Clinical Application of Human Mesenchymal Stromal Cells for Bone Tissue Engineering

The gold standard in the repair of bony defects is autologous bone grafting, even though it has drawbacks in terms of availability and morbidity at the harvesting site. Bone-tissue engineering, in which osteogenic cells and scaffolds are combined, is considered as a potential bone graft substitute strategy. Proof-of-principle for bone tissue engineering using mesenchymal stromal cells (MSCs) has been demonstrated in various animal models. In addition, 7 human clinical studies have so far been conducted. Because the experimental design and evaluation parameters of the studies are rather heterogeneous, it is difficult to draw conclusive evidence on the performance of one approach over the other. However, it seems that bone apposition by the grafted MSCs in these studies is observed but not sufficient to bridge large bone defects. In this paper, we discuss the published human clinical studies performed so far for bone-tissue regeneration, using culture-expanded, nongenetically modified MSCs from various sources and extract from it points of consideration for future clinical studies

GeneHopper: a web-based search engine to link gene-expression platforms through GenBank accession numbers

Global gene-expression analysis is carried out using different technologies that are either array- or sequence-tag-based. To compare experiments that are performed on these different platforms, array probes and sequence tags need to be linked. An additional challenge is cross-referencing between species, to compare human profiles with those obtained in a mouse model, for example. We have developed the web-based search engine GeneHopper to link different expression resources based on UniGene clusters and HomoloGene orthologs databases of the National Center for Biotechnology Information (NCBI)

Unravelling variation in feeding, social interaction and growth patterns among pigs using an agent-based model

Domesticated pigs, Sus scrofa, vary considerably in feeding, social interaction and growth patterns. This variation originates partly from genetic variation that affects physiological factors and partly from behavioural strategies (avoid or approach) in competitive food resource situations. Currently, it is unknown how variation in physiological factors and in behavioural strategies among animals contributes to variation in feeding, social interaction and growth patterns in animals. The aim of this study was to unravel causation of variation in these patterns among pigs. We used an agent-based model to explore the effects of physiological factors and behavioural strategies in pigs on variation in feeding, social interaction and growth patterns. Model results show that variation in feeding, social interaction and growth patterns are caused partly by chance, such as time effects and coincidence of conflicts. Furthermore, results show that seemingly contradictory empirical findings in literature can be explained by variation in pig characteristics (i.e. growth potential, positive feedback, dominance, and coping style). Growth potential mainly affected feeding and growth patterns, whereas positive feedback, dominance and coping style affected feeding patterns, social interaction patterns, as well as growth patterns. Variation in behavioural strategies among pigs can reduce aggression at group level, but also make some pigs more susceptible to social constraints inhibiting them from feeding when they want to, especially low-ranking pigs and pigs with a passive coping style. Variation in feeding patterns, such as feeding rate or meal frequency, can indicate social constraints. Feeding patterns, however, can say something different about social constraints at group versus individual level. A combination of feeding patterns, such as a decreased feed intake, an increased feeding rate, and an increased meal frequency might, therefore, be needed to measure social constraints at individual level

MEASUREMENT OF THE SHORTEST PATH LENGTH; DISTANCE ESTIMATION WITHIN THE 3D BORDERS OF A TISSUE OF INTEREST

Volume data, such as 3D reconstructions from histological sections orMRI and CT data, are commonly used in studies in biology and medicine. The quantification of morphological parameters and changes within a region of interest is a key concern in such studies. Specifically, it is often required to measure the distance between two points. These distance measurements have to follow a track through the tissue when measuring in sheetlike or contorted organs like the developing heart. A tool was developed that enables this kind of distance measurements. Three existing neighborhood estimators were compared; two of Verwer and one of Kiryati, all originally designed to compute chamfer distances in data sets with isotropic, cubic voxels. The estimators were therefore adjusted to handle non-isotropic data sets. Moreover, the shortest path along a track within a given tissue was calculated. The measurement of known distances, through a simplified model of an early heart tube, with anisotropic voxels was used decide which of the three estimators should be implemented. The observed Root Mean Square (RMS) errors were similar to the ones reported in literature in the unrestrained isotropic case. The adjusted Verwer estimator measuring in a 53 neighborhood performed best by far with the lowest mean and RMS errors

Human Papillomavirus Deregulates the Response of a Cellular Network Comprising of Chemotactic and Proinflammatory Genes

Despite the presence of intracellular pathogen recognition receptors that allow infected cells to attract the immune system, undifferentiated keratinocytes (KCs) are the main targets for latent infection with high-risk human papilloma viruses (hrHPVs). HPV infections are transient but on average last for more than one year suggesting that HPV has developed means to evade host immunity. To understand how HPV persists, we studied the innate immune response of undifferentiated human KCs harboring episomal copies of HPV16 and 18 by genome-wide expression profiling. Our data showed that the expression of the different virus-sensing receptors was not affected by the presence of HPV. Poly(I:C) stimulation of the viral RNA receptors TLR3, PKR, MDA5 and RIG-I, the latter of which indirectly senses viral DNA through non-self RNA polymerase III transcripts, showed dampening in downstream signalling of these receptors by HPVs. Many of the genes downregulated in HPV-positive KCs involved components of the antigen presenting pathway, the inflammasome, the production of antivirals, pro-inflammatory and chemotactic cytokines, and components downstream of activated pathogen receptors. Notably, gene and/or protein interaction analysis revealed the downregulation of a network of genes that was strongly interconnected by IL-1β, a crucial cytokine to activate adaptive immunity. In summary, our comprehensive expression profiling approach revealed that HPV16 and 18 coordinate a broad deregulation of the keratinocyte's inflammatory response, and contributes to the understanding of virus persistence

Midterm Outcomes and Aneurysm Sac Dynamics Following Fenestrated Endovascular Aneurysm Repair after Previous Endovascular Aneurysm Repair

Objective: Fenestrated endovascular aneurysm repair (FEVAR) is a feasible option for aortic repair after endovascular aneurysm repair (EVAR), due to improved peri-operative outcomes compared with open conversion. However, little is known regarding the durability of FEVAR as a treatment for failed EVAR. Since aneurysm sac evolution is an important marker for success after aneurysm repair, the aim of the study was to examine midterm outcomes and aneurysm sac dynamics of FEVAR after prior EVAR. Methods:Patients undergoing FEVAR for complex abdominal aortic aneurysms from 2008 to 2021 at two hospitals in The Netherlands were included. Patients were categorised into primary FEVAR and FEVAR after EVAR. Outcomes included five year mortality rate, one year aneurysm sac dynamics (regression, stable, expansion), sac dynamics over time, and five year aortic related procedures. Analyses were done using Kaplan–Meier methods, multivariable Cox regression analysis, chi square tests, and linear mixed effect models. Results: One hundred and ninety-six patients with FEVAR were identified, of whom 27% (n = 53) had had a prior EVAR. Patients with prior EVAR were significantly older (78 ± 6.7 years vs. 73 ± 5.9 years, p &lt; .001). There were no significant differences in mortality rate. FEVAR after EVAR was associated with a higher risk of aortic related procedures within five years (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.1 – 6.5, p = .037). Sac dynamics were assessed in 154 patients with available imaging. Patients with a prior EVAR showed lower rates of sac regression and higher rates of sac expansion at one year compared with primary FEVAR (sac expansion 48%, n = 21/44, vs. 8%, n = 9/110, p &lt; .001). Sac dynamics over time showed similar results, sac growth for FEVAR after EVAR, and sac shrinkage for primary FEVAR (p &lt; .001). Conclusion: There were high rates of sac expansion and a need for more secondary procedures in FEVAR after EVAR than primary FEVAR patients, although this did not affect midterm survival. Future studies will have to assess whether FEVAR after EVAR is a valid intervention, and the underlying process that drives aneurysm sac growth following successful FEVAR after EVAR.</p

Tracing timing of growth in cultured molluscs using strontium spiking

Introduction: Growth experiments present a powerful tool for determining the effect of environmental parameters on growth and carbonate composition in biogenic calcifiers. For successful proxy calibration and biomineralization studies, it is vital to identify volumes of carbonate precipitated by these organisms at precise intervals during the experiment. Here, we investigate the use of strontium labelling in mollusc growth experiments. Methods: Three bivalve species (Cerastoderma edule, Mytilus edulis and Ostrea edulis) were grown under monitored field conditions. The bivalves were regularly exposed to seawater with elevated concentrations of dissolved strontium chloride (SrCl2). In addition, the size of their shells was determined at various stages during the experiment using calliper measurements and digital photography. Trace element profiles were measured in cross sections through the shells of these molluscs using laser ablation ICPMS and XRF techniques. Results: Our results show that doses of dissolved strontium equivalent to 7-8 times the background marine value (~0.6 mmol/L) are sufficient to cause reproducible peaks in shell-incorporated strontium in C. edule and M. edulis shells. No negative effects were observed on shell calcification rates. Lower doses (3-5 times background values) resulted in less clearly identifiable peaks, especially in M. edulis. Strontium spiking labels in shells of O. edulis are more difficult to detect, likely due to their irregular growth. Discussion: Strontium spiking is a useful technique for creating time marks in cultured shells and a reproducible way to monitor shell size during the growing season while limiting physical disturbance of the animals. However, accurate reconstructions of growth rates at high temporal resolution require frequent spiking with high doses of strontium

TNO at TRECVID 2013 : multimedia event detection and instance search

We describe the TNO system and the evaluation results for TRECVID 2013 Multimedia Event Detection (MED) and instance search (INS) tasks. The MED system consists of a bag-of-word (BOW) approach with spatial tiling that uses low-level static and dynamic visual features, an audio feature and high-level concepts. Automatic speech recognition (ASR) and optical character recognition (OCR) are not used in the system. In the MED case with 100 example training videos, support-vector machines (SVM) are trained and fused to detect an event in the test set. In the case with 0 example videos, positive and negative concepts are extracted as keywords from the textual event description and events are detected with the high-level concepts. The MED results show that the SIFT keypoint descriptor is the one which contributes best to the results, fusion of multiple low-level features helps to improve the performance, and the textual event-description chain currently performs poorly. The TNO INS system presents a baseline open-source approach using standard SIFT keypoint detection and exhaustive matching. In order to speed up search times for queries a basic map-reduce scheme is presented to be used on a multi-node cluster. Our INS results show above-median results with acceptable search times.This research for the MED submission was performed in the GOOSE project, which is jointly funded by the enabling technology program Adaptive Multi Sensor Networks (AMSN) and the MIST research program of the Dutch Ministry of Defense. The INS submission was partly supported by the MIME project of the creative industries knowledge and innovation network CLICKNL.peer-reviewe

The Influence of Radiograph Obliquity on Böhler's and Gissane's Angles in Calcanei

In calcaneal fractures, Böhler's and Gissane's angles are considered important parameters to guide treatment strategy and provide prognostic information during follow-up visits. Therefore, lateral radiographs have to be accurate. The aim of this study was to evaluate the effect of craniocaudal and posteroanterior angular variations (i.e., simulate lower leg malposition) from the true lateral radiograph on Böhler's and Gissane's angles. In this radioanatomical study, 15 embalmed, skeletally mature, human anatomic lower limb specimens were used. Using predefined criteria, a true lateral radiograph (i.e., 0° angular variation) was obtained. Angular variations from this true lateral radiograph were made from –30° to +30° deviation in the craniocaudal and posteroanterior direction at 5° intervals. Böhler's and Gissane angles were independently assessed by 2 experienced trauma surgeons. Böhler's angle decreased with increasing caudal angular variations (maximum –4.3° deviation at –30°). With increasing of the posterior angular variations, Böhler's angle increased (maximum 5.0° deviation at +30°) from the true lateral radiograph, but all deviations were within the measurement error. The deviation of the angle of Gissane was most pronounced in the cranial direction, with the mean angle decreasing by