Microenvironment

Pilon fractures are commonly caused by high energy trauma and can result in long-term immobilization of patients. The use of an external fixator i.e. the (1) Delta, (2) Mitkovic or (3) Unilateral frame for treating type III pilon fractures is generally recommended by many experts owing to the stability provided by these constructs. This allows this type of fracture to heal quickly whilst permitting early mobilization. However, the stability of one fixator over the other has not been previously demonstrated. This study was conducted to determine the biomechanical stability of these external fixators in type III pilon fractures using finite element modelling. Three-dimensional models of the tibia, fibula, talus, calcaneus, navicular, cuboid, three cuneiforms and five metatarsal bones were reconstructed from previously obtained CT datasets. Bones were assigned with isotropic material properties, while the cartilage was assigned as hyperelastic springs with Mooney-Rivlin properties. Axial loads of 350N and 70N were applied at the tibia to simulate the stance and the swing phase of a gait cycle. To prevent rigid body motion, the calcaneus and metatarsals were fixed distally in all degrees of freedom. The results indicate that the model with the Delta frame produced the lowest relative micromovement (0.03mm) compared to the Mitkovic (0.05mm) and Unilateral (0.42mm) fixators during the stance phase. The highest stress concentrations were found at the pin of the Unilateral external fixator (509.2MPa) compared to the Mitkovic (286.0MPa) and the Delta (266.7MPa) frames. In conclusion, the Delta external fixator was found to be the most stable external fixator for treating type III pilon fractures.

Vascular system plays critical roles in tumor progression and metastasis. Tumor vessels generally sprout from preexisting vascular cells. In addition, pluripotent progenitor cells also participate in tumor neovascularization. The latter populations include endothelial progenitor cells, hematopoietic stem cells and mesenchymal stem cells that are stimulated and attracted into the lesion. Recent studies on tumor microenvironment have disclosed that BM (bone marrow)-derived progenitor cells contain unique subpopulations that do not become fully-differentiated vascular constituents; instead, they show the nature of immature myeloid or mesenchymal lineage, and they enhance tumor angiogenic milieu in close contact with tumor vessels. BM-derived cells also migrate into pre-metastatic niche and stimulate vascular beds of distant organ for attracting circulating tumor cells. Currently, several antiangiogenic molecules are under clinical trials and they are expected to improve overall prognosis. Humanized monoclonal antibody bevacizumab specifically targeting VEGF (vascular endothelial growth factor), and several tyrosine kinase inhibitors targeting VEGF receptors-mediated pathways are the most widely studied agents in several types of advanced cancers. It is obvious that VEGF contributes to tumor neovascularization as a mastermind molecule. On the other hand, the mechanism has also been elucidated how tumors evade VEGF targeting therapies. To establish safer and more effective antiangiogenic therapies, it is important to understand the crosscommunication between tumors and hosts in proinflammatory milieu. In this review, we discuss features of tumor angiogenic vessels and their microenvironment. Recent topics on the contribution of BM-derived cells, complexities of VEGFtargeting approaches, and chemoattractants that activate tumor vascular beds are summarized.

Researchers are currently trying to understand why some men with prostate cancer go on to develop aggressive disease whilst others maintain slow growing tumors. Although endogenous genetic anomalies within the tumor cell are important, the prevailing view is that the tissue microenvironment as a whole is the determinant factor. Many studies have focussed on the role of soluble factors in modulating the nature of the tumor microenvironment. There is however a growing interest in the role of extracellular vesicles, including exosomes, as regulators of disease progression. A variety of resident cells, as well as infiltrating cells, all contribute to a heterogeneous population of exosomes within the tumor microenvironment. Studies focussing on the role of exosomes in prostate cancer are however relatively rare. In this review, evidence from various cancers, including prostate, is used to present numerous potential roles of exosomes in prostate cancer. Whilst further validation of some functions may remain necessary it is clear that exosomes play a major role in intercellular communication between various cell types within the tumor microenvironment and are necessary for driving disease progression.

Effects of the pharmacological EPCR blockade in the prometastatic activity of 1833 cells. A. Specificity of anti-EPCR antibodies, RCR252, and its F(ab´)2 fraction, by surface plasmon resonance (SPR). EPCR (500 RU) was immobilized through the anti-EPCR antibody RCR2 (that does not bind in the ligand-receptor domain) on a CM5 chip. The binding of 250 nM of RCR252 and its F(ab´)2 fraction to the EPCR were monitored. A representative experiment is shown. RU resonance units; s, seconds. B. Outline of the experiment (n = 8 per group). C. Photon flux quantification in hind limbs. D. Tumor area quantification in H&E-stained bone sections. E. Osteolytic bone area quantification in X-ray images from day 28 post-injection. F. Representative images of BLI (top), X-rays (middle), and H&E staining (bottom) at day 28 post-injection. All data are represented by mean ± SEM. (PPTX 1540 kb)

The notion of nudge effects was investigated in two field experiments which focused on influencing customers’ purchases by manipulating the location and availability of food in a University canteen setting. Study 1 manipulated the location of fruit and confectionary. Study 2 restricted the types of bread (i.e. brown only not white) that customers could choose for their sandwiches. The results of the Study1 showed that the fruit sales increased when positioned away from the checkouts. The majority of interviewed customers bought fruit intentionally but those who bought confectionary did it on impulse. In the Study 2, a restricted choice of baguettes did not reduce sales, with customers simply buying more brown baguettes. This increase did not persist after the intervention. Simple changes in the location and availability of food items can nudge the customers ’ purchases towards the choice of healthier options. There may be different processes that guide the purchase of fruit (intenti...

The purposes of this study were: i) to demonstrate the assessment of personal exposure from various RF-EMF sources across different microenvironments in Australia and Belgium, with two on-body calibrated exposimeters, in contrast to earlier studies which employed single, non-on-body calibrated exposimeters; ii) to systematically evaluate the performance of the exposimeters using (on-body) calibration and cross-talk measurements; and iii) to compare the exposure levels measured for one site in each of several selected microenvironments in the two countries. A human subject took part in an on-body calibration of the exposimeter in an anechoic chamber. The same subject collected data on personal exposures across 38 microenvironments (19 in each country) situated in urban, suburban and rural regions. Median personal RF-EMF exposures were estimated: i) of all microenvironments, and ii) across each microenvironment, in two countries. The exposures were then compared across similar microen...