Direct Analysis of Aerosolized Chemical Warfare Simulants Captured on a Modified Glass-Based Substrate by "Paper-Spray" Ionization.

Paper spray ionization mass spectrometry offers a rapid alternative platform requiring no sample preparation. Aerosolized chemical warfare agent (CWA) simulants trimethyl phosphate, dimethyl methylphosphonate, and diisopropyl methylphosphonate were captured by passing air through a glass fiber filter disk within a disposable paper spray cartridge. CWA simulants were aerosolized at varying concentrations using an in-house built aerosol chamber. A custom 3D-printed holder was designed and built to facilitate the aerosol capture onto the paper spray cartridges. The air flow through each of the collection devices was maintained equally to ensure the same volume of air sampled across methods. Each approach yielded linear calibration curves with R2 values between 0.98-0.99 for each compound and similar limits of detection in terms of disbursed aerosol concentration. While the glass fiber filter disk has a higher capture efficiency (≈40%), the paper spray method produces analogous results even with a lower capture efficiency (≈1%). Improvements were made to include glass fiber filters as the substrate within the paper spray cartridge consumable. Glass fiber filters were then treated with ammonium sulfate to decrease chemical interaction with the simulants. This allowed for improved direct aerosol capture efficiency (>40%). Ultimately, the limits of detection were reduced to levels comparable to current worker population limits of 1 × 10-6 mg/m3.

Detection of chemical warfare agent simulants and hydrolysis products in biological samples by paper spray mass spectrometry.

Paper spray ionization coupled to a high resolution tandem mass spectrometer (a quadrupole orbitrap) was used to identify and quantitate chemical warfare agent (CWA) simulants and their hydrolysis products in blood and urine. Three CWA simulants, dimethyl methylphosphonate (DMMP), trimethyl phosphate (TMP), and diisopropyl methylphosphonate (DIMP), and their isotopically labeled standards were analyzed in human whole blood and urine. Calibration curves were generated and tested with continuing calibration verification standards. Limits of detection for these three compounds were in the low ng mL-1 range for the direct analysis of both blood and urine samples. Five CWA hydrolysis products, ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), cyclohexyl methylphosphonic acid (CHMPA), and pinacolyl methylphosphonic acid (PinMPA), were also analyzed. Calibration curves were generated in both positive and negative ion modes. Limits of detection in the negative ion mode ranged from 0.36 ng mL-1 to 1.25 ng mL-1 in both blood and urine for the hydrolysis products. These levels were well below those found in victims of the Tokyo subway attack of 2 to 135 ng mL-1. Improved stability and robustness of the paper spray technique in the negative ion mode was achieved by the addition of chlorinated solvents. These applications demonstrate that paper spray mass spectrometry (PS-MS) can be used for rapid, sample preparation-free detection of chemical warfare agents and their hydrolysis products at physiologically relevant concentrations in biological samples.

A review of the safety and efficacy of bariatric surgery in adults over the age of 60: 2002-2013.

PURPOSE: The purpose of this review is to compare outcomes of bariatric surgery in adults over 60 to younger patients. This analysis is important to determine if nurse practitioners (NPs) and other providers should recommend bariatric surgery to obese older adults. DATA SOURCES: This review included 15 studies published between 2002 and 2013. CONCLUSIONS: Although older adults seem to experience less weight loss, bariatric surgery has potential benefits for these patients. Significant improvements in hypertension, diabetes, and, to a lesser extent, dyslipidemia are noted. Mortality and surgical complications in older adults are low, while differences in length of hospital stay are inconclusive. IMPLICATIONS FOR PRACTICE: The risks of bariatric surgery in older adults need to be carefully evaluated based on individual medical condition. Overall the evidence suggests that bariatric surgery can be safely performed in older adults but more research is needed to determine which older adult patients are the best candidates for bariatric surgery. As bariatric surgery among older adults increases, interdisciplinary teams will continue to serve an important role in the management of bariatric surgery patients. NPs must be aware of trends in this emerging population of bariatric surgery patients.

Thermal separation to facilitate Direct Analysis in Real Time (DART) of mixtures.

We explore a thermal separation technique for use with Direct Analysis in Real Time (DART). By applying gas temperature ramping, we are able to disburse a mixture of compounds in time. The three components were selected to create a challenging mixture that would not likely be discerned solely using exact mass capabilities. While the thermal separation technique is of low resolution, it preserves the inherent rapid, non-contact, ambient characteristics of the ion source.

Ricin activity assay by direct analysis in real time mass spectrometry detection of adenine release.

Biotoxin activity assays typically involve multistep sample preparation, multicomponent reactions, multistep analysis, or a combination thereof. We report a single-step, real-time ricin activity assay that requires little or no sample preparation and employs direct analysis in real time mass spectrometry. The release of adenine from the inhomogeneous substrate herring sperm DNA by ricin was determined to be 53 +/- 2 pmol adenine per picomole of ricin per hour. This procedure can be readily adapted to any enzyme for which a reactant or product of low molecular weight (up to approximately 600) can be identified.

Quantitation of chemical warfare agents using the direct analysis in real time (DART) technique.

Direct analysis in real time (DART) is an ion source that permits rapid mass spectrometric detection of gases, liquids, and solids in open air under ambient conditions. It is a unique technology in the field of chemical weapons detectors in that it does not require a vapor pressure, does not require sample preparation, and is nondestructive to the original sample. While the DART technique has had success as a first line instrument of detection, there have been lingering doubts over the technique's quantitative reliability and reproducibility. Here, we demonstrate its capability to produce linear calibration curves (R(2) = 0.99 or better) for the nerve agents GA, GB, and VX as well as the blister agent HD. Independently prepared check standards measured against these curves typically have recovery errors less than 3%. We show the DART instrument response to be linear over roughly 3 orders of magnitude. Furthermore, this study shows that averaging as few as three measurements for each data point is sufficient to produce high quality calibration curves, thus reducing data collection time and providing quicker results.

Maspin expression profile in human prostate cancer (CaP) and in vitro induction of Maspin expression by androgen ablation.

PURPOSE: Expression of tumor suppressor gene, MASPIN, is associated with inhibition of tumor cell invasion and metastasis. Loss of or decreased expression of Maspin is found frequently in breast and prostate cancer cells. The objective of this study is to investigate Maspin expression in prostate tumor specimens and explore the mechanisms of hormonal regulation of Maspin expression in prostate tumors. EXPERIMENTAL DESIGN: Immunohistochemical staining of Maspin expression was performed on surgical whole-mounted prostate specimens. The expression of Maspin was scored on individual tumors. Correlation of Maspin expression with clinicopathological features was analyzed for statistical significance. Androgen ablation-induced Maspin expression was analyzed by Maspin promoter luciferase reporter assay and quantitative reverse transcription-PCR analysis of endogenous Maspin expression in LNCaP cells in vitro and in animal model. RESULTS: Comprehensive evaluation of Maspin expression profile in multiple tumor foci from whole mounted prostate specimens of prostate cancer patients revealed absence of Maspin expression in a significant fraction (63%). However, Maspin expression is significantly higher in tumor specimens (92%) of patients treated with neoadjuvant androgen ablation therapy before radical prostatectomy. LNCaP cells cultured in androgen-depleted medium show induction of Maspin promoter activity in a promoter luciferase reporter assay. In addition, Maspin expression is increased after castration in LNCaP prostate cancer cells derived tumors in nude mice. CONCLUSIONS: Maspin expression is frequently absent in primary prostate cancers. Up-regulation of MASPIN in response to androgen ablation strongly suggests a physiological role of Maspin in growth inhibition and/or apoptosis of prostate cancer cells during androgen ablation.