The influence of anesthesia and fluid-structure interaction on simulated shear stress patterns in the carotid bifurcation of mice

Background: Low and oscillatory wall shear stresses (WSS) near aortic bifurcations have been linked to the onset of atherosclerosis. In previous work, we calculated detailed WSS patterns in the carotid bifurcation of mice using a Fluid-structure interaction (FSI) approach. We subsequently fed the animals a high-fat diet and linked the results of the FSI simulations to those of atherosclerotic plaque location on a within-subject basis. However, these simulations were based on boundary conditions measured under anesthesia, while active mice might experience different hemodynamics. Moreover, the FSI technique for mouse-specific simulations is both time- and labor-intensive, and might be replaced by simpler and easier Computational Fluid Dynamics (CFD) simulations. The goal of the current work was (i) to compare WSS patterns based on anesthesia conditions to those representing active resting and exercising conditions; and (ii) to compare WSS patterns based on FSI simulations to those based on steady-state and transient CFD simulations. Methods: For each of the 3 computational techniques (steady state CFD, transient CFD, FSI) we performed 5 simulations: 1 for anesthesia, 2 for conscious resting conditions and 2 more for conscious active conditions. The inflow, pressure and heart rate were scaled according to representative in vivo measurements obtained from literature. Results: When normalized by the maximal shear stress value, shear stress patterns were similar for the 3 computational techniques. For all activity levels, steady state CFD led to an overestimation of WSS values, while FSI simulations yielded a clear increase in WSS reversal at the outer side of the sinus of the external carotid artery that was not visible in transient CFD-simulations. Furthermore, the FSI simulations in the highest locomotor activity state showed a flow recirculation zone in the external carotid artery that was not present under anesthesia. This recirculation went hand in hand with locally increased WSS reversal. Conclusions: Our data show that FSI simulations are not necessary to obtain normalized WSS patterns, but indispensable to assess the oscillatory behavior of the WSS in mice. Flow recirculation and WSS reversal at the external carotid artery may occur during high locomotor activity while they are not present under anesthesia. These phenomena might thus influence plaque formation to a larger extent than what was previously assumed. (C) 2016 Elsevier Ltd. All rights reserved

Expression profiling of migrated and invaded breast cancer cells predicts early metastatic relapse and reveals Krüppel-like factor 9 as a potential suppressor of invasive growth in breast cancer

Cell motility and invasion initiate metastasis. However, only a subpopulation of cancer cells within a tumor will ultimately become invasive. Due to this stochastic and transient nature, in an experimental setting, migrating and invading cells need to be isolated from the general population in order to study the gene expression profiles linked to these processes. This report describes microarray analysis on RNA derived from migrated or invaded subpopulations of triple negative breast cancer cells in a Transwell set-up, at two different time points during motility and invasion, pre-determined as “early” and “late” in real-time kinetic assessments. Invasion- and migration-related gene expression signatures were generated through comparison with non-invasive cells, remaining at the upper side of the Transwell membranes. Late-phase signatures of both invasion and migration indicated poor prognosis in a series of breast cancer data sets. Furthermore, evaluation of the genes constituting the prognostic invasion-related gene signature revealed Krüppel-like factor 9 (KLF9) as a putative suppressor of invasive growth in breast cancer. Next to loss in invasive vs non-invasive cell lines, KLF9 also showed significantly lower expression levels in the “early” invasive cell population, in several public expression data sets and in clinical breast cancer samples when compared to normal tissue. Overexpression of EGFP-KLF9 fusion protein significantly altered morphology and blocked invasion and growth of MDA-MB-231 cells in vitro. In addition, KLF9 expression correlated inversely with mitotic activity in clinical samples, indicating anti-proliferative effects

Neuroprotective effects of a specific multi-nutrient intervention against Aβ42-induced toxicity in rats

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly. Substantial evidence suggests a role for nutrition in the management of AD and especially suggests that interventions with combinations of nutrients are more effective than single-nutrient interventions. The specific multi-nutrient combination Fortasyn™Connect (FC), shown to improve memory in AD, provides phosphatide precursors and cofactors and is designed to stimulate the formation of phospholipids, neuronal membranes, and synapses. The composition comprises nucleotides, omega-3 polyunsaturated fatty acids (n3 PUFA), choline, B-vitamins, phospholipids, and antioxidants. The current study explored the protective properties of FC in a membrane toxicity model of AD, the amyloid-β 1-42 (Aβ42) infused rat, which shows reduced exploratory behavior in an Open Field and impaired cholinergic functioning. To this end, rats were fed an FC enriched diet or a control diet and five weeks later infused with vehicle or Aβ42 into the lateral ventricle. Ten weeks post-infusion Aβ42-rats fed the FC diet showed increased membrane n3 PUFA and phosphatidylcholine content while they did not show the reductions in exploratory behavior or in choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) immunoreactivity that were seen in Aβ42-rats fed the control diet. We conclude that FC protects the cholinergic system against Aβ42-induced toxicity and speculate that the effects of FC on membrane formation and composition might be supportive for this protective effect. Based on these data a long-term intervention study was started in the prodromal stages of AD (NTR1705, LipiDiDiet, EU FP7)

Antidepressant and anticonvulsant prescription rates in patients with osteoarthritis:A population-based cohort study

Objectives: There are signs that antidepressants and anticonvulsants are being prescribed more often for OA patients, despite limited evidence. Our objectives were to examine prescription rates and time trends for antidepressants and anticonvulsants in OA patients, to assess the percentage of long-term prescriptions, and to determine patient characteristics associated with antidepressant or anticonvulsant prescription. Methods: A population-based cohort study was conducted using the Integrated Primary Care Information database. First, episodic and prevalent prescription rates for antidepressants (amitriptyline, nortriptyline and duloxetine) and anticonvulsants (gabapentinoids) in OA patients were calculated for the period 2008-17. Logistic regression was used to assess which patient characteristics were associated with prescriptions.  Results: In total, 164 292 OA patients were included. The prescription rates of amitriptyline, gabapentin and pregabalin increased over time. The increase in prescription rates for pregabalin was most pronounced. Episodic prescription rate increased from 7.1 to 13.9 per 1000 person-years between 2008 and 2017. Amitriptyline was prescribed most (15.1 episodic prescriptions per 1000 person-years in 2017). Prescription rates of nortriptyline and duloxetine remained stable at 3.0 and 2.0 episodic prescriptions per 1000 person-years, respectively. For ≤3% of patients with incident OA, medication was prescribed long-term (≥3 months). In general, all medication was prescribed more frequently for older patients (except duloxetine), women, patients with OA in ≥2 joints, patients with spinal OA and patients with musculoskeletal disorders.  Conclusion: Prescription rates of amitriptyline, gabapentin and pregabalin increased over time. Since there is little evidence to support prescription in OA, caution is necessary when prescribing. </p

Tumorbank@uza: A Collection of Tissue, Fluid Samples and Associated Data of Oncology Patients for the Use in Translational Research

Tumorbank@UZA is an academic hospital integrated biobank that collects tissue, blood and urine samples from oncology patients. We work according to a quality management system and have established SOPs for all work procedures in the biobank. Tumorbank@UZA is funded by the National Cancer Plan, an initiative from the Belgian government since 2009. Samples from our biobank are available for both academic as well as commercial researchers, through a well-established access procedure. Currently the collection consists of more than 85.000 samples of more than 8000 patients. Funding statement: Tumorbank@UZA is funded by the National Cancer Plan (initiative 27) from the Ministry of Health of the Belgian Federal Government.</p

Opioid prescriptions in patients with osteoarthritis: a population-based cohort study

OBJECTIVES: To examine the incidence, prevalence and trends for opioid prescriptions in patients with OA. Furthermore, types of opioids prescribed and long-term prescription rates were examined. Finally, the patient characteristics associated with the prescription of opioids wer

M & L Jaargang 18/2

E. Ignace De Wilde Boerenkrijgmonumenten van 1898. [Memorials to the Peasantsrevolt of 1898.]Antoon Fauconnier en Patrick Roose Een van Peteghem-orgel uit Diest in de kerk van de Landcommanderij Alden Biesen. [A Van Peteghem organ from Diest in the land&nbspcommandery Alden Biesen.]Anne-Sophie Augustyniak, Ingrid Geelen en Myriam Serck-Dewaide Het laatgotisch Sint-Annaretabel (1533) van de Sint-Salvatorskathedraal te Brugge. [The late gothic Saint Annas retable in Bruges St. Salvators cathedral.]Summar

Infraglenoidal scapular notching in reverse total shoulder replacement: a prospective series of 60 cases and systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The impact of infraglenoidal scapular notching in reversed total shoulder arthroplasty (RTSA) is still controversially discussed. Our goal was to evaluate its potential influence on subjective shoulder stability and clinical outcome. We hypothesized that subjective instability and clinical outcome after implantation of RTSA correlates with objective scapular notching.</p> <p>Methods</p> <p>Sixty shoulders were assessed preoperatively and at minimum 2-year follow-up for active range of motion and by use of the Oxford instability score, Rowe score for instability, Constant score for pain, Constant shoulder score, DASH score. All shoulders were evaluated on anterior-posterior and axillary lateral radiographic views. These X-ray scans were classified twice by two orthopaedic surgeons with respect to infraglenoidal scapular notching according to the classification of Nerot. Notching was tested for correlation with clinical outcome scores to the evaluated notching.</p> <p>Results</p> <p>We found no significant correlation between infraglenoidal scapular notching and clinical outcomes after a mid-term follow-up from 24 to 60 months, but at the final follow-up of 60 months and more, we did see statistically significant, positive correlations between infraglenoidal scapular notching and the Constant pain score as well as active range of motion. At mean follow-up of 42 months (range from 24 to 96 months) we found no significant correlation between subjective instability and infraglenoidal scapular notching.</p> <p>Conclusions</p> <p>We conclude that patients' subjective impression on their shoulders' stability is not correlating with radiological signs of infraglenoidal scapular notching. Nevertheless clinical parameters are affected by infraglenoidal scapular notching, at least in the long term</p