Analyzing the Cost of Hospital Contact Isolation Practices: Implications for Nursing Administrator Practice, Research, and Policy.

OBJECTIVES: This study aimed to determine the weekly costs of contact precaution (CP) use with medically stable patients infected/colonized with methicillin-resistant Staphylococcus aureus (MRSA) and to estimate the annual financial and environmental costs of CP. BACKGROUND: The increasing use of disposables for infection control contributes to increasing hospital costs and amounts of solid waste at rates that are becoming unsustainable. METHODS: A cost analysis was conducted using data from time/motion observations and previous waste audit study, along with hospital finance department values and US Department of Labor salary rates. RESULTS: Weekly and annual costs were $521.67 and $557 463 (5% hospital multidrug-resistant organism [MDRO] rate assumed). Personal protective equipment accounted for 43% of the waste produced (approximately 1600 pounds annually). CONCLUSIONS: Implications for nurse administrators include reevaluating activities that require personal protective equipment (PPE) and partnering with materials and human factor engineers to develop more financially and environmentally sustainable infection control practices.

Use of differential scanning fluorimetry as a high-throughput assay to identify nuclear receptor ligands.

Identification of ligands that interact with nuclear receptors is both a major biological problem and an important initial step in drug discovery. Several in vitro and in vivo techniques are commonly used to screen ligand candidates against nuclear receptors; however, none of the current assays allow screening without modification of either the protein and/or the ligand in a high-throughput fashion. Differential scanning fluorimetry (DSF) allows unmodified potential ligands to be screened as 10µL reactions in 96-well format against partially purified protein, revealing specific interactors. As a proof of principle, we used a commercially-available nuclear receptor ligand candidate chemical library to identify interactors of the human estrogen receptor α ligand binding domain (ERα LBD). Compounds that interact specifically with ERα LBD stabilize the protein and result in an elevation of the thermal denaturation point, as monitored by the environmentally-sensitive dye SYPRO orange. We successfully identified all three compounds in the library that have previously been identified to interact with ERα, with no false positive results.

The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta.

Heme is a ligand for the human nuclear receptors (NR) REV-ERBalpha and REV-ERBbeta, which are transcriptional repressors that play important roles in circadian rhythm, lipid and glucose metabolism, and diseases such as diabetes, atherosclerosis, inflammation, and cancer. Here we show that transcription repression mediated by heme-bound REV-ERBs is reversed by the addition of nitric oxide (NO), and that the heme and NO effects are mediated by the C-terminal ligand-binding domain (LBD). A 1.9 A crystal structure of the REV-ERBbeta LBD, in complex with the oxidized Fe(III) form of heme, shows that heme binds in a prototypical NR ligand-binding pocket, where the heme iron is coordinately bound by histidine 568 and cysteine 384. Under reducing conditions, spectroscopic studies of the heme-REV-ERBbeta complex reveal that the Fe(II) form of the LBD transitions between penta-coordinated and hexa-coordinated structural states, neither of which possess the Cys384 bond observed in the oxidized state. In addition, the Fe(II) LBD is also able to bind either NO or CO, revealing a total of at least six structural states of the protein. The binding of known co-repressors is shown to be highly dependent upon these various liganded states. REV-ERBs are thus highly dynamic receptors that are responsive not only to heme, but also to redox and gas. Taken together, these findings suggest new mechanisms for the systemic coordination of molecular clocks and metabolism. They also raise the possibility for gas-based therapies for the many disorders associated with REV-ERB biological functions.

The Drosophila nuclear receptor e75 contains heme and is gas responsive.

Nuclear receptors are a family of transcription factors with structurally conserved ligand binding domains that regulate their activity. Despite intensive efforts to identify ligands, most nuclear receptors are still "orphans." Here, we demonstrate that the ligand binding pocket of the Drosophila nuclear receptor E75 contains a heme prosthetic group. E75 absorption spectra, resistance to denaturants, and effects of site-directed mutagenesis indicate a single, coordinately bound heme molecule. A correlation between the levels of E75 expression and the levels of available heme suggest a possible role as a heme sensor. The oxidation state of the heme iron also determines whether E75 can interact with its heterodimer partner DHR3, suggesting an additional role as a redox sensor. Further, the E75-DHR3 interaction is also regulated by the binding of NO or CO to the heme center, suggesting that E75 may also function as a diatomic gas sensor. Possible mechanisms and roles for these interactions are discussed.

Nuclear hormone receptors, metabolism, and aging: what goes around comes around. Transcription factors link lipid metabolism and aging-related processes.

Previous studies have linked the mysterious and inevitable process of aging to essential processes such as metabolism, maturation, and fecundity. Each of these processes is controlled to a large extent by nuclear hormone receptors (NHRs). NHRs also play important roles in the control of periodical processes, the most recently implicated being circadian rhythm. This Review stresses the mounting evidence for tight relationships between each of these NHR-regulated processes and the processes of aging.