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Purpose of this study was to compare bioactive glass and autogenous bone as a bone substitute material in tibial plateau fractures. We designed a prospective, randomized study consisting of 25 consecutive operatively treated patients with depressed unilateral tibial comminuted plateau fracture (AO classification 41 B2 and B3).14 patients (7 females, 7 males, mean age 57 years, range 25–82) were randomized in the bioglass group (BG) and 11 patients (6 females, 5 males, mean age 50 years, range 31–82) served as autogenous bone control group (AB). Clinical examination of the patients was performed at 3 and 12 months, patients’ subjective and functional results were evaluated at 12 months. Radiological analysis was performed preoperatively, immediately postoperatively and at 3 and 12 months. The postoperative redepression for both studied groups was 1 mm until 3 months and remained unchanged at 12 months. No differences were identified in the subjective evaluation, functional tests and clinical examination between the two groups during 1 year follow-up. We conclude that bioactive glass granules can be clinically used as filler material instead of autogenous bone in the lateral tibial plateau compression fractures.

Abstract Whereas nonlinear relationships between genes are acknowledged, there exist only a few methods for estimating nonlinear gene coexpression networks or gene regulatory networks (GCNs/GRNs) with common deficiencies. These methods often consider only pairwise associations between genes, and are, therefore, poorly capable of identifying higher-order regulatory patterns when multiple genes should be considered simultaneously. Another critical issue in current nonlinear GCN/GRN estimation approaches is that they consider linear and nonlinear dependencies at the same time in confounded form nonparametrically. This severely undermines the possibilities for nonlinear associations to be found, since the power of detecting nonlinear dependencies is lower compared to linear dependencies, and the sparsity-inducing procedures might favor linear relationships over nonlinear ones only due to small sample sizes. In this paper, we propose a method to estimate undirected nonlinear GCNs independently from the linear associations between genes based on a novel semiparametric neighborhood selection procedure capable of identifying complex nonlinear associations between genes. Simulation studies using the common DREAM3 and DREAM9 datasets show that the proposed method compares superiorly to the current nonlinear GCN/GRN estimation methods.

Understanding the dynamic cellular behaviors and underlying molecular mechanisms that drive morphogenesis is an ongoing challenge in biology. Live imaging provides the necessary methodology to unravel the synergistic and stereotypical cell and molecular events that shape the embryo. Genetically-encoded reporters represent an essential tool for live imaging. Reporter strains can be engineered by placing cis-regulatory elements of interest to direct the expression of a desired reporter gene. In the case of canonical Wnt signaling, also referred to as Wnt/[beta]-catenin signaling, since the downstream transcriptional response is well understood, reporters can be designed that reflect sites of active Wnt signaling, as opposed to sites of gene transcription, as is the case with many fluorescent reporters. However, even though several transgenic Wnt/[beta]-catenin reporter strains have been generated, to date, none provides the single-cell resolution favored for live imaging studies. We have placed six copies of a TCF/Lef responsive element and an hsp68 minimal promoter in front of a fluorescent protein fusion comprising human histone H2B to GFP and used it to generate a strain of mice that would report Wnt/[beta]-catenin signaling activity. Characterization of developmental and adult stages of the resulting TCF/Lef:H2B-GFP strain revealed discrete and specific expression of the transgene at previously characterized sites of Wnt/[beta]-catenin signaling. In support of the increased sensitivity of the TCF/Lef:H2B-GFP reporter, additional sites of Wnt/[beta]-catenin signaling not documented with other reporters but identified through genetic and embryological analysis were observed. Furthermore, the sub-cellular localization of the reporter minimized reporter perdurance, and allowed visualization and tracking of individual cells within a cohort, so facilitating the detailed analysis of cell behaviors and signaling activity during morphogenesis. By combining the Wnt activity read-out efficiency of multimerized TCF/Lef DNA binding sites, together with the high-resolution imaging afforded by subcellularly-localized fluorescent fusion proteins such as H2B-GFP, we have created a mouse transgenic line that faithfully recapitulates Wnt signaling activity at single-cell resolution. The TCF/Lef:H2B-GFP reporter represents a unique tool for live imaging the in vivo processes triggered by Wnt/[beta]-catenin signaling, and thus should help the formulation of a high-resolution understanding of the serial events that define the morphogenetic process regulated by this signaling pathway.

The purpose of this study was to investigate the effect of fiber orientation of a fiber-reinforced composite (FRC) made of poly-methyl-methacrylate (PMMA) and E-glass to the surface fabrication process by solvent dissolution. Intention of the dissolution process was to expose the fibers and create a macroporous surface onto the FRC to enhance bone bonding of the material. The effect of dissolution and fiber direction to the bone bonding capability of the FRC material was also tested. Three groups of FRC specimens ( n  = 18/group) were made of PMMA and E-glass fiber reinforcement: (a) group with continuous fibers parallel to the surface of the specimen, (b) continuous fibers oriented perpendicularly to the surface, (c) randomly oriented short (discontinuous) fibers. Fourth specimen group ( n  = 18) made of plain PMMA served as controls. The specimens were subjected to a solvent treatment by tetrahydrofuran (THF) of either 5, 15 or 30 min of time ( n  = 6/time point), and the advancement of the dissolution (front) was measured. The solvent treatment also exposed the fibers and created a surface roughness on to the specimens. The solvent treated specimens were embedded into plaster of Paris to simulate bone bonding by mechanical locking and a pull-out test was undertaken to determine the strength of the attachment. All the FRC specimens dissolved as function of time, as the control group showed no marked dissolution during the study period. The specimens with fibers along the direction of long axis of specimen began to dissolve significantly faster than specimens in other groups, but the test specimens with randomly oriented short fibers showed the greatest depth of dissolution after 30 min. The pull-out test showed that the PMMA specimens with fibers were retained better by the plaster of Paris than specimens without fibers. However, direction of the fibers considerably influenced the force of attachment. The fiber reinforcement increases significantly the dissolution speed, and the orientation of the glass fibers has great effect on the dissolving depth of the polymer matrix of the composite, and thus on the exposure of fibers. The glass fibers exposed by the solvent treatment enhanced effectively the attachment of the specimen to the bone modeling material.

Polymethylmethacrylate (PMMA) has been used in many orthopedic and dental applications since the 1960s. Biocompatibility of newly developed surface porous fiber reinforced (SPFR) PMMA based composite has not been previously proven in cell culture environment. Analysis of rat bone marrow stromal cells grown on the different test materials showed only little difference in normalized cell activity or bone sialoprotein (BSP) production between the test materials, but the osteocalcin (OC) levels remained higher ( P  < 0.015–0.005) through out the test with SPFR-material when compared to tissue culture poly styrene (TCPS). The cells grown on SP-FRC material also showed highest calcium depletion from the culture medium ( P  < 0.026–0.001) when compared to all other test substrates. SEM images of the cultured samples confirmed that all the materials enabled cell spreading and growth on their surface, but the roughened surface remarkably enhanced this process of cell attachment, division and calcified nodule formation. This study shows that the SP-FRC composite material does not elicit harmful/toxic reactions in cell cultures more than neutral TCPS and can be considered biocompatible. The material possesses good capabilities to form new mineralized tissue onto its surface, and through that a possibility to bond directly to bone. Rough surface seems to enhance osteoblast proliferation and formation of mineralized extracellular matrix.

Injectable composites (Glepron) of particulate bioactive glass S53P4 (BAG) and Poly(epsilon-caprolactone-co-D,L-lactide) as thermoplastic carrier matrix were investigated as bone fillers in cancellous and cartilagineous subchondral bone defects in rabbits. Composites were injected as viscous liquid or mouldable paste. The glass granules of the composites resulted in good osteoconductivity and bone bonding that occurred initially at the interface between the glass and the host bone. The bone bioactivity index (BBI) indicating bone contacts between BAG and bone, as well as the bone coverage index (BCI) indicating bone ongrowth, correlated with the amount of glass in the composites. The indices were highest with 70 wt % of BAG, granule size 90-315 microm and did not improve by the addition of sucrose as in situ porosity creating agent in the composite or by using smaller (<45 microm) glass granules. The percentage of new bone ingrowth into the composite with 70 wt % of BAG was 6-8% at 23 weeks. At the articular surface cartilage regeneration with chondroblasts and mature chondrocytes was often evident. The composites were osteoconductive and easy to handle with short setting time. They were biocompatible with low foreign body cellular reaction. Results indicate a suitable working concept as a filler bone substitute for subchondral cancellous bone defects.

Purpose Safe intrathoracic placement of chest tubes is a continual challenge. Current techniques for determining the intrathoracic location of the thoracostomy site include blunt dissection and digital exploration, with subsequent tube placement. Using current techniques, complication rates for this procedure approach 30 %. We present a novel technique using available endotracheal intubation technology for determining intrathoracic placement of tube thoracostomy. Methods One cadaver was used for placement of tube thoracostomy. Both sides of the thorax were prepared in the standard fashion for tube thoracostomy placement, and tube thoracostomy was performed on each hemithorax at interspaces 3 through 7. The right side of the thorax was used for standard thoracostomy placement, and the left side was used for fiberoptic visualization of thoracostomy placement using a video laryngoscope. Thoracic wall thickness was measured at all thoracostomy sites. Proper placement and any injuries were documented for each site. Results Chest wall thickness ranged from 2.4 to 3.8 cm on the right and 2.8 to 4.0 cm on the left. With use of fiberoptic thoracostomy, no injuries were generated. During the standard thoracostomy placement in the sixth intercostal space, a pulmonary laceration was caused using blunt dissection. Conclusions Use of a fiberoptic laryngoscope offers a novel technique for direct visualization the thoracic space during tube thoracostomy. Further studies are needed to determine the safety of this technique in patients.

Wood is a natural fiber reinforced composite. It structurally resembles bone tissue to some extent. Specially heat-treated birch wood has been used as a model material for further development of synthetic fiber reinforced composites (FRC) for medical and dental use. In previous studies it has been shown, that heat treatment has a positive effect on the osteoconductivity of an implanted wood. In this study the effects of two different heat treatment temperatures (140 and 200°C) on wood were studied in vitro. Untreated wood was used as a control material. Heat treatment induced biomechanical changes were studied with flexural and compressive tests on dry birch wood as well as on wood after 63 days of simulated body fluid (SBF) immersion. Dimensional changes, SBF sorption and hydroxylapatite type mineral formation were also assessed. The results showed that SBF immersion decreases the biomechanical performance of wood and that the heat treatment diminishes the effect of SBF immersion on biomechanical properties. With scanning electron microscopy and energy dispersive X-ray analysis it was shown that hydroxylapatite type mineral precipitation formed on the 200°C heat-treated wood. An increased weight gain of the same material during SBF immersion supported this finding. The results of this study give more detailed insight of the biologically relevant changes that heat treatment induces in wood material. Furthermore the findings in this study are in line with previous in vivo studies.