EDITORIAL Water, water, every where, but rarely any drop to drink

I would like to give all readers a very warm welcome to 2014 and the first issue of the tenth volume of Metabolomics. As you may be able to work out: the front cover is a celebration of this achievement, and I thank my colleague Dr Steve O’Hagan for his artistry. I am delighted that the journal is in such good shape and this is due to the excellent papers that are submitted and published, and of course the very valuable reviewing that many of you do. Metabolomics has an excellent Editorial board and I am also very grateful to them for their valuable support. You may be pondering over the title, so let me explain. Whilst I have somewhat moderated the quote from ‘‘The Rime of the Ancient Mariner’ ’ by Samuel Taylor Coleridge written in 1797–1798, the water does not refer to any liquid substance per se, nor does the drinking to the ‘dryathlon 1 ’ that I did early last year and will be doing so again to combat any Christmas excesses. Rather the water is an analogy to data—both metabolomics and metadata. Water here is a very apt comparison, as it seems rather ironic that a typical metabolomics experiments generates so much data that it is often referred to in terms of natural disasters—like data floods, data torrents or even data tsunamis. Yet even more ironic that very rarely do we make publicly available the metabolomics data (raw or processed) and the associated metadata with our publications. These metadata are as important as the metabolite data as these refer to the data about the data. We mainly think of these in terms of the important traits or features that we may want to predict, but these also refer to our experimental protocols that ar

Implementation of rapid rule out of myocardial infarction using high-sensitivity troponin : cross-sectional survey of English hospitals

OBJECTIVES: Recent guidance recommended use of high-sensitivity troponin for rapid rule out of myocardial infarction (MI) in the English health service. We aimed to determine the extent of implementation of this guidance across English hospitals. METHODS: This study conducted a cross-sectional questionnaire survey of 131 English acute hospitals with over 10 000 admissions per year. RESULTS: We received 125/131 responses (95%), with 110/125 (88%) reporting use of a high-sensitivity troponin assay and responses showing progressive implementation over the last 10 years. High-sensitivity troponin was reported to be used for rapid rule out of MI in 92/110 Trusts (84%). Review of guidelines received from 95/110 Trusts identified that 71/95 (75%) provided guidance for rapid MI rule out with high-sensitivity troponin: 57 recommended testing at 0 and 3 hours, 4 recommended testing at 0 and 2 hours, and 9 recommended testing at 0 and 1 hour, and timing was unclear at one Trust. CONCLUSIONS: English acute hospital Trusts report widespread implementation of high-sensitivity troponin for rapid rule out of MI, with most recommending testing at 0 and 3 hours

Periodic cometary showers: Real or imaginary?

Since the initial reports in 1980, a considerable body of chemical and physical evidence has been accumulated to indicate that a major impact event occurred on earth 65 million years ago. The effects of this event were global in extent and have been suggested as the cause of the sudden demise or mass extinction of a large percentage of life, including the dinosaurs, at the end of the geologic time period known as the Cretaceous. Recent statistical analyses of extinctions in the marine faunal record for the last 250 million years have suggested that mass extinctions may occur with a periodicity of every 26 to 30 million years. Following these results, other workers have attempted to demonstrate that these extinction events, like that at the end of the Cretaceous, are temporally correlated with large impact events. A recent scenario suggests that they are the result of periodic showers of comets produced by either the passage of the solar system through the galactic plane or by perturbations of the cometary cloud in the outer solar system by a, as yet unseen, solar companion. This hypothesized solar companion has been given the name Nemesis

tuppence-based SERS for the detection of illicit materials

Deposition of silver onto British 2p coins has been demonstrated as an efficient and cost effective approach to producing substrates capable of promoting surface enhanced Raman scattering (SERS). Silver application to the copper coins is undemanding taking just 20 s, and results in the formation of multiple hierarchial dendritic structures. To demonstrate that the silver deposition sites were capable of SERS the highly fluorescent Rhodamine 6G (R6G) probe was used. Analyses indicated that Raman enhancement only occurs at the silver deposition sites and not from the roughened copper surface. The robustness of the substrate in the identification and discrimination of illegal and legal drugs of abuse was then explored. Application of the drugs to the substrates was carried out using spotting and soaking methodologies. Whilst little or no SERS spectra of the drugs were generated upon spotting, soaking of the substrate in a methanolic solution of the drugs yielded a vast amount of spectral information. Excellent reproducibility of the SERS method and classification of three of the drugs, 4-methylmethcathinone (mephedrone), 5,6-methylenedioxy-2-aminoindane (MDAI) and 3,4-methylenedioxy-N-methylamphetamine (MDMA) were demonstrated using principal components analysis and partial least squares

pH plays a role in the mode of action of trimethoprim on Escherichia coli

Metabolomics-based approaches were applied to understand interactions of trimethoprim with Escherichia coli K-12 at sub-minimum inhibitory concentrations (MIC≈0.2, 0.03 and 0.003 mg L-1). Trimethoprim inhibits dihydrofolate reductase and thereby is an indirect inhibitor of nucleic acid synthesis. Due to the basicity of trimethoprim, two pH levels (5 and 7) were selected which mimicked healthy urine pH. This also allowed investigation of the effect on bacterial metabolism when trimethoprim exists in different ionization states. UHPLC-MS was employed to detect trimethoprim molecules inside the bacterial cell and this showed that at pH 7 more of the drug was recovered compared to pH 5; this correlated with classical growth curve measurements. FT-IR spectroscopy was used to establish recovery of reproducible phenotypes under all 8 conditions (3 drug levels and control in 2 pH levels) and GC-MS was used to generate global metabolic profiles. In addition to finding direct mode-of-action effects where nucleotides were decreased at pH 7 with increasing trimethoprim levels, off-target pH-related effects were observed for many amino acids. Additionally, stress-related effects were observed where the osmoprotectant trehalose was higher at increased antibiotic levels at pH 7. This correlated with glucose and fructose consumption and increase in pyruvate-related products as well as lactate and alanine. Alanine is a known regulator of sugar metabolism and this increase may be to enhance sugar consumption and thus trehalose production. These results provide a wider view of the action of trimethoprim. Metabolomics indicated alternative metabolism areas to be investigated to further understand the off-target effects of trimethoprim

Implementation of Fourier transform infrared spectroscopy for the rapid typing of uropathogenic Escherichia coli.

In this paper, we demonstrate that Fourier transform infrared (FT-IR) spectroscopy is able to discriminate rapidly between uropathogenic Escherichia coli (UPEC) of key lineages with only relatively simple sample preparation. A total of 95 bacteria from six different epidemiologically important multilocus sequence types (ST10, ST69, ST95, ST73, ST127 and ST131) were used in this project and principal component-discriminant function analysis (PC-DFA) of these samples produced clear separate clustering of isolates, based on the ST. Analysis of data using partial least squares-discriminant analysis (PLS-DA), incorporating cross-validation, indicated a high prediction accuracy of 91.19% for ST131. These results suggest that FT-IR spectroscopy could be a useful method for the rapid identification of members of important UPEC STs

Absolute Quantification of Uric Acid in Human Urine Using Surface Enhanced Raman Scattering with the Standard Addition Method.

High levels of uric acid in urine and serum can be indicative of hypertension and the pregnancy related condition, preeclampsia. We have developed a simple, cost-effective, portable surface enhanced Raman scattering (SERS) approach for the routine analysis of uric acid at clinically relevant levels in urine patient samples. This approach, combined with the standard addition method (SAM), allows for the absolute quantification of uric acid directly in a complex matrix such as that from human urine. Results are highly comparable and in very good agreement with HPLC results, with an average <9% difference in predictions between the two analytical approaches across all samples analyzed, with SERS demonstrating a 60-fold reduction in acquisition time compared with HPLC. For the first time, clinical prepreeclampsia patient samples have been used for quantitative uric acid detection using a simple, rapid colloidal SERS approach without the need for complex data analysis

Effects of high relative humidity and dry purging on VOCs obtained during breath sampling on common sorbent tubes.

BACKGROUND:Offline breath analysis by GC-MS requires the use of sorbent traps to concentrate and store volatile compounds. The selection of which sorbent to use and best practices for managing water retention are important considerations to allow for reproducible, untargeted, biomarker discovery in water saturated breath samples. OBJECTIVE:To assess three commonly used sorbent materials for their use in breath volatile sampling and determine how the high relative humidity inherent in such samples effects the capture of volatile compounds of interest. METHODS:TenaxGR, TenaxTA/Carbograph1TD and TenaxTA/Carbograph5TD tubes were selected as they are the most commonly used sorbents in the breath sampling literature. The recovery of 29 compounds in a standard mix loaded using high humidity gas was tested for each sorbent and compared to loading in dry gas. Water retention and dry purge rates were determined. Finally, breath samples were sampled simultaneously on to each sorbent type using the ReCIVA and analysed by TD-GC-MS. RESULTS:All three sorbents exhibited acceptable reproducibility when loaded with the standard mix in dry gas. Loading the standard mix in humid gas led to reduced recovery of compounds based on their chemical properties. Dry purging performance for each sorbent material was assessed and was shown to be 1.14, 1.13 and 0.89 mg H2O min-1for TenaxGR, TenaxTA/Carbograph1TD and TenaxTA/Carbograph5TD respectively. A comparison of breath profiles on different sorbents showed differences in background artefacts (sulfur dioxide, cyclopenten-1-one and 3-nonene) and endogenous breath compounds (2-methyl-furan and furfural). CONCLUSIONS:High relative humidity during sampling reduces the ability of sorbent tubes to capture volatile compounds and could impact method detection limits during breath sampling. Sufficient water to impair accurate analysis was retained on all tubes. Minimal differences were observed between sorbent materials when used to sample breath, however, suggestions are provided for sorbent selection for future studies