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INTRODUCTIONIntravenous (IV) fluid resuscitation is recommended first line therapy in septic shock, but the effectiveness and safety of this approach has been questioned. To investigate potential mechanisms of harm from IV fluid resuscitation, we measured biomarkers of endothelial glycocalyx (EG) shedding, activation of the vascular endothelium and inflammation over the first 24 hours in a clinical trial comparing a fluid-restricted resuscitation regimen to usual care with no IV fluid restriction. METHODSA planned biomarker sub-study of the REFRESH trial in which emergency department (ED) patients) with suspected sepsis and a systolic blood pressure of

The potential health benefits of phenolic acids found in food and beverages has been suggested from a number of large population studies. However, the mechanism of how these compounds may exert biological effects is less well established. It is also now recognised that many complex polyphenols in the diet are metabolised to simple phenolic acids which can be taken up in the circulation. In this paper a number of selected phenolic compounds have been tested for their bioactivity in two cell culture models. The expression and activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells and the uptake of glucose in muscle cells. Our data indicate that while none of the compounds tested had a significant effect on eNOS expression or activation in endothelial cells, several of the compounds increased glucose uptake in muscle cells. These compounds also enhanced the translocation of the glucose transporter GLUT4 to the plasma membrane, which may explain the observed increase in cellular glucose uptake. These results indicate that simple cell culture models may be useful to help understand the bioactivity of phenolic compounds in relation to cardiovascular protection.

Accessibility of tumors for highly effective local treatment represents a major challenge for anticancer therapy. Immunostimulatory oligodeoxynucleotides (ODN) with CpG motifs are ligands of TLR9, which prime spontaneous antitumor immunity, but are less effective when applied systemically. We therefore developed a liposome-based agent for selective delivery of CpG-ODN into the tumor environment. A peptide that specifically targets angiogenic endothelial cells in a transgenic tumor model for islet cell carcinogenesis was engrafted into CpG-ODN containing liposomes. Intravenous injection of these liposomes resulted in specific accumulation around tumor vessels, increased uptake by tumor-resident macrophages, and retention over time. In contrast, nontargeted liposomes did not localize to the tumor vasculature. Consequently, only vascular targeting of CpG-ODN liposomes provoked a marked inflammatory response at vessel walls with enhanced CD8+ and CD4+ T cell infiltration and, importantly, activation of spontaneous, tumor-specific cytotoxicity. In a therapeutic setting, 40% of tumor-bearing, transgenic mice survived beyond week 45 after systemic administration of vascular-directed CpG-ODN liposomes. In contrast, control mice survived up to 30 wk. Therapeutic efficacy was further improved by increasing the frequency of tumor-specific effector cells through adoptive transfers. NK cells and CD8+ T cells were major effectors which induced tumor cell death and acted in conjunction with antivascular effects. Thus, tumor homing with CpG-ODN-loaded liposomes is as potent as direct injection of free CpG-ODN and has the potential to overcome some major limitations of conventional CpG-ODN monotherapy.

The International Baccalaureate has received a great deal of press in the past year or two, but there is much more to it than being an alternative to A-levels, including a comprehensive early years element.

This chapter focuses on two interactive projects involving artists and adults from the local community in research projects which have informed general access and education programmes at the Irish Museum of Modern Art. The first project, entitled Unspoken Truths, concentrates on an experimental process which introduced working class inner city Dublin women to contemporary art and artists in the context of the Museum and engaged with the community development sector in Ireland. It represented a defining moment in the development of the Museum. It also had a big impact on how marginalised working class communities reconsidered their relationships to museums, suggesting a model for access and informed thinking in this context both within the museum and in the wider world. The participants in the second project, all local older people were strongly empowered on seeing that exhibition and having it mediated by the women who created it. They began to consider seriously for the first time the validity of their own lives as source for their art work. Older people’s contact and involvement with contemporary art and artists is keenly felt to be essential to the exploration of new forms of expression and personal creativity. It contributes to the ongoing process of dealing with change in society.

Apart from knowing of his name, I feel obliged to confess ignorance in regard to Raymond Hanson. This little book, despite its size, does much to redress this. On finishing it one cannot help feeling considerable interest in the man and his music. It inspired me to find copies of some of Hanson7#x0027;s piano music in our library and play it through, and I can only hope this book will introduce others to his undeservedly neglected music.