The effects of collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering.

In this study, we examined the effects of varying collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering. Three different collagen contents (0.25%, 0.5% and 1% collagen) and two different dehydrothermal (DHT) crosslinking processes [1] 105 degrees C for 24 h and [2] 150 degrees C for 48 h were investigated. These scaffolds were assessed for (1) pore size, (2) permeability (3) compressive strength and (4) cell viability. The largest pore size, permeability rate, compressive modulus, cell number and cell metabolic activity was all found to occur on the 1% collagen scaffold due to its increased collagen composition and the DHT treatment at 150 degrees C was found to significantly improve the mechanical properties and not to affect cellular number or metabolic activity. These results indicate that doubling the collagen content to 1% and dehydrothermally crosslinking the scaffold at 150 degrees C for 48 h has enhanced mechanical and biological properties of the scaffold making it highly attractive for use in bone tissue engineering

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.

Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone\u27s capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis

Proteomic analysis of Pseudomonas aeruginosa strains in response to bronchial epithelia

Poste

High rate of Human T Lymphotropic Virus Type IIa infection in HIV 1-infected intravenous drug abusers in Ireland.

This study investigated HTLV-II infections in a cohort of HIV-I-infected intravenous drug users (IVDAs)(n=103)in Dublin. Serological and molecular analyses have demonstrated that 15 (14.6%) were infected with HTLV-II, which is the highest rate of infection so far documented in Europe, and is equivalent to that in urban areas of the United States. Restriction fragment length polymorphism (RFLP) analysis of the env region of the provirus revealed only HTLV-IIa infection. There was no evidence of HTLV-IIb subtype infection. Phlyogenetic analysis of the nucleotide sequences of the long terminal repeat (LTR) confirmed infection with the HTLVE-IIa subtype, and the demonstrated that the viruses clustered closely with HTLV-IIa isolates from North American IVDAs. Previous observations that IVDAs in southern Europe appear to be infected predominantly with the HTLV-IIb sub-type, along with the present report and evidence that the IVDAs in Sweden are infected with HTLV-IIa subtype, suggest different origins of HTLV-II infection in Europe

Construction of p16Slux, a Novel Vector for Improved Bioluminescent Labeling of Gram-Negative Bacteria▿

A novel vector has been constructed for the constitutive luminescent tagging of gram-negative bacteria by site-specific integration into the 16S locus of the bacterial chromosome. A number of gram-negative pathogens were successfully tagged using this vector, and the system was validated during murine infections of living animals

Safety critical software development – extending quality management system practices to achieve compliance with regulatory requirements

Software is increasingly being used to provide functionality in safety critical domains. The complexity involved in the development of software for these domains can bring challenges concerned with safety and security. International standards are published, providing information on practices which must be implemented in order to satisfy the regulations. This paper details an investigation of the relevant standards that companies need to implement in order to satisfy the regulatory requirements. A literature review was conducted which examines the relevant Quality management system, Risk Management and Software development standards across the safety critical domains. To examine the challenges in implementing these standards, interviews were conducted with a medical device software development company having a Quality management system in place and beginning to implement the relevant Software development standards. In addition, an interview was conducted with a consultancy company who have experience in the implementation and maintenance of Quality management systems in small and medium enterprises. Future work will focus on the integration of practices which need to be implemented by companies developing safety critical software

Pseudomonas aeruginosa RsmA Plays an Important Role during Murine Infection by Influencing Colonization, Virulence, Persistence, and Pulmonary Inflammation▿

The ability of Pseudomonas aeruginosa to cause a broad range of infections in humans is due, at least in part, to its adaptability and its capacity to regulate the expression of key virulence genes in response to specific environmental conditions. Multiple two-component response regulators have been shown to facilitate rapid responses to these environmental conditions, including the coordinated expression of specific virulence determinants. RsmA is a posttranscriptional regulatory protein which controls the expression of a number of virulence-related genes with relevance for acute and chronic infections. Many membrane-bound sensors, including RetS, LadS, and GacS, are responsible for the reciprocal regulation of genes associated with acute infection and chronic persistence. In P. aeruginosa this is due to sensors influencing the expression of the regulatory RNA RsmZ, with subsequent effects on the level of free RsmA. While interactions between an rsmA mutant and human airway epithelial cells have been examined in vitro, the role of RsmA during infection in vivo has not been determined yet. Here the function of RsmA in both acute and chronic models of infection was examined. The results demonstrate that RsmA is involved in initial colonization and dissemination in a mouse model of acute pneumonia. Furthermore, while loss of RsmA results in reduced colonization during the initial stages of acute infection, the data show that mutation of rsmA ultimately favors chronic persistence and results in increased inflammation in the lungs of infected mice