Advances in testing for sample manipulation in clinical and forensic toxicology - Part A: urine samples

In many countries, adherence testing is used to monitor consumption behavior or to prove abstinence. Urine and hair are most commonly used, although other biological fluids are available. Positive test results are usually associated with serious legal or economic consequences. Therefore, various sample manipulation and adulteration strategies are used to circumvent such a positive result. In these critical review articles on sample adulteration of urine (part A) and hair samples (part B) in the context of clinical and forensic toxicology, recent trends and strategies to improve sample adulteration and manipulation testing published in the past 10 years are described and discussed. Typical manipulation and adulteration strategies include undercutting the limits of detection/cut-off by dilution, substitution, and adulteration. New or alternative strategies for detecting sample manipulation attempts can be generally divided into improved detection of established urine validity markers and direct and indirect techniques or approaches to screening for new adulteration markers. In this part A of the review article, we focused on urine samples, where the focus in recent years has been on new (in)direct substitution markers, particularly for synthetic (fake) urine. Despite various and promising advances in detecting manipulation, it remains a challenge in clinical and forensic toxicology, and simple, reliable, specific, and objective markers/techniques are still lacking, for example, for synthetic urine

Metabolic profiling of diabetic cats in remission

Background: The majority of diabetic cats in remission have abnormal glucose tolerance, and approximately one third relapse within 1 year. Greater understanding of the metabolic characteristics of diabetic cats in remission, and predictors of relapse is required to effectively monitor and manage these cats. Objectives: To identify and compare differences in plasma metabolites between diabetic cats in remission and healthy control cats using a metabolomics approach. Secondly, to assess whether identified metabolites are predictors of diabetic relapse. Animals: Twenty cats in diabetic remission for a median of 101 days, and 22 healthy matched control cats. Methods: Cats were admitted to a clinic, and casual blood glucose was recorded. After a 24 h fast, blood glucose concentration was measured, then a blood sample was taken for metabolomic (GCMS and LCMS) analyses. Three hours later, a simplified intravenous glucose tolerance test (1 g glucose/kg) was performed. Cats were monitored for diabetes relapse for at least 9 months (270 days) after baseline testing. Results: Most cats in remission continued to display impaired glucose tolerance. Concentrations of 16 identified metabolites differed (P ≤ 0.05) between remission and control cats: 10 amino acids and stearic acid (all lower in remission cats), and glucose, glycine, xylitol, urea and carnitine (all higher in remission cats). Moderately close correlations were found between these 16 metabolites and variables assessing glycaemic responses (most |r| = 0.31 to 0.69). Five cats in remission relapsed during the study period. No metabolite was identified as a predictor of relapse. Conclusion and clinical importance: This study shows that cats in diabetic remission have abnormal metabolism

Biomarkers of meat and seafood intake : an extensive literature review

Meat, including fish and shellfish, represents a valuable constituent of most balanced diets. Consumption of different types of meat and fish has been associated with both beneficial and adverse health effects. While white meats and fish are generally associated with positive health outcomes, red and especially processed meats have been associated with colorectal cancer and other diseases. The contribution of these foods to the development or prevention of chronic diseases is still not fully elucidated. One of the main problems is the difficulty in properly evaluating meat intake, as the existing self-reporting tools for dietary assessment may be imprecise and therefore affected by systematic and random errors. Dietary biomarkers measured in biological fluids have been proposed as possible objective measurements of the actual intake of specific foods and as a support for classical assessment methods. Good biomarkers for meat intake should reflect total dietary intake of meat, independent of source or processing and should be able to differentiate meat consumption from that of other protein-rich foods; alternatively, meat intake biomarkers should be specific to each of the different meat sources (e.g., red vs. white; fish, bird, or mammal) and/or cooking methods. In this paper, we present a systematic investigation of the scientific literature while providing a comprehensive overview of the possible biomarker(s) for the intake of different types of meat, including fish and shellfish, and processed and heated meats according to published guidelines for biomarker reviews (BFIrev). The most promising biomarkers are further validated for their usefulness for dietary assessment by published validation criteria

Nuclear magnetic resonance spectroscopy based metabolomics to identify novel biomarkers of alcohol-dependence

Alcohol misuse is a ravaging public health and social problem. Its harm can affect the drinkers and the whole society. Alcohol-dependence is a phase of alcohol misuse in which the drinker consumes excessive amounts of alcohol and has a continuous urge to consume alcohol. Current methods of alcohol dependence diagnoses are questionnaires and some biomarkers. However, both methods lack specificity and sensitivity. Metabolomics is a scientific field which deals with the identification and the quantification of the metabolites present in the metabolome using spectroscopic techniques such as nuclear magnetic resonance (NMR). Metabolomics helps to indicate the perturbation in the levels of metabolites in cells and tissues due to diseases or ingestion of any substances. NMR is one of the most widely used spectroscopic techniques in metabolomics because of its reproducibility and speed. Some recent metabolomics studies were conducted on alcohol consumption and alcohol misuse in animals and humans. However, few focused on identifying alcohol dependence novel biomarkers. A sensitive and specific technique such as NMR based metabolomics applied to find novel biomarkers in plasma and urine can be useful to diagnose alcohol-dependence

Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics

Heat induces multiomic and phenotypic stress propagation in zebrafish embryos

Heat alters biology from molecular to ecological levels, but may also have unknown indirect effects. This includes the novel concept that animals exposed to abiotic stress can induce stress in naive receivers. Here, we provide a comprehensive picture of the molecularsignatures of this process, by integrating multiomic and phenotypic data. In individual zebrafish embryos, repeated heat peakselicited both a molecular response and a burst of accelerated growth followed by a growth slowdown in concert with reducedresponses to novel stimuli. Metabolomes of the media of heat treated vs. untreated embryos revealed candidate stress metabolitesincluding sulfur-containing compounds and lipids. These stress metabolites elicited transcriptomic changes in naive receivers related to immune response, extracellular signaling, glycosaminoglycan/keratan sulfate, and lipid metabolism. Consequently, non–heatexposed receivers (exposed to stress metabolites only) experienced accelerated catch-up growth in concert with reduced swimming performance. The combination of heat and stress metabolites accelerated development the most, mediated by apelin signaling. Our results prove the concept of indirect heat-induced stress propagation toward naive receivers, inducing phenotypes comparable with those resulting from direct heat exposure, but utilizing distinct molecular pathways. Group-exposing a nonlaboratory zebrafish line, we independently confirm that the glycosaminoglycan biosynthesis–related gene chs1 and the mucus glycoprotein gene prg4a, functionally connected to the candidate stress metabolite classes sugars and phosphocholine, are differentially expressed in receivers. This hints at the production of Schreckstoff-like cues in receivers, leading to further stress propagation within groups, which may have ecological and animal welfare implications for aquatic populations in a changing climate