Bij agressief B-cel lymfoom screenen op aanwezigheid MYC-breuk

​Sietse Aukema: Role of MYC in pediatric and adult B-cell lymphoma patients Door middel van de fluorescentie in situ hybridisatie (FISH) techniek …

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Molecular insight into specific 14-3-3 modulators: Inhibitors and stabilisers of protein-protein interactions of 14-3-3.

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Molecular insight into specific 14-3-3 modulators: Inhibitors and stabilisers of protein-protein interactions of 14-3-3.

Eur J Med Chem. 2017 Apr 24;136:573-584

Authors: Hartman AM, Hirsch AKH

Abstract
The 14-3-3 protein family is implicated in several diseases and biological processes. Several recent reviews have summarised knowledge on certain aspects of 14-3-3 proteins, ranging from a historic overview to the structure, function and regulation. This review focuses on the structures and molecular recognition of the modulators by the 14-3-3 proteins, and small modifications of certain modulators are proposed where cocrystal structures have been reported. Our analysis opens up possibilities for the optimisation of the reported compounds. It is very timely to analyse the current status of recently developed modulators given that the field has seen a lot of activity in recent years. This review provides an overview combined with a critical analysis of each class of modulators, keeping their suitability for future development in mind.

PMID: 28549334 [PubMed – as supplied by publisher]

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Mms1 binds to G-rich regions in Saccharomyces cerevisiae and influences replication and genome stability.

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Mms1 binds to G-rich regions in Saccharomyces cerevisiae and influences replication and genome stability.

Nucleic Acids Res. 2017 May 23;:

Authors: Wanzek K, Schwindt E, Capra JA, Paeschke K

Abstract
The regulation of replication is essential to preserve genome integrity. Mms1 is part of the E3 ubiquitin ligase complex that is linked to replication fork progression. By identifying Mms1 binding sites genome-wide in Saccharomyces cerevisiae we connected Mms1 function to genome integrity and replication fork progression at particular G-rich motifs. This motif can form G-quadruplex (G4) structures in vitro. G4 are stable DNA structures that are known to impede replication fork progression. In the absence of Mms1, genome stability is at risk at these G-rich/G4 regions as demonstrated by gross chromosomal rearrangement assays. Mms1 binds throughout the cell cycle to these G-rich/G4 regions and supports the binding of Pif1 DNA helicase. Based on these data we propose a mechanistic model in which Mms1 binds to specific G-rich/G4 motif located on the lagging strand template for DNA replication and supports Pif1 function, DNA replication and genome integrity.

PMID: 28535251 [PubMed – as supplied by publisher]

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Beter inzicht in gevolgen van AAV-medicatie op vruchtbaarheid

Janneke Tuin: Consequences
of disease and treatment in ANCA-associated vasculitis ” ​ ​​Janneke Tuin onderzocht welke gevolgen verschillende …

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Eiwit FGF1 mogelijk geschikt medicijn tegen insulineresistentie

​Vera Nies: Adipose tissue: Target and toolbox for the treatment of metabolic disease Onderzoek van bioloog Vera Nies toont aan dat het eiwit FGF1, …

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Positive affective functioning in anhedonic individuals’ daily life: Anything but flat and blunted.

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Positive affective functioning in anhedonic individuals’ daily life: Anything but flat and blunted.

J Affect Disord. 2017 Apr 21;218:437-445

Authors: Heininga VE, Van Roekel E, Ahles JJ, Oldehinkel AJ, Mezulis AH

Abstract
BACKGROUND: Anhedonia, the decreased interest and pleasure, is often described as ‘flat’ or ‘blunted’ positive affect (PA). Yet, little is known about PA functioning in anhedonic individuals’ daily lives. The current study investigates PA reactivity to pleasurable experiences in anhedonia together with its relevant temporal dynamics (i.e., variability, instability, and inertia), and expands current knowledge by exploring the role of arousal therein.
METHODS: Using the Experience Sampling Method (ESM), we collected 90 assessments of real-life PA experiences across 30 days in 18-24 year old individuals with anhedonia (N=69) and without anhedonia (N=69).
RESULTS: Multilevel analyses showed that anhedonia was associated with less intense pleasure experience, and lower levels of PA. Contrary to predictions from laboratory research and depression theory, individuals with anhedonia showed more variability and less stability in PA, and no signs of blunted PA reactivity. In fact, when exploring high and low arousal PA, individuals with anhedonia showed a slightly stronger reactivity to pleasurable experiences in high-arousal PA but not low-arousal PA.
LIMITATIONS: We did not control for previous pleasure experiences and, instead of the last positive event, accumulation of positive events may have determined the change in high-arousal PA.
CONCLUSIONS: Individuals with anhedonia are likely less ‘flat’ or ‘blunted’ than generally thought. Although replication is warranted, impairments in high-arousal positive emotions may be of particular interest in the clinical treatment of anhedonia.

PMID: 28531841 [PubMed – as supplied by publisher]

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Dankzij nieuwe data-analyse beter inzicht in subtypes bij depressie

​Rei Tendeiro-Monden: Deconstructing depression Met behulp van een datagedreven statistische benadering is het mogelijk om verschillende subtypen van …

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Drieëndertig graden Celsius beste kerntemperatuur voor brein tijdens hartchirurgie

​Linde Kok: Techniques to improve neurological outcome after cardiac surgery Onderzoek in een cohort van achtduizend patiënten laat zien dat een …

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Neonatal bloodspot screening for Medium-Chain Acyl-CoA dehydrogenase deficiency: evaluation of different screening parameters.

Background: Early diagnosis of Medium-Chain Acyl-Coenzyme A Dehydrogenase (MCAD) deficiency through neonatal bloodspot screening (NBS) and treatment significantly reduce morbidity and mortality. However, the NBS also detects false-positives (FP) as well as patients with ‘mild’ MCAD deficiency. In this study we investigated whether additional parameters could optimize the Dutch NBS, reduce FP and differentiate between severe and ‘mild’ MCAD deficiency.
Methods: A retrospective study of the NBS protocol detecting MCAD deficiency in the Dutch birth cohort between 2007-2015 was performed. The screening parameters C8, C6, C10, C10:1 and ratios C8/C10 and C8/C2 were evaluated in relation to genotypes and MCAD enzyme activity. In this study ‘mild’ MCAD deficiency was defined by ‘variant’ genotypes (genotypes that had not been identified in patients with clinical symptomatology) and/or high residual MCAD enzyme activity (≥10% measured in lymphocytes or leukocytes).
Results: 194 MCAD-deficient patients were identified in this study, of which 189 were detected through NBS. The prevalence of MCAD deficiency was 1/8,288 (95% CI: 1/7,265 – 1/9,645). The C8-cut-off showed a 99% sensitivity and approximately 100% specificity. The ratios C8/C10 and C8/C2 also correlated strongly with MCAD deficiency and combining the three parameters reduces the number of FP with 70%, at the expense of 22% of the ‘mild’ MCAD deficient patients. The C8/C10-ratio differentiated better than C8 and C8/C2 between severe and ‘mild’ MCAD deficiency.
Conclusion: This study confirms that the primary screening marker C8 is extremely effective to detect MCAD deficiency. Though, adding the ratios C8/C10 and C8/C2 would further improve the NBS protocol.

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KIM-1 mediates the uptake of exosomes and transfer of MHC II

Urinary exosomes (EXO) are lipid membrane bound structures that mediate intercellular signaling through the transfer of proteins, miRNA and other factors. Kidney injury molecule 1 (KIM-1) acts as a phosphatidylserine (PS) receptor, inducing the uptake of apoptotic cells and necrotic debris. We hypothesize that KIM-1 acts as an endocytosis receptor, taking up EXO containing PS and mediating the intercellular exchange of signaling molecules, such as MHC II. LLC-PK1 cells expressing KIM-1 (PK1-KIM1) and cells expressing empty vector (PK1-pcDNA) were incubated with liposomes composed of PS and fluorescently labeled phosphatidylcholine (PC) or EXO isolated from LLC-PK1 cells, mouse dendritic cells (DC) or human urine by ultracentrifugation. EXO were fluorescently labeled with CytoTracker dye or MHC II-GFP. Uptake was quantified by measuring fluorescence intensity and flow cytometry. EXO were characterized by western blot and electron microscopy. MHC-II levels in urinary EXO from healthy subjects and CKD patients were determined by western blot. PK1-KIM-1 took up significantly more liposomes than PK1-pcDNA. EXO derived from LLC-PK1 cells, DCs and urine were positive for EXO markers HSP70, Flot-1 and TSG101. The diameter of EXO were between 30-150 nm. KIM-1 expressing cells took up significantly more EXO than empty vector expressing cells independent of the source of EXO. Urinary EXO from CKD patients were found to carry MHC II while EXO from healthy subjects were MHC II negative. We found the transfer of MHC II to primary PTCs to be greater in cells expressing KIM-1 after incubation with DC-derived EXO. We conclude that KIM-1 is a PTC receptor for EXO. MHC-II on EXO can be transferred to and presented by KIM-1 positive cells, suggesting EXO may serve to link dendritic cell activation to PTC MHC II expression and antigen presentation cells in inflammatory settings.

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FDG-PET/CT as a New Method for Diagnosis and Whole-Body Evaluation of Lemierre Syndrome.

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FDG-PET/CT as a New Method for Diagnosis and Whole-Body Evaluation of Lemierre Syndrome.

Clin Nucl Med. 2017 May 19;:

Authors: Pijl JP, Glaudemans AWJM, Slart RHJA, Kwee TC

Abstract
Lemierre syndrome is a rare disease that is defined by a pharyngeal infection, complicated by septicemia and internal jugular vein thrombosis followed by septic emboli. Because of its rarity, a delay in diagnosis is not uncommon. However, given the mortality rate of approximately 2%, prompt diagnosis and detection of septic emboli are essential to initiate prompt treatment, preventing organ damage and ongoing sepsis. We present 3 cases that demonstrate the value of FDG-PET/CT as a possible alternative or adjunct to conventional imaging methods for diagnosis and whole-body evaluation of Lemierre syndrome.

PMID: 28525463 [PubMed – as supplied by publisher]

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Measuring BDNF in saliva using commercial ELISA: Results from a small pilot study.

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Measuring BDNF in saliva using commercial ELISA: Results from a small pilot study.

Psychiatry Res. 2017 Apr 22;254:340-346

Authors: Vrijen C, Schenk HM, Hartman CA, Oldehinkel AJ

Abstract
Brain-derived neurotrophic factor (BDNF) is a protein often studied in psychiatric populations. Commercial ELISA kits have been validated for measuring BDNF in blood plasma and serum, but blood collection is an invasive method which cannot always be used. The aim of this pilot study was to explore the noninvasive alternative of measuring BDNF in saliva. Three different commercial ELISA kits were used to analyze parallel plasma and saliva samples from six healthy adults. In total 33 plasma and 33 saliva samples were analyzed according to manufacturers’ standard protocols. BDNF was successfully measured in plasma in two of the three kits, of which the results correlated highly (rs =.88). BDNF could not be measured reliably in saliva. The results of this pilot study suggest that techniques of commercial BDNF kits may not be ready for noninvasive saliva measurements, which limits the sampling frequency and settings.

PMID: 28525789 [PubMed – as supplied by publisher]

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Optimum Management of Pulmonary Nodules.

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Optimum Management of Pulmonary Nodules.

Radiology. 2017 Jun;283(3):917-919

Authors: de Koning HJ, Oudkerk M, Lammers JJ

PMID: 28514222 [PubMed – in process]

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Impact of Muscarinic M3 Receptor Antagonism on the Risk of Type 2 Diabetes in Antidepressant-Treated Patients: A Case-Controlled Study

Original language English
Journal Cns Drugs
State E-pub ahead of print – 19-May-2017
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Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease: A Systematic Review and Practical Guide.

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Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease: A Systematic Review and Practical Guide.

Inflamm Bowel Dis. 2017 Jun;23(6):894-902

Authors: Heida A, Park KT, van Rheenen PF

Abstract
BACKGROUND: In asymptomatic patients with inflammatory bowel disease (IBD), “monitoring” involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review.
METHODS: An electronic search was performed in Medline, Embase, and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist.
RESULTS: A total of 1719 articles were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study’s cutoff level had a 53% to 83% probability of developing disease relapse within the next 2 to 3 months. Patients with repeated normal FC values had a 67% to 94% probability to remain in remission in the next 2 to 3 months. The ideal FC cutoff for monitoring could not be identified because of the limited number studies meeting inclusion criteria and heterogeneity between selected studies.
CONCLUSIONS: Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes.

PMID: 28511198 [PubMed – in process]

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M2 macrophage is the predominant phenotype in airways inflammatory lesions in patients with granulomatosis with polyangiitis

Original language English
Article number 100
Number of pages 10
Journal Arthritis Research and Therapy
Volume 19
Issue number 1
State Published – 18-May-2017
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Educational gains in cause-specific mortality: Accounting for cognitive ability and family-level confounders using propensity score weighting.

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Educational gains in cause-specific mortality: Accounting for cognitive ability and family-level confounders using propensity score weighting.

Soc Sci Med. 2017 May 08;184:49-56

Authors: Bijwaard GE, Myrskylä M, Tynelius P, Rasmussen F

Abstract
A negative educational gradient has been found for many causes of death. This association may be partly explained by confounding factors that affect both educational attainment and mortality. We correct the cause-specific educational gradient for observed individual background and unobserved family factors using an innovative method based on months lost due to a specific cause of death re-weighted by the probability of attaining a higher educational level. We use data on men with brothers from the Swedish Military Conscription Registry (1951-1983), linked to administrative registers. This dataset of some 700,000 men allows us to distinguish between five education levels and many causes of death. The empirical results reveal that raising the educational level from primary to tertiary would result in an additional 20 months of survival between ages 18 and 63. This improvement in mortality is mainly attributable to fewer deaths from external causes. The highly educated gain more than nine months due to the reduction in deaths from external causes, but gain only two months due to the reduction in cancer mortality and four months due to the reduction in cardiovascular mortality. Ignoring confounding would lead to an underestimation of the gains by educational attainment, especially for the less educated. Our results imply that if the education distribution of 50,000 Swedish men from the 1951 cohort were replaced with that of the corresponding 1983 cohort, 22% of the person-years that were lost to death between ages 18 and 63 would have been saved for this cohort.

PMID: 28501020 [PubMed – as supplied by publisher]

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Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing

Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing

Johansson, L. F., de Boer, E. N., de Weerd, H. A., van Dijk, F., Elferink, M. G., Schuring-Blom, G. H., Suijkerbuijk, R. F., Sinke, R. J., Te Meerman, G. J., Sijmons, R. H., Swertz, M. A. & Sikkema-Raddatz, B. 12-May-2017 In : Scientific Reports. 7, 1, 11 p., 1838

Research output: Scientific – peer-reviewArticle

Original language English
Article number 1838
Number of pages 11
Journal Scientific Reports
Volume 7
Issue number 1
State Published – 12-May-2017
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Stability and relative validity of the Neuromuscular Disease Impact Profile (NMDIP)

Original language English
Article number 87
Number of pages 8
Journal BMC NEUROLOGY
Volume 17
Issue number 1
State Published – 11-May-2017
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Lichaamseigen signaalstoffen dragen bij aan het ontstaan van COPD

S.D. Pouwels: DAMPs, endogenous danger signals fueling airway inflammation in COPD In Nederland leiden 600.000 mensen aan COPD en jaarlijks komen er …

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