We show here that fundamental aspects of antitumor immunity in mice are significantly influenced by ambient housing temperature. Standard housing temperature for laboratory mice in research facilities is mandated to be between 20-26°C; however, these subthermoneutral temperatures cause mild chronic cold stress, activating thermogenesis to maintain normal body temperature. When stress is alleviated by housing at thermoneutral ambient temperature (30-31°C), we observe a striking reduction in tumor formation, growth rate and metastasis. This improved control of tumor growth is dependent upon the adaptive immune system. We observe significantly increased numbers of antigen-specific CD8 + T lymphocytes and CD8 + T cells with an activated phenotype in the tumor microenvironment at thermoneutrality. At the same time there is a significant reduction in numbers of immunosuppressive MDSCs and regulatory T lymphocytes. Notably, in temperature preference studies, tumor-bearing mice select a higher ambient temperature than non-tumor-bearing mice, suggesting that tumor-bearing mice experience a greater degree of coldstress. Overall, our data raise the hypothesis that suppression of antitumor immunity is an outcome of cold stress-induced thermogenesis. Therefore, the common approach of studying immunity against tumors in mice housed only at standard room temperature may be limiting our understanding of the full potential of the antitumor immune response. murine tumor models | metabolism

Summary Reactive oxygen species (ROS) activate NF-E2-related transcription factor 2 (Nrf2), a key transcriptional regulator driving antioxidant gene expression and protection from oxidant injury. Here we report that in response to elevation of intracellular ROS above a critical threshold, Nrf2 stimulates expression of transcription Kruppel-like factor 9 (Klf9), resulting in further Klf9-dependent increases in ROS and subsequent cell death. We demonstrated that Klf9 independently causes increased ROS levels in various types of cultured cells and in mouse tissues and is required for pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Mechanistically, Klf9 binds to the promoters and alters the expression of several genes involved in the metabolism of ROS, including suppression of thioredoxin reductase 2, an enzyme participating in ROS clearance. Our data reveal an Nrf2-dependent feed-forward regulation of ROS and identify Klf9 as a novel ubiquitous regulator of oxidative stress and lung injury.

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This review aims to determine how head shape is measured and describes the use of orthoses in the management of deformational plagiocephaly. A systematic review was conducted and papers published in English up to and including 2006 were sourced from nine databases. After initial screening, 20 papers were included; three literature reviews and 17 original papers. Of the original papers, eight concerned the method of head shape measurement.

Background: There is a considerable demand for lower limb prostheses globally due to vascular disease, war, conflict, land mines and natural disasters. Conventional composite materials used for prosthetic limb sockets include acrylic resins, glass and carbon fibres, which produce harmful gasses and dust in their manufacture.Objectives: To investigate the feasibility of using a renewable plant oil-based polycarbonate-polyurethane copolymer resin and plant fibre composite, instead of conventional materials, to improve safety and accessibility of prosthetic limb manufacture.Study Design: Experimental, bench research.Methods: Test pieces of the resin with a range of plant fibres (10.0% by volume) were prepared and tensile strengths were tested. Test sockets of both conventional composite materials and plant resin with plant fibres were constructed and tested to destruction.Results: Combinations of plant resin and either banana or ramie fibres gave high tensile strengths. The conventional composite material socket and plant resin with ramie composite socket failed at a similar loading, exceeding the ISO 10328 standard. Both wall thickness and fibre-matrix adhesion played a significant role in socket strength.Conclusions: From this limited study we conclude that the plant resin and ramie fibre composite socket has the potential to replace the standard layup. Further mechanical and biocompatibility testing as well as a full economic analysis is required.Clinical relevanceUsing readily sourced and renewable natural fibres and a low-volatile bio-resin has potential to reduce harm to those involved in the manufacture of artificial limb sockets, without compromising socket strength and benefitting clinicians working in poorer countries where safety equipment is scarce. Such composite materials will reduce environmental impact.