Utilizing the STOP-Bang Questionnaire to Assess Risk of Obstructive Sleep Apnea in Hospitalized Patients with Heart Failure to Facilitate Sleep Medicine Referrals Upon Discharge

Background: Obstructive sleep apnea (OSA) is the most common sleep-breathing disorder. Undiagnosed OSA is highly prevalent in the population, especially in those with heart failure. OSA and heart failure combined create a negative feedback loop that can lead to poor clinical outcomes. Unfortunately, many cardiac patients are never screened for OSA. Purpose: The purpose of this project is to improve screening rates for OSA via the STOP-Bang questionnaire and establish an efficient and effective process for referrals to sleep medicine for heart failure patients screening high-risk. Methods: The design was a quality improvement project with pre- and post-testing and a retrospective and prospective chart review of patient data. The study took place in the cardiovascular intensive care unit (CVICU) at UK HealthCare over three 30-day phases. The intervention of the study was a nursing education session on the STOP-Bang questionnaire and an automatic warning for a sleep medicine referral for those screening high-risk. Results: There was no positive effect on screening rates following the education session despite nurses reporting increased knowledge and confidence in administering the tool. The intervention of the discharge warning had no significant effect on referrals to sleep medicine. Conclusion: There is still more work to be done to address undiagnosed OSA in heart failure patients. Although reported knowledge and confidence increased following the education session, screening rates were not positively affected. Addressing the barriers to screening for OSA needs to be done to get as close as possible to all patients being screened. The automatic discharge warning did not improve referral rates despite many patients screening high-risk. Future interventions should incorporate provider involvement, address screening barriers, and expand the automatic warning to more patient populations within the hospital setting

THE MECHANISMS OF α-AMANITIN RESISTANCE IN THE FRUIT FLY DROSOPHILA MELANOGASTER

Insect pesticide resistance has become a costly problem in the US. To make things more problematic, resistance to one pesticide is often associated with cross-resistance to other toxins, including pesticides that have not yet even been developed. In this study, we investigated a possible type of cross-resistance in the model fruit fly Drosophila melanogaster, some stocks of which are resistant to the very potent mushroom toxin α-amanitin. Because α-amanitin is solely produced by mushrooms, and because D. melanogaster does not feed on mushrooms in nature, the fruit flies should not be resistant to this toxin. In order to understand how this mushroom toxin resistance evolved, we first examined the physiological aspects of α-amanitin resistance in three D. melanogaster stocks, which were isolated in Asia half a century ago: Ama-KTT, Ama-MI, and Ama-KLM. We showed that all three fly stocks have not lost their α-amanitin resistance over time, even though they were maintained in the absence of selective pressure over the past ~1,200 generations. When we reared these flies on sub-lethal α-amanitin concentrations in our laboratory, the females unexpectedly doubled their fecundity. This effect could have dramatic ecological consequences by enabling D. melanogaster to invade the toxic mushroom niche. As a result of this potential niche switch, other mushroom-feeding flies could be driven to extinction. However, we also noted signs of developmental retardation and a shortened life span of the flies in response to increasing α-amanitin concentrations in the food, suggesting that the flies are not yet well adapted to the toxin. We next elucidated the molecular mechanisms causing α-amanitin resistance by performing a whole genome microarray study. Our data suggest that 1) cuticular proteins block α-amanitin from entering cells, 2) phase I and phase II detoxification enzymes modify α-amanitin to prepare it for excretion, 3) intracellular lipid particles sequester α-amanitin in the cytoplasm, and 4) peptidases cleave α-amanitin. Because the most highly up-regulated genes in our microarray study were Cytochrome P450/phase I detoxification genes that are known to detoxify pesticides, we speculate that the use of pesticides was the primary cause for the observed cross-resistance to the mushroom toxin α-amanitin

PAH Removal, Fate and Transport in Stormwater Bioretention Systems Amended with Biochar and Fungi

Bioretention is a widely implemented form of Green Stormwater Infrastructure used to prevent the pollution of receiving waters by stormwater runoff. Polycyclic Aromatic Hydrocarbons (PAHs) are a family of organic contaminants which are ubiquitous in stormwater. Several PAHs are toxic to aquatic species. Little is known about the transport and fate of individual PAH compounds in bioretention systems. Even less is known about how amendments to standard bioretention formulations might optimize PAH treatment. We conducted a mesocosm-scale experiment to evaluate the removal of PAHs using four types of bioretention media. We used a standard, planted bioretention media mixture (60:40 sand:compost by volume) and three other formulations containing the standard mixture and two amendments – biochar and fungi. This mixture was amended with biochar (50% replacement of compost) or inoculated with Stropharia rugosoannulata. Twelve bioretention columns (4 treatments in triplicate) were dosed with highway runoff during 8 storm events. Influent and effluent samples from each mesocosm were analyzed for 24 parent PAHs. Samples of bioretention media were taken horizontally from ports in the columns four times throughout the study and analyzed for 20 parent PAH compounds. Our results showed that all media types provided efficient PAH removal (\u3e97% removal for 54 of 56 samples). Fluoranthene, pyrene, and phenanthrene were the predominant PAHs in runoff and media samples. Initial Total PAH concentrations were twice as high in columns that did not contain the 50% compost replacement with biochar. We observed a net loss of PAHs in all mesocosms despite repeated PAH inputs from stormwater and almost no breakthrough in the effluent. Our results suggest that bioretention media containing sand and compost provides excellent PAH treatment at the influent concentrations used in this study (0.089-4.62 ug/L). We hypothesize that our bioretention systems support internal PAH loss mechanisms through microbial bioremediation and plant uptake

Effects of Differences in Lipid A Structure on TLR4 Pro-Inflammatory Signaling and Inflammasome Activation

The vertebrate immune system exists in equilibrium with the microbial world. The innate immune system recognizes pathogen-associated molecular patterns via a family of Toll-like receptors (TLR) that activate cells upon detection of potential pathogens. Because some microbes benefit their hosts, mobilizing the appropriate response, and then controlling that response is critical in the maintenance of health. TLR4 recognizes the various forms of lipid A produced by Gram-negative bacteria. Depending on the structural form of the eliciting lipid A molecule, TLR4 responses range from a highly inflammatory endotoxic response involving inflammasome and other pro-inflammatory mediators, to an inhibitory, protective response. Mounting the correct response against an offending microbe is key to maintaining health when exposed to various bacterial species. Further study of lipid A variants may pave the way to understanding how TLR4 responses are generally able to avoid chronic inflammatory damage