The influence of BMI and smoking at disease onset on long-term joint damage measured with the RAAD score in patients with rheumatoid arthritis

Introduction: after the development of new effective medication and the introduction of “treat-to-target” strategies directed at obtaining remission, the prognosis of RA greatly improved. Remarkably, obesity is named as a predictor of less radiographic progression. The literature is not clear about the relation between body mass index (BMI) and long-term joint damage. Little evidence about the long-term effect of smoking on joint damage is available. Time consuming radiographic scoring methods, such as the Sharp van der Heijde (SHS) and Larsen score, are frequently used in clinical research to evaluate joint damage of hands and feet. In order to have an easy applicable instrument to measure joint damage, Zijlstra et al. developed the RAAD score in 2002. A high correlation between the RAAD score and the SHS has been found. The present study investigated whether BMI and smoking at the moment of diagnosis are related with irreversible joint damage at long-term, measured with the RAAD score.
Patients and methods: the research population consists of all patients who received treatment for RA in the ZGT from January 1996 until December 2015. From this population patients with a RAAD score, determined between 2014 and April the first of 2016, and a disease duration of at least five years at the moment of the RAAD score were included. Baseline data were collected through retrospective record research and through verifying information during an outpatient visit. Smoking at disease onset was categorized in three groups: current smoker, former smoker, non smoker. Mann Whitney U tests, Spearman’s correlations, Kruskal-Wallis tests and multivariate regression analysis were performed.
Results: baseline characteristics study population (n=521): 67.8% woman, mean (SD) age in years 49.0 (13.7), mean (SD) BMI in kg/m2 25.7 (3.9), 79.5% RF positive, 72.6% anti-CCP positive, 36.8% non smoker, 28.4% former smoker, 34.8% smoker. Median [IQR] RAAD score was 2.0 [0-6.0]. A significant, weak correlation between BMI and the RAAD score (correlation coefficient -0.14, p=0.003) was found. No significant difference in RAAD score was found between patients with different smoking status. Obviously, the RAAD score was correlated with disease duration, irreversible damage can only increase. Disease duration was correlated with BMI. There was an increasing trend in BMI at disease during the decades. When corrected for this trend, through adjusting for disease duration, no significant correlation was found between BMI and the RAAD score.
Conclusion: BMI and smoking status at the moment of diagnosis of RA are not related with irreversible joint damage at long-term as measured with the RAAD score, when adjusted for disease duration. For the trend in BMI throughout the decades was corrected with disease duration.

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The effect of mutant SOD1 on cell viability

Mutations in the gene encoding for superoxide dismutase 1 (mSOD1) lead to protein aggregation and
are associated with 20% of familial amyotrophic lateral sclerosis (ALS) cases. Multiple molecular
chaperones are known to influence mSOD1 aggregation and cytotoxicity. Still, the relation between
protein aggregation and cytotoxicity remains elusive.
In the current project, human osteosarcoma cell lines stably expressing SOD1-WT or SOD1-A4V
(U2OS-WT, U2OS-A4V) were exposed to endoplasmatic reticular stress, proteasomal inhibition and
autophagy inhibition. Phenotypes of SOD1-A4V cytotoxicity were then correlated to levels of mSOD1
expression and aggregation. Additionally, overexpression of the molecular chaperones HSPA1A and
HSPA1L was investigated for their potential to rescue the mSOD1 associated phenotype.
Endoplasmatic reticular (ER) stress induced by Tunicamycin treatment was the only stressor that
produced a reproducible phenotype characterised by a decrease in U2OS-A4V cell viability compared
to U2OS-WT. No correlation with mSOD1 aggregation could be established. HSPA1A and HSPA1L
overexpression both resulted in a marginal relative rescue of cell viability specific to U2OS-A4V under
Tunicamycin treatment.
Interpretation of the results was hampered by the marginal differences in cell viability, the low
expression levels of SOD1-A4V and the expression of endogenous SOD1. An experimental
endogenous SOD1 knockout model, with expression levels of the proteins of interest close to
endogenous expression of SOD1, is proposed to substantiate the findings of this study. Further
investigation of the relationship between ER stress and mSOD1 cytotoxicity can be centred around
the in literature described interaction between mSOD1 and Derlin-1, through which mSOD1 is
proposed to mediate its cytotoxicity.

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Implementation of a transcutaneous bilirubinometer in a newborn nursery : A randomized Controlled Trial

Objective: The aim of this study is to provide quantitative data on the reduction of blood sampling when using transcutaneous bilirubinometry to assess hyperbilirubinemia in healthy jaundiced newborns.
Study-design: In a randomized controlled trial in jaundiced infants (≥36 weeks gestational age) in a Dutch newborn nursery ward, the need for total serum bilirubin (TSB) measurement to determine hyperbilirubinemia was assessed by either a transcutaneous bilirubin (TcB) measurement (JM-103) (intervention group) or visual assessment of jaundice (control group). When TcB was within 50μmol/L below the threshold for phototherapy on the bilirubin nomogram, a TSB was obtained.
Results: A total of 254 neonates were randomized to either the intervention group (n=127) or the control group (n = 127). In the intervention group 43 neonates (33.9%) needed one or more TSB measurements taken versus 85 neonates (66.9%) in the control group (difference 33.0; 95% CI 21.4 to 44.6, P = <0.001). There was a significant reduction of 46.9% in blood sampling for TSB assays in the intervention group compared to the control group (0.50±0.80 vs 0.94±0.83, difference -0.44 (-0.64 to -0.24), P = <0.001). The number needed to treat is 3.0. There were no differences between groups in treatment, treatment duration or hospitalization. Conclusion: Use of a transcutaneous device to assess hyperbilirubinemia significantly and safely reduced blood draws for TSB assays in 47% in healthy jaundiced near-term and term neonates in the newborn nursery.

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Het effect van interventie op de orthostatische bloeddruk profielen van syncope patiënten die zich presenteren op de spoedeisende hulp.

Introduction Orthostatic hypotension is a common cause of syncope at the emergency department (ED). Frequently an intervention is started for example intravenous fluid or medication. Recent studies described different orthostatic blood pressure recovery patterns visualized by a non-invasive beat-to-beat blood pressure monitor (Nexfin®). However, until now no research has been conducted about the effect of an intervention started at the ED on orthostatic blood pressure recovery patterns.
Objective To evaluate the effect of intervention on orthostatic blood pressure recovery patterns of syncope patients at the ED. Besides, we want to determine if it’s better to detect the effect of an intervention with Nexfin® or with the conventional intermittent blood pressure method (cBD).
Material and Methods During 14 weeks 30 patients ≥18 years were included with (pre)syncope at the ED and they were randomized in two groups. At both groups the blood pressure was measured at the ED and the outside department in lying and standing position with the cBD and in group 1 also with the Nexfin® simultaneously.
Results In the group of patients who received an intervention 71% showed a recovered blood pressure pattern at the outpatient department, in comparison to 20% of the patients who did not receive an intervention (p = 0,05). The Nexfin® also detected significantly more patients with an abnormal blood pressure recovery pattern (p = 0,03) in comparison to the cBD.
Conclusion Despite the small study population it appears that an intervention results into normalization of orthostatic blood pressure recovery patterns. Beside this we also found that the Nexfin® detected more abnormal orthostatic blood pressure recovery patterns in comparison to the cBD.

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Flavor pleasantness processing in the ventral emotion network.

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Flavor pleasantness processing in the ventral emotion network.

PLoS One. 2017;12(2):e0170310

Authors: Dalenberg JR, Weitkamp L, Renken RJ, Nanetti L, Ter Horst GJ

Abstract
The ventral emotion network-encompassing the amygdala, insula, ventral striatum, and ventral regions of the prefrontal cortex-has been associated with the identification of emotional significance of perceived external stimuli and the production of affective states. Functional magnetic resonance imaging (fMRI) studies investigating chemosensory stimuli have associated parts of this network with pleasantness coding. In the current study, we independently analyzed two datasets in which we measured brain responses to flavor stimuli in young adult men. In the first dataset, participants evaluated eight regular off the shelf drinking products while participants evaluated six less familiar oral nutritional supplements (ONS) in the second dataset. Participants provided pleasantness ratings 20 seconds after tasting. Using independent component analysis (ICA) and mixed effect models, we identified one brain network in the regular products dataset that was associated with flavor pleasantness. This network was very similar to the ventral emotion network. Although we identified an identical network in the ONS dataset using ICA, we found no linear relation between activation of any network and pleasantness scores within this dataset. Our results indicate that flavor pleasantness is processed in a network encompassing amygdala, ventral prefrontal, insular, striatal and parahippocampal regions for familiar drinking products. For more unfamiliar ONS products the association is not obvious, which could be related to the unfamiliarity of these products.

PMID: 28207751 [PubMed – in process]

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The effect of fluid resuscitation on the effective circulating volume in patients undergoing liver surgery: a post-hoc analysis of a randomized controlled trial

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β2→ 1-fructans modulate the immune system in vivo by direct interaction with the mucosa in a microbiota-independent fashion

β2→ 1-fructans modulate the immune system in vivo by direct interaction with the mucosa in a microbiota-independent fashion

Fransen, F., Sahasrabudhe, N., Elderman, M., Bosveld, M., El Aidy, S., Hugenholtz, F., Borghuis, T., Kousemaker, B., Winkel, S., van der Gaast-de Jongh, C., Jonge, M. I. D., Boekschoten, M. V., Smidt, H., Schols, H. A. & de Vos, P. 16-Feb-2017 In : Frontiers in Immunology. 14 p., 154

Research output: Scientific – peer-reviewArticle

Original language English
Article number 154
Number of pages 14
Journal Frontiers in Immunology
State Published – 16-Feb-2017
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β2→ 1-fructans modulate the immune system in vivo by direct interaction with the mucosa in a microbiota-independent fashion

β2→ 1-fructans modulate the immune system in vivo by direct interaction with the mucosa in a microbiota-independent fashion

Fransen, F., Sahasrabudhe, N., Elderman, M., Bosveld, M., El Aidy, S., Hugenholtz, F., Borghuis, T., Kousemaker, B., Winkel, S., van der Gaast-de Jongh, C., Jonge, M. I. D., Boekschoten, M. V., Smidt, H., Schols, H. A. & de Vos, P. 16-Feb-2017 In : Frontiers in Immunology. 14 p., 154

Research output: Scientific – peer-reviewArticle

Original language English
Article number 154
Number of pages 14
Journal Frontiers in Immunology
State Published – 16-Feb-2017
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The diagnostic application of sonication on heart valves with suspected infective endocarditis

Introduction: Infective endocarditis (IE) is a very serious disease. Although relatively uncommon (5-11 per 100,000 people per year), it is associated with a high mortality and morbidity. The infection is predominantly caused by bacteria. However, in 10-20% of cases no causative organism is identified. This is a serious limitation to the ability of clinicians to provide the afflicted patients with optimal treatment.
Infected heart valves may become damaged through the disease process, resulting in impaired functioning. Valves affected by IE may require surgical replacement. An explanted heart valve may provide important additional opportunity to obtain information pertaining to the causative microorganism, particularly in cases of blood culture-negative IE. However, standard microbiological tests on explanted heart valves frequently lead to negative results (up to 49%). An increase in sensitivity for the detection of microorganisms would be beneficial to the diagnosis and treatment of IE.
Sonication has demonstrated an increased microbiological yield when carried out on various prosthetic materials that were suspect for infection, mainly in prosthetic joint infections. The added value is particularly apparent in material cultures of patients that were receiving prior antimicrobial therapy. It is hypothesized that similar added value may be seen when applied to explanted (prosthetic or native) heart valves.
Methods: Through a prospective case-control study, the results obtained from the experimental sonication protocol were compared to the results of the standard diagnostic protocol for explanted cardiac material. Results were obtained through cultures on agar plates, inoculation of aerobic and anaerobic blood culture bottles, and 16S PCRs. The sonication tests were always done after the standard workup, avoiding interference with regular diagnostics necessary for the clinics. Explanted valves with no suspicion of IE were used as negative controls, in order to assess the reliability of the method.
Based on a power analysis for dependent samples with α=0.05, β=0.80, and d=0.3, the necessary number of valves was determined to be n=16. Based on the UMCG’s records, the expected time needed to collect 16 valves per study group would exceed 1 year. The project was set up as a pilot study in order to evaluate and optimise the proposed study protocol, and to start with the collection of patient data. The results presented in this report are therefore limited to the number of valves collected within a 3 month period, between 01-04-2016 and 01-07-2016.
Results: Fourteen valves were included, of which 7 were suspected of IE. Polymerase chain reaction (PCR) methods identified microbial deoxyribonucleic acid (DNA) from present microorganisms on 4 of these valves. Cultures identified the presence of viable microorganisms on 2 of these valves. All negative control valves showed no evidence of microbial presence according the standard diagnostic method and the sonication protocol.
Notably, there was one clinical case that illustrates the potential for sonication as an addition to the standard workup for explanted valves from patients with IE, by making a significant contribution to the diagnosis and resulting therapy. Indeed, only sonication was able to demonstrate the presence of viable Propionibacterium acnes (P. acnes) in this case of culture-negative IE. The presence of P. acnes was confirmed by 16S PCR on the heart valve.
Conclusion: Based on the currently available data there is insufficient evidence to draw definite conclusions, though initial results are promising. However, this project enabled me to carefully formulate and validate a standard operating procedure (SOP) for the sonication of heart valves in the microbiology laboratory. This method has demonstrated the ability to
2
detect the presence of microorganisms. In one case sonication demonstrated additive value by detecting the presence of a bacterium through cultures that was not cultured using the standard diagnostic protocol, allowing for antibiotic susceptibility testing, which is crucial for final patient treatment. This finding suggests that there seems to be benefit to the detection of microorganisms by using sonication. Continuation of data collection will be needed to provide conclusive evidence.

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The diagnostic application of sonication on heart valves with suspected infective endocarditis

Introduction: Infective endocarditis (IE) is a very serious disease. Although relatively uncommon (5-11 per 100,000 people per year), it is associated with a high mortality and morbidity. The infection is predominantly caused by bacteria. However, in 10-20% of cases no causative organism is identified. This is a serious limitation to the ability of clinicians to provide the afflicted patients with optimal treatment.
Infected heart valves may become damaged through the disease process, resulting in impaired functioning. Valves affected by IE may require surgical replacement. An explanted heart valve may provide important additional opportunity to obtain information pertaining to the causative microorganism, particularly in cases of blood culture-negative IE. However, standard microbiological tests on explanted heart valves frequently lead to negative results (up to 49%). An increase in sensitivity for the detection of microorganisms would be beneficial to the diagnosis and treatment of IE.
Sonication has demonstrated an increased microbiological yield when carried out on various prosthetic materials that were suspect for infection, mainly in prosthetic joint infections. The added value is particularly apparent in material cultures of patients that were receiving prior antimicrobial therapy. It is hypothesized that similar added value may be seen when applied to explanted (prosthetic or native) heart valves.
Methods: Through a prospective case-control study, the results obtained from the experimental sonication protocol were compared to the results of the standard diagnostic protocol for explanted cardiac material. Results were obtained through cultures on agar plates, inoculation of aerobic and anaerobic blood culture bottles, and 16S PCRs. The sonication tests were always done after the standard workup, avoiding interference with regular diagnostics necessary for the clinics. Explanted valves with no suspicion of IE were used as negative controls, in order to assess the reliability of the method.
Based on a power analysis for dependent samples with α=0.05, β=0.80, and d=0.3, the necessary number of valves was determined to be n=16. Based on the UMCG’s records, the expected time needed to collect 16 valves per study group would exceed 1 year. The project was set up as a pilot study in order to evaluate and optimise the proposed study protocol, and to start with the collection of patient data. The results presented in this report are therefore limited to the number of valves collected within a 3 month period, between 01-04-2016 and 01-07-2016.
Results: Fourteen valves were included, of which 7 were suspected of IE. Polymerase chain reaction (PCR) methods identified microbial deoxyribonucleic acid (DNA) from present microorganisms on 4 of these valves. Cultures identified the presence of viable microorganisms on 2 of these valves. All negative control valves showed no evidence of microbial presence according the standard diagnostic method and the sonication protocol.
Notably, there was one clinical case that illustrates the potential for sonication as an addition to the standard workup for explanted valves from patients with IE, by making a significant contribution to the diagnosis and resulting therapy. Indeed, only sonication was able to demonstrate the presence of viable Propionibacterium acnes (P. acnes) in this case of culture-negative IE. The presence of P. acnes was confirmed by 16S PCR on the heart valve.
Conclusion: Based on the currently available data there is insufficient evidence to draw definite conclusions, though initial results are promising. However, this project enabled me to carefully formulate and validate a standard operating procedure (SOP) for the sonication of heart valves in the microbiology laboratory. This method has demonstrated the ability to
2
detect the presence of microorganisms. In one case sonication demonstrated additive value by detecting the presence of a bacterium through cultures that was not cultured using the standard diagnostic protocol, allowing for antibiotic susceptibility testing, which is crucial for final patient treatment. This finding suggests that there seems to be benefit to the detection of microorganisms by using sonication. Continuation of data collection will be needed to provide conclusive evidence.

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Informatievoorziening en communicatie rondom chemotherapie :Mogelijke verbeteringen in de informatievoorziening en communicatie met patiënten die chemotherapie krijgen in het Medisch Spectrum Twente.

Background: In the care around cancer patients receiving chemotherapy, it is important to provide good information and effective communication: this leads to fewer mental health problems, aproved ability to cope with diagnosis and treatment, better self-care and higher overall satisfaction. Objective: This study examines which aspects of information and communication to patients receiving chemotherapy for the first time at the Medisch Spectrum Twente (MST) can be improved by evaluating which information and communication needs exist and to which extent these needs are met.
Methods: We conducted a research consisting of a prospective and retrospective studyline. In the prospective studyline, a total of 30 patients, that got their first chemotherapy treatment in the period between 15 February 2016 and 10 June 2016, completed a questionnaire based on the QUOTEchemo-Importance before the start of their treatment. After their first chemotherapy cycle, they completed a questionnaire based on the QUOTEchemo-Performance. In the retrospective studyline, 52 patients who received chemotherapy for the first time in 2015, completed the two questionnaires at once. Both questionnaires have been developed and validated to measure information and communication needs and experiences around chemotherapy treatment. Results: Patients attached most importance to aspects associated with ‘prognosis’, ‘treatment-related information’and ‘affective communication’. Almost all aspects of information and communication can be improved. The greatest potential for improvement was found for the aspects associated with ‘coping information’, ‘interpersonal communication’ and ‘alternative sources of information’.
Conclusion: In general, the patiens are satisfied with the information and communication around their treatment. However, there is room for improvement in different areas. In particular, there is a clear need for improvement regarding the attention for wishes, questions and support needs of relatives of the patient. The same applies to the assistence that is provided in finding reliable websites. When dealing with their illness and treatment, patients would like to get more support from the caretakers in the form of information on psychosocial care and support groups. They also like to see improvement in possibilities that are available to discuss concerns, fears and emotions.

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Motorische stoornissen meten met sensoren

​Motorische stoornissen kunnen beter worden gediagnosticeerd en gemonitord met behulp van sensoren. Dat concludeert Octavio Martinez Manzanera in …

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Slaapproblemen mogelijk risicofactor voor depressie

​Slaapproblemen hangen ook op korte termijn samen met depressieklachten. Dat schrijft Mara Bouwmans in haar proefschrift over slaap en depressie. Zij …

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Orthostatische hypotensie en hypertensie bij ouderen onder de loep

​Veel ouderen die uit een liggende houding opstaan, hebben last van een bloeddrukdaling, met daarbij soms duizeligheid en flauwvallen. Laura Hartog …

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Impact and outcome of abnormal loading on the right ventricle in children and adults with repaired tetralogy of Fallot

1. Cross-sectional study Right ventricular remodeling in response to abnormal loading in repaired tetralogy of Fallot. Aims The long-term outcome of repaired tetralogy of Fallot (TOF) depends on multiple factors, including the pathophysiological remodeling of the right ventricle (RV) to abnormal loading. This multi-center study was designed to evaluate the impact of abnormal pressure and volume loading on RV morphology and function.
Methods Cardiac magnetic resonance imaging and echocardiographic data were retrospectively analyzed. We assessed the associations of RV volumes and mass with RV function, pulmonary regurgitation fraction (PRF) and echocardiographic derived pressures.
Results A total of 401 studies were included. PRF correlated with RV end-diastolic volume indexed for body surface area (RVEDVi)(r=0.57, p<0.001), RV mass index (r=0.26, p<0.001), volume ratio RV/ left ventricle (LV) (r=0.64, p<0.001), RV stroke volume index (r=0.58, p<0.001) and RV mass/ volume ratio (r=-0.40, p<0.001). The RV/LV volume ratio had a stronger relation with PRF than RVEDVi (r=0.64 vs. 0.57, p<0.001), and was more accurate in predicting severe PR (i.e. PRF ≥20%, c-statistic 0.83 versus 0.80, p<0.001). RV mass was independently associated with pulmonary valve peak gradient (β=0.2; Standard Error (SE)=0.03; p<0001) and RV systolic pressure (β=0.2; SE=0.04; p<0001) after adjustment for PRF and RV volumes. RV mass was an independent predictor of reduced RV ejection fraction (β = -0.10, SE=0.04, p=0.02). Conclusion RV/LV volume ratio is superior to RVEDVi in the differentiation of severe from non-severe PR and is a more accurate reflection of RV dilatation due to chronic volume loading. RV hypertrophy, as a result of combined pressure and volume loading, is independently associated with RV systolic dysfunction in repaired TOF patients. 2. Longitudinal study Risk stratification in children and adults with repaired tetralogy of Fallot. Aims Cardiac arrhythmias are the leading cause of sudden cardiac death (SCD) in patients with repaired tetralogy of Fallot (TOF). We evaluated risk factors for SCD, ventricular tachyarrhythmias (VT) and atrial tachyarrhythmias (AT) in these patients. Methods Consecutive TOF patients were included in this multi-center study. Cardiac magnetic resonance imaging (CMR), echocardiographic, electrocardiographic and clinical data were analyzed. Results A total of 401 patients were included. During a median follow-up of 4.3 (1.3 - 6.1) years, 27 (7%) patients reached the primary endpoint of VT/SCD and 45 (11%) the secondary endpoint of AT. Right ventricular (RV) mass index ≥50.7g/m2 (Hazard ratio [HR] 6.45; 95% confidence interval [CI] 2.73 - 15.2; p<0.001), QRS-duration ≥164ms (HR 5.72; 95% CI 2.33 - 14.0; p<0.001) and age (HR 1.04; 95% CI 1.01 - 1.07; p=0.02) were independent predictors of VT/SCD. In patients with no risk factors 98%, one risk factor 82% and two risk factors 41% remained free from VT after nine years from CMR (log rank p<0.001). Body mass index (HR 1.13; 95% CI 1.09 - 1.21; p<0.001), age at TOF repair (HR 1.05; 95% CI 1.02 - 1.09; p=0.003) and age (HR 1.06; 95% CI 1.03 - 1.08; p<0.001) were independent predictors of AT. Percentage freedom from AT nine years from CMR were: no risk factor 97%; one risk factor 67%; two risk factors 52% [log rank p<0.001]). Conclusion In patients with repaired TOF, RV hypertrophy, prolonged QRS-duration and older age are independent predictors of VT. Obesity, older age at TOF repair and age are independently associated with the occurrence of AT.

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Verstoring van hersennetwerken bij schizofrenie

​Leonie Bais: Exciting links: imaging and modulation of neural networks underlying key symptoms of schizophrenia Bij patiënten met schizofrenie lijkt …

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het bouwen en valideren van een opstelling om de contrastgevoeligheid bij hoge lichtniveaus te meten : Een pilotstudy

Glaucoma is a chronic progressive eye disease which causes damage to the optic nerve. It could lead to blindness if left untreated. Many glaucoma patients complain of seeing in low, high and changing light conditions. Recent research focused on the low and changing light conditions. In the literature, little is known about the visual functioning in high light conditions. This pilot study will focus on the visual functioning in the high light conditions.
The primary aim of this study is to build and validate an experimental setup in which the contrast sensitivity in high light conditions can be measured.
The experimental setup was built with a rear projection screen and an Acer P1387W projector. 10 ophthalmic healthy subjects were included, aged between 24 and 67 years. The contrast sensitivity was measured in an already existing and a new experimental setup in normal light conditions. In addition, the examination of contrast sensitivity was also performed on the new experimental setup in high light conditions.
The mean contrast sensitivity and the shape of the contrast sensitivity function does not depend on the setup on which it is determined (p = 0,22 and p = 0,29 respectively). The mean contrast sensitivity and the shape of the contrast sensitivity does not different significantly between the light conditions in which it was tested (p = 0,16 and p = 0,26 respectively).
Further research will measure visual function in high light conditions in a larger group of healthy subjects and glaucoma patients. The aim of the follow-up study is to objectify the complaints of glaucoma patients in high light conditions.

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Ashy Dermatose – de histopathologische inter-observer correlatie

Background and objectives Ashy Dermatosis (AD) is a rare pigment disorder clinically characterized by ‘ash –gray’ discoloration of the skin. It is an acquired slowly progressive, persistent skin disease of unknown etiology. There is no well proven effective treatment. It is cosmetically very disturbing for patients. The aim of this study is to clarify the histopathology of AD, because in that part little research has been done. We want to investigate if we can identify a clear histopathological pattern by an inter-observer correlation analysis.
Material and methods Three dermatologists and one pathologist, all specialized in dermatopathology and/or pigment disorders, reviewed 54 skin biopsies from patients who were previously diagnosed with AD. The observers scored histopathological characteristics and gave the most suspect diagnosis. The location of biopsy was reported only, the clinical symptoms and differential diagnosis were not mentioned. The inter-observer correlation is measured by pair-wise similarities and multirater Fleiss’ Kappa.
Results 81.5% of the included patients were female. Skin type IV and V were most common. The ages ranged between 16 and 73 years. The Fleiss’ kappa for diagnosis was 0.18 which can be interpreted as a ‘slight’ correlation. In many biopsies other diagnoses seemed more likely than AD. The percentage of pairwise similarities for assessing characteristics was between 61 and 96 % with kappa values between -0.01 and 0.41 (bad to reasonable agreements) except for ‘subepidermal fibrosis’ (35% pairwise agreement and κ = -0.33). In only four cases they all agreed AD as the pathology conclusion. They scored respectively 28, 27, 14 and 28 times AD as diagnosis. The characteristics of these cases were displayed graphically per observer. The average AD case had pigment-incontinence, superficial lymfohistiocytair perivascular infiltrate and mild vacuolization of the basal cell layer. Epidermal atrophy, hyperkeratosis and exocytosis of lymphocytes could be quite possible. The presence of civatte bodies differed per observer.
Conclusion It appears that there was no unilateral agreement of histopathological pattern for AD according to the observers. They often set other criteria and pointed different biopies as AD. But they also differ in scoring histological characteristics, which is an interesting finding for histopathological diagnosing in general. The absence of clinic and differential diagnosis is apparently important for a proper diagnosis of this skin disorder. A clear criterium for histopathology is necessary in future. It seems to be a ‘diagnosis per exclusionem’ right now. When it has anamnestic no triggers, it persists, is resistant for treatment and pathology seems not only conform but also closes out other disease, it can be diagnosed as AD.

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Prevalence of Psychiatric Comorbidities among Women Undergoing Autologous Breast Reconstruction

Background. Patients undergoing mastectomy and autologous breast reconstruction (BR)
are required to have sufficient and long-lasting coping mechanisms. Although mental health
problems are a widespread problem in the United States, information regarding the
prevalence of psychiatric diagnosis among this patient group is lacking.
Methods. Retrospective analysis was performed using data from a large tertiary teaching
hospital. Additionally, this was compared to nationwide data provided by the Nationwide
Inpatient Sample (NIS) database. Patients undergoing autologous BR were included and
divided into different psychiatric diagnosis groups. Prevalence of each disorder, the moment
of diagnosis, and data per age group were reviewed.
Results. In total, 26,804 patients (2008 – 2012) were included in the comparison of
institutional data and nationwide data. Pre-operative, 15.3% of the patients were diagnosed
with a psychiatric disorder within the institutional database, and 17.6% in the NIS database.
There was no significant difference in prevalence between the two databases.
For the analysis of moment of diagnosis and different age groups, institutional data from 817
patients (2004 – 2014) was utilized. Post-operative, an additional 20.5% of the patients were
diagnosed with one or more psychiatric disorder. No major differences in prevalence preoperative
were seen between the age groups. Women ≤ 39 year old showed the highest
increase of prevalence post-operative.
Conclusions. Approximately one in six patients were diagnosed with a psychiatric
comorbidity before autologous breast reconstruction. Post-operative, an additional 20.5%
developed a psychiatric disorder. There was no difference in prevalence and moment of
diagnosis between the age groups.

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Vitamin D inhibits lymphangiogenesis through VDR-dependent mechanisms

Vitamin D inhibits lymphangiogenesis through VDR-dependent mechanisms

Yazdani, S., Poosti, F., Toro, L., Wedel, J., Mencke, R., Mirkovic, K., de Borst, M. H., Alexander, J. S., Navis, G., van Goor, H., van den Born, J. & Hillebrands, J-L. 7-Feb-2017 In : Scientific Reports. 26 p.

Research output: Scientific – peer-reviewArticle

Original language English
Number of pages 26
Journal Scientific Reports
State Accepted/In press – 7-Feb-2017
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