Identification of Pathway-Specific Serum Biomarkers of Response to Glucocorticoid and Infliximab Treatment in Children with Inflammatory Bowel Disease

Objective: Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial. Methods: We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed by quantitative real time PCR. Concordance of longitudinal changes between the groups was used to identify markers responsive to treatment. Bioinformatic analysis was used to build insight into mechanisms of changes in response to treatment. Results: We identified 18 proteins and three miRNAs responsive to both prednisone and infliximab. Eight markers that decreased are associated with inflammation and have gene promoters regulated by nuclear factor (NF)-κB. Several that increased are associated with resolving inflammation and tissue damage. We also identified six markers that appear to be steroid-specific, three of which have glucocorticoid receptor binding elements in their promoter region. Conclusions: Serum markers regulated by the inflammatory transcription factor NF-κB are potential candidates for pharmacodynamic biomarkers that, if correlated with later outcomes like endoscopic or histologic healing, could be used to monitor treatment, optimize dosing, and enhance drug development. The pharmacodynamic biomarkers identified here hold potential to improve both clinical care and drug development. Further studies are warranted to investigate these markers as early predictors of response, or possibly surrogate outcomes

The Impact of a Novel Computer-Based Decision Aid on Shared Decision-Making for Colorectal Cancer Screening: A Randomized Trial (Running head: SDM for CRC Screening)

Eliciting patients’ preferences within a framework of shared decision-making (SDM) has been advocated as a strategy for increasing colorectal cancer (CRC) screening adherence. Our objective was to assess the effectiveness of a novel decision aid on SDM in the primary care setting

Aid-Assisted Decision-Making and Colorectal Cancer Screening: A Randomized Controlled Trial

Shared decision-making (SDM) is a widely recommended yet unproven strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer

Evaluation of host-seeking behavior in a diverse group of nematode species

One of the behaviors of parasitic nematodes that is essential for successful parasitism is host seeking, a complex behavior requiring nematodes to integrate sensory cues to find suitablehosts in which to complete their life cycles. Olfaction is a critical component of this response; many nematode parasites use carbon dioxide and other host-produced volatiles to locate their hosts. I investigated the odor responses of four species of skin penetrating mammalian-parasitic nematodes: the rat parasites Strongyloides ratti and Nippostrongylus brasiliensis, the possum parasite Parastrongyloides trichosuri, and the human parasite Strongyloides stercoralis. For comparison, I also profiled responses of the insect parasites Heterorhabditis bacteriophora and Steinernema carpocapsae, as well as those of the free-living nematode Caenorhabditis elegans. The mammalian parasites were found to show significant response to some components of human/mammalian odors, though the matter of attraction to live hosts remains unresolved. Likewise, clustering analysis grouping species by odor responses was inconclusive

Reducing Acute Kidney Injury Due to Contrast Material: How Nurses Can Improve Patient Safety.

BACKGROUND: Acute kidney injury due to contrast material occurs in 3% to 15% of the 2 million cardiac catheterizations done in the United States each year. OBJECTIVE: To reduce acute kidney injury due to contrast material after cardiovascular interventional procedures. METHODS: Nurse leaders in the Northern New England Cardiovascular Disease Study Group, a 10-center quality improvement consortium in Maine, New Hampshire, and Vermont, formed a nursing task force to reduce acute kidney injury due to contrast material after cardiovascular interventional procedures. Data were prospectively collected January 1, 2007, through June 30, 2012, on consecutive nonemergent patients (n = 20 147) undergoing percutaneous coronary interventions. RESULTS: Compared with baseline rates, adjusted rates of acute kidney injury among the 10 centers were significantly reduced by 21% and by 28% in patients with baseline estimated glomerular filtration rate less than 60 mL/min per 1.73 m CONCLUSIONS: Standardization of evidence-based best practices in nursing care may reduce the incidence of acute kidney injury due to contrast material