Biofilm formation by bacteria isolated from retrieved failed prosthetic hip implants in an in vitro model of hip arthroplasty antibiotic prophylaxis

Bacterial infection primarily with Staphylococcus spp. and Propionibacterium acnes remains a significant complication following total hip replacement. In this in vitro study, we investigated the efficacy of gentamicin loading of bone cement and pre- and postoperative administration of cefuroxime in the prevention of biofilm formation by clinical isolates. High and low initial inocula, representative of the number of bacteria that may be present at the operative site as a result of overt infection and skin contamination, respectively, were used. When a high initial inoculum was used, gentamicin loading of the cement did not prevent biofilm formation by the 10 Staphylococcus spp. and the 10 P. acnes isolates tested. Similarly, the use of cefuroxime in the fluid phase with gentamicin-loaded cement did not prevent biofilm formation by four Staphylococcus spp. and four P. acnes isolates tested. However, when a low bacterial inoculum was used, a combination of both gentamicin-loaded cement and cefuroxime prevented biofilm formation by these eight isolates. Our results indicate that this antibiotic combination may protect against infection after intra-operative challenge with bacteria present in low numbers as a result of contamination from the skin but would not protect against bacteria present in high numbers as a result of overt infection of an existing implant.

Error sensitive historical GIS: Identifying areal interpolation errors in time series data

Historical GIS has the potential to re-invigorate our use of statistics from historical censuses and related sources. In particular, areal interpolation can be used to create long-run time-series of spatially detailed data that will enable us to enhance significantly our understanding of geographical change over periods of a century or more. The difficulty with areal interpolation, however, is that the data that it generates are estimates which will inevitably contain some error. This paper describes a technique that allows the automated identification of possible errors at the level of the individual data values.

Kinetics of phase transformations in a model with metastable fluid-fluid separation: A molecular dynamics study

By molecular dynamics (MD) simulations we study the crystallization process in a model system whose particles interact by a spherical pair potential with a narrow and deep attractive well adjacent to a hard repulsive core. The phase diagram of the model displays a solid-fluid equilibrium, with a metastable fluid-fluid separation. Our computations are restricted to fairly small systems (from 2592 to 10368 particles) and cover long simulation times, with constant energy trajectories extending up to 76x10(6) MD steps. By progressively reducing the system temperature below the solid-fluid line, we first observe the metastable fluid-fluid separation, occurring readily and almost reversibly upon crossing the corresponding line in the phase diagram. The nucleation of the crystal phase takes place when the system is in the two-fluid metastable region. Analysis of the temperature dependence of the nucleation time allows us to estimate directly the nucleation free energy barrier. The results are compared with the predictions of classical nucleation theory. The critical nucleus is identified, and its structure is found to be predominantly fcc. Following nucleation, the solid phase grows steadily across the system, incorporating a large number of localized and extended defects. We discuss the relaxation processes taking place both during and after the crystallization stage. The relevance of our simulation for the kinetics of protein crystallization under normal experimental conditions is discussed. (C) 2002 American Institute of Physics.

Systematic Usage of Embedded Modelling Languages in Automated Model Transformation Chains

Annotation of programs using embedded Domain-Specific Languages (embedded DSLs), such as the program annotation facility for the Java programming language, is a well-known practice in computer science. In this paper we argue for and propose a specialized approach for the usage of embedded Domain-Specific Modelling Languages (embedded DSMLs) in Model-Driven Engineering (MDE) processes that in particular supports automated many-step model transformation chains. It can happen that information defined at some point, using an embedded DSML, is not required in the next immediate transformation step, but in a later one. We propose a new approach of model annotation enabling flexible many-step transformation chains. The approach utilizes a combination of embedded DSMLs, trace models and a megamodel. We demonstrate our approach based on an example MDE process and an industrial case study.

Adrenomedullin Gene Delivery is Cardio-protective in a Model of Chronic Nitric Oxide Deficiency Combining Pressure Overload, Oxidative Stress and Cardiomyocyte Hypertrophy

BACKGROUND/AIMS:
Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial ischemia, oxidative stress and hypertrophy; expression of the vasodilator peptide, adrenomedullin (AM) and its receptors is augmented in cardiomyocytes, indicating that the myocardial AM system may be activated in response to pressure loading and ischemic insult to serve a counter-regulatory, cardio-protective role. The study examined the hypothesis that oxidative stress and hypertrophic remodeling in NO-deficient cardiomyocytes are attenuated by adenoviral vector-mediated delivery of the human adrenomedullin (hAM) gene in vivo.

METHODS:
The NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 15mg . kg(-1) . day(-1)) was given to rats for 4 weeks following systemic administration via the tail vein of a single injection of either adenovirus harbouring hAM cDNA under the control of the cytomegalovirus promoter-enhancer (Ad.CMV-hAM-4F2), or for comparison, adenovirus alone (Ad.Null) or saline. Cardiomyocytes were subsequently isolated for assessment of the influence of each intervention on parameters of oxidative stress and hypertrophic remodelling.

RESULTS: Cardiomyocyte expression of the transgene persisted for > or =4 weeks following systemic administration of adenoviral vector. In L-NAME treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i) reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated increased cardiomyocyte width and mRNA expression of hypertrophic (sk-alpha-actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension.

CONCLUSIONS: Adenoviral vector mediated delivery of hAM resulted in attenuation of myocardial oxidative stress and hypertrophic remodelling in the absence of blood pressure reduction in this model of chronic NO-deficiency. These findings are consistent with a direct cardio-protective action in the myocardium of locally-derived hAM which is not dependant on NO generation.

Oral Resveratrol Reduces Neuronal Damage in a Model of Multiple Sclerosis

Background: Neuronal loss in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), correlates with permanent neurological dysfunction. Current MS therapies have limited the ability to prevent neuronal damage. Methods: We examined whether oral therapy with SRT501, a pharmaceutical grade formulation of resveratrol, reduces neuronal loss during relapsing-remitting EAE. Resveratrol activates SIRT1, an NAD-dependent deacetylase that promotes mitochondrial function. Results: Oral SRT501 prevented neuronal loss during optic neuritis, an inflammatory optic nerve lesion in MS and EAE. SRT501 also suppressed neurological dysfunction during EAE remission, and spinal cords from SRT501-treated mice had significantly higher axonal density than vehicle-treated mice. Similar neuroprotection was mediated by SRT1720, another SIRT1-activating compound; and sirtinol, an SIRT1 inhibitor, attenuated SRT501 neuroprotective effects. SIRT1 activators did not prevent inflammation. Conclusions: These studies demonstrate that SRT501 attenuates neuronal damage and neurological dysfunction in EAE by a mechanism involving SIRT1 activation. SIRT1 activators are a potential oral therapy in MS. © 2010 by North American Neuro-Ophthalmology Society.

Role of endoreduplication and apomeiosis during parthenogenetic reproduction in the model brown alga Ectocarpus

The filamentous brown alga Ectocarpus has a complex life cycle, involving alternation between independent and morphologically distinct sporophyte and gametophyte generations. In addition to this basic haploid–diploid life cycle, gametes can germinate parthenogenetically to produce parthenosporophytes. This article addresses the question of how parthenosporophytes, which are derived from a haploid progenitor cell, are able to produce meiospores in unilocular sporangia, a process that normally involves a reductive meiotic division.
We used flow cytometry, multiphoton imaging, culture studies and a bioinformatics survey of the recently sequenced Ectocarpus genome to describe its life cycle under laboratory conditions and the nuclear DNA changes which accompany key developmental transitions.
Endoreduplication occurs during the first cell cycle in about one-third of parthenosporophytes. The production of meiospores by these diploid parthenosporophytes involves a meiotic division similar to that observed in zygote-derived sporophytes. By contrast, meiospore production in parthenosporophytes that fail to endoreduplicate occurs via a nonreductive apomeiotic event.
Our results highlight Ectocarpus’s reproductive and developmental plasticity and are consistent with previous work showing that its life cycle transitions are controlled by genetic mechanisms and are independent of ploidy.

Cell cycles and endocycles in the model brown seaweed, Ectocarpus siliculosus

The recent announcement of the first genome sequence of a brown macroalga, the filamentous Ectocarpus, has been accompanied by a number of companion papers in New Phytologist. In a paper which contributes to this special issue, we classified the core cell cycle components of Ectocarpus, comparing them to the previously studied cell cycle components of diatoms. We then carried out fluorescence microscopy experiments to show that the Ectocarpus cell cycle could be deregulated during early development to give endopolyploid adults. We discuss here how our findings complement recent studies on endopolyploidy in plant and algal systems.

Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration

A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse