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1.
Ester Coutinho Ana M Silva Cláudia Freitas Ernestina Santos 《Journal of medical case reports》2011,5(1):68
Introduction
Pseudotumor cerebri is an entity characterized by elevated intracranial pressure with normal cerebrospinal fluid and no structural abnormalities detected on brain MRI scans. Common secondary causes include endocrine pathologies. Hyperthyroidism is very rarely associated and only three case reports have been published so far.Case presentation
We report the case of a 31-year-old Luso-African woman with clinical symptoms and laboratory confirmation of Graves' disease that presented as pseudotumor cerebri.Conclusion
This is a rare form of presentation of Graves' disease and a rare cause of pseudotumor cerebri. It should be remembered that hyperthyroidism is a potential cause of pseudotumor cerebri.2.
Alexandre Seyer Samia Boudah Simon Broudin Christophe Junot Benoit Colsch 《Metabolomics : Official journal of the Metabolomic Society》2016,12(5):91
Introduction
Due to its proximity with the brain, cerebrospinal fluid (CSF) could be a medium of choice for the discovery of biomarkers of neurological and psychiatric diseases using untargeted analytical approaches.Objectives
This study explored the CSF lipidome in order to generate a robust mass spectral database using an untargeted lipidomic approach.Methods
Cerebrospinal fluid samples from 45 individuals were analyzed by liquid chromatography coupled to high-resolution mass spectrometry method (LC-HRMS). A dedicated data processing workflow was implemented using XCMS software and adapted filters to select reliable features. In addition, an automatic annotation using an in silico lipid database and several MS/MS experiments were performed to identify CSF lipid species.Results
Using this complete workflow, 771 analytically relevant monoisotopic lipid species corresponding to 550 unique lipids which represent five major lipid families (i.e., free fatty acids, sphingolipids, glycerophospholipids, glycerolipids, and sterol lipids) were detected and annotated. In addition, MS/MS experiments enabled to improve the annotation of 304 lipid species. Thanks to LC-HRMS, it was possible to discriminate between isobaric and also isomeric lipid species; and interestingly, our study showed that isobaric ions represent about 50 % of the total annotated lipid species in the human CSF.Conclusion
This work provides an extensive LC/HRMS database of the human CSF lipidome which constitutes a relevant foundation for future studies aimed at finding biomarkers of neurological disorders.3.
Background
Encephalitis with anti-N-methyl-D-aspartate receptor antibodies (anti-NMDAR-Ab) is a rapid-onset encephalitis including psychosis, seizures, various movement disorders and autonomic system disturbances.Case presentation
We report a very unusual case of extensive myelitis associated with anti-NMDAR-Ab. MRI also revealed a hyperintense T2 lesion, non-suggestive of MS, which progressively extended, associated with periventricular gadolinium enhancement visualized on brain MRI. Ophthalmological evaluation showed subclinical right optic neuritis. The absence of anti-AQP4 antibody argued against neuromyelitis optica spectrum disorder. A slight psychomotor slowing prompted us to search for various causes of autoimmune encephalitis. Anti-NMDAR-Ab was found in cerebrospinal fluid.Conclusion
In patients with extensive myelitis who are seronegative for anti-AQP4 antibodies, and after other classical causes have been excluded, the hypothesis of atypical anti-NMDAR-Ab encephalitis should also be considered.4.
Background
Synaptic degeneration is an early pathogenic event in Alzheimer’s disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples.Results
We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer’s disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer’s disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer’s disease from controls with area under the curve of 0.901 (P?<?0.0001).Conclusions
We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials.5.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.6.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.7.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.8.
Introduction
Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.Objectives
Assessment of the quality of raw data processing in untargeted metabolomics.Methods
Five published untargeted metabolomics studies, were reanalyzed.Results
Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.Conclusion
Incomplete raw data processing shows unexplored potential of current and legacy data.9.
Nwora Lance Okeke Damian M. Craig Michael J. Muehlbauer Olga Ilkayeva Meredith E. Clement Susanna Naggie Svati H. Shah 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):23
Introduction
Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.Methods
Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.Results
Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p?=?0.08) and glutamine/valine (p?=?0.003) were elevated in CAD cases compared to controls.Conclusion
SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.10.
Renato de Souza Pinto Lemgruber Kaspar Valgepea Mark P. Hodson Ryan Tappel Sean D. Simpson Michael Köpke Lars K. Nielsen Esteban Marcellin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):35
Introduction
Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.Objective
To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.Methods
Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.Results
Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.Conclusion
Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.11.
Jamie V. de Seymour Stephanie Tu Xiaoling He Hua Zhang Ting-Li Han Philip N. Baker Karolina Sulek 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):79
Introduction
Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.Objective
Investigate the maternal hair metabolome for predictive biomarkers of ICP.Methods
The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.Results
Of 105 metabolites detected in hair, none were significantly associated with ICP.Conclusion
Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.12.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.13.
Sonia Liggi Christine Hinz Zoe Hall Maria Laura Santoru Simone Poddighe John Fjeldsted Luigi Atzori Julian L. Griffin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):52
Introduction
Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.Objectives
Merge in the same platform the steps required for metabolomics data processing.Methods
KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.Results
The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.Conclusion
KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.14.
Gajanan Sathe Chan Hyun Na Santosh Renuse Anil Madugundu Marilyn Albert Abhay Moghekar Akhilesh Pandey 《Clinical proteomics》2018,15(1):29
Background
Cerebrospinal fluid (CSF) is an important source of potential biomarkers that affect the brain. Biomarkers for neurodegenerative disorders are needed to assist in diagnosis, monitoring disease progression and evaluating efficacy of therapies. Recent studies have demonstrated the involvement of tyrosine kinases in neuronal cell death. Thus, neurodegeneration in the brain is related to altered tyrosine phosphorylation of proteins in the brain and identification of abnormally phosphorylated tyrosine peptides in CSF has the potential to ascertain candidate biomarkers for neurodegenerative disorders.Methods
In this study, we used an antibody-based tyrosine phosphopeptide enrichment method coupled with high resolution Orbitrap Fusion Tribrid Lumos Fourier transform mass spectrometer to catalog tyrosine phosphorylated peptides from cerebrospinal fluid. The subset of identified tyrosine phosphorylated peptides was also validated using parallel reaction monitoring (PRM)-based targeted approach.Results
To date, there are no published studies on global profiling of phosphotyrosine modifications of CSF proteins. We carried out phosphotyrosine profiling of CSF using an anti-phosphotyrosine antibody-based enrichment and analysis using high resolution Orbitrap Fusion Lumos mass spectrometer. We identified 111 phosphotyrosine peptides mapping to 66 proteins, which included 24 proteins which have not been identified in CSF previously. We then validated a set of 5 tyrosine phosphorylated peptides in an independent set of CSF samples from cognitively normal subjects, using a PRM-based targeted approach.Conclusions
The findings from this deep phosphotyrosine profiling of CSF samples have the potential to identify novel disease-related phosphotyrosine-containing peptides in CSF.15.
John M. Wentworth Naiara G. Bediaga Megan A. S. Penno Esther Bandala-Sanchez Komal N. Kanojia Konstantinos A. Kouremenos Jennifer J. Couper Leonard C. Harrison ENDIA Study Group 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):130
Background
Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.Method
Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.Results
Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.Conclusion
Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.16.
Antonella Del-Corso Mario Cappiello Roberta Moschini Francesco Balestri Umberto Mura 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):2
Introduction
While the evolutionary adaptation of enzymes to their own substrates is a well assessed and rationalized field, how molecules have been originally selected in order to initiate and assemble convenient metabolic pathways is a fascinating, but still debated argument.Objectives
Aim of the present study is to give a rationale for the preferential selection of specific molecules to generate metabolic pathways.Methods
The comparison of structural features of molecules, through an inductive methodological approach, offer a reading key to cautiously propose a determining factor for their metabolic recruitment.Results
Starting with some commonplaces occurring in the structural representation of relevant carbohydrates, such as glucose, fructose and ribose, arguments are presented in associating stable structural determinants of these molecules and their peculiar occurrence in metabolic pathways.Conclusions
Among other possible factors, the reliability of the structural asset of a molecule may be relevant or its selection among structurally and, a priori, functionally similar molecules.17.
Nadine Strehmel David Strunk Veronika Strehmel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):135
Introduction
Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.Objectives
To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.Methods
The extracted compounds were analyzed by LC/MS and GC/MS.Results
The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.Conclusion
From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.18.
Li-Chiu Wang Hui-Wen Yao Chuan-Fa Chang Shainn-Wei Wang Shih-Min Wang Shun-Hua Chen 《Journal of biomedical science》2017,24(1):94
Background
Enterovirus A71 (EV-A71) infection can induce fatal encephalitis in young children. Clinical reports show that interleukin-6 (IL-6) levels in the serum and cerebrospinal fluid of infected patients with brainstem encephalitis are significantly elevated. We used a murine model to address the significance of endogenous IL-6 in EV-A71 infection.Results
EV-A71 infection transiently increased serum and brain IL-6 protein levels in mice. Most importantly, absence of IL-6 due to gene knockout or depletion of IL-6 using neutralizing monoclonal antibody enhanced the mortality and tissue viral load of infected mice. Absence of IL-6 increased the damage in the central nervous system and decreased the lymphocyte and virus-specific antibody responses of infected mice.Conclusions
Endogenous IL-6 functions to clear virus and protect the host from EV-A71 infection. Our study raises caution over the use of anti-IL-6 antibody or pentoxifylline to reduce IL-6 for patient treatment.19.
Background
This study was aimed to evaluate the ability of left ventricular end-diastolic volume variations (LVEDVV) measured by transesophageal echocardiography (TEE) compared with stroke volume variation (SVV) obtained by the FloTrac/Vigileo monitor to predict fluid responsiveness, in patients undergoing craniotomy with goal direct therapy.Methods
We used SVV obtained by the FloTrac/Vigileo monitor to manage intraoperative hypotension in adult patients undergoing craniotomy (ASA III – IV) after obtaining IRB approval and informed consent. The LVEDVV were measured by TEE through the changes of left ventricular short diameter of axle simultaneously. When cardiac index (CI)?≤?2.5 and SVV?≥?15%, comparisons were made between the two devices before and after volume expansion.Results
We enrolled twenty-six patients referred for craniotomy in this study and 145 pairs of data were obtained. Mean Vigileo-SVV and TEE-LVEDVV were 17.8?±?2.78% and 22.1?±?7.25% before volume expansion respectively, and were 10.95?±?2.8% and 13.58?±?3.78% after volume expansion respectively (P <?0.001). The relationship between Vigileo-SVV and TEE-LVEDVV was significant (r2?=?0.55; p <?0.001). Agreement between Vigileo-SVV and TEE-LVEDVV was 3.3%?±?3.9% (mean bias ± SD, Bland-Altman).Conclusions
For fluid responsiveness of patients during craniotomy in ASA III-IV, LVEDVV measured by left ventricular short diameter of axle using M type echocaidiographic measurement seems an acceptable monitoring indicator. This accessible method has promising clinical applications in situations where volume and cardiac function monitoring is of great importance during surgery.Trial registration
Chinese Clinical Trial Registry, ChiCTR-TRC-13003583, August 20, 2013.20.
Thijs Welle Anna T. Hoekstra Ineke A. J. J. M. Daemen Celia R. Berkers Matheus O. Costa 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):83