PubMed

Related Articles The Advent of Salivary Breast Cancer Biomarker Detection Using Affinity Sensors. Sensors (Basel). 2019 May 23;19(10): Authors: Abrao Nemeir I, Saab J, Hleihel W, Errachid A, Jafferzic-Renault N, Zine N Abstract Breast Cancer is one of the world's most notorious diseases affecting two million women in 2018 worldwide. It is a highly heterogeneous disease, making it difficult to treat. However, its linear progression makes it a candidate for early screening programs, and the earlier its detection the higher the chance of recovery. However, one key hurdle for breast cancer screening is the fact that most screening techniques are expensive, time-consuming, and cumbersome, making them impractical for use in several parts of the world. One current trend in breast cancer detection has pointed to a possible solution, the use of salivary breast cancer biomarkers. Saliva is an attractive medium for diagnosis because it is readily available in large quantities, easy to obtain at low cost, and contains all the biomarkers present in blood, albeit in lower quantities. Affinity sensors are devices that detect molecules through their interactions with biological recognition molecules. Their low cost, high sensitivity, and selectivity, as well as rapid detection time make them an attractive alternative to traditional means of detection. In this review article, we discuss the current status of breast cancer diagnosis, its salivary biomarkers, as well as the current trends in the development of affinity sensors for their detection. PMID: 31126047 [PubMed - indexed for MEDLINE]

Related Articles Transcriptome and Proteome Profiling of Different Colored Rice Reveals Physiological Dynamics Involved in the Flavonoid Pathway. Int J Mol Sci. 2019 May 18;20(10): Authors: Chen X, Tao Y, Ali A, Zhuang Z, Guo D, Guo Q, Riaz A, Zhang H, Xu P, Liao Y, Wang J, Sun C, Xiang Q, Wu X Abstract Black and red rice are rich in both anthocyanin and proanthocyanin content, which belong to a large class of flavonoids derived from a group of phenolic secondary metabolites. However, the molecular pathways and mechanisms underlying the flavonoid biosynthetic pathway are far from clear. Therefore, this study was undertaken to gain insight into physiological factors that are involved in the flavonoid biosynthetic pathway in rice cultivars with red, black, and white colors. RNA sequencing of caryopsis and isobaric tags for relative and absolute quantification (iTRAQ) analyses have generated a nearly complete catalog of mRNA and expressed proteins in different colored rice cultivars. A total of 31,700 genes were identified, of which 3417, 329, and 227 genes were found specific for red, white, and black rice, respectively. A total of 13,996 unique peptides corresponding to 3916 proteins were detected in the proteomes of black, white, and red rice. Coexpression network analyses of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) among the different rice cultivars showed significant differences in photosynthesis and flavonoid biosynthesis pathways. Based on a differential enrichment analysis, 32 genes involved in the flavonoid biosynthesis pathway were detected, out of which only CHI, F3H, ANS, and FLS were detected by iTRAQ. Taken together, the results point to differences in flavonoid biosynthesis pathways among different colored rice cultivars, which may reflect differences in physiological functions. The differences in contents and types of flavonoids among the different colored rice cultivars are related to changes in base sequences of Os06G0162500, Os09G0455500, Os09G0455500, and Os10G0536400. Current findings expand and deepen our understanding of flavonoid biosynthesis and concurrently provides potential candidate genes for improving the nutritional qualities of rice. PMID: 31109052 [PubMed - indexed for MEDLINE]

Related Articles Lack of the brain-specific isoform of apoptosis-inducing factor aggravates cerebral damage in a model of neonatal hypoxia-ischemia. Cell Death Dis. 2018 12 18;10(1):3 Authors: Rodriguez J, Zhang Y, Li T, Xie C, Sun Y, Xu Y, Zhou K, Huo K, Wang Y, Wang X, Andersson D, Ståhlberg A, Xing Q, Mallard C, Hagberg H, Modjtahedi N, Kroemer G, Blomgren K, Zhu C Abstract Apoptosis-inducing factor (AIF) may contribute to neuronal cell death, and its influence is particularly prominent in the immature brain after hypoxia-ischemia (HI). A brain-specific AIF splice-isoform (AIF2) has recently been discovered, but has not yet been characterized at the genetic level. The aim of this study was to determine the functional and regulatory profile of AIF2 under physiological conditions and after HI in mice. We generated AIF2 knockout (KO) mice by removing the AIF2-specific exon and found that the relative expression of Aif1 mRNA increased in Aif2 KO mice and that this increase became even more pronounced as Aif2 KO mice aged compared to their wild-type (WT) littermates. Mitochondrial morphology and function, reproductive function, and behavior showed no differences between WT and Aif2 KO mice. However, lack of AIF2 enhanced brain injury in neonatal mice after HI compared to WT controls, and this effect was linked to increased oxidative stress but not to caspase-dependent or -independent apoptosis pathways. These results indicate that AIF2 deficiency exacerbates free radical production and HI-induced neonatal brain injury. PMID: 30584234 [PubMed - indexed for MEDLINE]

Related Articles Endoscopic Hemostasis in Porcine Gastrointestinal Tract Using CO2 Low-Temperature Plasma Jet. J Surg Res. 2019 02;234:334-342 Authors: Kurosawa M, Takamatsu T, Kawano H, Hayashi Y, Miyahara H, Ota S, Okino A, Yoshida M Abstract BACKGROUND: Recently, atmospheric low-temperature plasma (LTP) has attracted attention as a novel medical tool that might be useful for achieving hemostasis. However, conventional plasma sources are too big for use with endoscopes, and the efficacy of LTP for achieving hemostasis in cases of gastrointestinal bleeding is difficult to investigate. In this study, to solve the problem, we developed a 3D-printed LTP jet that has a diameter of 2.8 mm and metal body for endoscopic use. The characteristics, hemostasis efficacy, and safety were investigated. MATERIALS AND METHODS: On investigating the basic characteristics of the developed plasma jet, the electron densities, gas temperatures, and reactive species were measured by emission spectroscopy and thermocouple. To evaluate the efficacy of such hemostatic treatment, porcine gastrointestinal bleeding was treated with the device. In addition, to investigate the safety of such treatment, the CO2 LTP-treated tissue was compared with tissue that was treated with clipping-based or argon plasma coagulation-based hemostasis for 5 d, and hematoxylin and eosin staining was used to evaluate tissue damage in the treated regions. RESULTS: The measurement of emission spectroscopy, power, and electron density of various gas plasmas suggested that a high-density (1014 cm-3) LTP of CO2 was generated by the LTP jet, and the gas temperature was 41.5°C at 3 mm from the outlet of the LTP jet. The CO2 LTP achieved hemostasis of oozing blood by 70 ± 20 s. In addition, the CO2 LTP resulted in earlier recovery than clipping-based or argon plasma coagulation-based hemostases, and the treated regions had no damage by the CO2 LTP treatment. CONCLUSIONS: These results indicated that the developed LTP plasma jet has the potential to be used for endoscopic hemostasis. PMID: 30527494 [PubMed - indexed for MEDLINE]

Related Articles An integrative UHPLC-MS/MS untargeted metabonomics combined with quantitative analysis of the therapeutic mechanism of Si-Ni-San. Anal Biochem. 2019 02 15;567:128-135 Authors: Wen J, Yang L, Qin F, Zhao L, Xiong Z Abstract A UHPLC-MS/MS untargeted serum metabonomic method combined with quantitative analysis of five potential biomarkers in rat serum was developed and validated, to further understand the anti-liver injury effect of Si-Ni-San and its mechanism on liver injury rats in this study. The metabolites were separated and identified on BEH C18 column (100 mm × 2.1 mm, 1.7 μm) using the ACQUITY UHPLC-MS system (Waters Corp., Milford, MA, USA). Principal component analysis (PCA) was used to identify potential biomarkers. Primary potential biomarkers including phenylalanine, tryptophan, Glycochenodeoxycholic acid (GCDCA) and hysophosphatidylcholine (LPC), which were related to amino acid metabolism, lipid metabolism, bile acid biosynthesis and oxidation-antioxidation balance, were found in the untargeted metabonomic research. Moreover, these targeted biomarkers were further separated and quantified in multiple-reaction monitoring (MRM) with positive ionization mode. The proposed method was linear for each analyte with correlation coefficients over 0.99. The intra- and inter-day precision values (relative standard deviation, RSD) were less than 13.1% and accuracy (relative error, RE) was from -9.5% to 10.3% at all quality control (QC) levels. The validated method was successfully applied to study the serum samples of control group, model group, positive control group (silymarin group) and Si-Ni-San group in rats. PMID: 30367881 [PubMed - indexed for MEDLINE]

Related Articles Comprehensive metabolite profiling of Solanum tuberosum L. (potato) leaves by HPLC-ESI-QTOF-MS. Food Res Int. 2018 10;112:390-399 Authors: Rodríguez-Pérez C, Gómez-Caravaca AM, Guerra-Hernández E, Cerretani L, García-Villanova B, Verardo V Abstract The objective of this work was to study the non-targeted metabolite profiling of potato leaves using high performance liquid chromatography coupled to quadrupole-time of flight mass spectrometry (HPLC-ESI-QTOF-MS). The mass accuracy, true isotopic pattern in both MS and MS/MS spectra provided by QTOF-MS made possible the tentative identification of 109 compounds present in potato leaves, including organic acids, amino acids and derivatives, phenolic acids, flavonoids, iridoids, oxylipins and other polar and semi-polar compounds. Among them, 32 compounds have been found for the first time in potato leaf and in the Solanaceae family. Quinic acid and its derivatives represented more than 45% of the bioactive compounds quantified in the extract. Derivatives of hydroxybenzoic acid and gentisic acid were also founded at considerable concentrations. This study shed light on the composition of potato leaf extract and will serve as a base for further research into activities of the various compounds found in this matrix which has demonstrated a potential use as functional ingredients. PMID: 30131151 [PubMed - indexed for MEDLINE]

Related Articles CD38-Mediated Immunosuppression as a Mechanism of Tumor Cell Escape from PD-1/PD-L1 Blockade. Cancer Discov. 2018 09;8(9):1156-1175 Authors: Chen L, Diao L, Yang Y, Yi X, Rodriguez BL, Li Y, Villalobos PA, Cascone T, Liu X, Tan L, Lorenzi PL, Huang A, Zhao Q, Peng D, Fradette JJ, Peng DH, Ungewiss C, Roybal J, Tong P, Oba J, Skoulidis F, Peng W, Carter BW, Gay CM, Fan Y, Class CA, Zhu J, Rodriguez-Canales J, Kawakami M, Byers LA, Woodman SE, Papadimitrakopoulou VA, Dmitrovsky E, Wang J, Ullrich SE, Wistuba II, Heymach JV, Qin FX, Gibbons DL Abstract Although treatment with immune checkpoint inhibitors provides promising benefit for patients with cancer, optimal use is encumbered by high resistance rates and requires a thorough understanding of resistance mechanisms. We observed that tumors treated with PD-1/PD-L1 blocking antibodies develop resistance through the upregulation of CD38, which is induced by all-trans retinoic acid and IFNβ in the tumor microenvironment. In vitro and in vivo studies demonstrate that CD38 inhibits CD8+ T-cell function via adenosine receptor signaling and that CD38 or adenosine receptor blockade are effective strategies to overcome the resistance. Large data sets of human tumors reveal expression of CD38 in a subset of tumors with high levels of basal or treatment-induced T-cell infiltration, where immune checkpoint therapies are thought to be most effective. These findings provide a novel mechanism of acquired resistance to immune checkpoint therapy and an opportunity to expand their efficacy in cancer treatment.Significance: CD38 is a major mechanism of acquired resistance to PD-1/PD-L1 blockade, causing CD8+ T-cell suppression. Coinhibition of CD38 and PD-L1 improves antitumor immune response. Biomarker assessment in patient cohorts suggests that a combination strategy is applicable to a large percentage of patients in whom PD-1/PD-L1 blockade is currently indicated. Cancer Discov; 8(9); 1156-75. ©2018 AACR.See related commentary by Mittal et al., p. 1066This article is highlighted in the In This Issue feature, p. 1047. PMID: 30012853 [PubMed - indexed for MEDLINE]

Related Articles Identification of Novel Pathways of Osimertinib Disposition and Potential Implications for the Outcome of Lung Cancer Therapy. Clin Cancer Res. 2018 05 01;24(9):2138-2147 Authors: MacLeod AK, Lin, Huang JT, McLaughlin LA, Henderson CJ, Wolf CR Abstract Purpose: Osimertinib is a third-generation inhibitor of the epidermal growth factor receptor used in treatment of non-small cell lung cancer. A full understanding of its disposition and capacity for interaction with other medications will facilitate its effective use as a single agent and in combination therapy.Experimental Design: Recombinant cytochrome P450s and liver microsomal preparations were used to identify novel pathways of osimertinib metabolism in vitro A panel of knockout and mouse lines humanized for pathways of drug metabolism were used to establish the relevance of these pathways in vivoResults: Although some osimertinib metabolites were similar in mouse and human liver samples there were several significant differences, in particular a marked species difference in the P450s involved. The murine Cyp2d gene cluster played a predominant role in mouse, whereas CYP3A4 was the major human enzyme responsible for osimertinib metabolism. Induction of this enzyme in CYP3A4 humanized mice substantially decreased circulating osimertinib exposure. Importantly, we discovered a further novel pathway of osimertinib disposition involving CPY1A1. Modulation of CYP1A1/CYP1A2 levels markedly reduced parent drug concentrations, significantly altering metabolite pharmacokinetics (PK) in humanized mice in vivoConclusions: We demonstrate that a P450 enzyme expressed in smokers' lungs and lung tumors has the capacity to metabolise osimertinib. This could be a significant factor in defining the outcome of osimertinib treatment. This work also illustrates how P450-humanized mice can be used to identify and mitigate species differences in drug metabolism and thereby model the in vivo effect of critical metabolic pathways on anti-tumor response. Clin Cancer Res; 24(9); 2138-47. ©2018 AACR. PMID: 29437786 [PubMed - indexed for MEDLINE]

29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/11/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/11/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/11/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/11/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/11/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/11/09PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Effects of Selective Exclusion of Patients on Preterm Birth Test Performance. Obstet Gynecol. 2019 Nov 04;: Authors: Boniface JJ, Burchard J, Saade GR Abstract The need to reduce the rate of preterm delivery and the recent emergence of technologies that measure hundreds of biological analytes (eg, genomics, transcriptomics, metabolomics, proteomics; collectively referred to as "omics approaches") have led to proliferation of potential diagnostic biomarkers. On review of the literature, a concern must be raised regarding experimental design and data analysis reporting. Specifically, inaccurate performance has often been reported after selective exclusion of patients around the definition boundary of preterm birth. For example, authors may report the performance of a preterm delivery predictor by using patients who delivered early preterm compared with deliveries at 37 weeks of gestation or greater. A key principle that must be maintained during the development of any predictive test is to communicate performance for all patients for whom the test will be applicable clinically (ie, the intended-use population), which for prediction of preterm birth includes patients delivering throughout the spectrum of gestational ages, as this is what is to be predicted, and not known at the time of testing. Using biomarker data collected from the U.S.-based Proteomic Assessment of Preterm Risk clinical trial, we provide examples where the area under the receiver operating characteristic curve for the same test artifactually improves from 0.68 (for preterm delivery at less than 37 weeks of gestation) or 0.76 (for preterm delivery at less than 32 weeks of gestation) to 0.91 when patients who deliver late preterm are excluded. We review this phenomenon in this commentary and offer recommendations for clinicians and investigators going forward. FUNDING SOURCE:: Sera Prognostics. PMID: 31698391 [PubMed - as supplied by publisher]

Related Articles Coupling metabolomics analysis and DOE optimization strategy towards enhanced IBDV production by chicken embryo fibroblast DF-1 cells. J Biotechnol. 2019 Nov 04;: Authors: Lin J, Yi X, Zhuang Y Abstract Infectious bursal disease (IBD) caused by IBD virus (IBDV) is highly contagious viral and vaccination in chicken embryo has been an effective mean to prevent acute infection. However, the current production of IBDV vaccine faces serious batch instability and external contamination. The chicken embryonic fibroblast cell line DF-1 is widely used for the proliferation of avian viruses and vaccine production. Thus, optimizing the production of IBDV by DF-1 cells has an important application value. Combining metabolomics analysis and a Design of Experiments (DOE) statistical strategy, this study successfully optimized the process of IBDV production by DF-1 cells. Differential analysis and time series analysis of metabolite data in both IBDV-infected and uninfected DF-1 cells were performed by multivariate statistical analysis. The results showed that the intracellular metabolite intensities of glycolysis, the pentose phosphate pathway, the nucleoside synthesis pathway, lipid metabolism, and glutathione metabolism were upregulated, and the TCA cycle underwent a slight downregulation after IBDV infection of DF-1 cells. Based on the metabolome results and DOE statistical optimization method, the additive components suitable for IBDV proliferation were determined. The IBDV titer increased by 20.7 times upon exogenous addition of cysteine, methionine, lysine and nucleosides in the control medium, which is consistent with the predicted result (20.0 times) by a multivariate quadratic equation. This study provides a strategy for the efficient production of IBDV vaccines and could potentially be utilized to improve the production of other viral vaccines and biologics. PMID: 31697974 [PubMed - as supplied by publisher]

Related Articles High-Resolution Ion Mobility Spectrometry-Mass Spectrometry of Isomeric/Isobaric Ribonucleotide Variants. J Mass Spectrom. 2019 Nov 07;: Authors: Kenderdine T, Nemati R, Baker A, Palmer M, Ujma J, Fitzgibbon M, Deng L, Royzen M, Langridge J, Fabris D Abstract In this report, we explored the benefits of cyclic ion mobility (cIM) mass spectrometry in the analysis of isomeric post-transcriptional modifications of RNA. Standard methyl-cytidine samples were initially utilized to test the ability to correctly distinguish different structures sharing the same elemental composition, and thus molecular mass. Analyzed individually, the analytes displayed characteristic arrival times (tD ) determined by the different positions of the modifying methyl groups onto the common cytidine scaffold. Analyzed in mixture, the widths of the respective signals resulted in significant overlap that initially prevented their resolution on the tD scale. The separation of the four isomers was achieved by increasing the number of passes through the cIM device, which enabled to fully differentiate the characteristic ion mobility behaviors associated with very subtle structural variations. The placement of the cIM device between the mass-selective quadrupole and the time-of-flight analyzer allowed us to perform gas-phase activation of each of these ion populations, which had been first isolated according to a common mass-to-charge ratio, and then separated on the basis of different ion mobility behaviors. The observed fragmentation patterns confirmed the structures of the various isomers, thus substantiating the benefits of complementing unique tD information with specific fragmentation data to reach more stringent analyte identification. These capabilities were further tested by analyzing natural mono-nucleotide mixtures obtained by exonuclease digestion of total RNA extracts. In particular, the combination of cIM separation and post-mobility dissociation allowed us to establish the composition of methyl-cytidine and methyl-adenine components present in the entire transcriptome of HeLa cells. For this reason, we expect that this technique will benefit not only epitranscriptomics studies requiring the determination of identity and expression levels of RNA modifications, but also metabolomics investigations involving the analysis of natural extracts that may possibly contain subsets of isomeric/isobaric species. PMID: 31697854 [PubMed - as supplied by publisher]

Related Articles Metabolomics profiles associated with HbA1c levels in patients with type 2 diabetes. PLoS One. 2019;14(11):e0224274 Authors: Yun JH, Lee HS, Yu HY, Kim YJ, Jeon HJ, Oh T, Kim BJ, Choi HJ, Kim JM Abstract Glycated hemoglobin (HbA1c) is an indicator of the average blood glucose concentration. Failing to control HbA1c levels can accelerate the development of complications in patients with diabetes. Although metabolite profiles associated with HbA1c level in diabetes patients have been characterized using different platforms, more studies using high-throughput technology will be helpful to identify additional metabolites related to diabetes. Type 2 diabetes (T2D) patients were divided into two groups based on the HbA1c level: normal (HbA1c ≤6%) and high (HbA1c ≥9%) in both discovery and replication sets. A targeted metabolomics approach was used to quantify serum metabolites and multivariate logistic regression was used to identify significant differences between groups. The concentrations of 22 metabolites differed significantly between the two groups in the discovery set. In the replication set, the levels of 21 metabolites, including 16 metabolites identified in the discovery set, differed between groups. Among these, concentrations of eleven amino acids and one phosphatidylcholine (PC), lysoPC a C16:1, were higher and four metabolites, including three PCs (PC ae C36:1, PC aa C26:0, PC aa C34:2) and hexose, were lower in the group with normal HbA1c group than in the group with high HbA1c. Metabolites with high concentrations in the normal HbA1c group, such as glycine, valine, and PCs, may contribute to reducing HbA1c levels in patients with T2D. The metabolite signatures identified in this study provide insight into the mechanisms underlying changes in HbA1c levels in T2D. PMID: 31697702 [PubMed - in process]

Related Articles The MRL/MpJ mouse strain is not protected from muscle atrophy and weakness after rotator cuff tear. J Orthop Res. 2019 Nov 07;: Authors: Talarek JR, Piacentini AN, Konja AC, Wada S, Swanson JB, Nussenzweig SC, Dines JS, Rodeo SA, Mendias CL Abstract Chronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared to the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing, and shotgun metabolomics and lipidomics were also performed. Muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis-associated genes and a reduction in mitochondrial metabolism genes. Markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain-specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear. This article is protected by copyright. All rights reserved. PMID: 31696955 [PubMed - as supplied by publisher]

Related Articles Metabolic framework for the improvement of autism spectrum disorders by a modified ketogenic diet: a pilot study. J Proteome Res. 2019 Nov 07;: Authors: Mu C, Corley MJ, Lee RWY, Wong M, Pang A, Arakaki G, Miyamoto R, Rho JM, Mickiewicz B, Dowlatabadi R, Vogel HJ, Korchemagin Y, Shearer J Abstract The ketogenic diet (KD) can improve the core features of autism spectrum disorders (ASD) in some children, but the effects on overall metabolism remain unclear. This pilot study investigated behavioural parameters in relation to blood metabolites and trace elements in a cohort of 10 typically developed controls (TC) and 17 children with ASD at baseline and following a 3-month treatment with a modified KD regimen. A non-targeted, multiplatform metabolomics approach was employed, including Gas Chromatography-Mass Spectrometry, 1H Nuclear Magnetic Resonance Spectroscopy, and Inductively Coupled Plasma-Mass Spectrometry. Associations between plasma metabolites, trace elements, and behavior scores were investigated. Employing a combination of metabolomics platforms, 118 named metabolites and 73 trace elements were assessed. Relative to TC, a combination of glutamate, galactonate, and glycerol discriminated ASD with 88% accuracy. ASD had higher concentrations of galactose intermediates, gut microbe-derived trimethylamine N-oxide and N-acetylserotonin, and lower concentrations of 3-hydroxybutyrate and selenium at baseline. Following 3mo KD intervention, levels of circulating ketones and acetylcarnitine were increased. KD restored lower selenium levels in ASD to that of controls and correlation analysis identified a novel negative correlation between changes in selenium and behaviour scores. Based on the different behavior responses to the KD, we found that high responders had greater concentrations of 3-hydroxybutyrate and ornithine, with lower galactose. These findings enhance our current understanding of metabolic derangements present in ASD and may be of utility in predicting favorable responses to KD intervention. PMID: 31696714 [PubMed - as supplied by publisher]