Retardation of atherosclerosis in immunocompetent apolipoprotein (apo) E-deficient mice followingliver-directed administration of a [E1-, E3-,polymerase-] adenovirus vector containing the elongation factor-1a promoter driving expression of human apoE cDNA

Although gene transfer of human apolipoprotein E (apoE), a 34-kDa circulating glycoprotein, to the liver of apoEdeficient(apoE-/-) mice using recombinant adenoviral vectors (rAd) is antiatherogenic, its full therapeutic potentialhas yet to be realized. First generation vectors led to immune clearance of transduced hepatocytes, while animproved vector with adenovirus regions E1, E3 and DNA polymerase deleted also had transient effects due tocellular shutdown of the cytomegalovirus (CMV) promoter. Here, we have studied an alternative promoter from thecellular elongation factor 1a (EF-1a) gene, injecting 6-8 week old apoE-/- mice intravenously with 2x1010 virusparticles (vp) of the [E1-, E3-, polymerase-] rAd vector Ad-EF1·-apoE. Plasma apoE levels were low (18-55 ng/ml)and failed to reduce plasma cholesterol or normalize the adverse lipoprotein profile. By contrast, thehyperlipidaemic phenotype of apoE-/- mice treated with Ad-CMV-apoE (2x1010 vp) was transiently normalized.Nevertheless, at termination (265 days) the aortic lesion areas in animals given Ad-EF1·-apoE were significantlyreduced by 15% (P<0.05) compared to untreated animals, a decrease approaching that in Ad-CMV-apoE-treatedmice (23%; P<0.02). Importantly, the attenuation of apoE transgene expression noted with the CMV promoter wasabsent with the EF-1a promoter, which gave relatively sustained, albeit low, levels of plasma apoE throughout thestudy period

Negative pressure wound therapy for managementof the surgical incision in orthopaedic surgery: A review of evidence and mechanisms for an emerging indication.

OBJECTIVES: The period of post-operative treatment before surgical wounds are completely closed remains a key window, during which one can apply new technologies that can minimise complications. One such technology is the use of negative pressure wound therapy to manage and accelerate healing of the closed incisional wound (incisional NPWT). METHODS: We undertook a literature review of this emerging indication to identify evidence within orthopaedic surgery and other surgical disciplines. Literature that supports our current understanding of the mechanisms of action was also reviewed in detail. RESULTS: A total of 33 publications were identified, including nine clinical study reports from orthopaedic surgery; four from cardiothoracic surgery and 12 from studies in abdominal, plastic and vascular disciplines. Most papers (26 of 33) had been published within the past three years. Thus far two randomised controlled trials - one in orthopaedic and one in cardiothoracic surgery - show evidence of reduced incidence of wound healing complications after between three and five days of post-operative NPWT of two- and four-fold, respectively. Investigations show that reduction in haematoma and seroma, accelerated wound healing and increased clearance of oedema are significant mechanisms of action. CONCLUSIONS: There is a rapidly emerging literature on the effect of NPWT on the closed incision. Initiated and confirmed first with a randomised controlled trial in orthopaedic trauma surgery, studies in abdominal, plastic and vascular surgery with high rates of complications have been reported recently. The evidence from single-use NPWT devices is accumulating. There are no large randomised studies yet in reconstructive joint replacement. Cite this article: Bone Joint Res 2013;2:276-84.The authors are members of an Expert Panel on incisional NPWT in orthopaedic surgery funded by Smith & Nephew

Modelling the evaporation of thin films of colloidal suspensions using Dynamical Density Functional Theory

Recent experiments have shown that various structures may be formed during the evaporative dewetting of thin films of colloidal suspensions. Nano-particle deposits of strongly branched `flower-like', labyrinthine and network structures are observed. They are caused by the different transport processes and the rich phase behaviour of the system. We develop a model for the system, based on a dynamical density functional theory, which reproduces these structures. The model is employed to determine the influences of the solvent evaporation and of the diffusion of the colloidal particles and of the liquid over the surface. Finally, we investigate the conditions needed for `liquid-particle' phase separation to occur and discuss its effect on the self-organised nano-structures

Microstructural and environmental effects on stress corrosion and corrosion fatigue of 7075 aluminum alloy

The design and development of high performance structural materials requires a thorough understanding of the relationship between environment, mechanical stresses, microstructure, and properties. The corrosion and fatigue behavior of aluminum alloys is greatly influenced by environment and precipitate structure. A comprehensive, mechanistic understanding of the role of environment on cyclic fatigue of Al alloys is needed. The relationship between environmental and mechanical effects is not well understood. The driving force at the crack tip is clearly a combination of chemical and mechanical processes operating together. A synergy between these processes is also present. In this talk, the role of moisture on stress corrosion and corrosion-fatigue of 7075 Al alloy will be presented. Rolled 7075 Al alloy was heat-treated to underaged, peak-aged, and overaged conditions. To investigate the effects of corrosion and fatigue on peak-aged 7075 aluminum alloy, corroded samples were tested via in situ x-Ray tomography. The samples were mechanically polished, then soaked in covered 3.5 wt.% NaCl for fifteen days to allow for significant corrosion to occur. Then, they were fatigue tested in situ in 3.5 wt.% NaCl using synchrotron x-ray tomography to analyze the fatigue crack initiation and growth characteristics. Hydrogen bubbles were observed between the sample and the fluid upon crack initiation, indicating chemical changes in the sample during in situ corrosion fatigue. The effect of oxide layers forming during corrosion and 2nd phase inclusions, on fatigue initiation and propagation, will be discussed. The microstructure and morphology of the fracture surfaces were examined by scanning electron microscopy (SEM) and correlated with the crack growth behavior. The crack initiation, growth, and damage were also quantified by sophisticated three dimensional (3D) in situ x-ray synchrotron tomography technique. This technique provided interesting insights into the onset of crack initiation and growt

A third of patients treated at a tertiary-level surgical service could be treated at a secondary-level facility

Background. South Africa (SA) has an overburdened public healthcare system. Some patients admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), SA, may not require tertiary care, but the numbers and details are uncertain. Clinical research in SA is limited by scarce skills and limited access to data.Objective. To determine the proportion of and length of stay for secondary-, tertiary- and quaternary-level patients discharged from the Department of Surgery at CMJAH over 1 year.Methods. This is a retrospective analysis of electronic discharge (ED) summaries from the Department of Surgery at CMJAH between 1 April 2015 and 1 April 2016. An SQL query of the database generated a .csv file of all discharges with the following fields: database reference number, length of stay and level of care. The details of each record were verified by MBBCh V students, using a defined level-ofcare template and the full discharge summary. The data were reviewed by a senior clinician.Results. There were 3 007 discharge summaries – 97 were not classifiable, two were test records and one was a duplicate. These 100 records were excluded. There were no primary-level records. Secondary-level patients represented 29% (854) of those discharged and 19% of total bed days. Tertiary- and quaternary-level patients together represented 71% of the total and 81% of bed days. The average length of stay was 4.31 days for secondary, 6.98 days for tertiary and 9.77 days for quaternary level-of-care allocation.Conclusion. Almost one-third (29%) of patients discharged from CMJAH’s Department of Surgery were deemed suitable for secondarylevel care. These patients had a shorter length of stay and comprised 19% of total bed days. Students and electronic databases represent an important research resource

Competition of stress corrosion crack branches observed in-situ using time-lapse 3D x-ray synchrotron computed tomography

The progress of a stress corrosion crack in a sensitized AA7075 alloy was studied by in-situ x-ray synchrotron computed tomography. A load was applied to a pre-cracked specimen inside an environmental cell containing moist air and the propagation of the stress corrosion crack was observed. Measurements from the 3D image of the crack have already been shown to provide better quantification compared to observations of the crack from the outer surface. In this paper we study in detail the progress of the stress corrosion crack as it propagates through the material. We reveal how the formation of metal ligaments occurs and the competition of the ‘main’ crack and its branches. We have visualized these features to show the complexity of the local variation in crack morphology in a way that brings new insight into the interaction of the stress corrosion crack with the microstructure of the material

In situ three-dimensional study of corrosion fatigue crack initiation and growth of corroded 7075 aluminum alloys

Corrosion fatigue crack initiation in aluminum alloys can have significant effects on part life. An improved understanding of the mechanisms governing corrosion and corrosion fatigue damage of Al alloys is necessary. Alloy design and environmental chemistry have significant effects on corrosion fatigue crack initiation and growth. Influential alloy design features include alloy chemistry, precipitate structure, and grain structure. Environmental factors such as environmental chemistry and preexisting corrosion damage can also effect the corrosion fatigue behavior of the alloys. To investigate the effects of environment and precipitate size on corrosion fatigue of aluminum alloys, the in situ corrosion fatigue testing of corroded peak-aged and overaged 7075 Al alloys in 3.5 wt% NaCl solution will be presented. For this study, rolled 7075 Al alloy was heat-treated to peak-aged, overaged, and highly overaged conditions. The samples were machined, mechanically polished, masked, and then soaked in 3.5 wt.% NaCl solution for fifteen days to yield significant corrosion damage in a region of interest. The corroded specimens were fatigue tested in situ in 3.5 wt.% NaCl using synchrotron X-ray tomography to gain three dimensional information regarding fatigue crack initiation and growth characteristics. Hydrogen bubbles were observed within the crack during propagation, indicating chemical changes in the sample during corrosion fatigue. The crack initiation, growth, and bubble evolution were quantified and discussed. A relationship was observed between the bubble volume and crack surface area as the test progressed, which suggested an effect from stress at the crack tip. Ultimately, this in situ study provided new insights regarding the localized processes occurring during the corrosion fatigue cracking of aluminum alloys which previous post-mortem and two dimensional studies were unable to discover

ciliaFA : a research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software

Background: Analysis of ciliary function for assessment of patients suspected of primary ciliary dyskinesia (PCD) and for research studies of respiratory and ependymal cilia requires assessment of both ciliary beat pattern and beat frequency. While direct measurement of beat frequency from high-speed video recordings is the most accurate and reproducible technique it is extremely time consuming. The aim of this study was to develop a freely available automated method of ciliary beat frequency analysis from digital video (AVI) files that runs on open-source software (ImageJ) coupled to Microsoft Excel, and to validate this by comparison to the direct measuring high-speed video recordings of respiratory and ependymal cilia. These models allowed comparison to cilia beating between 3 and 52 Hz. Methods: Digital video files of motile ciliated ependymal (frequency range 34 to 52 Hz) and respiratory epithelial cells (frequency 3 to 18 Hz) were captured using a high-speed digital video recorder. To cover the range above between 18 and 37 Hz the frequency of ependymal cilia were slowed by the addition of the pneumococcal toxin pneumolysin. Measurements made directly by timing a given number of individual ciliary beat cycles were compared with those obtained using the automated ciliaFA system. Results: The overall mean difference (± SD) between the ciliaFA and direct measurement high-speed digital imaging methods was −0.05 ± 1.25 Hz, the correlation coefficient was shown to be 0.991 and the Bland-Altman limits of agreement were from −1.99 to 1.49 Hz for respiratory and from −2.55 to 3.25 Hz for ependymal cilia. Conclusions: A plugin for ImageJ was developed that extracts pixel intensities and performs fast Fourier transformation (FFT) using Microsoft Excel. The ciliaFA software allowed automated, high throughput measurement of respiratory and ependymal ciliary beat frequency (range 3 to 52 Hz) and avoids operator error due to selection bias. We have included free access to the ciliaFA plugin and installation instructions in Additional file 1 accompanying this manuscript that other researchers may use