Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis

Objectives This prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). Methods Thirty patients with inducible perfusion abnormalities on standard (caffeine-abstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. Results Despite significant increases in caffeine [mean difference 3,106 μg/L (95% CI 2,460 to 3,752 μg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change −0.003 for every 100 μg/L increase; 95% CI −0.17 to 0.16; P = .97). Conclusion There was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI—based on limited studies—appear ill-founded.

The persistence of phase-separation in LiFePO4 with two-dimensional Li+ transport : the Cahn-Hilliard-reaction equation and the role of defects

We examine the solution of the two-dimensional Cahn-Hilliard-reaction (CHR) equation in the xy plane as a model of Li+ intercalation into LiFePO4 material. We validate our numerical solution against the solution of the depth-averaged equation, which has been used to model intercalation in the limit of highly orthotropic diffusivity and gradient penalty tensors. We then examine the phase-change behaviour in the full CHR system as these parameters become more isotropic, and find that as the Li+ diffusivity is increased in the x direction, phase separation persists at high currents, even in small crystals with averaged coherency strain included. The resulting voltage curves decrease monotonically, which has previously been considered a hallmark of crystals that fill homogeneously.

Influence of pre-exsiting surface defects on the vibrational properties of Ag nanowires

Large-scale molecular dynamics simulations are performed to characterize the effects of pre-existing surface defects on the vibrational properties of Ag nanowires. It is found that the first order natural frequency of the nanowire appears insensitive to different surface defects, indicating a defect insensitivity property of the nanowire’s Young’s modulus. In the meanwhile, an increase of the quality (Q)-factor is observed due to the presence of defects. Particular, a beat phenomenon is observed for the nanowire with the presence of a surface edge defect, which is driven by a single actuation. It is concluded that different surface defects could act as an effective mean to tune the vibrational properties of nanowires. This study sheds lights on the better understanding of nanowire’s mechanical performance when surface defects are presented, which would benefit the development of nanowire-based devices.

Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical-sized segmental tibial bone defects in aged sheep

Mesenchymal progenitor cells (MPCs) represent an attractive cell population for bone tissue engineering. Their special immunological characteristics suggest that MPCs may be used in an allogenic application. The objective of this study was to compare the regenerative potential of autologous vs. allogenic MPCs in an ovine critical-sized segmental defect model. Ovine MPCs were isolated from bone marrow aspirates, expanded and cultured with osteogenic media for two weeks before implantation. Autologous and allogenic transplantation was performed by using the cell-seeded scaffolds, unloaded scaffolds and the application of autologous bone grafts served as control groups (n=6). Bone healing was assessed twelve weeks after surgery by radiology, micro computed tomography, biomechanical testing and histology. Radiology, biomechanical testing and histology revealed no significant difference in bone formation between the autologous and allogenic group. Both cell groups showed more bone formation than the scaffold alone, whereas the biomechanical data showed no significant differences between the cell-groups and the unloaded scaffolds. The results of the study suggest that scaffold based bone tissue engineering using allogenic cells offers the potential for an off the shelf product. Therefore, the results of this study serve as an important baseline for the translation of the assessed concepts into clinical application.

Quantitative and qualitative assessment of the regenerative potential of osteoblasts versus bone marrow derived mesenchymal stem cells in the reconstruction of critical sized segmental tibial bone defects in a large animal model

This thesis is about the use of different cells for bone tissue engineering. The cells were used in combination with a novel biomaterial in a large tibial bone defects in a sheep model. Furthermore this study developed a novel cell delivery procedure for bone tissue engineering. This novel procedure of cell delivery could overcome the current problems of cell-based tissue engineering and serve as a baseline for the translation of novel concepts into clinical application.

Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

Bending properties of Ag nanowires with pre-existing surface defects

Materials used in the engineering always contain imperfections or defects which significantly affect their performances. Based on the large-scale molecular dynamics simulation and the Euler–Bernoulli beam theory, the influence from different pre-existing surface defects on the bending properties of Ag nanowires (NWs) is studied in this paper. It is found that the nonlinear-elastic deformation, as well as the flexural rigidity of the NW is insensitive to different surface defects for the studied defects in this paper. On the contrary, an evident decrease of the yield strength is observed due to the existence of defects. In-depth inspection of the deformation process reveals that, at the onset of plastic deformation, dislocation embryos initiate from the locations of surface defects, and the plastic deformation is dominated by the nucleation and propagation of partial dislocations under the considered temperature. Particularly, the generation of stair-rod partial dislocations and Lomer–Cottrell lock are normally observed for both perfect and defected NWs. The generation of these structures has thwarted attempts of the NW to an early yielding, which leads to the phenomenon that more defects does not necessarily mean a lower critical force.

The role of defects, or active states, in surface electrochemistry with particular reference to gold in neutral solution

Metastable, active, or nonequilibrium states due to the presence of abnormal structures and various types of defects are well known in metallurgy. The role of such states at gold surfaces in neutral aqueous media (an important electrode system in the microsensor area) was explored using cyclic voltammetry. It was demonstrated that, as postulated in earlier work from this laboratory, there is a close relationship between premonolayer oxidation, multilayer hydrous oxide reduction and electrocatalytic behaviour in the case of this and other metal electrode systems. Some of the most active, and therefore most important, entities at surfaces (e.g., metal adatoms) are not readily imageable or detectable by high resolution surface microscopy techniques. Cyclic voltammetry, however, provides significant, though not highly specific, information about such species. The main conclusion is that further practical and theoretical work on active states of metal surfaces is highly desirable as their behaviour is not simple and is of major importance in many electrocatalytic processes.

Effect of defects on fracture strength of graphene sheets

With a hexagonal monolayer network of carbon atoms, graphene has demonstrated exceptional electrical 22 and mechanical properties. In this work, the fracture of graphene sheets with Stone–Wales type defects and vacancies were investigated using molecular dynamics simulations at different temperatures. The initiation of defects via bond rotation was also investigated. The results indicate that the defects and vacancies can cause significant strength loss in graphene. The fracture strength of graphene is also affected by temperature and loading directions. The simulation results were compared with the prediction from the quantized fracture mechanics.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.

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.

Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage

We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified (“gene activated”) tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.

Reconstruction of critical-sized ovine mandibular defects - a pilot study

Establishing the sheep model for translational research of mandible (jaw) segmental defect regeneration. Providing a framework from which additional experimentation and evaluation of novel tissue engineered constructs may be undertaken, compared and collated. For current and future novel approaches to mandible segmental defect reconstruction that may be transferable to the human condition and, ultimately, the operative table.

Defects induced ferromagnetism in plasma-enabled graphene nanopetals

Ferromagnetism in graphene is fascinating, but it is still a big challenge for practical applications due to the weak magnetization. In order to enhance the magnetization, here, we design plasma-enabled graphene nanopetals with ultra-long defective edges of up to 105 m/g, ultra-dense lattice vacancies, and hydrogen chemisorptions. The designed graphene nanopetals display robust ferromagnetism with large saturation magnetization of up to 2 emu/g at 5 K and 1.2 emu/g at room temperatures. This work identifies the plasma-enabled graphene nanopetals as a promising candidate for graphene-based magnetic devices.

Harnessing the influence of reactive edges and defects of graphene substrates for achieving complete cycle of room-temperature molecular sensing

Molecular doping and detection are at the forefront of graphene research, a topic of great interest in physical and materials science. Molecules adsorb strongly on graphene, leading to a change in electrical conductivity at room temperature. However, a common impediment for practical applications reported by all studies to date is the excessively slow rate of desorption of important reactive gases such as ammonia and nitrogen dioxide. Annealing at high temperatures, or exposure to strong ultraviolet light under vacuum, is employed to facilitate desorption of these gases. In this article, the molecules adsorbed on graphene nanoflakes and on chemically derived graphene-nanomesh flakes are displaced rapidly at room temperature in air by the use of gaseous polar molecules such as water and ethanol. The mechanism for desorption is proposed to arise from the electrostatic forces exerted by the polar molecules, which decouples the overlap between substrate defect states, molecule states, and graphene states near the Fermi level. Using chemiresistors prepared from water-based dispersions of single-layer graphene on mesoporous alumina membranes, the study further shows that the edges of the graphene flakes (showing p-type responses to NO2 and NH3) and the edges of graphene nanomesh structures (showing n-type responses to NO2 and NH3) have enhanced sensitivity. The measured responses towards gases are comparable to or better than those which have been obtained using devices that are more sophisticated. The higher sensitivity and rapid regeneration of the sensor at room temperature provides a clear advancement towards practical molecule detection using graphene-based materials.