Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies.

It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies

Bacterial microevolution and the Pangenome

The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history

Using Intervention Mapping to develop an occupational advice intervention to aid return to work following hip and knee replacement in the United Kingdom

Background There are increasing numbers of total hip replacements (THR) and total knee replacements (TKR) being performed in patients of working age. Providing patients undergoing TKR and THR with return to work advice might facilitate return to work. The aim of this paper is to report on the process used to systematically develop an occupational advice intervention to be delivered in hospital for those undergoing arthroplasty. Methods The six-step Intervention Mapping (IM) approach to development, implementation and evaluation of a theory and evidence-based interventions was followed. This paper reports on the development of the intervention covered by steps 1 to 4 of the IM process. Steps 1-3 gathered data on current practice and barriers to change using a mixed methods approach (cohort study of patients undergoing THR or TKR, stakeholder interviews, survey of practice, evidence synthesis) and provided a theoretical framework for intervention development. Step 4 used information from steps 1-3 in combination with a Delphi consensus process to develop the intervention and the associated tools and materials to facilitate its delivery. Results The final intervention identified included a number of core principles including: early patient identification; delivery of key information to patients and their employers; assessment and support by a member of the orthopaedic team; procedures for escalation based on patient need; mechanisms to support communication; and training and support for the clinical teams delivering care. A total of 13 patient and 20 staff performance objectives as delivery requirements, supported by a range of tools, roles and training resources. The intervention addressed outcomes based at the individual and interpersonal levels of the ecological model. Conclusions Following the IM approach resulted in a structured and justified occupational intervention for delivery in secondary care for patients undergoing total hip and knee replacement. The feasibility of the intervention will subsequently be tested alongside further investigation to establish its effectiveness and cost-effectiveness. Key Words Intervention Mapping Return to Work Occupational advice Arthroplasty Hip Kne

Renin, endothelial no synthase and endothelin gene expression in the 2Kidney-1clip goldblatt model of long-term renovascular hypertension

<p>Abstract</p> <p>Objective</p> <p>Numerous reports have shown the influence of renin, nitric oxide (NO) and the endothelin (ET) systems for regulation of blood pressure and renal function. Furthermore, interactions between these peptides have been reported. Aim of our study was to investigate the relative contribution of these compounds in long-term renovascular hypertension/renal ischemia.</p> <p>Methods</p> <p>Hypertension/left-sided renal ischemia was induced using the 2K1C-Goldblatt rat model. Renal renin, ET-1, ET-3 and endothelial NO synthase (eNOS) gene expression was measured by means of RNAse protection assay at different timepoints up to 10 weeks after induction of renal artery stenosis.</p> <p>Results</p> <p>Plasma renin activity and renal renin gene expression in the left kidney were increased in the clipped animals while eNOS expression was unchanged. Furthermore, an increase in ET-1 expression and a decrease of ET-3 expression was detected in early stenosis.</p> <p>Conclusions</p> <p>While renin is obviously involved in regulation of blood pressure and renal function in unilateral renal artery stenosis, ET-1, ET-3 and endothelium derived NO do not appear to play an important role in renal adaptation processes in long-term renal artery stenosis, although ET-1 and ET-3 might be involved in short-term adaptation processes.</p

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

Femoral revision knee Arthroplasty with Metaphyseal sleeves: the use of a stem is not mandatory of a structural point of view

Purpose Metaphyseal sleeves are an option for patients with severe metaphyseal bony defects requiring TKA revision. Although sleeves are usually used with stems, little is known about the exact contribution/need of the stem for the initial sleeve-bone interface stability, particularly in the femur, if the intramedullary canal is deformed or bowed. It is hypothesised that diaphyseal-stem addition increases the sleeve-femur interface stability and the strain-shielding effect on the metaphyseal femur relatively to the stemless condition. Material and methods Synthetic-femur was used to measure cortex strain behaviour and implant cortex micromotions for three techniques: only femoral-component, stemless-sleeve and stemmed-sleeve. Paired t-tests were performed to evaluate the statistical significance of the difference between mean principal strains and implant-cortex micromotions. Finite-element models were developed to assess the cancellous-bone strain behaviour and sleeve-bone interface micromotions; these models were validated against the measurements. Results Cortex strains are reduced significantly (p<0.05) in 83% of strain gauges on stemmed-sleeve, which compares with 33% in stemless condition. Both techniques presented a cancellous bone strain reduction of 50% at the distal region and an increase of nearly four times at the sleeve proximal region relative to the model only with the femoral component. Both techniques presented sleeve-bone micromotions amplitude below 50-150μm, suitable for bone ingrowth. Conclusions The use of a supplemental diaphyseal-stem potentiates the risk of cortex bone resorption compared with the stemless-sleeve condition; however, the stem is not vital for increasing the initial sleeve-bone stability and has a minor effect on the cancellous-bone strain behaviour. Of a purely structural point view, appears that the use of a diaphyseal-femoral-stem with the metaphyseal sleeve is not mandatory in the revision TKA which is particularly relevant in cases where the use of stems is impracticable.publishe

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

Processing and analyzing multiple genomes alignments with MafFilter

As the number of available genome sequences from both closely related species and individuals withinspecies increased, theoretical and methodological convergences between the fields of phylogenomics andpopulation genomics emerged. Population genomics typically focuses on the analysis of variants, whilephylogenomics heavily relies on genome alignments. However, these are playing an increasingly importantrole in studies at the population level. Multiple genome alignments of individuals are used when structuralvariation is of primary interest and when genome architecture permits to assemblede novogenomesequences. Here I describe MafFilter, a command-line-driven program allowing to process genome align-ments in the Multiple Alignment Format (MAF). Using concrete examples based on publicly availabledatasets, I demonstrate how MafFilter can be used to develop efficient and reproducible pipelines withquality assurance for downstream analyses. I further show how MafFilter can be used to perform both basicand advanced population genomic analyses in order to infer the patterns of nucleotide diversity alonggenomes

Identification of diagnostic serum protein profiles of glioblastoma patients

Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and is based on cerebral imaging and histological examination. Serum-based biomarkers may support detection of GBM. Here, we explored serum protein concentrations of GBM patients and used data mining to explore profiles of biomarkers and determine whether these are associated with the clinical status of the patients. Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differently expressed in tumors and in normal brain tissues. Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects. Data-mining methods involving all 14 proteins were used as an initial evaluation step to find clinically informative profiles. Data mining identified a serum protein profile formed by BMP2, HSP70, and CXCL10 that enabled correct assignment to the GBM group with specificity and sensitivity of 89 and 96%, respectively (p < 0.0001, Fischer’s exact test). Survival for more than 15 months after tumor resection was associated with a profile formed by TSP1, HSP70, and IGFBP3, enabling correct assignment in all cases (p < 0.0001, Fischer’s exact test). No correlation was found with tumor size or age of the patient. This study shows that robust serum profiles for GBM may be identified by data mining on the basis of a relatively small study cohort. Profiles of more than one biomarker enable more specific assignment to the GBM and survival group than those based on single proteins, confirming earlier attempts to correlate single markers with cancer. These conceptual findings will be a basis for validation in a larger sample size

Whole brain radiotherapy with radiosensitizer for brain metastases

<p>Abstract</p> <p>Purpose</p> <p>To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment.</p> <p>Methods</p> <p>A meta-analysis of randomized controlled trials (RCT) was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently.</p> <p>Results</p> <p>A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77). Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03) and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3) when the two arms were compared.</p> <p>Conclusion</p> <p>Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide), have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast) to have positive action in lung and breast carcinoma brain metastases in association with WBRT.</p