Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2

Background Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. Methods A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 mg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Results Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Conclusions Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. Clinical Relevance These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bonehealing is problematic.

Ability of recombinant human bone morphogenetic protein 2 to enhance bone healing in the presence of tobramycin : evaluation in a rat segmental defect model

Objective To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur. Methods The influence of tobramycin on the osteogenic differentiation of mesenchymal stem cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 μg)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing. Results Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stem cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin. Conclusions Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stem cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.

Interpreting and comparing risks in the presence of competing events

Competing events are common in medical research. Ignoring them in the statistical analysis can easily lead to flawed results and conclusions. This article uses a real dataset and a simple simulation to show how standard analysis fails and how such data should be analysed

The presence of ultrasonic harmonics in the calls of the rifleman (Acanthisitta chloris)

Ultrasonic vocalisations (frequencies > 20 kHz) have been extensively studied in the context of echolocation by bats and other mammals (Sales & Pye 1974; Wilson & Hare 2004). Ultrasonic calls have also been recorded from birds, including the blue-throated hummingbird ( Lampornis clemenciae ) (Pytte et al. 2004), where it was first thought that individuals made use of high pitch calls to avoid masking by background noise in a visually obscured environment. Similarly, city-dwelling great tits ( Parus major ) use song with a higher minimum frequency (although not ultrasonic) compared to woodland birds to communicate with conspecifics to avoid the predominantly low-frequency background noise in the city (Slabbekorn & Peet 2003). The theory that birds use ultrasound to avoid noise masking was discarded when it was discovered that there was no corresponding auditory brainstem response (i.e. sensory perception) to the ultrasonic calls in the hummingbirds producing those calls.

FGF-2 induces the proliferation of human periodontal ligament cells and modulates their osteoblastic phenotype by affecting Runx2 expression in the presence and absence of osteogenic inducers

The exact phenotype of human periodontal ligament cells (hPDLCs) remains a controversial area. Basic fibroblast growth factor (FGF‑2) exhibits various functions and its effect on hPDLCs is also controversial. Therefore, the present study examined the effect of FGF‑2 on the growth and osteoblastic phenotype of hPDLCs with or without osteogenic inducers (dexamethasone and β‑glycerophosphate). FGF‑2 was added to defined growth culture medium and osteogenic inductive culture medium. Cell proliferation, osteogenic differentiation and mineralization were measured. The selected differentiation markers, Runx2, collagen type Ⅰ, α1 (Col1a1), osteocalcin (OCN) and epidermal growth factor receptor (EGFR), were investigated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Runx2 and OCN protein expression was measured by western blotting. FGF‑2 significantly increased the proliferation of hPDLCs, but did not affect alkaline phosphatase activity. RT‑qPCR analysis revealed enhanced mRNA expression of Runx2, OCN and EGFR, but suppressed Col1a1 gene expression in the absence of osteogenic inducers, whereas all these gene levels had no clear trend in their presence. The Runx2 protein expression was clearly increased, but the OCN protein level showed no evident trend. The mineralization assay demonstrated that FGF‑2 inhibited mineralized matrix deposition with osteogenic inducers. These results suggested that FGF‑2 induces the growth of immature hPDLCs, which is a competitive inhibitor of epithelial downgrowth, and suppresses their differentiation into mineralized tissue by affecting Runx2 expression. Therefore, this may lead to the acceleration of periodontal regeneration.

Stochastic analysis of a radial-inflow turbine in the presence of parametric uncertainties

This paper presents an uncertainty quantification study of the performance analysis of the high pressure ratio single stage radial-inflow turbine used in the Sundstrand Power Systems T-100 Multi-purpose Small Power Unit. A deterministic 3D volume-averaged Computational Fluid Dynamics (CFD) solver is coupled with a non-statistical generalized Polynomial Chaos (gPC) representation based on a pseudo-spectral projection method. One of the advantages of this approach is that it does not require any modification of the CFD code for the propagation of random disturbances in the aerodynamic and geometric fields. The stochastic results highlight the importance of the blade thickness and trailing edge tip radius on the total-to-static efficiency of the turbine compared to the angular velocity and trailing edge tip length. From a theoretical point of view, the use of the gPC representation on an arbitrary grid also allows the investigation of the sensitivity of the blade thickness profiles on the turbine efficiency. The gPC approach is also applied to coupled random parameters. The results show that the most influential coupled random variables are trailing edge tip radius coupled with the angular velocity.

Financially optimized scheduling of electric energy storage in presence of renewable energy resources

The increasing integration of Renewable Energy Resources (RER) and the role of Electric Energy Storage (EES) in distribution systems has created interest in using energy management strategies. EES has become a suitable resource to manage energy consumption and generation in smart grid. Optimize scheduling of EES can also maximize retailer’s profit by introducing energy time-shift opportunities. This paper proposes a new strategy for scheduling EES in order to reduce the impact of electricity market price and load uncertainty on retailers’ profit. The proposed strategy optimizes the cost of purchasing energy with the objective of minimizing surplus energy cost in hedging contract. A case study is provided to demonstrate the impact of the proposed strategy on retailers’ financial benefit.

The presence of executive deficits in patients with Obstructive Sleep Apnoea

Obstructive sleep apnoea (OSA) is a chronic condition in which the upper airways collapse repeatedly during sleep, completely or partially obstructing breathing. This obstruction leads to chronic intermittent hypoxia and severe sleep fragmentation, disrupting the restorative functions of sleep. Beebe and Gozal (2002)a developed a theory which hypothesises that disruption of the restorative functions of sleep lead to a chronic low level brain damage most evident in executive functions (EF). Neuropsychological testing of EF, volumetric MRI, magnetic resonance spectroscopy, event related potentials and CSF biomarkers all provide support for this theory. Little research has been done to explore the nature of the subjective complaint and it’s impact on the activities of daily living.

A novel fluorescent probe involving a graphene quantum dot-enzyme hybrid system for the analysis of hydroquinone in the presence of toxic resorcinol and catechol

An efficient method for the analysis of hydroquinone at trace levels in water samples has been developed in the form of a fluorescent probe based on graphene quantum dots (GQDs). The analytical variable, fluorescence quenching, was generated from the formation of benzoquinone intermediates, which formed during the catalytic oxidation of hydroquinone by horseradish peroxidase (HRP). In general, the reaction mechanism involved hydroquinone, as an electron acceptor, which affected the surface state of GQDs via an electron transfer effect. The water-soluble GQDs were directly prepared by the pyrolysis of citric acid and with the use of the mentioned hybrid enzyme system, the detection limit for hydroquinone was as low as 8.4 × 10−8 M. Furthermore, this analysis was almost unaffected by other phenol and quinine compounds, such as phenol, resorcinol and other quinines, and therefore, the developed GQD method produced satisfactory results for the analysis of hydroquinone in several different lake water samples.

Structure matters: Adoption of structured classification Approach in the context of cognitive presence classification

Within online learning communities, receiving timely and meaningful insights into the quality of learning activities is an important part of an effective educational experience. Commonly adopted methods – such as the Community of Inquiry framework – rely on manual coding of online discussion transcripts, which is a costly and time consuming process. There are several efforts underway to enable the automated classification of online discussion messages using supervised machine learning, which would enable the real-time analysis of interactions occurring within online learning communities. This paper investigates the importance of incorporating features that utilise the structure of on-line discussions for the classification of "cognitive presence" – the central dimension of the Community of Inquiry framework focusing on the quality of students' critical thinking within online learning communities. We implemented a Conditional Random Field classification solution, which incorporates structural features that may be useful in increasing classification performance over other implementations. Our approach leads to an improvement in classification accuracy of 5.8% over current existing techniques when tested on the same dataset, with a precision and recall of 0.630 and 0.504 respectively.

Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis

The objective of this study was to investigate TNF promoter region polymorphisms for association with susceptibility to ankylosing spondylitis (AS). The TNF -238 and -308 polymorphisms were genotyped in 306 English AS cases and 204 ethnically matched healthy B27-positive controls, and 96 southern German AS cases, 58 B27-positive and 251 B27-negative ethnically matched controls. Additionally, the TNF -376 polymorphism was genotyped in the southern German cases and controls. In the southern German AS patients a significant reduction in TNF -308.2 alleles was seen, compared with B27 positive controls (odds ratio 0.4, P= 0.03, 95% confidence interval 0.2-0.9), but no difference in allele frequencies was observed at TNF -238. Significant association between AS and both TNF -238 and TNF -308 was excluded in the English cases. These results confirm previous observations in the southern German population of association between TNF promoter region polymorphisms and AS, but the lack of association in the English population suggests that these polymorphisms themselves are unlikely to be directly involved. More likely, a second, non-HLA-B, MHC locus is involved in susceptibility to AS in these two populations.

Soft-particle model analysis of effect of LPS on electrophoretic softness of Acidithiobacillus ferrooxidans grown in presence of different metal ions

The effect of Surface lipopolysaccharides (LPS) on the electrophoretic softness and fixed charge density in the ion-penetrable layer of Acidithiobacillus ferrooxidans cells grown in presence of copper or arsenic ions have been discussed, The electrophoretic mobility data were analyzed using the soft-particle electrophoresis theory. Cell surface potentials of all the strains based on soft-particle theory were lower than those estimated using the conventional Smoluchowski theory, Exposure to metal ions increased the Surface electrophoretic softness with decrease in the fixed charge density. Effect of cell surface lipopolysaccharides on the model parameters are investigated and discussed.