Treatment of Failed Allograft Prosthesis Composites Used for Hip Arthroplasty in the Setting of Severe Proximal Femoral Bone Defects

This study assessed failures of allograft prosthesis composites (APC) and revisions with a new APC. Twenty-one patients with failed APC’s after revision hip arthroplasty with severe proximal femoral bone loss underwent revision with a new APC. Causes of failure were aseptic loosening (18 patients), infection (3 patients). Of these 21 APC revisions, two patients failed (after 60, 156 months). The 5 and 10 year survival rates were 83.5% (95% CI, 79–100%, number at risk 12 and 6 accordingly). In addition, two patients had non-union at the host-allograft bone junction and were augmented with bone autograft and plate. These results suggest that failed APCs may be revised to a new APC with a predictable outcome.     

Critical Dynamics of Defects and Mechanisms of Damage-Failure Transitions in Fatigue

An experimental methodology was developed for estimating a very high cycle fatigue (VHCF) life of the aluminum alloy AMG-6 subjected to preliminary deformation. The analysis of fatigue damage staging is based on the measurement of elastic modulus decrement according to “in situ” data of nonlinear dynamics of free-end specimen vibrations at the VHCF test. The correlation of fatigue damage staging and fracture surface morphology was studied to establish the scaling properties and kinetic equations for damage localization, “fish-eye” nucleation, and transition to the Paris crack kinetics. These equations, based on empirical parameters related to the structure of the material, allows us to estimate the number of cycles for the nucleation and advance of fatigue crack.     

Laser-driven structural transformations in dextran-graft-PNIPAM copolymer/Au nanoparticles hybrid nanosystem: the role of plasmon heating and attractive optical forces

Laser induced structural transformations in a dextran grafted-poly(N-isopropylacrylamide) copolymer/Au nanoparticles (D-g-PNIPAM/AuNPs) hybrid nanosystem in water have been observed. The laser induced local plasmonic heating of Au NPs leads to Lower Critical Solution Temperature (LCST) phase transition in D-g-PNIPAM/AuNPs macromolecules accompanied by their shrinking and aggregation. The hysteresis non-reversible character of the structural transformation in D-g-PNIPAM/AuNPs system has been observed at the decrease of laser intensity, i.e. the aggregates remains in solution after the turn-off the laser illumination. This is an essential difference comparing to the case of usual heating–cooling cycles when there is no formation of aggregates and structural transformations are reversible. Such a fundamental difference has been rationalized as the result of action of attractive optical forces arising due to the excitation of surface plasmons in Au NPs. The attractive plasmonic forces facilitate the formation of the aggregates and counteract their destruction. The laser induced structural transformations have been found to be very sensitive to matching conditions of the resonance of the laser light with surface plasmon resonance proving the plasmonic nature of observed phenomena.

Structural transformations in D-g-PNIPAM/AuNPs hybrid nanosystem arise from the synergetic action of plasmonic heating and attractive optical plasmonic forces.     

Phosphoinositide 3-kinase(p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy

An unresolved question in cardiac biology is whether distinct signaling pathways are responsible for the development of pathological and physiological cardiac hypertrophy in the adult. Physiological hypertrophy is characterized by a normal organization of cardiac structure and normal or enhanced cardiac function, whereas pathological hypertrophy is associated with an altered pattern of cardiac gene expression, fibrosis, cardiac dysfunction, and increased morbidity and mortality. The elucidation of signaling cascades that play distinct roles in these two forms of hypertrophy will be critical for the development of more effective strategies to treat heart failure. We examined the role of the p110alpha isoform of phosphoinositide 3-kinase (PI3K) for the induction of pathological hypertrophy (pressure overload-induced) and physiological hypertrophy (exercise-induced) by using transgenic mice expressing a dominant negative (dn) PI3K(p110alpha) mutant specifically in the heart. dnPI3K transgenic mice displayed significant hypertrophy in response to pressure overload but not exercise training. dnPI3K transgenic mice also showed significant dilation and cardiac dysfunction in response to pressure overload. Thus, PI3K(p110alpha) appears to play a critical role for the induction of physiological cardiac growth but not pathological growth. PI3K(p110alpha) also appears essential for maintaining contractile function in response to pathological stimuli.     

Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1

Human XPF-ERCC1 is a DNA endonuclease that incises a damaged DNA strand on the 5' side of a lesion during nucleotide excision repair and has additional role(s) in homologous recombination and DNA interstrand crosslink repair. We show that a truncated form of XPF lacking the N-terminal helicase-like domain in complex with ERCC1 exhibits a structure-specific endonuclease activity with similar specificity to that of full-length XPF-ERCC1. Two domains of ERCC1, a central domain and a C-terminal tandem helix-hairpin-helix (HhH2) dimerization domain, bind to ssDNA. The central domain of ERCC1 binds ssDNA/dsDNA junctions with a defined polarity, preferring a 5' single-stranded overhang. The XPF-ERCC1 HhH2 domain heterodimer contains two independent ssDNA-binding surfaces, which are revealed by a crystal structure of the protein complex. A crystal structure of the central domain of ERCC1 shows its fold is strikingly similar to that of the nuclease domains of the archaeal Mus81/XPF homologs, despite very low sequence homology. A groove lined with basic and aromatic residues on the surface of ERCC1 has apparently been adapted to interact with ssDNA. On the basis of these crystallographic and biochemical studies, we propose a model in which XPF-ERCC1 recognizes a branched DNA substrate by binding the two ssDNA arms with the two HhH2 domains of XPF and ERCC1 and by binding the 5'-ssDNA arm with the central domain of ERCC1.     

Glass carbomer and compomer for ART restorations: 3-year results of a randomized clinical trial

Clinical Oral Investigations - To evaluate the survival of atraumatic restorative treatment (ART) restorations using high viscosity glass ionomer cement (GIC), compomer (COM), and glass carbomer...     

Two-photon excitation improves multifocal structured illumination microscopy in thick scattering tissue

Multifocal structured illumination microscopy (MSIM) provides a twofold resolution enhancement beyond the diffraction limit at sample depths up to 50 µm, but scattered and out-of-focus light in thick samples degrades MSIM performance. Here we implement MSIM with a microlens array to enable efficient two-photon excitation. Two-photon MSIM gives resolution-doubled images with better sectioning and contrast in thick scattering samples such as Caenorhabditis elegans embryos, Drosophila melanogaster larval salivary glands, and mouse liver tissue.Fluorescence microscopy is an invaluable tool for biologists. Protein distributions in cells have an interesting structure down to the nanometer scale, but features smaller than 200–300 nm are blurred by diffraction in widefield and confocal fluorescence microscopes. Superresolution techniques like photoactivated localization microscopy (1), stochastic optical reconstruction microscopy (2), or stimulated emission depletion (STED) (3) microscopy allow the imaging of details beyond the limit imposed by diffraction, but usually trade acquisition speed or straightforward sample preparation. And although STED can provide resolution down to 40 nm, STED-specific fluorophores are recommended and it often requires light intensities that are orders of magnitude above widefield and confocal microscopy. On the other hand, structured illumination microscopy (SIM) (4) gives twice the resolution of a conventional fluorescence microscope with light intensities on the order of widefield microscopes and can be used with most common fluorophores. SIM uses contributions from both the excitation and emission point spread functions (PSFs) to substantially improve the transverse resolution and is generally performed by illuminating the sample with a set of sharp light patterns and collecting fluorescence on a multipixel detector, followed by image processing to recover superresolution detail from the interaction of the light pattern with the sample. A related technique, image scanning microscopy (ISM), uses a scanned diffraction-limited spot as the light pattern (5, 6). Multifocal SIM (MSIM) parallelizes ISM by using many excitation spots (7), and has been shown to produce optically sectioned images with ∼145-nm lateral and ∼400-nm axial resolution at depths up to ∼50 µm and at ∼1 Hz imaging frequency. In MSIM, images are excited with a multifocal excitation pattern, and the resulting fluorescence in the multiple foci are pinholed, locally scaled, and summed to generate an image [multifocal-excited, pinholed, scaled, and summed (MPSS)] with root 2-improved resolution relative to widefield microscopy, and improved sectioning compared with SIM due to confocal-like pinholing. Deconvolution is applied to recover the final MSIM image which has a full factor of 2 resolution improvement over the diffraction limit.MSIM works well in highly transparent samples (such as zebrafish embryos), but performance degrades in light scattering samples (such as the Caenorhabditis elegans embryo). Imaging in scattering samples can be improved by two-photon microscopy (8) and although the longer excitation wavelength reduces the resolution in nondescanned detection configurations, this can be partially offset by descanned detection and the addition of a confocal pinhole into the emission path. Whereas the nondescanned mode collects the most signal, the addition of a pinhole in the emission path of a point-scanning system can improve resolution when the pinhole is closed (9). In practice this is seldom done for biological specimens because signal-to-noise decays as the pinhole diameter decreases (9–11).SIM is an obvious choice in improving resolution without a dramatic loss in signal-to-noise, but the high photon density needed for efficient two-photon excitation is likely difficult to achieve in the typical widefield SIM configuration. This has led to other methods, such as line scanning (12) to achieve better depth penetration than confocal microscopy and up to twofold improvements in axial resolution (but with only ∼20% gain in lateral resolution). Multiphoton Bessel plane illumination (13) achieved an anisotropic lateral resolution of 180 nm (only in one direction) but requires an instrument design with two objectives in an orthogonal configuration. Cells and embryos can be readily imaged, but the multiaxis design may hinder the intravital imaging of larger specimens. Here, a combination of multiphoton excitation with MSIM is shown to improve both lateral and axial resolutions twofold compared with conventional multiphoton imaging while improving the sectioning and contrast of MSIM in thick, scattering samples.