A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation.

There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.

Assessing methods to estimate emissions of non-methane organic compounds from landfills.

The non-methane organic compound (NMOC) emission rate is used to assess compliance with landfill gas emission regulations by the United States Environmental Protection Agency (USEPA). A recent USEPA Report (EPA/600/R-11/033) employed a ratio method to estimate speciated NMOC emissions (i.e., individual NMOC emissions): speciated NMOC emissions=measured methane (CH4) emission multiplied by the ratio of individual NMOCs concentration relative to CH4 concentration (C(NMOCs)/C(CH4)) in the landfill header gas. The objectives of this study were to (1) evaluate the efficacy of the ratio method in estimating speciated NMOC flux from landfills; (2) determine for what types of landfills the ratio method may be in error and why, using recent field data to quantify the spatial variation of (C(NMOCs)/C(CH4)) in landfills; and (3) formulate alternative models for estimating NMOC emissions from landfills for cases in which the ratio method results in biased estimates. This study focuses on emissions through landfill covers measured with flux chambers and evaluates the utility of the ratio method for estimating NMOC emission through this pathway. Evaluation of the ratio method was performed using CH4 and speciated NMOC concentration and flux data from 2012/2013 field sampling of four landfills, an unpublished landfill study, and literature data from three landfills. The ratio method worked well for landfills with thin covers (<40 cm), predicting composite NMOC flux (as hexane-C) to within a factor of 10× for 13 out of 15 measurements. However, for thick covers (⩾40 cm) the ratio method overestimated NMOC emissions by ⩾10× for 8 out of 10 measurements. Alternative models were explored incorporating other chemical properties into the ratio method. A molecular weight squared (MW)(2)-modified ratio equation was shown to best address the tendency of the current ratio method to overestimate NMOC fluxes for thick covers. While these analyses were only performed using NMOC fluxes through landfill covers measured with flux chambers, results indicate the current USEPA approach for estimating NMOC emissions may overestimate speciated NMOC emission ⩾10× for many compounds.

Improved predictive models for plasma glucose estimation from multi-linear regression analysis of exhaled volatile organic compounds.

Exhaled volatile organic compounds (VOCs) represent ideal biomarkers of endogenous metabolism and could be used to noninvasively measure circulating variables, including plasma glucose. We previously demonstrated that hyperglycemia in different metabolic settings (glucose ingestion in pediatric Type 1 diabetes) is paralleled by changes in exhaled ethanol, acetone, and methyl nitrate. In this study we integrated these gas changes along with three additional VOCs (2 forms of xylene and ethylbenzene) into multi-linear regression models to predict plasma glucose profiles in 10 healthy young adults, during the 2 h following an intravenous glucose bolus (matched samples of blood, exhaled and room air were collected at 12 separate time points). The four-gas model with highest predictive accuracy estimated plasma glucose in each subject with a mean R value of 0.91 (range 0.70-0.98); increasing the number of VOCs in the model only marginally improved predictions (average R with best 5-gas model = 0.93; with 6-gas model = 0.95). While practical development of this methodology into clinically usable devices will require optimization of predictive algorithms on large-scale populations, our data prove the feasibility and potential accuracy of breath-based glucose testing.

Treatment of severe tricyclic antidepressant overdose with extracorporeal sorbent detoxification.

Tricyclic overdose can be a medical emergency, and therapy with intravenous bicarbonate is not always successful in preventing cardiac toxicity or coma. Mortality in patients developing these complications is from 1% to 15%. Extracorporeal detoxification with sorbents has been used in treatment of patients with very high drug levels and declining clinical condition. Ten patients with serious drug overdose caused by tricyclics failed to respond quickly to standard therapy and were in stage 3-4 encephalopathy. Nine of these patients were on respirator support, 5 had hypotension, and 6 had QRS widening. Average level was 1,423 microg/L at presentation. Enteral activated charcoal and intravenous (IV) bicarbonate were initiated in the emergency room. The patients were treated for 3 to 4 hours with the Liver Dialysis Unit, a hemodiabsorption device using a cellulosic plate dialyzer and sorbent suspension as dialysate. Inflow and outflow blood levels indicated that the hemodetoxifier removed modest amounts of the tricyclics, metabolites, and other consumed drugs. The clinical improvement of the patients was dramatic, with patients reaching stage 0 or 1 encephalopathy during the treatment. Ventilator support was removed at the end of treatment for 3 patients who had not already developed pneumonia, and for others was prolonged up to 48 hours because of pneumonia, rather than mental status. Average length of stay in the intensive care unit (ICU) was 4.8 days (range 1 to 7 days). None of the patients died despite their high risk for ventricular arrhythmias, seizures, and death. Clinical improvement may have been attributable to removal of free drug from the blood or to removal of drug metabolites.