2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung

<p>Abstract</p> <p>Background</p> <p><it>Pseudomonas aeruginosa </it>infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of <it>Ps. aeruginosa </it>releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA).</p> <p>Methods</p> <p>We investigated 2-AA for its specificity to <it>Ps. aeruginosa </it>and its suitability as a potential breath biomarker of colonisation or infection by Solid Phase Micro Extraction and Gas Chromatography-Mass Spectrometry (GC/MS).</p> <p>Results</p> <p>Cultures of 20 clinical strains of <it>Ps. aeruginosa </it>but not other respiratory pathogens had high concentrations of 2-AA in the head space of <it>in vitro </it>cultures when analysed by GC/MS. 2-AA was stable for 6 hours in deactivated glass sampling bulbs but was not stable in Tedlar^®bags. Optimisation of GC/MS allowed detection levels of 2-AA to low pico mol/mol range in breath. The 2-AA was detected in a significantly higher proportion of subjects colonised with <it>Ps. aeruginosa </it>15/16 (93.7%) than both the healthy controls 5/17 (29%) (p < 0.0002) and CF patients not colonised with <it>Ps. aeruginosa </it>4/13(30.7%) (p < 0.001). The sensitivity and specificity of the 2-AA breath test compared to isolation of <it>Ps. aeruginosa </it>in sputum and/or BALF was 93.8% (95% CI, 67-99) and 69.2% (95% CI, 38-89) respectively. The peak integration values for 2-AA analysis in the breath samples were significantly higher in <it>Ps. aeruginosa </it>colonised subjects (median 242, range 0-1243) than the healthy controls (median 0, range 0-161; p < 0.001) and CF subjects not colonised with <it>Ps. aeruginosa </it>(median 0, range 0-287; p < 0.003)</p> <p>Conclusions</p> <p>Our results report 2-AA as a promising breath biomarker for the detection of <it>Ps. aeruginosa </it>infections in the cystic fibrosis lung.</p

Plasma Lipids and Betaine Are Related in an Acute Coronary Syndrome Cohort

BACKGROUND: Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these. METHODOLOGY: Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment. PRINCIPAL FINDINGS: Plasma betaine negatively correlated with triglyceride (Spearman's r(s) = -0.22, p<0.0001) and non-high-density lipoprotein cholesterol (r(s) = -0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin. CONCLUSION: Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk

Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial

Objective: To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Design: Opportunistic addition to an established randomised double blind placebo controlled trial. Setting: Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. Participants: 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Intervention Participants were randomised to receive an oral dose of either 200 000 IU vitamin D3 monthly for two months then 100 000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. Main outcome measure This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of “psychological” adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. Results: 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ2 P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ2 P=0.03). The number of psychological adverse events—such as fatigue, stress, anxiety, and insomnia—that participants reported at their usual monthly appointments was significantly higher after the earthquake (χ2 P=0.007) but did not differ between treatment groups. Conclusion: In this trial, vitamin D supplementation did not reduce the adverse impact of earthquakes in healthy adults. Trial registration Australian New Zealand Clinical Trials Registry (anzctr.org.au) ACTRN1260900048622

Displaying the Heterogeneity of the SN 2002cx-like Subclass of Type Ia Supernovae with Observations of the Pan-STARRS-1 Discovered SN2009ku

SN2009ku, discovered by Pan-STARRS-1, is a Type Ia supernova (SNIa), and a member of the distinct SN2002cx-like class of SNeIa. Its light curves are similar to the prototypical SN2002cx, but are slightly broader and have a later rise to maximum in g. SN2009ku is brighter (~0.6 mag) than other SN2002cx-like objects, peaking at M_V = -18.4 mag - which is still significantly fainter than typical SNeIa. SN2009ku, which had an ejecta velocity of ~2000 kms^-1 at 18 days after maximum brightness is spectroscopically most similar to SN2008ha, which also had extremely low-velocity ejecta. However, SN2008ha had an exceedingly low luminosity, peaking at M_V = -14.2 mag, ~4 mag fainter than SN2009ku. The contrast of high luminosity and low ejecta velocity for SN2009ku is contrary to an emerging trend seen for the SN2002cx class. SN2009ku is a counter-example of a previously held belief that the class was more homogeneous than typical SNeIa, indicating that the class has a diverse progenitor population and/or complicated explosion physics. As the first example of a member of this class of objects from the new generation of transient surveys, SN2009ku is an indication of the potential for these surveys to find rare and interesting objects.Comment: 7 pages, 3 figure

Computerized Ultrasound Risk Evaluation (CURE) System: Development of Combined Transmission and Reflection Ultrasound with New Reconstruction Algorithms for Breast Imaging

Our Computerized Ultrasound Risk Evaluation (CURE) system has been developed to the engineering prototype stage and generated unique data sets of both transmission and reflection ultrasound (US). This paper will help define the clinical underpinnings of the developmental process and interpret the imaging results from a similar perspective. The CURE project was designed to incorporate numerous diagnostic parameters to improve upon two major areas of early breast cancer detection. CURE may provide improved tissue characterization of breast masses and reliable detection of abnormal microcalcifications found in some breast cancers and ductal carcinoma in situ (DCIS). Current breast US is limited to mass evaluation, whereas mammography also detects and guides biopsy of malignant calcifications. Screening with CURE remains a distant goal, but improved follow-up of mammographic abnormalities may represent a feasible breakthrough. Improved tissue characterization could result in reduction of the estimated one million benign biopsies each year in the United States, costing up to several billion dollars. Most breast calcifications are benign and comprise-80% of stereotactic biopsies guided by mammography. Ultrasound has the capability of finding some groups of calcifications, but further improvements in resolution should also address tissue characterization to define the soft tissue filling of ducts by DCIS. In this manner, CURE may be able to more accurately identify the malignant calcifications associated with progression of DCIS or early cancers. Currently, high-resolution US images of the breast are performed in the reflection mode at higher frequencies, which also limits depth of penetration. Reconstruction of reflection ultrasound images relies upon acoustic impedance differences in the tissue and includes only direct backscatter of the ultrasound signal. Resolution and tissue contrast of current US continues to improve with denser transducer arrays and image processing, but the operator dependent nature of using a moveable transducer head remains a significant problem for thorough coverage of the entire breast. We have therefore undertaken the development of a whole breast (i.e., including auxiliary tail) system, with improved resolution and tissue characterization abilities. The extensive ultrasound physics considerations, engineering, materials process development and subsequent algorithm reconstruction are beyond the scope of this initial paper. The proprietary nature of these processes will be forthcoming as the intellectual property is fully secured. We will focus here on the imaging outcomes as they apply to eventual expansion into clinical use

Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

BACKGROUND: Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. METHODS: Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. PRINCIPAL FINDINGS: The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). CONCLUSIONS: Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk