Results of conventional
Polymerase Chain Reactions (PCR) showed that TRP channels are widely expressed
in IBC, with a unique pattern. While treatment with the selective TRPV-1 agonist
capsaicin showed a difference in emboli size, treatment with non-selective TRPC
antagonist progesterone caused a significant difference in emboli number, size,
morphology, and invasive capabilities. These results suggest a role for TRP channels
in the metastatic behaviour of IBC, but further research is needed to confirm this
hypothesis and determine the involved molecular pathways.

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How well is LDL cholesterol treated in patients with type 2 Diabetes Mellitus?

Background: Macrovascular complications are the chief cause of major morbidity and death in patients with diabetes. Dyslipidaemia increases the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). Earlier research has shown a reduction in CVD when LDL cholesterol is lowered, also in patients with diabetes mellitus. Lowering LDL cholesterol can be achieved by lipid-lowering medication, diet and physical activity. However, much remains unclear about the use of lipid-lowering medication and the contribution of lipid-lowering medication, diet and physical activity on the LDL cholesterol in patient with T2DM.
Objective: This study investigates the statin use in patients with T2DM and the contribution of lipid-lowering medication, diet and physical activity on LDL cholesterol.
Methods: In this cross-sectional cohort study 432 patients with T2DM from a second-line centre were included. Data were collected through questionnaires about diet and physical activity, physical examination and analyses of blood and urine samples. Body measurements, lipid-lowering medication, diet, physical activity, serum lipid profile and comorbidity were evaluated. Association between independent predictors and LDL cholesterol was assessed by multivariate regression analysis.
Results: The prevalence of statin use in T2DM patients in a secondary care setting is 71.6% (n=304). Of all patients who use or have used a statin 7.1% (n=24) experience side effects. The final predictive model for LDL cholesterol includes 2 independent variables: statin use
(r = -0.445) and waist circumference (r = -0.123). There was no association between diet or physical activity and LDL cholesterol.
Conclusion: Our study shows that LDL cholesterol strongly dependents on statin use. With the normal diet and exercise patterns as seen in our study group, we see no impact of lifestyle. Keeping in mind the strong relation between statin use and LDL cholesterol in diabetic patients, the importance of statin use in the population is underlined. Therefore it is important not to just stop using statins. If there is an indication for statin use and a statin is not tolerated, it is important to try another statin or other lipid-lowering medication.

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Meer inzicht in familieleden van het ondersteunende eiwit COMDD1

​Alina Fedoseienko: Identification of a novel multiprotein complex in cargo sorting that preserves metabolic pathways in the liver Alina Fedoseienko …

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Nieuwe celsorterings- en kweektechnieken brengen toepassing stamceltherapie voor beschadigde speekselklieren een grote stap dichterbij

​Martti Maimets: Potential of salivary gland stem cells in regenerative medicine Martti Maimets maakte deel uit van de UMCG-onderzoeksgroep die zich …

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Speciale coating maakt biomateriaal veel minder vatbaar voor bacteriën

​Steven Roest: Synthesis of quaternary ammonium coated surfaces Het is hét grote probleem bij het gebruik van implantaten: bacteriën die zich aan het …

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Pilotstudie Cognitieve Adaptie Training voor mensen met ernstige psychiatrische aandoening

​Annemarie
Stiekem: On the road to recovery Kijken naar wat ernstig psychiatrische patiënten nog wél kunnen, en ze helpen bij het realiseren van …

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