A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

Pain language and gender differences when describing a past pain event.

Pain is a largely subjective experience, and one which is difficult to convey to others, and relies significantly on language to be communicated. The language used to describe pain is therefore an important aspect of understanding and assessing another's pain. A growing body of research has reported differences in the pain experienced by men and women. However, few studies have examined gender differences, where gender is understood in both the biological and the social sense, in the language used when reporting pain. The purpose of this descriptive and analytical study was to explore gender differences in the language used by articulate men and women when describing a recollected painful event. Two-hundred and one students from an Australian university (35.32% males and 64.68% females) provided written descriptions of a past pain event. These descriptions were analysed using content analysis. Gender differences were identified in the words and patterns of language used, the focus of pain descriptions, and the reported emotional response to pain. Women were found to use more words (t=4.87, p<0.001), more McGill Pain Questionnaire descriptors (chi(2)=3.07, p<0.05), more graphic language than men, and typically focused on the sensory aspects of their pain event. Men used fewer words, less descriptive language, and focused on events and emotions. Common themes were the functional limitations caused by pain, difficulty in describing pain, and the dual nature of pain. Clinical implications include the value of gathering free pain descriptions as part of assessment, and the use of written pain descriptions.

Nursing education and genetics. Miles to go before we sleep.

The discoveries of the Human Genome Project (HGP), established in 1990 at the National Institutes of Health and the United States Department of Energy, are bringing important new technologies for genetic diagnosis and treatment to nearly all areas of health care delivery. Nurses, who play an integral role in supporting health consumers as they respond to health and illness, require up-to-date genetic knowledge for conducting clinical practice, engaging in nursing research, and educating a new generation of nurses.