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1.
Metabolomics of biomarker discovery in ovarian cancer: a systematic review of the current literature
Onur Turkoglu Amna Zeb Stewart Graham Thomas Szyperski J. Brian Szender Kunle Odunsi Ray Bahado-Singh 《Metabolomics : Official journal of the Metabolomic Society》2016,12(4):60
Introduction
Metabolomics is the emerging member of “omics” sciences advancing the understanding, diagnosis and treatment of many cancers, including ovarian cancer (OC).Objectives
To systematically identify the metabolomic abnormalities in OC detection, and the dominant metabolic pathways associated with the observed alterations.Methods
An electronic literature search was performed, up to and including January 15th 2016, for studies evaluating the metabolomic profile of patients with OC compared to controls. QUADOMICS tool was used to assess the quality of the twenty-three studies included in this systematic review.Results
Biological samples utilized for metabolomic analysis include: serum/plasma (n = 13), urine (n = 4), cyst fluid (n = 3), tissue (n = 2) and ascitic fluid (n = 1). Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in OC. Increased levels of tricarboxylic acid cycle intermediates and altered metabolites of the glycolytic pathway pointed to perturbations in cellular respiration. Alterations in lipid metabolism included enhanced fatty acid oxidation, abnormal levels of glycerolipids, sphingolipids and free fatty acids with common elevations of palmitate, oleate, and myristate. Increased levels of glutamine, glycine, cysteine and threonine were commonly reported while enhanced degradations of tryptophan, histidine and phenylalanine were found. N-acetylaspartate, a brain amino acid, was found elevated in primary and metastatic OC tissue and ovarian cyst fluid. Further, elevated levels of ketone bodies including 3-hydroxybutyrate were commonly reported. Increased levels of nucleotide metabolites and tocopherols were consistent through out the studies.Conclusion
Metabolomics presents significant new opportunities for diagnostic biomarker development, elucidating previously unknown mechanisms of OC pathogenesis.2.
Ole Østergaard Christoffer Tandrup Nielsen Julia T. Tanassi Line V. Iversen Søren Jacobsen Niels H. H. Heegaard 《Clinical proteomics》2017,14(1):23
Background
The pathogenesis of systemic lupus erythematosus (SLE) is poorly understood but has been linked to defective clearance of subcellular particulate material from the circulation. This study investigates the origin, formation, and specificity of circulating microparticles (MPs) in patients with SLE based on comprehensive MP proteome profiling using patients with systemic sclerosis (SSc) and healthy donors (HC) as controls.Methods
We purified MPs from platelet-poor plasma using differential centrifugation of samples from SLE (n = 45), SSc (n = 38), and two sets of HC (n = 35, n = 25). MP proteins were identified and quantitated after trypsin digestion by liquid chromatography-tandem mass spectrometry. The abundance of specific proteins was compared between the groups using univariate statistics and false discovery rate correction for multiple comparisons. Specific proteins and protein ratios were explored for diagnostic and disease activity information using receiver-operating characteristic curves and by analysis of correlations of protein abundance with disease activity scores.Results
We identify and quantitate more than 1000 MP proteins and show that a subpopulation of SLE-MPs (which we propose to call luposomes) are highly specific for SLE, i.e. not found in MP preparations from HC or patients with another autoimmune, systemic disease, SSc. In SLE-MPs platelet proteins and mitochondrial proteins are significantly diminished, cytoskeletal proteins deranged, and glycolytic enzymes and apoptotic proteins significantly increased.Conclusions
Normal MPs are efficiently removed in SLE, but aberrant MPs, derived from non-lymphoid leukocytes, are less efficiently removed and abundantly produced leading to an altered MP proteome in SLE. The data suggest that an abnormal generation of MPs may partake in the pathology of SLE and that new diagnostic, monitoring, and treatment strategies targeting these processes may be advantageous.3.
Amanda J. Lloyd Manfred Beckmann Kathleen Tailliart Wendy Y. Brown John Draper David Allaway 《Metabolomics : Official journal of the Metabolomic Society》2016,12(4):72
Introduction
Dog breeds are a consequence of artificial selection for specific attributes. These closed genetic populations have metabolic and physiological characteristics that may be revealed by metabolomic analysis.Objectives
To identify and characterise the drivers of metabolic differences in the fasted plasma metabolome and then determine metabolites differentiating breeds.Methods
Fasted plasma samples were collected from dogs maintained under two environmental conditions (controlled and client-owned at home). The former (n = 33) consisted of three breeds (Labrador Retriever, Cocker Spaniel and Miniature Schnauzer) fed a single diet batch, the latter (n = 96), client-owned dogs consisted of 9 breeds (Beagle, Chihuahua, Cocker Spaniel, Dachshund, Golden Retriever, Greyhound, German Shepherd, Labrador Retriever and Maltese) consuming various diets under differing feeding regimens. Triplicate samples were taken from Beagle (n = 10) and Labrador Retriever (n = 9) over 3 months. Non-targeted metabolite fingerprinting was performed using flow infusion electrospray-ionization mass spectrometry which was coupled with multivariate data analysis. Metadata factors including age, gender, sexual status, weight, diet and breed were investigated.Results
Breed differences were identified in the plasma metabolome of dogs housed in a controlled environment. Triplicate samples from two breeds identified intra-individual variability, yet breed separation was still observed. The main drivers of variance in dogs maintained in the home environment were associated with breed and gender. Furthermore, metabolite signals were identified that discriminated between Labrador Retriever and Cocker Spaniels in both environments.Conclusion
Metabolite fingerprinting of plasma samples can be used to investigate breed differences in client-owned dogs, despite added variance of diet, sexual status and environment.4.
Miguel A. Velasco Rafael Raya Luca Muzzioli Daniela Morelli Abraham Otero Marco Iosa Febo Cincotti Eduardo Rocon 《Biomedical engineering online》2017,16(1):74
Background
This paper presents the preliminary results of a novel rehabilitation therapy for cervical and trunk control of children with cerebral palsy (CP) based on serious videogames and physical exercise.Materials
The therapy is based on the use of the ENLAZA Interface, a head mouse based on inertial technology that will be used to control a set of serious videogames with movements of the head.Methods
Ten users with CP participated in the study. Whereas the control group (n = 5) followed traditional therapies, the experimental group (n = 5) complemented these therapies with a series of ten sessions of gaming with ENLAZA to exercise cervical flexion–extensions, rotations and inclinations in a controlled, engaging environment.Results
The ten work sessions yielded improvements in head and trunk control that were higher in the experimental group for Visual Analogue Scale, Goal Attainment Scaling and Trunk Control Measurement Scale (TCMS). Significant differences (27% vs. 2% of percentage improvement) were found between the experimental and control groups for TCMS (p < 0.05). The kinematic assessment shows that there were some improvements in the active and the passive range of motion. However, no significant differences were found pre- and post-intervention.Conclusions
Physical therapy that combines serious games with traditional rehabilitation could allow children with CP to achieve larger function improvements in the trunk and cervical regions. However, given the limited scope of this trial (n = 10) additional studies are needed to corroborate this hypothesis.5.
Background
Studies have shown an increase in mortality and morbidity during heatwaves, especially among the elderly. We assessed the knowledge of the general population of Brussels and Amsterdam on groups at risk and protective measures for heat-related health effects.Results
Six locations with mixed populations were selected in each city. Passer-by’s in both cities were asked to participate in a short survey. Respondents in Brussels (n = 120) had significantly more knowledge on risk groups and protective measures than respondents in Amsterdam (n = 133). In both cities, individuals with higher education had better knowledge on risk groups and protective measures than individuals with lower education.Conclusions
Efforts at heat-awareness raising must be strengthened, especially in Amsterdam, and public health actions should effectively target vulnerable groups with lower education in both cities.6.
Basetti Madhu Greg L. Shaw Anne Y. Warren David E. Neal John R. Griffiths 《Metabolomics : Official journal of the Metabolomic Society》2016,12(7):120
Introduction
The androgen receptor (AR) is the master regulator of prostate cancer cell metabolism. Degarelix is a novel gonadotrophin-releasing hormone blocker, used to decrease serum androgen levels in order to treat advanced human prostate cancer. Little is known of the rapid metabolic response of the human prostate cancer tissue samples to the decreased androgen levels.Objectives
To investigate the metabolic responses in benign and cancerous tissue samples from patients after treatment with Degarelix by using HRMAS 1H NMR spectroscopy.Methods
Using non-destructive HR-MAS 1H NMR spectroscopy we analysed the metabolic changes induced by decreased AR signalling in human prostate cancer tissue samples. Absolute concentrations of the metabolites alanine, lactate, glutamine, glutamate, citrate, choline compounds [t-choline = choline + phosphocholine (PC) + glycerophosphocholine (GPC)], creatine compounds [t-creatine = creatine (Cr) + phosphocreatine (PCr)], taurine, myo-inositol and polyamines were measured in benign prostate tissue samples (n = 10), in prostate cancer specimens from untreated patients (n = 7) and prostate cancer specimens from patients treated with Degarelix (n = 6).Results
Lactate, alanine and t-choline concentrations were significantly elevated in high-grade prostate cancer samples when compared to benign samples in untreated patients. Decreased androgen levels resulted in significant decreases of lactate and t-choline concentrations in human prostate cancer biopsies.Conclusions
The reduced concentrations of lactate and t-choline metabolites due to Degarelix could in principle be monitored by in vivo 1H MRS, which suggests that it would be possible to monitor the effects of physical or chemical castration in patients by that non-invasive method.7.
Stewart F. Graham Olivier P. Chevallier Praveen Kumar Onur Türkoğlu Ray O. Bahado-Singh 《Metabolomics : Official journal of the Metabolomic Society》2016,12(4):62
Introduction
Autism spectrum disorders (ASD) is a group of neurodevelopmental disorders believed to have a multifactorial basis. Presently, diagnosis is based on behavioral and developmental signs in children before the age of 3 and no reliable clinical biomarkers are available for early detection.Objectives
This study aimed to biochemically profile the cerebellum from post-mortem human brain from ASD sufferers (n = 11) and compare their profiles to that of age-matched controls (n = 11) with no known brain disorder.Methods
Using liquid chromatography combined with LTQ-Orbitrap mass spectrometry we detected 14,328 features in ESI+ mode in polar extracts of post-mortem brain.Results
Of these only 37 were found to be statistically significantly different between ASD and controls (p < 0.05; fdr < 0.05). A panel of four features had a predictive power of 96.64 %, following statistical cross validation, for ASD detection. This model produced an AUC = 0.874 (CI 0.768–0.944) and a Fisher’s exact score of p = 4.50E?29.Conclusion
Whilst at this time we were unable to chemically identify the four features of interest we believe that this study underscores the potential value of high resolution metabolomics for the study of ASD. Further characterization of the polar metabolome of post mortem ASD brains could lead to the identification of potential biomarkers and novel therapeutics for the disease. The development of accurate biomarkers could assist in the early detection of ASD and promote early intervention strategies to improve outcome.8.
Elavarasan Subramani Mainak Dutta Manivannan Jothiramajayam Mamata Joshi Sudha Srivastava Anita Mukherjee Baidyanath Chakravarty Koel Chaudhury 《Metabolomics : Official journal of the Metabolomic Society》2016,12(6):99
Introduction
Genital tuberculosis (GTB) in women is one of the common causes of infertility in emerging countries. As an intracellular pathogen, Mycobacterium tuberculosis in the endometrium significantly alters the host metabolism in dormant GTB cases. Nuclear magnetic resonance (NMR) based metabolic profiling has emerged as a useful tool for identification of biomarkers in biological fluids.Objective
To investigate NMR based serum metabolic profile of dormant GTB women as compared to controls.Methods
Dormant GTB women (n = 26) and unexplained infertile women (controls; n = 26), healthy proven fertile women undergoing voluntary sterilization (n = 25) and women undergoing recurrent spontaneous miscarriage (RSM) (n = 27) were included in the study. 700 MHz proton NMR spectra of serum collected from these patients were recorded. Multivariate analysis including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structure-discriminant analysis was applied to all the spectra. Association of dysregulated serum metabolites with our earlier findings related to altered endometrial tissue metabolites in dormant GTB women was studied using multiple correlation analysis.Results
This study indicates a clear metabolic differentiation between women with dormant GTB and controls. Metabolites including 3-hydroxybutyrate, succinate, citrate, acetate, l-glutamine, l-lysine, glutamate, l-threonine and 1-methyl histidine were found to be significantly upregulated in serum of women with dormant GTB compared with controls. Pearson’s correlation analysis showed a significant correlation between the expression of endometrial tissue and serum metabolites.Conclusions
The set of identified metabolites may be considered as candidate markers for the diagnosis of dormant GTB and help clinicians in early therapeutic management.9.
Shayne Mason A. Marceline Tutu van Furth Regan Solomons Ron A. Wevers Mari van Reenen Carolus J. Reinecke 《Metabolomics : Official journal of the Metabolomic Society》2016,12(7):110
Introduction
Tuberculous meningitis (TBM) is a severe manifestation of tuberculosis, presenting with high morbidity and mortality in children. Existing diagnostic methods for TBM are invasive and time-consuming and the need for highly sensitive and selective diagnosis remains high on the TBM agenda.Objective
Our aim was to exploit metabolomics as an approach to identify metabolites as potential diagnostic predictors for children with TBM through a non-invasive means.Methods
Urine samples selected for this study were from three paediatric groups: patients with confirmed TBM (n = 12), patients clinically suspected with TBM but later confirmed to be negative (n = 19) and age-matched controls (n = 29). Metabolomics data were generated through gas chromatography–mass spectrometry analysis and important metabolites were identified according to standard statistical procedures used for metabolomics data.Results
A global metabolite profile that characterized TBM was developed from the data, reflecting the host and microbial responses. Nine different logistic regression models were fitted to selected metabolites for the best combination as predictors for TBM. Four metabolites—methylcitric, 2-ketoglutaric, quinolinic and 4-hydroxyhippuric acids—showed excellent diagnostic ability and provided prognostic insight into our TBM patients.Conclusions
This study is the first to illustrate holistically the metabolic complexity of TBM and provided proof-of-concept that a biosignature of urinary metabolites can be defined for non-invasive diagnosis and prognosis of paediatric TBM patients. The biosignature should be developed and validated through future prospective studies to generate a medical algorithm for diagnosis in the initial stages of the disease and for monitoring of treatment strategies.10.
Yuka Torii Yoshihiko Kawano Hajime Sato Kazunori Sasaki Tamaki Fujimori Jun-ichi Kawada Osamu Takikawa Chai K. Lim Gilles J. Guillemin Yoshiaki Ohashi Yoshinori Ito 《Metabolomics : Official journal of the Metabolomic Society》2016,12(5):84
Introduction
Influenza-associated encephalopathy is a serious complication of influenza and is the most common form of acute encephalitis/encephalopathy in Japan. The number of reports from other countries is increasing, reflecting international recognition and concern.Objectives
Identification of a specific biomarker could provide important clues about the pathophysiology of influenza-associated encephalopathy.Methods
During the 2009–2011 flu seasons, 34 pediatric patients hospitalized with influenza complications, including influenza-associated encephalopathy, were enrolled in the study. Serum samples were collected during the acute and convalescent phases of disease. Patients were classified into encephalopathy (n = 12) and non-encephalopathy (n = 22) groups. Serum metabolites were identified and quantified by capillary electrophoresis coupled with time-of-flight mass spectrometry. Quantified data were evaluated for comparative analysis. Subsequently, a total of 55 patients with or without encephalopathy were enrolled for absolute quantification of serum kynurenine and quinolinic acid.Results
Based on m/z values and migration times, 136 metabolites were identified in serum samples. During the acute phase of disease, three metabolites (succinic acid, undecanoic acid, and kynurenine) were significantly higher, and two other metabolites (decanoic acid and cystine) were significantly lower, in the encephalopathy group compared to the non-encephalopathy group (p = 0.012, 0.022, 0.044, 0.038, 0.046, respectively). In a larger patient group, serum kynurenine and its downstream product in tryptophan metabolism, quinolinic acid, a known neurotoxin, were significantly higher in the encephalopathy than the non-encephalopathy without febrile seizure group.Conclusion
Comprehensive metabolite profiles revealed five metabolites as potential biomarkers for influenza-associated encephalopathy; the tryptophan–kynurenine metabolic process could be associated with its pathophysiology.11.
Emmanuel Amabebe Steven Reynolds Victoria L. Stern Jennifer L. Parker Graham P. Stafford Martyn N. Paley Dilly O. C. Anumba 《Metabolomics : Official journal of the Metabolomic Society》2016,12(4):67
Introduction
Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles.Objectives
We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB.Methods
A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer.Results
Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = ?0.62, p < 0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB < 37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not.Conclusion
High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation.12.
Background
Complications of ostomy significantly affect the quality of life of ostomates. There is little evidence on the rate of long-term complications in ostomates, especially from the developing countries which include Sri Lanka. This study was aimed to describe the long-term complications of enteral ostomies and their contributory factors.Methods
A retrospective analysis was carried out on 192 patients who underwent ostomy creation over a period of 5 years. Data on type of complications, age, sex, type of ostomy, type of surgery and perioperative care by enteric stoma therapist were gathered. Associations were established using Chi square test and multiple logistic regression.Results
Out of 192 patients, only 146 patients presented regularly for follow up. The mean follow up duration was 28 months (range: 3–183). Around 34.2% developed surgical long-term complications related to the ostomy. Common complications were prolapse (n = 24, 16.4%), skin excoriation (n = 22, 15.1%) and parastomal hernia (n = 14, 9.6%). Overall complication rate was significantly less in loop ostomies (p < 0.05) and defunctioning ostomies (p < 0.05). Skin excoriation was significantly high in males (p < 0.05) and in ileostomies (p < 0.001). Parastomal hernia was commoner in end ostomies (p < 0.05). Perioperative care by enteric stoma therapist reduced the overall and specific complications (p < 0.001).Conclusion
The overall complication rate in our cohort of patients was 34.2%. The perioperative care of a stoma therapist may be very effective in preventing complications particularly in a setting with limited resources.13.
Lu Fang Piyushkumar A. Mundra Fenling Fan Abby Galvin Jacquelyn M. Weir Gerard Wong Jaye Chin-Dusting Flavia Cicuttini Peter Meikle Anthony Michael Dart 《Metabolomics : Official journal of the Metabolomic Society》2016,12(8):136
Introduction
Rheumatoid arthritis (RA) is linked to increased cardiovascular morbidity and mortality, not completely explained by traditional risk factors. Importantly, the increased risk occurs despite lower levels of total and low-density lipoprotein cholesterol. Whilst systemic inflammation may be a factor, it is possible that changes in individual lipid species contribute to the increased cardiovascular risk.Objectives
In the present study, we characterized plasma lipidomic profiles in patients with RA in comparison with healthy controls.Methods
Patients with RA (n = 32) and age- and gender-matched healthy volunteers (n = 84) were recruited. Fasting plasma lipid profiles were measured using electrospray-ionisation tandem mass spectrometry. 24 lipid classes and subclasses were measured.Results
Patients with RA had normal total, low-density lipoprotein and high-density lipoprotein cholesterol, but higher triglycerides than controls. Five lipid classes (dihydroceramides, alkylphosphatidylethanolamine, alkenylphosphatidylethanolamine, lysophosphatidylinositol, phosphatidylserine) differed between patients with RA and controls. Then we measured 36 lipid species within these 5 classes and found that 11 lipid species were different between patients with RA and controls. Three lipid classes (dihydroceramides, lysophosphatidylinositol, phosphatidylserine) and 10 lipid species remained significantly associated with RA after adjusting for age, sex, body mass index, current smoking, systolic blood pressure and anti-hypertensive treatment in a binary logistic regression model.Conclusion
This study has identified lipid alterations in RA. These alterations of lipids warrant further investigation as they may be associated with accelerated atherosclerosis and joint inflammation in patient with RA.14.
Fernanda Bertuccez Cordeiro Thais Regiani Cataldi Lívia do Vale Teixeira da Costa Beatriz Zappellini de Souza Daniela Antunes Montani Renato Fraietta Carlos Alberto Labate Agnaldo Pereira Cedenho Edson Guimarães Lo Turco 《Metabolomics : Official journal of the Metabolomic Society》2017,13(10):120
Introduction
Endometriosis is an estrogen-dependent gynecological disease that causes infertility, and potential metabolomic biomarkers related to ovarian endometriosis and poor outcomes after assisted reproductive treatments are still lacking.Objectives
The present study analyzed the metabolomic profiling of follicular fluid samples from 40 patients undergoing in vitro fertilization.Methods
The follicular fluid samples were classified as controls (n = 22) and endometriosis patients (n = 18). The samples were submitted to Bligh and Dyer protocol followed by metabolomics analysis by ultra-performance liquid chromatography mass spectrometry. Clinical data was assessed by Students’ T-test and metabolomics data was analyzed by multivariate statistics by MetaboAnalyst 3.0 to obtain intrinsic characteristics that allowed for groups discrimination. The Receiver Operating Characteristic curve was carried out for the proposed biomarkers, aiming to determine their specificity and sensitivity, as a set and individually.Results
From the metabolomic analysis, 20 ion masses were selected as potential biomarkers from principal component analysis, which showed that all biomarkers were more abundant in the endometriosis group when compared to controls. Tentative attribution was performed by lipid maps database, demonstrating that these potential biomarkers correspond to fatty acids, carnitines, monoacylglycerols, lysophosphatidic acids, lysophosphatidylglycerols, diacylglycerols, lysophosphatidylcholines, phosphatidylserine, lysophosphatidylinositols and Phosphatidic Acid.Conclusion
The use of mass spectrometry-based metabolomics allowed for the identification of effective biomarkers for ovarian endometriosis, which may contribute for a better comprehension of the disease and how it affects the ovary, as well as assisting in the development of accessory tools for endometriosis diagnosis and infertility management.15.
Stéphane Grison Gaëlle Favé Matthieu Maillot Olivia Delissen Éric Blanchardon Isabelle Dublineau Jocelyne Aigueperse Sandra Bohand Jean-Charles Martin Maâmar Souidi 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):154
Introduction
Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake.Objectives
In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L?1; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose–effect pattern and identify additional potential biomarkers in urine samples.Methods
Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L?1). LC–MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages.Results
The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L?1. Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score.Conclusion
These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L?1.16.
Noah Obeng-Nkrumah Appiah-Korang Labi Naa Okaikor Addison Juliana Ewuramma Mbiriba Labi Georgina Awuah-Mensah 《Annals of clinical microbiology and antimicrobials》2016,15(1):49
Background
Bloodstream infections (BSI) are life-threatening emergencies. Identification of the common pathogens and their susceptibility patterns is necessary for timely empirical intervention.Methods
We conducted a 4-year retrospective analysis of blood cultures from all patients excluding neonates at the Korle-Bu Teaching hospital, Ghana, from January 2010 through December 2013. Laboratory report data were used to determine BSI, blood culture contamination, pathogen profile, and antimicrobial resistance patterns.Results
Overall, 3633 (23.16 %) out of 15,683 blood cultures were positive for various organisms. Pathogen-positive cultures accounted for 1451 (9.3 %, 95 % CI 8.5–9.8 %). Infants recorded the highest true blood culture positivity (20.9 %, n = 226/1083), followed by the elderly (13.3 %, n = 80/601), children (8.9 %, n = 708/8000) and adults (7.2 %, n = 437/6000) (p = 0.001 for Marascuilo’s post hoc). Overall occurrence of BSI declined with increasing age-group (p = 0.001) but the type of isolates did not vary with age except for Citrobacter, Escherichia coli, Klebsiella, Salmonella, and Enterococcus species. Gram negative bacteria predominated in our study (59.8 %, n = 867/1451), but the commonest bacterial isolate was Staphylococcus aureus (21.9 %, n = 318/1451)—and this trend run through the various age-groups. From 2010 to 2013, we observed a significant trend of yearly increase in the frequency of BSI caused by cephalosporin-resistant enterobacteria (Chi square for trend, p = 0.001). Meropenem maintained high susceptibility among all Gram-negative organisms ranging from 96 to 100 %. Among Staphylococcus aureus, susceptibility to cloxacillin was 76.6 %.Conclusion
Our study shows a significantly high blood culture positivity in infants as compared to children, adults and the elderly. There was a preponderance of S. aureus and Gram-negative bacteria across all age-groups. Meropenem was the most active antibiotic for Gram-negative bacteria. Cloxacillin remains a very useful anti-staphylococcal agent.17.
Anna Petrackova Andrea Smrzova Petr Gajdos Marketa Schubertova Petra Schneiderova Pavel Kromer Vaclav Snasel Martina Skacelova Frantisek Mrazek Josef Zadrazil Pavel Horak Eva Kriegova 《Clinical proteomics》2017,14(1):32
Background
Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index.Methods
We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23). Subgroup analysis was carried out on the basis of organ damage (with/without, 42/33) and biopsy-proven LN (with/without, 27/48; active LN, n = 13; inactive LN, n = 14).Results
Of thirty deregulated proteins between SLE and the healthy controls (P corr < 0.05), the top upregulated proteins in SLE were sirtuin 2, interleukin 18 (IL18), and caspase 8 (P corr < 0.0006). Of these, sirtuin 2 and caspase 8 had not yet been reported with SLE. Elevated levels of IL8, CCL2/MCP1, CCL11, and MMP10 (P corr < 0.05) were detected in patients with organ damage for which the serum levels of CCL11 and MMP10 were particularly informative in organ damage prediction. Comparing patients based on LN, elevated levels of CSF1, sIL15RA, sCD40, sCX3CL1, caspase 8, sIL18R1, bNGF, and GDNF (P corr < 0.05) were detected in active LN. Except GDNF, all LN-associated markers showed usefulness in prediction of active renal disease.Conclusions
This highly sensitive PEA analysis identified the serum pattern of SLE, organ damage, and active LN, with many novel candidate proteins detected. Their exact role and suitability as biomarkers in SLE deserve further investigation.18.
Wen-Han Chuang Arivajiagane Arundhathi Ching Lu Chang-Chiang Chen Wan-Chen Wu Hendra Susanto Jerry D. T. Purnomo Chih-Hong Wang 《Metabolomics : Official journal of the Metabolomic Society》2016,12(6):108
Introduction
Dysregulation of acylcarnitines (AcylCNs) and amino acids metabolism have implicated in abnormality of fatty acid oxidation in type 2 diabetes (T2D). However, it is not well known whether altered plasma AcylCN, and amino acid profiles are associated with albuminuria or diabetic nephropathy (DN) in T2D.Objective
The aim of this study was to elucidate alterations in plasma levels of AcylCNs and amino acids with respect to the T2D patients with various stages of albuminuria.Methods
We recruited 52 healthy subjects as control, and 156 T2D patients which were divided into 52 normoalbuminuria, 52 microalbuminuria, and 52 macroalbuminuria. Plasma 37 AcylCNs and 12 amino acids were analyzed by tandem mass spectrometry.Results
We found that T2D with normoalbuminuria and microalbuminuria had lower shot-, medium-, and long-chain AcylCNs, whereas T2D with macroalbuminuria had higher short-and medium-chain AcylCNs and lower long-chain AcylCNs than healthy subjects. Moreover, estimated glomerular filtration rate (eGFR) was a negative, independent and significant predictor of albumin to creatinine ratio (ACR) levels (β = ?0.376, P < 0.001), whereas plasma Low-density lipoprotein cholesterol (LDL-C) was significantly and positively associated with ACR levels (β = 0.169, P = 0.049). Furthermore, multivariate ordinal logistic regression analysis revealed that isobutyrylcarnitine (C4) was a positive, independent, and significant predictor of ACR levels with higher odds of having T2D patients with progression normoalbuminuria to microalbuminuria [OR = 9.93, 95 % CI (3.51–28.05), P < 0.001].Conclusions
The findings suggest that plasma C4 may serve as a potential biomarker for the early stages of DN.19.
Liming Weng Yan Gong Jeffrey Culver Stephen J. Gardell Christopher Petucci Alison M. Morse Reginald F. Frye Stephen T. Turner Arlene Chapman Eric Boerwinkle John Gums Amber L. Beitelshees Peggy R. Borum Julie A. Johnson Timothy J. Garrett Lauren M. McIntyre Rhonda M. Cooper-DeHoff 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):160
Introduction
Atenolol, a commonly prescribed β blocker for hypertension, is also associated with adverse cardiometabolic effects such as hyperglycemia and dyslipidemia. Knowledge of the mechanistic underpinnings of these adverse effects of atenolol is incomplete.Objective
We sought to identify biomarkers associated with risk for these untoward effects of atenolol. We measured baseline blood serum levels of acylcarnitines (ACs) that are involved in a host of different metabolic pathways, to establish associations with adverse cardiometabolic responses after atenolol treatment.Methods
Serum samples from Caucasian hypertensive patients (n = 224) who were treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study were interrogated using a quantitative LC/MS assay for a large number of unique ACs in serum. For the 23 ACs that were detected in serum from ≥80 % of all patients, we conducted linear regression for changes in cardiometabolic factors with baseline AC levels, baseline cardiometabolic factors, age, sex, and BMI as covariates. For the 5 ACs that were detected in serum from 20 to 79 % of the patients, we similarly modeled changes in cardiometabolic factors, but with specifying the AC as present/absent in the regression.Results
Among the 28 ACs, the presence (vs. absence) of arachidonoyl-carnitine (C20:4) was significantly associated with increased glucose (p = 0.0002), and was nominally associated with decreased plasma HDL-C (p = 0.017) and with less blood pressure (BP) lowering (p = 0.006 for systolic BP, p = 0.002 for diastolic BP), after adjustment.Conclusion
Serum level of C20:4 is a promising biomarker to predict adverse cardiometabolic responses including glucose and poor antihypertensive response to atenolol.20.
Mizuho Nagao Magnus P. Borres Mayumi Sugimoto Carl Johan Petersson Satoshi Nakayama Yu Kuwabara Sawako Masuda Patrik Dykiel Takao Fujisawa 《Clinical and molecular allergy : CMA》2017,15(1):4