Tracking Biocultural Pathways to Health Disparities: The Value of Biomarkers

Science.gov (United States)

Worthman, Carol M.; Costello, E. Jane

2009-01-01

Background Cultural factors and biomarkers are emerging emphases in social epidemiology that readily ally with human biology and anthropology. Persistent health challenges and disparities have established biocultural roots, and environment plays an integral role in physical development and function that form the bases of population health. Biomarkers have proven to be valuable tools for investigating biocultural bases of health disparities. Aims We apply recent insights from biology to consider how culture gets under the skin and evaluate the construct of embodiment. We analyze contrasting biomarker models and applications, and propose an integrated model for biomarkers. Three examples from the Great Smoky Mountains Study (GSMS) illustrate these points. Subjects and methods The longitudinal developmental epidemiological GSMS comprises a population-based sample of 1420 children with repeated measures including mental and physical health, life events, household conditions, and biomarkers for pubertal development and allostatic load. Results Analyses using biomarkers resolved competing explanations for links between puberty and depression, identified gender differences in stress at puberty, and revealed interactive effects of birthweight and postnatal adversity on risk for depression at puberty in girls. Conclusion An integrated biomarker model can both enrich epidemiology and illuminate biocultural pathways in population health. PMID:19381986

CSF biomarker variability in the Alzheimer's Association quality control program

NARCIS (Netherlands)

Mattsson, N.; Andreasson, U.; Persson, S.; Carrillo, M.C.; Collins, S.; Chalbot, S.; Cutler, N.; Dufour-Rainfray, D.; Fagan, A.M.; Heegaard, N.H.H.; Robin Hsiung, G.Y.; Hyman, B.; Iqbal, K.; Lachno, D.R.; Lleo, A.; Lewczuk, P.; Molinuevo, J.L.; Parchi, P.; Regeniter, A.; Rissman, R.; Rosenmann, H.; Sancesario, G.; Schroder, J.; Shaw, L.M.; Teunissen, C.E.; Trojanowski, J.Q.; Vanderstichele, H.; Vandijck, M.; Verbeek, M.M.; Zetterberg, H.; Blennow, K.; Kaser, S.A.; et al.,

2013-01-01

BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. METHODS: Data

CSF biomarker variability in the Alzheimer's Association quality control program

NARCIS (Netherlands)

Mattsson, N.; Andreasson, U.; Persson, S.; Carrillo, M.C.; Collins, S.; Chalbot, S.; Cutler, N.; Dufour-Rainfray, D.; Fagan, A.M.; Heegaard, N.H.H.; Hsiung, G.Y.R.; Hyman, B.; Iqbal, K.; Lachno, D.R.; Lleo, A.; Lewczuk, P.; Molinuevo, J.L.; Parchi, P.; Regeniter, A.; Rissman, R.; Rosenmann, H.; Sancesario, G.; Schroder, J.; Shaw, L.M.; Teunissen, C.E.; Trojanowski, J.Q.; Vanderstichele, H.; Vandijck, M.; Verbeek, M.M.; Zetterberg, H.; Blennow, K.; Kaser, S.A.

2013-01-01

Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods: Data

Rethinking developmental toxicity testing: Evolution or revolution?

NARCIS (Netherlands)

Scialli, Anthony R; Daston, George; Chen, Connie; Coder, Prägati S; Euling, Susan Y; Foreman, Jennifer; Hoberman, Alan M; Hui, Julia; Knudsen, Thomas; Makris, Susan L; Morford, LaRonda; Piersma, Aldert H; Stanislaus, Dinesh; Thompson, Kary E

2018-01-01

Current developmental toxicity testing adheres largely to protocols suggested in 1966 involving the administration of test compound to pregnant laboratory animals. After more than 50 years of embryo-fetal development testing, are we ready to consider a different approach to human developmental

Ribosomal proteins as biomarkers for bacterial identification by mass spectrometry in the clinical microbiology laboratory.

Science.gov (United States)

Suarez, Stéphanie; Ferroni, Agnès; Lotz, Aurélie; Jolley, Keith A; Guérin, Philippe; Leto, Julie; Dauphin, Brunhilde; Jamet, Anne; Maiden, Martin C J; Nassif, Xavier; Armengaud, Jean

2013-09-01

Whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a rapid method for identification of microorganisms that is increasingly used in microbiology laboratories. This identification is based on the comparison of the tested isolate mass spectrum with reference databases. Using Neisseria meningitidis as a model organism, we showed that in one of the available databases, the Andromas database, 10 of the 13 species-specific biomarkers correspond to ribosomal proteins. Remarkably, one biomarker, ribosomal protein L32, was subject to inter-strain variability. The analysis of the ribosomal protein patterns of 100 isolates for which whole genome sequences were available, confirmed the presence of inter-strain variability in the molecular weight of 29 ribosomal proteins, thus establishing a correlation between the sequence type (ST) and/or clonal complex (CC) of each strain and its ribosomal protein pattern. Since the molecular weight of three of the variable ribosomal proteins (L30, L31 and L32) was included in the spectral window observed by MALDI-TOF MS in clinical microbiology, i.e., 3640-12000 m/z, we were able by analyzing the molecular weight of these three ribosomal proteins to classify each strain in one of six subgroups, each of these subgroups corresponding to specific STs and/or CCs. Their detection by MALDI-TOF allows therefore a quick typing of N. meningitidis isolates. © 2013 Elsevier B.V. All rights reserved.

Validation of biomarkers for the study of environmental carcinogens: a review

DEFF Research Database (Denmark)

Gallo, Valentina; Khan, Aneire; Gonzales, Carlos

2008-01-01

There is a need for validation of biomarkers. Our aim is to review published work on the validation of selected biomarkers: bulky DNA adducts, N-nitroso compounds, 1-hydroxypyrene, and oxidative damage to DNA. A systematic literature search in PubMed was performed. Information on the variability...... and reliability of the laboratory tests used for biomarkers measurements was collected. For the evaluation of the evidence on validation we referred to the ACCE criteria. Little is known about intraindividual variation of DNA adduct measurements, but measurements have a good repeatability irrespective...... of the technique used for their identification; reproducibility improved after the correction for a laboratory factor. A high-sensitivity method is available for the measurement of 1-hydroxypyrene in urine. There is consensus on validation of biomarkers of oxidative damage DNA based on the comet assay...

Developmental origin of immune diseases-Environmental influences

DEFF Research Database (Denmark)

Strom, M.; Halldorsson, T. I.; Hansen, S.

2015-01-01

(PCBs), organochlorine pesticides, andmorerecently perfluoroalkyl substances (PFAS). Developmental exposures to PCBs have, for example, been associated with both otitis media and lower respiratory infections. Evidence regarding asthma and allergic disease is less well established, partly due to lack......Experimental studies have shown that developmental exposures to environmental chemicals may have long lasting adverse consequences for the development of the immune system. In humans such findings have mostly been explored for persistent organic pollutants (POPs) including polychlorinated biphenyls...... years of age we have examined the long term consequences of in utero exposure to POPs on offspring use of asthma medication and biomarkers of allergic airway disease. Using registry based information on offspring use of asthma medication until 20 years of age, prenatal exposures to PCB-118...

Application of bio-marker to study on tumor radiosensitivity

International Nuclear Information System (INIS)

Guo Wanfeng; Ding Guirong; Han Liangfu

2001-01-01

To definite tumor radiosensitivity is important for applying the schedules of individualization of patient radiotherapy. Many laboratories were carrying on the research which predict the tumor radiosensitivity with one bio-marker or/and multi-bio-marker in various levels. At present has not witnessed the specific bio-marker, but it provides an excellent model for predicting tumor radiosensitivity

Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System.

Science.gov (United States)

Bugel, Sean M; Bonventre, Josephine A; Tanguay, Robert L

2016-11-01

Flavonoids are a large, structurally diverse class of bioactive naturally occurring chemicals commonly detected in breast milk, soy based infant formulas, amniotic fluid, and fetal cord blood. The potential for pervasive early life stage exposures raises concerns for perturbation of embryogenesis, though developmental toxicity and bioactivity information is limited for many flavonoids. Therefore, we evaluated a suite of 24 flavonoid and flavonoid-like chemicals using a zebrafish embryo-larval toxicity bioassay-an alternative model for investigating developmental toxicity of environmentally relevant chemicals. Embryos were exposed to 1-50 µM of each chemical from 6 to 120 h postfertilization (hpf), and assessed for 26 adverse developmental endpoints at 24, 72, and 120 hpf. Behavioral changes were evaluated in morphologically normal animals at 24 and 72 hpf, at 120 hpf using a larval photomotor response (LPR) assay. Gene expression was comparatively evaluated for all compounds for effects on biomarker transcripts indicative of AHR (cyp1a) and ER (cyp19a1b, esr1, lhb, vtg) pathway bioactivity. Overall, 15 of 24 flavonoids elicited adverse effects on one or more of the developmental or behavioral endpoints. Hierarchical clustering and principle component analyses compared toxicity profiles and identified 3 distinct groups of bioactive flavonoids. Despite robust induction of multiple estrogen-responsive biomarkers, co-exposure with ER and GPER antagonists did not ameliorate toxicity, suggesting ER-independence and alternative modes of action. Taken together, these studies demonstrate that development is sensitive to perturbation by bioactive flavonoids in zebrafish that are not related to traditional estrogen receptor mode of action pathways. This integrative zebrafish platform provides a useful framework for evaluating flavonoid developmental toxicity and hazard prioritization. © The Author 2016. Published by Oxford University Press on behalf of the Society of

Searching for biomarkers of developmental toxicity with microarrays: normal eye morphogenesis in rodent embryos

International Nuclear Information System (INIS)

Nemeth, Kimberly A.; Singh, Amar V.; Knudsen, Thomas B.

2005-01-01

Gene expression arrays reveal the potential linkage of altered gene expression with specific adverse effects leading to disease phenotypes. But how closely do microarray data reflect early physiological or pharmacological measures that predict toxic event(s)? To explore this issue, we have undertaken experiments in early mouse embryos exposed to various teratogens during neurulation stages with the aim of correlating large-scale changes in gene expression across the critical period during exposure. This study reports some of the large-scale changes in gene expression that can be detected in the optic rudiment of the developing mouse and rat embryo across the window of development during which the eye is exceedingly sensitive to teratogen-induced micro-/anophthalmia. Microarray analysis was performed on RNA from the headfold or ocular region at the optic vesicle and optic cup stages when the ocular primordium is enriched for Pax-6, a master control gene for eye morphogenesis. Statistical selection of differentially regulated genes and various clustering techniques identified groups of genes in upward or downward trajectories in the normal optic primordium during early eye development in mouse and rat species. We identified 165 genes with significant differential expression during eye development, and a smaller subset of 58 genes that showed a tight correlation between mouse-rat development. Significantly over-represented functional categories included fatty acid metabolism (up-regulated) and glycolysis (down-regulated). From studies such as these that benchmark large-scale gene expression during normal embryonic development, we may be able to identify the panel of biomarkers that best correlate with species differences and the risks for developmental toxicity

Continuing harmonization of terminology and innovations for methodologies in developmental toxicology: Report of the 8th Berlin Workshop on Developmental Toxicity, 14-16 May 2014.

Science.gov (United States)

Solecki, Roland; Rauch, Martina; Gall, Andrea; Buschmann, Jochen; Clark, Ruth; Fuchs, Antje; Kan, Haidong; Heinrich, Verena; Kellner, Rupert; Knudsen, Thomas B; Li, Weihua; Makris, Susan L; Ooshima, Yojiro; Paumgartten, Francisco; Piersma, Aldert H; Schönfelder, Gilbert; Oelgeschläger, Michael; Schaefer, Christof; Shiota, Kohei; Ulbrich, Beate; Ding, Xuncheng; Chahoud, Ibrahim

2015-11-01

This article is a report of the 8th Berlin Workshop on Developmental Toxicity held in May 2014. The main aim of the workshop was the continuing harmonization of terminology and innovations for methodologies used in the assessment of embryo- and fetotoxic findings. The following main topics were discussed: harmonized categorization of external, skeletal, visceral and materno-fetal findings into malformations, variations and grey zone anomalies, aspects of developmental anomalies in humans and laboratory animals, and innovations for new methodologies in developmental toxicology. The application of Version 2 terminology in the DevTox database was considered as a useful improvement in the categorization of developmental anomalies. Participants concluded that initiation of a project for comparative assessments of developmental anomalies in humans and laboratory animals could support regulatory risk assessment and university-based training. Improvement of new methodological approaches for alternatives to animal testing should be triggered for a better understanding of developmental outcomes. Copyright © 2015. Published by Elsevier Inc.

The 2D:4D digit ratio as biomarker for substance abuse

NARCIS (Netherlands)

Fernstrand, A.M.; Van Den Borne, L.; Lensvelt, L.M.H.; Ribbert, L.L.A.; De With, A.C.; Goede, L.X.Y.; Garssen, J.; Verster, J.C.

2015-01-01

Purpose: The second (2D, index finger) to fourth (4D, ring finger) digit ratio is a biomarker for prenatal testosterone and estrogen exposure. It has been hypothesized that the developmental origins of health and behavior are modulated by the presence or absence of prenatal sex hormones. Several

Examining Autism Spectrum Disorders by Biomarkers: Example from the Oxytocin and Serotonin Systems

Science.gov (United States)

Hammock, Elizabeth; Veenstra-VanderWeele, Jeremy; Yan, Zhongyu; Kerr, Travis M.; Morris, Marianna; Anderson, George M.; Carter, C. Sue; Cook, Edwin H.; Jacob, Suma

2012-01-01

Objective: Autism spectrum disorder (ASD) is a heritable but highly heterogeneous neuropsychiatric syndrome, which poses challenges for research relying solely on behavioral symptoms or diagnosis. Examining biomarkers may give us ways to identify individuals who demonstrate specific developmental trajectories and etiological factors related to…

The high current, fast, 100ns, Linear Transformer Driver (LTD) developmental project at Sandia National Laboratories

International Nuclear Information System (INIS)

Ward, Kevin S.; Long, Finis W.; Sinebryukhov, Vadim A.; Kim, Alexandre A.; Wakeland, Peter Eric; McKee, G. Randall; Woodworth, Joseph Ray; McDaniel, Dillon Heirman; Fowler, William E.; Mazarakis, Michael Gerrassimos; Porter, John Larry Jr.; Struve, Kenneth William; Stygar, William A.; LeChien, Keith R.; Matzen, Maurice Keith

2010-01-01

Sandia National Laboratories, Albuquerque, N.M., USA, in collaboration with the High Current Electronic Institute (HCEI), Tomsk, Russia, is developing a new paradigm in pulsed power technology: the Linear Transformer Driver (LTD) technology. This technological approach can provide very compact devices that can deliver very fast high current and high voltage pulses straight out of the cavity with out any complicated pulse forming and pulse compression network. Through multistage inductively insulated voltage adders, the output pulse, increased in voltage amplitude, can be applied directly to the load. The load may be a vacuum electron diode, a z-pinch wire array, a gas puff, a liner, an isentropic compression load (ICE) to study material behavior under very high magnetic fields, or a fusion energy (IFE) target. This is because the output pulse rise time and width can be easily tailored to the specific application needs. In this paper we briefly summarize the developmental work done in Sandia and HCEI during the last few years, and describe our new MYKONOS Sandia High Current LTD Laboratory.

Overview of Biomarkers and Surrogate Endpoints in Drug Development

Directory of Open Access Journals (Sweden)

John A. Wagner

2002-01-01

Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics

International Nuclear Information System (INIS)

West, Paul R.; Weir, April M.; Smith, Alan M.; Donley, Elizabeth L.R.; Cezar, Gabriela G.

2010-01-01

Teratogens, substances that may cause fetal abnormalities during development, are responsible for a significant number of birth defects. Animal models used to predict teratogenicity often do not faithfully correlate to human response. Here, we seek to develop a more predictive developmental toxicity model based on an in vitro method that utilizes both human embryonic stem (hES) cells and metabolomics to discover biomarkers of developmental toxicity. We developed a method where hES cells were dosed with several drugs of known teratogenicity then LC-MS analysis was performed to measure changes in abundance levels of small molecules in response to drug dosing. Statistical analysis was employed to select for specific mass features that can provide a prediction of the developmental toxicity of a substance. These molecules can serve as biomarkers of developmental toxicity, leading to better prediction of teratogenicity. In particular, our work shows a correlation between teratogenicity and changes of greater than 10% in the ratio of arginine to asymmetric dimethylarginine levels. In addition, this study resulted in the establishment of a predictive model based on the most informative mass features. This model was subsequently tested for its predictive accuracy in two blinded studies using eight drugs of known teratogenicity, where it correctly predicted the teratogenicity for seven of the eight drugs. Thus, our initial data shows that this platform is a robust alternative to animal and other in vitro models for the prediction of the developmental toxicity of chemicals that may also provide invaluable information about the underlying biochemical pathways.

The NINDS Parkinson's disease biomarkers program: The Ninds Parkinson's Disease Biomarkers Program

Energy Technology Data Exchange (ETDEWEB)

Rosenthal, Liana S. [Department of Neurology, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Drake, Daniel [Department of Biostatistics, Columbia University, New York New York USA; Alcalay, Roy N. [Department of Neurology, Columbia University, New York New York USA; Babcock, Debra [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Bowman, F. DuBois [Department of Biostatistics, Columbia University, New York New York USA; Chen-Plotkin, Alice [Department of Neurology, University of Pennsylvania, Philadelphia Pennsylvania USA; Dawson, Ted M. [Department of Neurology, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Solomon H. Snyder Department of Neuroscience, Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Dewey, Richard B. [Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas USA; German, Dwight C. [Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas USA; Huang, Xuemei [Department of Neurology, Penn State Hershey Medical Center, Hershey Pennsylvania USA; Landin, Barry [Center for Information Technology, National Institutes of Health, Bethesda Maryland USA; McAuliffe, Matthew [Center for Information Technology, National Institutes of Health, Bethesda Maryland USA; Petyuk, Vladislav A. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland Washington USA; Scherzer, Clemens R. [Department of Neurology, Brigham & Women' s Hospital, Harvard Medical School, Cambridge Massachusetts USA; Hillaire-Clarke, Coryse St. [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Sieber, Beth-Anne [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Sutherland, Margaret [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Tarn, Chi [Coriell Institute for Medical Research, Camden New Jersey USA; West, Andrew [Department of Neurology, University of Alabama at Birmingham, Birmingham USA; Vaillancourt, David [Department of Applied Physiology and Kinesiology, University of Florida, Gainesville Florida USA; Zhang, Jing [Department of Pathology, University of Washington, Seattle Washington USA; Gwinn, Katrina [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA

2015-10-07

Background: Neuroprotection for Parkinson Disease (PD) remains elusive. Biomarkers hold the promise of removing roadblocks to therapy development. The National Institute of Neurological Disorders and Stroke (NINDS) has therefore established the Parkinson’s Disease Biomarkers Program (PDBP) to promote discovery of biomarkers for use in phase II-III clinical trials in PD. Methods: The PDBP facilitates biomarker development to improve neuroprotective clinical trial design, essential for advancing therapeutics for PD. To date, eleven consortium projects in the PDBP are focused on the development of clinical and laboratory-based PD biomarkers for diagnosis, progression tracking, and/or the prediction of prognosis. Seven of these projects also provide detailed longitudinal data and biospecimens from PD patients and controls, as a resource for all PD researchers. Standardized operating procedures and pooled reference samples have been created in order to allow cross-project comparisons and assessment of batch effects. A web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community for additional biomarker projects. Results: Here we describe the PDBP, highlight standard operating procedures for the collection of biospecimens and data, and provide an interim report with quality control analysis on the first 1082 participants and 1033 samples with quality control analysis collected as of October 2014. Conclusions: By making samples and data available to academics and industry, encouraging the adoption of existing standards, and providing a resource which complements existing programs, the PDBP will accelerate the pace of PD biomarker research, with the goal of improving diagnostic methods and treatment.

Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives.

Science.gov (United States)

Grandjean, Philippe; Barouki, Robert; Bellinger, David C; Casteleyn, Ludwine; Chadwick, Lisa H; Cordier, Sylvaine; Etzel, Ruth A; Gray, Kimberly A; Ha, Eun-Hee; Junien, Claudine; Karagas, Margaret; Kawamoto, Toshihiro; Paige Lawrence, B; Perera, Frederica P; Prins, Gail S; Puga, Alvaro; Rosenfeld, Cheryl S; Sherr, David H; Sly, Peter D; Suk, William; Sun, Qi; Toppari, Jorma; van den Hazel, Peter; Walker, Cheryl L; Heindel, Jerrold J

2015-10-01

The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks.

Potential of Mass Spectrometry in Developing Clinical Laboratory Biomarkers of Nonvolatiles in Exhaled Breath.

Science.gov (United States)

Beck, Olof; Olin, Anna-Carin; Mirgorodskaya, Ekaterina

2016-01-01

Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the potential future role and importance of mass spectrometry is discussed. Nonvolatile compounds exit the lung as aerosol particles that can be sampled easily and selectively. The clinical applications of potential biomarkers in exhaled breath comprise diagnosis of disease, monitoring of disease progress, monitoring of drug therapy, and toxicological investigations. © 2015 American Association for Clinical Chemistry.

An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories

Directory of Open Access Journals (Sweden)

Bailey Brian

2011-10-01

Full Text Available Abstract Background Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable. Findings This report describes an inter-laboratory comparison carried out to evaluate the comparability of 3-HPMA measurement between four laboratories. A common set of spiked and authentic smoker and non-smoker urine samples were used. Each laboratory used their in-house LC-MS/MS method and a common internal standard. A comparison of the repeatability ('r', reproducibility ('R', and coefficient of variation for 3-HPMA demonstrated that within-laboratory variation was consistently lower than between-laboratory variation. The average inter-laboratory coefficient of variation was 7% for fortified urine samples and 16.2% for authentic urine samples. Together, this represents an inter-laboratory variation of 12.2%. Conclusion The results from this first inter-laboratory comparison for the measurement of 3-HPMA in urine demonstrate a reasonably good consensus between laboratories. However, some consistent measurement biases were still observed between laboratories, suggesting that additional work may be required to further reduce the inter-laboratory coefficient of variation.

Developmental Light-Water Reactor Program

International Nuclear Information System (INIS)

Forsberg, C.W.

1989-12-01

This report summarizes the progress of the Developmental Light-Water Reactor (DLWR) Program at Oak Ridge National Laboratory in FY 1989. It also includes (1) a brief description of the program, (2) definition of goals, (3) earlier achievements, and (4) proposed future activities

Placenta-derived exosomes: potential biomarkers of preeclampsia

Directory of Open Access Journals (Sweden)

Pillay P

2017-10-01

Full Text Available Preenan Pillay,1,2 Kogi Moodley,1 Jagidesa Moodley,3 Irene Mackraj3 1Discipline of Human Physiology, Nelson R Mandela School of Medicine, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; 2Pearson Institute of Higher Education, Midrand, South Africa; 3Women’s Health and HIV Research Group, Nelson R Mandela School of Medicine, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal–fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia. Keywords: placenta-derived exosomes, preeclampsia, biomarkers

Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC

Science.gov (United States)

The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.

In situ evaluation of cadmium biomarkers in green algae

Energy Technology Data Exchange (ETDEWEB)

Simon, Dana F.; Davis, Thomas A. [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada); Tercier-Waeber, Mary-Lou [Analytical and Biophysical Environmental Chemistry, University of Geneva, Sciences II, 30 Quai Ernest-Ansermet, 1211 Geneva 4 (Switzerland); England, Roxane [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada); Wilkinson, Kevin J., E-mail: kj.wilkinson@umontreal.ca [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada)

2011-10-15

In situ measurements provide data that are the highly representative of the natural environment. In this paper, laboratory-determined biomarkers of Cd stress that were previously identified for the green alga Chlamydomonas reinhardtii, were tested in two French rivers: a contaminated site on the Riou Mort River and an 'uncontaminated' reference site on the Lot River. Transcript abundance levels were determined by real time qPCR for biomarkers thought to be Cd sensitive. Transcript levels were significantly higher (>5 fold) for organisms exposed to the contaminated site as compared to those exposed at the uncontaminated site. Biomarker mRNA levels were best correlated to free Cd (Cd{sup 2+}) rather than intracellular Cd, suggesting that they may be useful indicators of in situ stress. The paper shows that biomarker expression levels increased with time, were sensitive to metal levels and metal speciation and were higher in the 'contaminated' as opposed to the 'reference' site. - Highlights: > Biomarkers of Cd stress were tested in a contaminated and a reference site. > The organism was viable under exposure conditions and metal accumulation occurred. > Biomarker levels were correlated to Cd{sup 2+} and were higher in the contaminated site. - Algal transcription levels of several biomarkers were studied in two natural waters in situ.

Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

Science.gov (United States)

EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

TRWG developmental pathway for biospecimen-based assessment modalities

Energy Technology Data Exchange (ETDEWEB)

Translational Research Working Group; Srivastava, Sudhir; Gray, Joe W.; Reid, Brian J.; Grad, Oren; Greenwood, Addison; Hawk, Ernest T.

2008-09-03

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of NCI's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of biospecimen-based assays that utilize biomarkers for the detection, diagnosis, prognosis, and assessment of response to cancer treatment. The biospecimen-based assessment modality (BM) pathway was conceived not as comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of a candidate assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper introduces the pathway in the context of prior work and discusses key challenges associated with the biomarker development process in light of the pathway.

Nanomaterials based biosensors for cancer biomarker detection

International Nuclear Information System (INIS)

Malhotra, Bansi D; Kumar, Saurabh; Pandey, Chandra Mouli

2016-01-01

Biosensors have enormous potential to contribute to the evolution of new molecular diagnostic techniques for patients suffering with cancerous diseases. A major obstacle preventing faster development of biosensors pertains to the fact that cancer is a highly complex set of diseases. The oncologists currently rely on a few biomarkers and histological characterization of tumors. Some of the signatures include epigenetic and genetic markers, protein profiles, changes in gene expression, and post-translational modifications of proteins. These molecular signatures offer new opportunities for development of biosensors for cancer detection. In this context, conducting paper has recently been found to play an important role towards the fabrication of a biosensor for cancer biomarker detection. In this paper we will focus on results of some of the recent studies obtained in our laboratories relating to fabrication and application of nanomaterial modified paper based biosensors for cancer biomarker detection. (paper)

Biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*.

Science.gov (United States)

Massaro, An N; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B; Glass, Penny

2014-09-01

To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy. Prospective longitudinal cohort study. A level IV neonatal ICU in a freestanding children's hospital. Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period. Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia. Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia.

The use of biomarkers in occupational health research, practice, and policy.

Science.gov (United States)

Schulte, P A; Hauser, J E

2012-08-13

Biomarkers are potentially useful tools for occupational health and safety research, practice, and policy. However, the full realization of this potential has not been achieved. In this paper, the progress made in these three usage areas is reviewed to identify what efforts can be taken to realize the full promise of biomarkers. Biomarker uses are described by a diverse taxonomy that builds on the categories of exposure, effect and susceptibility, and the continuum between exposure and disease prognosis. The most significant uses of biomarkers in occupational health have been in biological monitoring of workers. Other important uses have been in enhancing research and assessing mechanisms of action of occupational toxicants at low exposures. Seven critical areas will influence the extent to which the potential of biomarkers in occupational health and safety is realized. These include: (1) adequate investment in validation; (2) obtaining international agreement on exposure guidelines; (3) exploring the utility of biomarkers in regulation; (4) applying biomarkers to critical occupational safety and health questions; (5) developing the exposome; (6) utilizing biomarkers to address emerging occupational health issues; and (7) continuing to address the ethical and social justice issues related to biomarkers. Overall, if biomarkers are to make a major contribution to occupational health and safety then a more holistic approach to bringing them from the laboratory to practice will be needed. Published by Elsevier Ireland Ltd.

Mobile devices for the remote acquisition of physiological and behavioral biomarkers in psychiatric clinical research.

Science.gov (United States)

W Adams, Zachary; McClure, Erin A; Gray, Kevin M; Danielson, Carla Kmett; Treiber, Frank A; Ruggiero, Kenneth J

2017-02-01

Psychiatric disorders are linked to a variety of biological, psychological, and contextual causes and consequences. Laboratory studies have elucidated the importance of several key physiological and behavioral biomarkers in the study of psychiatric disorders, but much less is known about the role of these biomarkers in naturalistic settings. These gaps are largely driven by methodological barriers to assessing biomarker data rapidly, reliably, and frequently outside the clinic or laboratory. Mobile health (mHealth) tools offer new opportunities to study relevant biomarkers in concert with other types of data (e.g., self-reports, global positioning system data). This review provides an overview on the state of this emerging field and describes examples from the literature where mHealth tools have been used to measure a wide array of biomarkers in the context of psychiatric functioning (e.g., psychological stress, anxiety, autism, substance use). We also outline advantages and special considerations for incorporating mHealth tools for remote biomarker measurement into studies of psychiatric illness and treatment and identify several specific opportunities for expanding this promising methodology. Integrating mHealth tools into this area may dramatically improve psychiatric science and facilitate highly personalized clinical care of psychiatric disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conceptual strategy for design, implementation, and validation of a biomarker-based biomonitoring capability

Energy Technology Data Exchange (ETDEWEB)

McCarthy, J.F.; Halbrook, R.S.; Shugart, L.R.

1991-12-01

This document describes a strategy for defining specific objectives for biomarker studies and for designing and implementing a biomonitoring study that focuses on these objectives. In researching this subject, it became clear to the authors that the subject of biomarkers created a great deal of interest among scientists and regulators but that general acceptance of biomarkers as a tool for environmental protection was hampered by lack of a clear notion of how to develop and apply this approach. We intend this document to be a user's guide'' that lays out a logical scheme for applying biomarkers in environmental monitoring. In addition, laboratory and field research components needed to develop and validate fundamental understanding and interpretation of biomarker responses are also described, as is a strategy for evolution of a biomarker-based biomonitoring capability. The document is divided into sections intended to lead the reader to an understanding of how biomarkers can be developed and applied.

Conceptual strategy for design, implementation, and validation of a biomarker-based biomonitoring capability

Energy Technology Data Exchange (ETDEWEB)

McCarthy, J.F.; Halbrook, R.S.; Shugart, L.R.

1991-12-01

This document describes a strategy for defining specific objectives for biomarker studies and for designing and implementing a biomonitoring study that focuses on these objectives. In researching this subject, it became clear to the authors that the subject of biomarkers created a great deal of interest among scientists and regulators but that general acceptance of biomarkers as a tool for environmental protection was hampered by lack of a clear notion of how to develop and apply this approach. We intend this document to be a ``user`s guide`` that lays out a logical scheme for applying biomarkers in environmental monitoring. In addition, laboratory and field research components needed to develop and validate fundamental understanding and interpretation of biomarker responses are also described, as is a strategy for evolution of a biomarker-based biomonitoring capability. The document is divided into sections intended to lead the reader to an understanding of how biomarkers can be developed and applied.

Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil.

Directory of Open Access Journals (Sweden)

Richard L Guerrant

Full Text Available Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6-26 month-old children with varying degrees of malnutrition (stunting or wasting in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old, and intestinal FABP (I-FABP, suggesting prior barrier disruption; and with citrulline, tryptophan and with lower serum amyloid A (SAA (suggesting impaired defenses. In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation. Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1 functional intestinal barrier disruption and translocation, 2 structural intestinal barrier disruption and inflammation and 3 systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how

Transformation and sorption of illicit drug biomarkers in sewer biofilms

DEFF Research Database (Denmark)

Ramin, Pedram; Brock, Andreas Libonati; Causanilles Llanes, Ana

2017-01-01

, 16 drug biomarkers were selected, including the major human metabolites of mephedrone, methadone, cocaine, heroin, codeine and tetrahydrocannabinol (THC). Transformation and sorption of these substances were assessed in targeted batch experiments using laboratory-scale biofilm reactors operated under...

Update on Biomarkers for the Detection of Endometriosis

Science.gov (United States)

Fassbender, Amelie; Burney, Richard O.; O, Dorien F.; D'Hooghe, Thomas; Giudice, Linda

2015-01-01

Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium. PMID:26240814

Update on Biomarkers for the Detection of Endometriosis

Directory of Open Access Journals (Sweden)

Amelie Fassbender

2015-01-01

Full Text Available Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium.

Biomarkers of Nutrition for Development—Iodine Review1234

Science.gov (United States)

Rohner, Fabian; Zimmermann, Michael; Jooste, Pieter; Pandav, Chandrakant; Caldwell, Kathleen; Raghavan, Ramkripa; Raiten, Daniel J.

2014-01-01

The objective of the Biomarkers of Nutrition for Development (BOND) project is to provide state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. Specifically, the BOND project seeks to develop consensus on accurate assessment methodologies that are applicable to researchers (laboratory/clinical/surveillance), clinicians, programmers, and policy makers (data consumers). The BOND project is also intended to develop targeted research agendas to support the discovery and development of biomarkers through improved understanding of nutrient biology within relevant biologic systems. In phase I of the BOND project, 6 nutrients (iodine, vitamin A, iron, zinc, folate, and vitamin B-12) were selected for their high public health importance because they typify the challenges faced by users in the selection, use, and interpretation of biomarkers. For each nutrient, an expert panel was constituted and charged with the development of a comprehensive review covering the respective nutrient’s biology, existing biomarkers, and specific issues of use with particular reference to the needs of the individual user groups. In addition to the publication of these reviews, materials from each will be extracted to support the BOND interactive Web site (http://www.nichd.nih.gov/global_nutrition/programs/bond/pages/index.aspx). This review represents the first in the series of reviews and covers all relevant aspects of iodine biology and biomarkers. The article is organized to provide the reader with a full appreciation of iodine’s background history as a public health issue, its biology, and an overview of available biomarkers and specific considerations for the use and interpretation of iodine biomarkers across a range of clinical and population-based uses. The review also includes a detailed research agenda to address priority gaps in our understanding of iodine biology and assessment

An MEG Investigation of Neural Biomarkers and Language in Nonverbal Children with Autism Spectrum Disorders

Science.gov (United States)

2014-09-01

1.Lord C, Risi S, Pickles A. Trajectory of language development in autistic spectrum disorders . In: Rice M, Warren S, eds. Developmental Language...Nonverbal Children with Autism Spectrum Disorders PRINCIPAL INVESTIGATOR: Kristina McFadden CONTRACTING ORGANIZATION: University of...SUBTITLE 5a. CONTRACT NUMBER An MEG Investigation of Neural Biomarkers and Language in Nonverbal Children with Autism Spectrum Disorders 5b

Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable.

Science.gov (United States)

Boyd, Lara A; Hayward, Kathryn S; Ward, Nick S; Stinear, Cathy M; Rosso, Charlotte; Fisher, Rebecca J; Carter, Alexandre R; Leff, Alex P; Copland, David A; Carey, Leeanne M; Cohen, Leonardo G; Basso, D Michele; Maguire, Jane M; Cramer, Steven C

2017-07-01

The most difficult clinical questions in stroke rehabilitation are "What is this patient's potential for recovery?" and "What is the best rehabilitation strategy for this person, given her/his clinical profile?" Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke.

Laboratories new to the ICRM.

Science.gov (United States)

Karam, Lisa; Anagnostakis, Marios J; Gudelis, Arunas; Marsoem, Pujadi; Mauring, Alexander; Wurdiyanto, Gatot; Yücel, Ülkü

2012-09-01

The Scientific Committee of the ICRM decided, for the 2011 Conference, to present laboratories that are at a key developmental stage in establishing, expanding or applying radionuclide metrology capabilities. The expansion of radionuclide metrology capabilities is crucial to meet evolving and emerging needs in health care, environmental monitoring, and nuclear energy. Five laboratories (from Greece, Lithuania, Indonesia, Norway and Turkey) agreed to participate. Each laboratory is briefly introduced, and examples of their capabilities and standardization activities are discussed. Published by Elsevier Ltd.

Biomarkers in cancer screening: a public health perspective.

Science.gov (United States)

Srivastava, Sudhir; Gopal-Srivastava, Rashmi

2002-08-01

The last three decades have witnessed a rapid advancement and diffusion of technology in health services. Technological innovations have given health service providers the means to diagnose and treat an increasing number of illnesses, including cancer. In this effort, research on biomarkers for cancer detection and risk assessment has taken a center stage in our effort to reduce cancer deaths. For the first time, scientists have the technologies to decipher and understand these biomarkers and to apply them to earlier cancer detection. By identifying people at high risk of developing cancer, it would be possible to develop intervention efforts on prevention rather than treatment. Once fully developed and validated, then the regular clinical use of biomarkers in early detection and risk assessment will meet nationally recognized health care needs: detection of cancer at its earliest stage. The dramatic rise in health care costs in the past three decades is partly related to the proliferation of new technologies. More recent analysis indicates that technological change, such as new procedures, products and capabilities, is the primary explanation of the historical increase in expenditure. Biomarkers are the new entrants in this competing environment. Biomarkers are considered as a competing, halfway or add-on technology. Technology such as laboratory tests of biomarkers will cost less compared with computed tomography (CT) scans and other radiographs. However, biomarkers for earlier detection and risk assessment have not achieved the level of confidence required for clinical applications. This paper discusses some issues related to biomarker development, validation and quality assurance. Some data on the trends of diagnostic technologies, proteomics and genomics are presented and discussed in terms of the market share. Eventually, the use of biomarkers in health care could reduce cost by providing noninvasive, sensitive and reliable assays at a fraction of the cost of

Search for Chemical Biomarkers on Mars Using the Sample Analysis at Mars Instrument Suite on the Mars Science Laboratory

Science.gov (United States)

Glavin, D. P.; Conrad, P.; Dworkin, J. P.; Eigenbrode, J.; Mahaffy, P. R.

2011-01-01

One key goal for the future exploration of Mars is the search for chemical biomarkers including complex organic compounds important in life on Earth. The Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) will provide the most sensitive measurements of the organic composition of rocks and regolith samples ever carried out in situ on Mars. SAM consists of a gas chromatograph (GC), quadrupole mass spectrometer (QMS), and tunable laser spectrometer to measure volatiles in the atmosphere and released from rock powders heated up to 1000 C. The measurement of organics in solid samples will be accomplished by three experiments: (1) pyrolysis QMS to identify alkane fragments and simple aromatic compounds; pyrolysis GCMS to separate and identify complex mixtures of larger hydrocarbons; and (3) chemical derivatization and GCMS extract less volatile compounds including amino and carboxylic acids that are not detectable by the other two experiments.

The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

DEFF Research Database (Denmark)

Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan

2011-01-01

. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.......The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories...

Biomarkers for bladder cancer management: present and future

Science.gov (United States)

Ye, Fei; Wang, Li; Castillo-Martin, Mireia; McBride, Russell; Galsky, Matthew D; Zhu, Jun; Boffetta, Paolo; Zhang, David Y; Cordon-Cardo, Carlos

2014-01-01

Accurate and sensitive detection of bladder cancer is critical to diagnose this deadly disease at an early stage, estimate prognosis, predict response to treatment, and monitor recurrence. In past years, laboratory diagnosis and surveillance of urinary bladder cancer have improved significantly. Although urine cytology remains the gold standard test, many new urinary biomarkers have been identified. Furthermore, recent advances in genomic studies of bladder cancer have helped to refine our understanding of the pathogenesis of the disease, the biological basis for outcome disparities, and to inform more efficient treatment and surveillance strategies. In this article, the established diagnostic tests, newly identified biomarkers and genomic landscape of bladder cancer will be reviewed. PMID:25374904

Cognitive impairment and major depressive disorder in HIV infection and cerebrospinal fluid biomarkers

Directory of Open Access Journals (Sweden)

Sergio Monteiro de Almeida

2013-09-01

Full Text Available Cognitive impairment and major depressive disorder (MDD are common HIV-1 central nervous system (CNS complications. Their frequencies in AIDS patients are 36% and 45%, respectively. The diagnoses of HIV cognitive impairment are made by clinical criteria, no single laboratory test or biomarker establishes the diagnosis. Factors of indirect neuronal injury related with the pathophysiology of the HIV infection in the CNS, are the factors studied as biomarkers. In the present no biomarker is established to the diagnosis of HIV cognitive impairment, much still needs to be done. We review in this paper some biomarkers in cerebrospinal fluid that could be valuable to the diagnosis of HIV cognitive impairment. Diagnosing depression in the context of HIV can be challenging, to identify a biomarker that could help in the diagnosis would be very important, although MDD risks and neurobiology are still poorly understood.

Immunohistochemistry of colorectal cancer biomarker phosphorylation requires controlled tissue fixation.

Directory of Open Access Journals (Sweden)

Abbey P Theiss

Full Text Available Phosphorylated signaling molecules are biomarkers of cancer pathophysiology and resistance to therapy, but because phosphoprotein analytes are often labile, poorly controlled clinical laboratory practices could prevent translation of research findings in this area from the bench to the bedside. We therefore compared multiple biomarker and phosphoprotein immunohistochemistry (IHC results in 23 clinical colorectal carcinoma samples after either a novel, rapid tissue fixation protocol or a standard tissue fixation protocol employed by clinical laboratories, and we also investigated the effect of a defined post-operative "cold" ischemia period on these IHC results. We found that a one-hour cold ischemia interval, allowed by ASCO/CAP guidelines for certain cancer biomarker assays, is highly deleterious to certain phosphoprotein analytes, specifically the phosphorylated epidermal growth factor receptor (pEGFR, but shorter ischemic intervals (less than 17 minutes facilitate preservation of phosphoproteins. Second, we found that a rapid 4-hour, two temperature, formalin fixation yielded superior staining in several cases with select markers (pEGFR, pBAD, pAKT compared to a standard overnight room temperature fixation protocol, despite taking less time. These findings indicate that the future research and clinical utilities of phosphoprotein IHC for assessing colorectal carcinoma pathophysiology absolutely depend upon attention to preanalytical factors and rigorously controlled tissue fixation protocols.

Inconsistent effects of developmental temperatureacclimation on low-temperature performance andmetabolism in Drosophila melanogaster

DEFF Research Database (Denmark)

Kristensen, Torsten Nygaard; Overgaard, Johannes; Hoffmann, Ary A

2012-01-01

Question: Does acclimation to developmental temperature consistently affect metabolismand low-temperature performance when measured in different laboratory and field assays? Hypothesis: Developmental acclimation reflecting naturally fluctuating thermal conditionsconsistently increases different...... conditions in the field, while constant cool rearingconditions led to high cold resistance. The fluctuating- and low-temperature rearing conditionsresulted in a similar metabolic profile, while the 24C rearing profile was distinct and showeda lack of plasticity. The effects of developmental acclimation...

Introduction of the land snail Eobania vermiculata as a bioindicator organism of terrestrial pollution using a battery of biomarkers

Energy Technology Data Exchange (ETDEWEB)

Itziou, A., E-mail: itziou@bio.auth.gr; Dimitriadis, V.K., E-mail: vdimitr@bio.auth.gr

2011-02-15

The present study aimed to enrich the group of sentinel organisms of terrestrial pollution biomonitoring, by investigating the efficacy of the land snail Eobania vermiculata. For this reason, a package of biomarkers was performed on land snails E. vermiculata collected from polluted areas in the field or treated with heavy metals in the laboratory. The biomarkers used were neutral red lysosomal retention assay of the haemocytes, acetylcholinesterase activity in the digestive gland and the haemolymph, and metallothionein content of the digestive gland. Moreover, the morphometric changes in the lysosomal system and the morphometric alterations of the neutral lipids were also investigated. In addition, the content of cadmium, lead and copper was evaluated in the digestive gland of the snails. The results revealed appreciable alterations in the biomarker values both in field- and laboratory-conditions, accompanied by significant correlations among the biomarkers. Therefore, this exploratory study suggests the utility of E. vermiculata as a sentinel organism for biomonitoring the biologic impact of terrestrial pollution, and supports the package's efficacy of the selected biomarkers. - Research Highlights: {yields} Significant changes were noted in the values of the applied biomarkers. {yields} A package of biomarkers is supported to be an efficient tool for biomoniroting studies. {yields} The land snail Eobania vermiculata is proposed to be a good bioindicator organism in terrestrial pollution studies.

Fine Sediment Effects on Brook Trout Eggs in Laboratory Streams

Science.gov (United States)

David G. Argent; Patricia A. Flebbe

1999-01-01

This study was designed to determine effects of different fine sediments (0.43-0.85 mm in diameter) on survival of brook trout (Salvelinus fontinalis) eggs during early developmental stages under laboratory conditions. Intragravel permeability and dissolved oxygen declined with increasing fine sediment amounts. Survival at each developmental stage...

Improved multimodal biomarkers for Alzheimer's disease and mild cognitive impairment diagnosis: data from ADNI

Science.gov (United States)

Martinez-Torteya, Antonio; Treviño-Alvarado, Víctor; Tamez-Peña, José

2013-02-01

The accurate diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) confers many clinical research and patient care benefits. Studies have shown that multimodal biomarkers provide better diagnosis accuracy of AD and MCI than unimodal biomarkers, but their construction has been based on traditional statistical approaches. The objective of this work was the creation of accurate AD and MCI diagnostic multimodal biomarkers using advanced bioinformatics tools. The biomarkers were created by exploring multimodal combinations of features using machine learning techniques. Data was obtained from the ADNI database. The baseline information (e.g. MRI analyses, PET analyses and laboratory essays) from AD, MCI and healthy control (HC) subjects with available diagnosis up to June 2012 was mined for case/controls candidates. The data mining yielded 47 HC, 83 MCI and 43 AD subjects for biomarker creation. Each subject was characterized by at least 980 ADNI features. A genetic algorithm feature selection strategy was used to obtain compact and accurate cross-validated nearest centroid biomarkers. The biomarkers achieved training classification accuracies of 0.983, 0.871 and 0.917 for HC vs. AD, HC vs. MCI and MCI vs. AD respectively. The constructed biomarkers were relatively compact: from 5 to 11 features. Those multimodal biomarkers included several widely accepted univariate biomarkers and novel image and biochemical features. Multimodal biomarkers constructed from previously and non-previously AD associated features showed improved diagnostic performance when compared to those based solely on previously AD associated features.

Science Academies' Refresher Course in Developmental Biology 16 ...

Indian Academy of Sciences (India)

IAS Admin

The objectives of this Refresher Course are to update the participants about the advances in the field of Developmental Biology; various small animal models used and give hands-on training on some modern biotechnological practices. A variety of teaching methods like lectures, discussion and laboratory work shall ...

Laboratories new to the ICRM

International Nuclear Information System (INIS)

Karam, Lisa; Anagnostakis, Marios J.; Gudelis, Arunas; Marsoem, Pujadi; Mauring, Alexander; Wurdiyanto, Gatot; Yücel, Ülkü

2012-01-01

The Scientific Committee of the ICRM decided, for the 2011 Conference, to present laboratories that are at a key developmental stage in establishing, expanding or applying radionuclide metrology capabilities. The expansion of radionuclide metrology capabilities is crucial to meet evolving and emerging needs in health care, environmental monitoring, and nuclear energy. Five laboratories (from Greece, Lithuania, Indonesia, Norway and Turkey) agreed to participate. Each laboratory is briefly introduced, and examples of their capabilities and standardization activities are discussed. - Highlights: ► Four laboratories in radionuclide metrology are described. ► Health, environment, and energy applications are motivators. ► Facilities and resources supporting research activities are discussed. ► Activities in primary and secondary standardizations are also discussed.

A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis.

Science.gov (United States)

Younossi, Zobair M; Page, Sandra; Rafiq, Nila; Birerdinc, Aybike; Stepanova, Maria; Hossain, Noreen; Afendy, Arian; Younoszai, Zahra; Goodman, Zachary; Baranova, Ancha

2011-04-01

Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis. This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables. Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated. Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65-M30 (necrosis) [AUC: 0.81, 95% CI, 0.70-0.89, 300 p value <9E 301 (-06)]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68-0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70-0.89; p value, 0.000062]. This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.

III: Use of biomarkers as Risk Indicators in Environmental Risk Assessment of oil based discharges offshore.

Science.gov (United States)

Sanni, Steinar; Lyng, Emily; Pampanin, Daniela M

2017-06-01

Offshore oil and gas activities are required not to cause adverse environmental effects, and risk based management has been established to meet environmental standards. In some risk assessment schemes, Risk Indicators (RIs) are parameters to monitor the development of risk affecting factors. RIs have not yet been established in the Environmental Risk Assessment procedures for management of oil based discharges offshore. This paper evaluates the usefulness of biomarkers as RIs, based on their properties, existing laboratory biomarker data and assessment methods. Data shows several correlations between oil concentrations and biomarker responses, and assessment principles exist that qualify biomarkers for integration into risk procedures. Different ways that these existing biomarkers and methods can be applied as RIs in a probabilistic risk assessment system when linked with whole organism responses are discussed. This can be a useful approach to integrate biomarkers into probabilistic risk assessment related to oil based discharges, representing a potential supplement to information that biomarkers already provide about environmental impact and risk related to these kind of discharges. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

Directory of Open Access Journals (Sweden)

A. J. Reinecke

2007-09-01

Full Text Available Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications. Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in

Pharmacogenomic Biomarkers

Directory of Open Access Journals (Sweden)

Sandra C. Kirkwood

2002-01-01

Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

Clinical significance of the serum biomarker index detection in children with Henoch-Schonlein purpura.

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Purevdorj, Narangerel; Mu, Yun; Gu, Yajun; Zheng, Fang; Wang, Ran; Yu, Jinwei; Sun, Xuguo

2018-02-01

To explore a panel of serum biomarkers for laboratory diagnosis of pediatric Henoch-Schönlein purpura (HSP). The blood white blood cells (WBC) and serum levels of serum amyloid A (SAA), interleukin 6 (IL-6), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin E (IgE), C-reactive protein (CRP), complement component 3 (C3), complement component 4 (C4), and ASO (anti-streptolysin O) were detected in 127 patients with Henoch-Schonlein purpura (HSP), 110 cases of septicemia patients, and 121 healthy volunteers. The diagnostic ability of biomarkers selected from HSP and septicemia patients was analyzed by ROC curve. By designing the calculation model, the biomarker index was calculated for laboratory diagnosis of HSP and differential diagnosis between HSP and septicemia. The levels of serum WBC, CRP, IL-6 and SAA in the septicemia patients were significantly higher than those in the control group (p<0.05). Compared with the healthy individuals, serum levels of WBC, CRP, IL-6, SAA, IgA and IgM were significantly increased in patients with HSP (p<0.05). The area under the curve (AUC) of SAA, IgA, IgM, WBC, IL-6, and CRP in the patients with HSP was 0.964, 0.855, 0.849, 0.787, 0.765, and 0.622, respectively. The values of SAA, IgA, IgM, WBC, IL-6, and CRP in septicemia patients were 0.700, 0.428, 0.689, 0.682, 0.891, and 0.853, respectively. Biomarker index=SAA+IgA/4000+IgM/4000×0.4CRPmean valueCRPi . The biomarker index in HSP patients was significantly higher than that of the healthy controls. However, the biomarker index in septicemia patients was significantly lower than the control. The biomarker index of HSP patients is higher than that of the control group. While in the infectious disease represented by septicemia, it is decreased. The detection of biomarker index could exclude the interference of infection as the auxiliary examination to HSP patients. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by

Combination of biomarkers

DEFF Research Database (Denmark)

Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

2012-01-01

The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

Clinical Risk Assessment in the Antiphospholipid Syndrome: Current Landscape and Emerging Biomarkers.

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Chaturvedi, Shruti; McCrae, Keith R

2017-07-01

Laboratory criteria for the classification of antiphospholipid syndrome include the detection of a lupus anticoagulant and/or anticardiolipin and anti-β2-glycoprotein I antibodies. However, the majority of patients who test positive in these assays do not have thrombosis. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile and traditional thrombotic risk factors. Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-β 2 GPI antibodies, antibodies to other phospholipids or phospholipid/protein antigens (such as anti-PS/PT), and functional/biological assays such as thrombin generation, complement activation, levels of circulating microparticles, and annexin A5 resistance. Clinical risk scores may also have value in predicting clinical events. Biomarkers that predict thrombosis risk in patients with antiphospholipid antibodies have been long sought, and several biomarkers have been proposed. Ultimately, integration of biomarkers with established assays and clinical characteristics may offer the best chance of identifying patients at highest risk of APS-related complications.

Household air pollution: a call for studies into biomarkers of exposure and predictors of respiratory disease.

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Rylance, Jamie; Gordon, Stephen B; Naeher, Luke P; Patel, Archana; Balmes, John R; Adetona, Olorunfemi; Rogalsky, Derek K; Martin, William J

2013-05-01

Household air pollution (HAP) from indoor burning of biomass or coal is a leading global cause of morbidity and mortality, mostly due to its association with acute respiratory infection in children and chronic respiratory and cardiovascular diseases in adults. Interventions that have significantly reduced exposure to HAP improve health outcomes and may reduce mortality. However, we lack robust, specific, and field-ready biomarkers to identify populations at greatest risk and to monitor the effectiveness of interventions. New scientific approaches are urgently needed to develop biomarkers of human exposure that accurately reflect exposure or effect. In this Perspective, we describe the global need for such biomarkers, the aims of biomarker development, and the state of development of tests that have the potential for rapid transition from laboratory bench to field use.

Non-Small Cell Carcinoma Biomarker Testing: The Pathologist's Perspective.

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Elisa eBrega

2014-07-01

Full Text Available Biomarker testing has become standard of care for patients diagnosed with non-small cell lung cancer. Although it can be successfully performed in circulating tu-mor cells, at present, the vast majority of investigations are carried out using di-rect tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically signifi-cant, particularly in cases of lung adenocarcinomas (ADC, which in turn, has prompted a new proposal for the histologic classification of such pulmonary neo-plasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist’s role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire pro-cess happens in a timely fashion. Therefore, it is part of the pathologist’s respon-sibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play NSCLC bi-omarker testing, as well as to provide a summarized review of the main NSCLC bi-omarkers of

Clinical protein science developments for patient monitoring in hospital central laboratories.

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Malm, Johan; Marko-Varga, György

2016-12-01

Patient care relies heavily on standardized tests performed in hospital laboratories, typically including clinical chemistry, pathology and microbiology. With the introduction of personalized medicine tremendous efforts have been made to identify new biomarkers of disease with various omics technologies, often including mass spectrometry. In order to validate new biomarkers and perform clinical studies high quality biobank samples are of key importance. In this editorial different aspects of mass spectrometry in future personalized medicine are discussed.

The metabolic syndrome, biomarkers, and the acculturation-health relationship among older Mexican Americans.

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González, Hector M; Tarraf, Wassim; Haan, Mary N

2011-10-01

To examine the acculturation-health relationship using metabolic syndrome biomarkers. Cross-sectional sample data. 1,789 Mexican Americans (60 years and older) from northern California. Biomarkers (waist circumference, blood pressure, fasting plasma glucose, triglycerides, and high-density lipids) were used to construct the metabolic syndrome indicator using American Heart Association criteria. MAIN PREDICTOR: Acculturation Rating Scale for Mexican Americans-II scores. Higher acculturation scores were associated with a significantly lower risk for the metabolic syndrome for foreign-born, but not U.S.-born, Mexican Americans. Immigrant health advantages over U.S.-born Mexican Americans are not evident in older adulthood. Higher acculturation was associated with lowered metabolic syndrome risk among older foreign-born Mexican Americans. This suggests that the prevailing acculturative stress hypothesis may not apply to the health of older adults and that any negative relationship between acculturation and health found in younger adults may yield to different developmental health influences in later adulthood.

Laboratory changes and levels of biomarkers in localized bacterial infections and sepsis in children

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Larysa Pypa

2017-08-01

Full Text Available Background. The success of sepsis treatment depends on early diagnosis of the generalization of bacterial infection, but the nonspecificity of clinical manifestations often makes the diagnosis delayed. Therefore, the search for highly specific and sensitive biomarkers for early diagnosis of sepsis is relevant. The aim of our research is investigate the laboratory features and diagnostic value of a number of modern biomarkers for the diagnosis of sepsis in children. Materials and methods. of general laboratory studies and determination of CRP level were performed in 115 children with generalized and localized forms of bacterial infections. The main group (47 children - children with sepsis, a comparison group (68 children - with a localized bacterial infection of various localization. The age of children was from 1 month. up to 18 years. Grouping was performed according to the presence of signs and symptoms of SIRS and organ dysfunction. Determination of the level of procalcitonin and TNF-α was performed in 31 children of the main group, 45 children in the comparison group and 30 children in the control group (children without signs of inflammation. Prespepsin levels were determined in 16 main group children,14 in the comparison group and26 in the control group. Results. During the study, it was found that the level of leukocytosis was much higher and continued 2.6 times longer in the main group than in the children of the comparison group (p <0.01.Anemia was found in 76.6% of the children in the main group, while in the comparator group, the anemia syndrome was diagnosed 3.7 times less frequently. In the study of CRP in the main group, its level reached 44.7 mg / l and 28.3 mg / l in the comparison group, the specificity and sensitivity for diagnosis of sepsis was 46.8% and 51.5% respectively. The mean TNF-α level in children in the main group was 280.3 pg / ml CI 95% [243.9-316.7], which was 1.5 times higher than in children with a localized

Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

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Stephanie J B Vos

Full Text Available BACKGROUND: Cerebrospinal fluid (CSF biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD. OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-β (Aβ 1-42, total tau (t-tau, and phosphorylated tau (p-tau by INNOTEST enzyme-linked-immunosorbent assays (ELISA in a memory clinic population (n = 126. Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

Validation of New Cancer Biomarkers

DEFF Research Database (Denmark)

Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

2015-01-01

BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

Biomarkers in Autism

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Robert eHendren

2014-08-01

Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS BIOMARKERS

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Kolyada T.I

2016-12-01

Full Text Available Current data concerning features of multiple sclerosis (MS etiology, pathogenesis, clinical course and treatment of disease indicate the necessity of personalized approach to the management of MS patients. These features are the variety of possible etiological factors and mechanisms that trigger the development of MS, different courses of disease, and significant differences in treatment efficiency. Phenotypic and pathogenetic heterogeneity of MS requires, on the one hand, the stratification of patients into groups with different treatment depending on a number of criteria including genetic characteristics, disease course, stage of the pathological process, and forms of the disease. On the other hand, it requires the use of modern methods for assessment of individual risk of developing MS, its early diagnosis, evaluation and prognosis of the disease course and the treatment efficiency. This approach is based on the identification and determination of biomarkers of MS including the use of systems biology technology platforms such as genomics, proteomics, metabolomics and bioinformatics. Research and practical use of biomarkers of MS in clinical and laboratory practice requires the use of a wide range of modern medical and biological, mathematical and physicochemical methods. The group of "classical" methods used to study MS biomarkers includes physicochemical and immunological methods aimed at the selection and identification of single molecular biomarkers, as well as methods of molecular genetic analysis. This group of methods includes ELISA, western blotting, isoelectric focusing, immunohistochemical methods, flow cytometry, spectrophotometric and nephelometric methods. These techniques make it possible to carry out both qualitative and quantitative assay of molecular biomarkers. The group of "classical methods" can also include methods based on polymerase chain reaction (including multiplex and allele-specific PCR and genome sequencing

Have biomarkers made their mark? A brief review of dental biomarkers

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Mohammed Kaleem Sultan

2014-01-01

Full Text Available Biomarkers are substances that are released into the human body by tumor cells or by other cells in response to tumor. A high level of a tumor marker is considered a sign of certain cancer, which makes biomarker the subject of many testing methods for the diagnosis of cancers. In recent times, these biomarkers have been successfully isolated to diagnose dental-related tumors, benign and malignant conditions. This article is a brief review of literature for various biomarkers used in the field of dentistry.

Implementation of External Quality Assurance Trials for Immunohistochemically Determined Breast Cancer Biomarkers in Germany.

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von Wasielewski, Reinhard; Krusche, Claudia A; Rüschoff, Joseph; Fisseler-Eckhoff, Anette; Kreipe, Hans

2008-01-01

Besides typing and grading of breast cancer, Pathologists are involved in the determination of biomarkers, such as steroid hormone receptors and HER2, which are of utmost importance in adjuvant therapy. There have been concerns with regard to security and reproducibility of the biomarker assays done on tissue sections applying either immunohistochemistry or in-situ hybridisation. In order to assure the quality of these biomarker assays, a number of measures are required, among them external proficiency testing. Therefore, external quality assurance trials have been implemented in Germany. In the period of 2002-2007, 5 consecutive trials were conducted with up to 180 participating laboratories. Tissue microarrays with 20-24 different breast cancer samples including cell lines enabled that a huge number of pathologists were challenged with identical samples which provides the prerequisite for comparability. Because there is no legal duress to undergo external proficiency testing in histopathology, all laboratories that took part volunteered to do so. These innovative quality assurance trials (Qualitätsinitiative Pathologie, QuIP) will be continued in the future on an annual or bi-annual basis. Participation is recommended for pathology departments involved in the service for breast units. The organisational frame work of the trials is described here.

1-Hydroxypyrene as a biomarker of PAH exposure in the marine polychaete Nereis diversicolor

DEFF Research Database (Denmark)

Tairova, Zhanna; Giessing, Anders; Hansen, Rikke

2009-01-01

The possibility of using the pyrene metabolite I-hydroxypyrene as a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure was investigated by exposure of the marine polychaete Nereis diversicolor to several PAHs in the laboratory. Animals were exposed to pyrene alone and to five different...

Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization.

Science.gov (United States)

Amur, S; LaVange, L; Zineh, I; Buckman-Garner, S; Woodcock, J

2015-07-01

The discovery, development, and use of biomarkers for a variety of drug development purposes are areas of tremendous interest and need. Biomarkers can become accepted for use through submission of biomarker data during the drug approval process. Another emerging pathway for acceptance of biomarkers is via the biomarker qualification program developed by the Center for Drug Evaluation and Research (CDER, US Food and Drug Administration). Evidentiary standards are needed to develop and evaluate various types of biomarkers for their intended use and multiple stakeholders, including academia, industry, government, and consortia must work together to help develop this evidence. The article describes various types of biomarkers that can be useful in drug development and evidentiary considerations that are important for qualification. A path forward for coordinating efforts to identify and explore needed biomarkers is proposed for consideration. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Biomarkers, lactate, and clinical scores as outcome predictors in systemic poisons exposures.

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Lionte, C; Sorodoc, V; Tuchilus, C; Cimpoiesu, D; Jaba, E

2017-07-01

Acute exposure to systemic poisons represents an important challenge in clinical toxicology. We aimed to analyze the potential role of cardiac biomarkers, routine laboratory tests, and clinical scores as morbidity and in-hospital mortality predictors in patients intoxicated with various systemic poisons. We conducted a prospective study on adults acutely exposed to systemic poisons. We determined the PSS, Glasgow Coma Scale (GCS), and we performed electrocardiogram, laboratory tests, lactate and cardiac biomarkers (which were reassessed 4 h, respectively 6 h later). Of 120 patients included, 45% developed complications, 19.2% had a poor outcome, and 5% died. Multivariate logistic regression sustained lactate (odds ratio (OR) 1.58; confidence interval (CI) 95%: 0.97-2.59; p 0.066), MB isoenzyme of creatine kinase (6h-CKMB; OR 1.08; CI 95%: 1.02-1.16; p 0.018) as predictors for a poor outcome. A GCS poisons exposure. Receiver operating characteristic analysis showed that brain natriuretic peptide (area under the curve (AUC), 0.96; CI 95%: 0.92-0.99; p poisons exposure.

Constructivist developmental theory is needed in developmental neuroscience

Science.gov (United States)

Arsalidou, Marie; Pascual-Leone, Juan

2016-12-01

Neuroscience techniques provide an open window previously unavailable to the origin of thoughts and actions in children. Developmental cognitive neuroscience is booming, and knowledge from human brain mapping is finding its way into education and pediatric practice. Promises of application in developmental cognitive neuroscience rests however on better theory-guided data interpretation. Massive amounts of neuroimaging data from children are being processed, yet published studies often do not frame their work within developmental models—in detriment, we believe, to progress in this field. Here we describe some core challenges in interpreting the data from developmental cognitive neuroscience, and advocate the use of constructivist developmental theories of human cognition with a neuroscience interpretation.

Oral Health Characteristics and Dental Rehabilitation of Children with Global Developmental Delay

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Saurabh Kumar

2017-01-01

Full Text Available Global developmental delay (GDD is a chronic neurological disturbance which includes defects in one or more developmental domains. The developmental domain can be motor, cognitive, daily activities, speech or language, and social or personal development. The etiology for GDD can be prenatal, perinatal, or postnatal. It can be diagnosed early in childhood as the delay or absence of one or more developmental milestones. Hence the role of pedodontist and pediatricians becomes more crucial in identifying this condition. The diagnosis of GDD requires a detailed history including family history and environmental risk factors followed by physical and neurological examinations. Investigations for GDD include diagnostic laboratory tests, brain imaging, and other evidence-based evaluations. GDD affects multiple developmental domains that not only have direct bearing on maintenance of oral health, but also require additional behavior management techniques to deliver optimal dental care. This paper describes two different spectra of children with GDD. Since the severity of GDD can vary, this paper also discusses the different behavior management techniques that were applied to provide dental treatment in such children.

Oral Health Characteristics and Dental Rehabilitation of Children with Global Developmental Delay.

Science.gov (United States)

Kumar, Saurabh; Pai, Deepika; Saran, Runki

2017-01-01

Global developmental delay (GDD) is a chronic neurological disturbance which includes defects in one or more developmental domains. The developmental domain can be motor, cognitive, daily activities, speech or language, and social or personal development. The etiology for GDD can be prenatal, perinatal, or postnatal. It can be diagnosed early in childhood as the delay or absence of one or more developmental milestones. Hence the role of pedodontist and pediatricians becomes more crucial in identifying this condition. The diagnosis of GDD requires a detailed history including family history and environmental risk factors followed by physical and neurological examinations. Investigations for GDD include diagnostic laboratory tests, brain imaging, and other evidence-based evaluations. GDD affects multiple developmental domains that not only have direct bearing on maintenance of oral health, but also require additional behavior management techniques to deliver optimal dental care. This paper describes two different spectra of children with GDD. Since the severity of GDD can vary, this paper also discusses the different behavior management techniques that were applied to provide dental treatment in such children.

Quality assurance in biomarker measurement.

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Aitio, A; Apostoli, P

1995-05-01

Quality assurance (QA) concerns the validity of all the analytical processes (from collection of the samples to interpretation of the results). It is not an abstract concept but must be adapted to the different situations such as the different exposure levels, the different analytical methods, and the context of use (risk assessment procedures, research, routine determinations). The main requirements in QA programmes regard the control of all the known sources of preanalytical and analytical variations, while the instruments with which adequate QA can be implemented are the certified materials and the quality control programmes (quality manual, internal and external quality controls). Another important concept in QA is that measurements must be placed a different metrological levels: at the highest there are the methods (definitive, reference) to be used for assessing accuracy of routine methods. QA programmes should enable a grading of biomarkers (from experimental only to full evaluated) and of the laboratories in order to identify the significance of the test and to assess the level at which a laboratory could operate.

Optimizing a waveguide-based sandwich immunoassay for tumor biomarkers

Energy Technology Data Exchange (ETDEWEB)

Mukundan, Harshini [Los Alamos National Laboratory; Swanson, Basil I [Los Alamos National Laboratory; Xie, Hongzhi [Los Alamos National Laboratory; Anderson, Aaron S [Los Alamos National Laboratory; Grace, W Kevin [Los Alamos National Laboratory; Shively, John E [NON LANL

2008-01-01

The sensor team at the Los Alamos National Laboratory has developed a waveguide-based optical biosensor for the detection of biomarkers associated with the disease. We have previously demonstrated the application of this technology to the sensitive detection of carcinoembryonic antigen in serum and nipple aspirate fluid from breast cancer patients. In this publication, we report improvements to this technology that will facilitate transition to a point-of-care diagnostic system and/or robust research tool.

Mass spectrometry for biomarker development

Energy Technology Data Exchange (ETDEWEB)

Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

2015-06-19

Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

Pb enamel biomarker: Deposition of pre- and postnatal Pb isotope injection in reconstructed time points along rat enamel transect

International Nuclear Information System (INIS)

Rinderknecht, A.L.; Kleinman, M.T.; Ericson, J.E.

2005-01-01

Exposure to lead (Pb) as well as other heavy metals in the environment is still a matter of public health concern. The development of the enamel biomarker for heavy metal exposure assessment is designed to improve studies of dose-effect relationships to developmental anomalies, particularly embryonic dysfunctions, and to provide a time-specific recount of past exposures. The work presented in this paper demonstrates maternal transfer across the placental barrier of the enriched isotope 206 Pb tracer to the enamel of the rat pup. Likewise, injections of 204 Pb-enriched tracer in the neonate rat resulted in deposition of the tracer in the enamel histology as measured by secondary ion microprobe spectrometry. Through enamel, we were able to observe biological removal and assimilation of prenatal and postnatal tracers, respectively. This research demonstrates that enamel can be used as a biomarker of exposure to Pb and may illustrate the toxicokinetics of incorporating Pb into fetal and neonatal steady-state system processes. The biomarker technique, when completely developed, may be applied to cross-sectional and longitudinal epidemiological research

Use of Both Cumulus Cells’ Transcriptomic Markers and Zona Pellucida Birefringence to Select Developmentally Competent Oocytes in Human Assisted Reproductive Technologies

Science.gov (United States)

2015-01-01

Background Selection of the best oocyte for subsequent steps of fertilization and embryo transfer was shown to be the crucial step in human infertility treatment procedure. Oocyte selection using morphological criteria mainly Zona pellucida (ZP) has been the gold standard method in assisted reproductive technologies (ART) clinics, but this selection approach has limitations in terms of accuracy, objectivity and constancy. Recent studies using OMICs-based approaches have allowed the identification of key molecular markers that quantitatively and non-invasively predict the oocyte quality for higher pregnancy rates and efficient infertility treatment. These biomarkers are a valuable reinforcement of the morphological selection criteria widely used in in vitro fertilization (IVF) clinics. In this context, this study was designed to investigate the relationship between transcriptomic predictors of oocyte quality found by our group and the conventional morphological parameters of oocyte quality mainly the ZP birefringence. Results Microarray data revealed that 48 and 27 differentially expressed candidate genes in cumulus cells (CCs) were respectively overexpressed and underexpressed in the ZGP (Zona Good Pregnant) versus ZBNP (Zona Bad Non Pregnant) groups. More than 70% of previously reported transcriptomic biomarkers of oocyte developmental competence were confirmed in this study. The analysis of possible association between ZP birefringence versus molecular markers approach showed an absence of correlation between them using the current set of markers. Conclusions This study suggested a new integrative approach that matches morphological and molecular approaches used to select developmentally competent oocytes able to lead to successful pregnancy and the delivery of healthy baby. For each ZP birefringence score, oocytes displayed a particular CCs' gene expression pattern. However, no correlations were found between the 7 gene biomarkers of oocyte developmental

Biomarkers of Pediatric Brain Tumors

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Mark D Russell

2013-03-01

Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents.

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Gilbert, Scott F; Bosch, Thomas C G; Ledón-Rettig, Cristina

2015-10-01

The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis.

Can the integration of multiple biomarkers and sediment geochemistry aid solving the complexity of sediment risk assessment? A case study with a benthic fish

International Nuclear Information System (INIS)

Costa, Pedro M.; Caeiro, Sandra; Vale, Carlos; DelValls, T. Àngel; Costa, Maria H.

2012-01-01

Surveying toxicity of complex geochemical media as aquatic sediments often yields results that are either difficult to interpret or even contradictory to acknowledged theory. Multi-level biomarkers were investigated in a benthic fish exposed to estuarine sediments through laboratory and in situ bioassays, to evaluate their employment either in ecological risk assessment or in more mechanistic approaches to assess sediment-bound toxicity. Biomarkers reflecting lesions (such as genotoxicity or histopathology), regardless of their low or absent specificity to contaminants, are efficient in segregating exposure to contaminated from uncontaminated sediments even when classical biomarkers like CYP1A and metallothionein induction are inconclusive. Conversely, proteomics and gene transcription analyses provided information on the mechanics of toxicity and aided explaining response variation as a function of metabolic imbalance and impairment of defences against insult. In situ bioassays, although less expedite and more affected by confounding factors, produced data better correlated to overall sediment contamination. Highlights: ► Sediment-bound contaminant mixtures can yield unexpected biomarker responses in fish. ► Biomarkers reflecting lesions are sturdier predictors of pollution by mixed xenobiotics. ► Proteomics and gene transcription analyses disclosed the existence of complex patterns of response to toxicity. ► Laboratory bioassays are less impacted by noise variables but tend to lose ecological relevance. - Evaluation of multi-level biomarker responses in fish for ecological risk assessment

Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss.

Directory of Open Access Journals (Sweden)

Christian Dejaco

Full Text Available Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss with highly active disease. The role of these biomarkers in relapsing disease is unclear.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients. Epidemiological, clinical and laboratory data were available for all visits.At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.

Use of ribosomal proteins as biomarkers for identification of Flavobacterium psychrophilum by MALDI-TOF mass spectrometry.

Science.gov (United States)

Fernández-Álvarez, Clara; Torres-Corral, Yolanda; Santos, Ysabel

2018-01-06

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) is a rapid methodology for identification of bacteria that is increasingly used in diagnostic laboratories. This work aimed at evaluating the potential of MALDI-TOF-MS for identification of the main serotypes of Flavobacterium psychrophilum isolated from salmonids, and its discrimination from closely related Flavobacterium spp. A mass spectra library was constructed by analysing 70 F. psychrophilum strains representing the serotypes O1, O2a, O2b and O3, including reference and clinical isolates. Peak mass lists were examined using the Mass-Up software for the detection of potential biomarkers, similarity and cluster analysis. Fourteen species-identifying biomarkers were detected in all the F. psychrophilum isolates tested, moreover, sets of serotype-identifying biomarkers ions were selected. F. psychrophilum-specific biomarkers were identified as ribosomal proteins by matching with protein databases. Furthermore, sequence variation corresponding to amino acid exchanges in several biomarker proteins were tentatively assigned. Closely related Flavobacterium species (F. flevense, F. succinicans, F. columnare, F. branchiophilum and F. johnsoniae) could be differentiated from F. psychrophilum by defining species identifying biomarkers and hierarchical cluster analysis. These results demonstrated that MALDI-TOF spectrometry represents a powerful tool for an accurate identification of the fish pathogen F. psychrophilum as well as for epidemiological studies. The results obtained in this study demonstrated that MALDI-TOF mass spectrometry represents a powerful tool that can be used by diagnostic laboratories for rapid identification of the fish pathogen Flavobacterium psychrophilum and its differentiation from other Flavobacterium-related species. Analysis of mass peak lists revealed the potential of the MALDI-TOF technique to identify epidemiologically important serotypes affecting

Mining of hospital laboratory information systems

DEFF Research Database (Denmark)

Søeby, Karen; Jensen, Peter Bjødstrup; Werge, Thomas

2015-01-01

of hospital laboratory data as a source of information, we analyzed enzymatic plasma creatinine as a model analyte in two large pediatric hospital samples. Methods: Plasma creatinine measurements from 9700 children aged 0-18 years were obtained from hospital laboratory databases and partitioned into high...... in creatinine levels at different time points after birth and around the early teens, which challenges the establishment and usefulness of reference intervals in those age groups. Conclusions: The study documents that hospital laboratory data may inform on the developmental aspects of creatinine, on periods...... with pronounced heterogeneity and valid reference intervals. Furthermore, part of the heterogeneity in creatinine distribution is likely due to differences in biological and chronological age of children and should be considered when using age-specific reference intervals....

Prognostic biomarkers in osteoarthritis

Science.gov (United States)

Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

2013-01-01

Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

Molecular Biomarkers in the Clinical Management of Prostate Cancer.

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Udager, Aaron M; Tomlins, Scott A

2018-01-08

Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection. Herein, we review the current state of the art regarding prostate cancer molecular biomarkers, emphasizing those with demonstrated utility in clinical practice. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Can microRNAs act as biomarkers of aging?

Science.gov (United States)

Kashyap, Luv

2011-02-07

Aging can be defined as a progressive decline in physiological efficiency regulated by an extremely complex multifactorial process. The genetic makeup of an individual appears to dictate this rate of aging in a species specific manner. For decades now, scientists have tried to look for tiny signatures or signs which might help us predict this rate of aging. MicroRNAs (miRNAs) are a unique class of short, non-coding RNAs that mediate the post-transcriptional regulation of gene expression ranging from developmental processes to disease induction or amelioration. Recently, they have also been implicated to have a role in aging in C.elegans. Based on the fact that there is a considerable similarity between aging in C.elegans and humans, these recent findings might suggest a possible role of miRNAs as bio-markers of aging. This mini-review brushes through the possibilities towards this direction.

Developmental aspects of a life course approach to healthy ageing

Science.gov (United States)

Cooper, C.; Aihie Sayer, A.; Eendebak, R. J.; Clough, G. F.; Beard, J. R.

2016-01-01

Abstract We examine the mechanistic basis and wider implications of adopting a developmental perspective on human ageing. Previous models of ageing have concentrated on its genetic basis, or the detrimental effects of accumulated damage, but also have raised issues about whether ageing can be viewed as adaptive itself, or is a consequence of other adaptive processes, for example if maintenance and repair processes in the period up to reproduction are traded off against later decline in function. A life course model places ageing in the context of the attainment of peak capacity for a body system, starting in early development when plasticity permits changes in structure and function induced by a range of environmental stimuli, followed by a period of decline, the rate of which depends on the peak attained as well as the later life conditions. Such path dependency in the rate of ageing may offer new insights into its modification. Focusing on musculoskeletal and cardiovascular function, we discuss this model and the possible underlying mechanisms, including endothelial function, oxidative stress, stem cells and nutritional factors such as vitamin D status. Epigenetic changes induced during developmental plasticity, and immune function may provide a common mechanistic process underlying a life course model of ageing. The life course trajectory differs in high and low resource settings. New insights into the developmental components of the life course model of ageing may lead to the design of biomarkers of later chronic disease risk and to new interventions to promote healthy ageing, with important implications for public health. PMID:26518329

The high current, fast, 100ns, Linear Transformer Driver (LTD) developmental project at Sandia Laboratories and HCEI

International Nuclear Information System (INIS)

Ward, Kevin S.; Long, Finis W.; Sinebryukhov, Vadim A.; Kim, Alexandre A.; Wakeland, Peter Eric; McKee, G. Randall; Woodworth, Joseph Ray; McDaniel, Dillon Heirman; Fowler, William E.; Mazarakis, Michael Gerrassimos; Porter, John Larry Jr.; Struve, Kenneth William; Savage, Mark Edward; Stygar, William A.; LeChien, Keith R.; Matzen, Maurice Keith

2010-01-01

Sandia National Laboratories, Albuquerque, N.M., USA, in collaboration with the High Current Electronic Institute (HCEI), Tomsk, Russia, is developing a new paradigm in pulsed power technology: the Linear Transformer Driver (LTD) technology. This technological approach can provide very compact devices that can deliver very fast high current and high voltage pulses straight out of the cavity with out any complicated pulse forming and pulse compression network. Through multistage inductively insulated voltage adders, the output pulse, increased in voltage amplitude, can be applied directly to the load. The load may be a vacuum electron diode, a z-pinch wire array, a gas puff, a liner, an isentropic compression load (ICE) to study material behavior under very high magnetic fields, or a fusion energy (IFE) target. This is because the output pulse rise time and width can be easily tailored to the specific application needs. In this paper we briefly summarize the developmental work done in Sandia and HCEI during the last few years, and describe our new MYKONOS Sandia High Current LTD Laboratory. An extensive evaluation of the LTD technology is being performed at SNL and the High Current Electronic Institute (HCEI) in Tomsk Russia. Two types of High Current LTD cavities (LTD I-II, and 1-MA LTD) were constructed and tested individually and in a voltage adder configuration (1-MA cavity only). All cavities performed remarkably well and the experimental results are in full agreement with analytical and numerical calculation predictions. A two-cavity voltage adder is been assembled and currently undergoes evaluation. This is the first step towards the completion of the 10-cavity, 1-TW module. This MYKONOS voltage adder will be the first ever IVA built with a transmission line insulated with deionized water. The LTD II cavity renamed LTD III will serve as a test bed for evaluating a number of different types of switches, resistors, alternative capacitor configurations, cores

LEARNING AND MEMORY TESTS IN DEVELOPMENTAL NEUROTOXICITY TESTING: A CROSS-LABORATORY COMPARISON OF CONTROL DATA.

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The US EPA Developmental Neurotoxicity (DNT) Study Test Guideline (OPPTS 870.6300) calls for functional tests to assess the impact of chemicals on cognitive function in offspring following maternal exposure. A test of associative learning and memory is to be conducted around th...

Biomarkers in Prostate Cancer Epidemiology

Directory of Open Access Journals (Sweden)

Mudit Verma

2011-09-01

Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos.

Science.gov (United States)

Hu, Miao; Hu, Nan; Ding, Dexin; Zhao, Weichao; Feng, Yongfu; Zhang, Hui; Li, Guangyue; Wang, Yongdong

2016-11-01

This study aimed to evaluate the biological effects of gamma irradiation on zebrafish embryos. Different doses of gamma rays (0.01, 0.05, 0.1, 0.5 and 1 Gy) were used to irradiate zebrafish embryos at three developmental stages (stage 1, 6 h post-fertilization (hpf); stage 2, 12 hpf; stage three, 24 hpf), respectively. The survival, malformation and hatching rates of the zebrafish embryos were measured at the morphological endpoint of 96 hpf. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed. Morphology analysis showed that gamma irradiation inhibited hatching and induced developmental toxicity in a dose-dependent manner. Interestingly, after irradiation the malformation rate changed not only in a dose-dependent manner but also in a developmental stage-dependent manner, indicating that the zebrafish embryos at stage 1 were more sensitive to gamma rays than those at other stages. Biochemical analysis showed that gamma irradiation modulated the activities of antioxidant enzymes in a dose-dependent manner. A linear relationship was found between GPx activity and irradiation dose in 0.1-1 Gy group, and GPx was a suitable biomarker for gamma irradiation in the dose range from 0.1 to 1 Gy. Furthermore, the activities of SOD, CAT, GR and GPx of the zebrafish embryos at stage 3 were found to be much higher than those at other stages, indicating that the zebrafish embryos at stage 3 had a greater ability to protect against gamma rays than those at other stages, and thus the activities of antioxidant enzymes changed in a developmental stage-dependent manner.

Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos

International Nuclear Information System (INIS)

Hu, Miao; Hu, Nan; Ding, Dexin; Zhao, Weichao; Feng, Yongfu; Zhang, Hui; Li, Guangyue; Wang, Yongdong

2016-01-01

This study aimed to evaluate the biological effects of gamma irradiation on zebrafish embryos. Different doses of gamma rays (0.01, 0.05, 0.1, 0.5 and 1 Gy) were used to irradiate zebrafish embryos at three developmental stages (stage 1, 6 h post-fertilization (hpf); stage 2, 12 hpf; stage three, 24 hpf), respectively. The survival, malformation and hatching rates of the zebrafish embryos were measured at the morphological endpoint of 96 hpf. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed. Morphology analysis showed that gamma irradiation inhibited hatching and induced developmental toxicity in a dose-dependent manner. Interestingly, after irradiation the malformation rate changed not only in a dose-dependent manner but also in a developmental stage-dependent manner, indicating that the zebrafish embryos at stage 1 were more sensitive to gamma rays than those at other stages. Biochemical analysis showed that gamma irradiation modulated the activities of antioxidant enzymes in a dose-dependent manner. A linear relationship was found between GPx activity and irradiation dose in 0.1-1 Gy group, and GPx was a suitable biomarker for gamma irradiation in the dose range from 0.1 to 1 Gy. Furthermore, the activities of SOD, CAT, GR and GPx of the zebrafish embryos at stage 3 were found to be much higher than those at other stages, indicating that the zebrafish embryos at stage 3 had a greater ability to protect against gamma rays than those at other stages, and thus the activities of antioxidant enzymes changed in a developmental stage-dependent manner. (orig.)

Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos

Energy Technology Data Exchange (ETDEWEB)

Hu, Miao; Hu, Nan; Ding, Dexin; Zhao, Weichao; Feng, Yongfu; Zhang, Hui; Li, Guangyue; Wang, Yongdong [University of South China, Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, Hengyang, Hunan Province (China)

2016-11-15

This study aimed to evaluate the biological effects of gamma irradiation on zebrafish embryos. Different doses of gamma rays (0.01, 0.05, 0.1, 0.5 and 1 Gy) were used to irradiate zebrafish embryos at three developmental stages (stage 1, 6 h post-fertilization (hpf); stage 2, 12 hpf; stage three, 24 hpf), respectively. The survival, malformation and hatching rates of the zebrafish embryos were measured at the morphological endpoint of 96 hpf. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed. Morphology analysis showed that gamma irradiation inhibited hatching and induced developmental toxicity in a dose-dependent manner. Interestingly, after irradiation the malformation rate changed not only in a dose-dependent manner but also in a developmental stage-dependent manner, indicating that the zebrafish embryos at stage 1 were more sensitive to gamma rays than those at other stages. Biochemical analysis showed that gamma irradiation modulated the activities of antioxidant enzymes in a dose-dependent manner. A linear relationship was found between GPx activity and irradiation dose in 0.1-1 Gy group, and GPx was a suitable biomarker for gamma irradiation in the dose range from 0.1 to 1 Gy. Furthermore, the activities of SOD, CAT, GR and GPx of the zebrafish embryos at stage 3 were found to be much higher than those at other stages, indicating that the zebrafish embryos at stage 3 had a greater ability to protect against gamma rays than those at other stages, and thus the activities of antioxidant enzymes changed in a developmental stage-dependent manner. (orig.)

Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing

NARCIS (Netherlands)

Sabatté, G.S.; Feitsma, H.; Evers, T.H.; Prins, M.W.J.

2011-01-01

It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers

Adaptive developmental delay in Chagas disease vectors: an evolutionary ecology approach.

Directory of Open Access Journals (Sweden)

Frédéric Menu

2010-05-01

Full Text Available The developmental time of vector insects is important in population dynamics, evolutionary biology, epidemiology and in their responses to global climatic change. In the triatomines (Triatominae, Reduviidae, vectors of Chagas disease, evolutionary ecology concepts, which may allow for a better understanding of their biology, have not been applied. Despite delay in the molting in some individuals observed in triatomines, no effort was made to explain this variability.We applied four methods: (1 an e-mail survey sent to 30 researchers with experience in triatomines, (2 a statistical description of the developmental time of eleven triatomine species, (3 a relationship between development time pattern and climatic inter-annual variability, (4 a mathematical optimization model of evolution of developmental delay (diapause.85.6% of responses informed on prolonged developmental times in 5(th instar nymphs, with 20 species identified with remarkable developmental delays. The developmental time analysis showed some degree of bi-modal pattern of the development time of the 5(th instars in nine out of eleven species but no trend between development time pattern and climatic inter-annual variability was observed. Our optimization model predicts that the developmental delays could be due to an adaptive risk-spreading diapause strategy, only if survival throughout the diapause period and the probability of random occurrence of "bad" environmental conditions are sufficiently high.Developmental delay may not be a simple non-adaptive phenotypic plasticity in development time, and could be a form of adaptive diapause associated to a physiological mechanism related to the postponement of the initiation of reproduction, as an adaptation to environmental stochasticity through a spreading of risk (bet-hedging strategy. We identify a series of parameters that can be measured in the field and laboratory to test this hypothesis. The importance of these findings is

Predictive Biomarkers for Asthma Therapy.

Science.gov (United States)

Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

2017-09-19

Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

Science.gov (United States)

Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

2015-01-01

Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

Preparation, Characterization, and UV Irradiation of Mars Soil Analogues Under Simulated Martian Conditions to Support Detection of Molecular Biomarkers

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Fornaro, T.; Brucato, J. R.; ten Kate, I. L.; Siljeström, S.; Steele, A.; Cody, G. D.; Hazen, R. M.

2018-04-01

We present laboratory activities of preparation, characterization, and UV irradiation processing of Mars soil analogues, which are key to support both in situ exploration and sample return missions devoted to detection of molecular biomarkers on Mars.

Cheating by exploitation of developmental prestalk patterning in Dictyostelium discoideum.

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Anupama Khare

2010-02-01

Full Text Available The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters-strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys have shown that cheaters are abundant in nature, but the cheating mechanisms are largely unknown. Here we describe cheater C (chtC, a strong facultative cheater mutant that cheats by affecting prestalk differentiation. The chtC gene is developmentally regulated and its mRNA becomes stalk-enriched at the end of development. chtC mutants are defective in maintaining the prestalk cell fate as some of their prestalk cells transdifferentiate into prespore cells, but that defect does not affect gross developmental morphology or sporulation efficiency. In chimerae between wild-type and chtC mutant cells, the wild-type cells preferentially give rise to prestalk cells, and the chtC mutants increase their representation in the spore mass. Mixing chtC mutants with other cell-type proportioning mutants revealed that the cheating is directly related to the prestalk-differentiation propensity of the victim. These findings illustrate that a cheater can victimize cooperative strains by exploiting an established developmental pathway.

Cheating by Exploitation of Developmental Prestalk Patterning in Dictyostelium discoideum

Science.gov (United States)

Khare, Anupama; Shaulsky, Gad

2010-01-01

The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters—strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys have shown that cheaters are abundant in nature, but the cheating mechanisms are largely unknown. Here we describe cheater C (chtC), a strong facultative cheater mutant that cheats by affecting prestalk differentiation. The chtC gene is developmentally regulated and its mRNA becomes stalk-enriched at the end of development. chtC mutants are defective in maintaining the prestalk cell fate as some of their prestalk cells transdifferentiate into prespore cells, but that defect does not affect gross developmental morphology or sporulation efficiency. In chimerae between wild-type and chtC mutant cells, the wild-type cells preferentially give rise to prestalk cells, and the chtC mutants increase their representation in the spore mass. Mixing chtC mutants with other cell-type proportioning mutants revealed that the cheating is directly related to the prestalk-differentiation propensity of the victim. These findings illustrate that a cheater can victimize cooperative strains by exploiting an established developmental pathway. PMID:20195510

Utility of Small Animal Models of Developmental Programming.

Science.gov (United States)

Reynolds, Clare M; Vickers, Mark H

2018-01-01

Any effective strategy to tackle the global obesity and rising noncommunicable disease epidemic requires an in-depth understanding of the mechanisms that underlie these conditions that manifest as a consequence of complex gene-environment interactions. In this context, it is now well established that alterations in the early life environment, including suboptimal nutrition, can result in an increased risk for a range of metabolic, cardiovascular, and behavioral disorders in later life, a process preferentially termed developmental programming. To date, most of the mechanistic knowledge around the processes underpinning development programming has been derived from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. This review will cover the utility of small animal models in developmental programming, the limitations of such models, and potential future directions that are required to fully maximize information derived from preclinical models in order to effectively translate to clinical use.

Cardiac biomarkers in Neonatology

OpenAIRE

Vijlbrief, D.C.

2015-01-01

In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

Mural granulosa cell gene expression associated with oocyte developmental competence

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Jiang Jin-Yi

2010-03-01

the developmental competence of oocytes. This finding suggests that the most differentially expressed gene, lysyl oxidase, may be a candidate biomarker of oocyte health and useful for the selection of good quality oocytes for assisted reproduction.

Alpha-Fetoprotein: From a Diagnostic Biomarker to a Key Role in Female Fertility

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Christelle De Mees

2006-01-01

Full Text Available Alpha-fetoprotein (AFP is a well-known diagnostic biomarker used in medicine to detect fetal developmental anomalies such as neural tube defects or Down's syndrome, or to follow up the development of tumors such as hepatocellular carcinomas. However, and despite the fact that the protein was discovered almost half a century ago, little was known about its physiological function. The study of Afp knock-out mice uncovered a surprising function of AFP: it is essential for female fertility and for expression of normal female behaviors, and this action is mediated through its estrogen binding capacity. AFP sequestrates estrogens and by so doing protects the female developing brain from deleterious (defeminizing/ masculinizing effects of these hormones

Mammalian developmental genetics in the twentieth century.

Science.gov (United States)

Artzt, Karen

2012-12-01

This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas.

Morphometric analysis of human embryos to predict developmental competence

DEFF Research Database (Denmark)

Ziebe, Søren

2013-01-01

pregnancy test, no matter what we choose in the laboratory. Still, both with the increasing complexity of infertile patients treated today and the important focus on reducing multiple pregnancies, it becomes increasingly important to improve our ability to predict the developmental competence of each embryo....... This involves an improved understanding of the basic biology controlling early embryonic development and, over the years, many groups have tried to identify parameters reflecting embryonic competence....

Current Approaches and Clinician Attitudes to the Use of Cerebrospinal Fluid Biomarkers in Diagnostic Evaluation of Dementia in Europe

DEFF Research Database (Denmark)

Miller, Anne-Marie; Balasa, Mircea; Blennow, Kaj

2017-01-01

BACKGROUND: BIOMARKAPD seeks to diminish the barriers associated with the clinical use of cerebrospinal fluid (CSF) biomarker analysis by reducing variation in CSF laboratory methodologies and generating consensus recommendations on their clinical interpretation and application for dementia diagn...

I. DEVELOPMENTAL METHODOLOGY AS A CENTRAL SUBDISCIPLINE OF DEVELOPMENTAL SCIENCE.

Science.gov (United States)

Card, Noel A

2017-06-01

This first chapter introduces the main goals of the monograph and previews the remaining chapters. The goals of this monograph are to provide summaries of our current understanding of advanced developmental methodologies, provide information that can advance our understanding of human development, identify shortcomings in our understanding of developmental methodology, and serve as a flagpost for organizing developmental methodology as a subdiscipline within the broader field of developmental science. The remaining chapters in this monograph address issues in design (sampling and big data), longitudinal data analysis, and issues of replication and research accumulation. The final chapter describes the history of developmental methodology, considers how the previous chapters in this monograph fit within this subdiscipline, and offers recommendations for further advancement. © 2017 The Society for Research in Child Development, Inc.

Biomarkers of sepsis

Science.gov (United States)

2013-01-01

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

Potential biomarkers of tardive dyskinesia: A multiplex analysis of blood serum

OpenAIRE

Boiko, Anastasia S; Kornetova, Elena G; Ivanova, Svetlana A.; Loonen, Antonius

2017-01-01

Potential biomarkers of tardive dyskinesia: a multiplex analysis of blood serum A.S. Boiko(1), E.G. Kornetova(2), S.A. Ivanova(1), A.J.M. Loonen(3) (1)Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Laboratory of Molecular Genetics and Biochemistry, Tomsk, Russia (2)Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Department of Endogenous Disorders, Tomsk, Russia (3)Univers...

Biomarkers for Detecting Mitochondrial Disorders

Directory of Open Access Journals (Sweden)

Josef Finsterer

2018-01-01

Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

Looking for biomarkers of Hg exposure by transcriptome analysis in the aquatic plant Elodea nuttallii

Directory of Open Access Journals (Sweden)

Regier N.

2013-04-01

Full Text Available Recently developed genomics tools have a promising potential to identify early biomarkers of exposure to toxicants. In the present work we used transcriptome analysis (RNA-seq of Elodea nuttallii –an invasive rooted macrophyte that is able to accumulate large amounts of metals- to identify biomarkers of Hg exposure. RNA-seq allowed identification of genes affected by Hg exposure and also unraveled plant response to the toxic metal: a change in energy/reserve metabolism caused by the inhibition of photosynthesis, and an adaptation of homeostasis networks to control accumulation of Hg. Data were validated by RT-qPCR and selected genes were further tested as biomarkers. Samples exposed in the field and to natural contaminated sediments clustered well with samples exposed to low metal concentrations under laboratory conditions. Our data suggest that this plant and/or this approach could be useful to develop new tests for water and sediment quality assessment.

Biomarkers of adverse drug reactions.

Science.gov (United States)

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

Developmental aspects of a life course approach to healthy ageing.

Science.gov (United States)

Hanson, M A; Cooper, C; Aihie Sayer, A; Eendebak, R J; Clough, G F; Beard, J R

2016-04-15

We examine the mechanistic basis and wider implications of adopting a developmental perspective on human ageing. Previous models of ageing have concentrated on its genetic basis, or the detrimental effects of accumulated damage, but also have raised issues about whether ageing can be viewed as adaptive itself, or is a consequence of other adaptive processes, for example if maintenance and repair processes in the period up to reproduction are traded off against later decline in function. A life course model places ageing in the context of the attainment of peak capacity for a body system, starting in early development when plasticity permits changes in structure and function induced by a range of environmental stimuli, followed by a period of decline, the rate of which depends on the peak attained as well as the later life conditions. Such path dependency in the rate of ageing may offer new insights into its modification. Focusing on musculoskeletal and cardiovascular function, we discuss this model and the possible underlying mechanisms, including endothelial function, oxidative stress, stem cells and nutritional factors such as vitamin D status. Epigenetic changes induced during developmental plasticity, and immune function may provide a common mechanistic process underlying a life course model of ageing. The life course trajectory differs in high and low resource settings. New insights into the developmental components of the life course model of ageing may lead to the design of biomarkers of later chronic disease risk and to new interventions to promote healthy ageing, with important implications for public health. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Biomarker Identification Using Text Mining

Directory of Open Access Journals (Sweden)

Hui Li

2012-01-01

Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

Meeting Report--NASA Radiation Biomarker Workshop

Energy Technology Data Exchange (ETDEWEB)

Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.

2008-05-01

A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

Multiple Sclerosis Cerebrospinal Fluid Biomarkers

Directory of Open Access Journals (Sweden)

Gavin Giovannoni

2006-01-01

Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

Addressing small sample size bias in multiple-biomarker trials: Inclusion of biomarker-negative patients and Firth correction.

Science.gov (United States)

Habermehl, Christina; Benner, Axel; Kopp-Schneider, Annette

2018-03-01

In recent years, numerous approaches for biomarker-based clinical trials have been developed. One of these developments are multiple-biomarker trials, which aim to investigate multiple biomarkers simultaneously in independent subtrials. For low-prevalence biomarkers, small sample sizes within the subtrials have to be expected, as well as many biomarker-negative patients at the screening stage. The small sample sizes may make it unfeasible to analyze the subtrials individually. This imposes the need to develop new approaches for the analysis of such trials. With an expected large group of biomarker-negative patients, it seems reasonable to explore options to benefit from including them in such trials. We consider advantages and disadvantages of the inclusion of biomarker-negative patients in a multiple-biomarker trial with a survival endpoint. We discuss design options that include biomarker-negative patients in the study and address the issue of small sample size bias in such trials. We carry out a simulation study for a design where biomarker-negative patients are kept in the study and are treated with standard of care. We compare three different analysis approaches based on the Cox model to examine if the inclusion of biomarker-negative patients can provide a benefit with respect to bias and variance of the treatment effect estimates. We apply the Firth correction to reduce the small sample size bias. The results of the simulation study suggest that for small sample situations, the Firth correction should be applied to adjust for the small sample size bias. Additional to the Firth penalty, the inclusion of biomarker-negative patients in the analysis can lead to further but small improvements in bias and standard deviation of the estimates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Interlaboratory trials for quality assurance of breast cancer biomarkers in Germany].

Science.gov (United States)

Krusche, C A; von Wasielewski, R; Rüschoff, J; Fisseler-Eckhoff, A; Kreipe, H H

2008-07-01

In the age of personalized medicine, and in addition to typing and grading, breast cancer pathologists are now also involved in determining biomarkers such as steroid hormone receptors and Her-2, which are of the utmost importance in adjuvant therapy. In order to assure quality of these biomarker assays, external proficiency testing has been implemented in Germany. Since 2002 trials have been conducted annually, with up to 180 participating laboratories. More than 85% of all participants achieved good results in clearly negative and positive cases seen in daily practice. If at all, discordant results were observed in the rarer low steroid-hormone receptor expressing tumors and Her-2 borderline cases (2+). Regular participation in interlaboratory testing leads to significantly improved immunohistochemical results, particularly in these problematic cases. Tissue microarrays (TMA) with 20-24 different breast cancer samples including cell lines meant that a huge number of pathologists were challenged with identical samples, providing the prerequisite for comparability. Participation is recommended for pathology departments involved in the service for breast units. The organizational frame work of the trials is described here. The confidence of cooperating disciplines in breast cancer biomarkers assessed by pathologists will be fostered by external proficiency testing as presented here.

Biomarkers in Airway Diseases

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Janice M Leung

2013-01-01

Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

Validation of biomarkers of food intake − critical assessment of candidate biomarkers

DEFF Research Database (Denmark)

Dragsted, Lars Ove; Gao, Qian; Scalbert, Augustin

2018-01-01

Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promis...

Early Effects of a Hypocaloric, Mediterranean Diet on Laboratory Parameters in Obese Individuals

OpenAIRE

Greco, Marta; Chiefari, Eusebio; Montalcini, Tiziana; Accattato, Francesca; Costanzo, Francesco S.; Pujia, Arturo; Foti, Daniela; Brunetti, Antonio; Gulletta, Elio

2014-01-01

Calorie restriction is a common strategy for weight loss in obese individuals. However, little is known about the impact of moderate hypocaloric diets on obesity-related laboratory parameters in a short-term period. Aim of this study was to evaluate the variation of laboratory biomarkers in obese individuals following a Mediterranean, hypocaloric (1400–1600 Kcal/die) diet. 23 obese, pharmacologically untreated patients were enrolled and subjected to the determination of anthropometric variabl...

Tracking and Quantifying Developmental Processes in C. elegans Using Open-source Tools.

Science.gov (United States)

Dutta, Priyanka; Lehmann, Christina; Odedra, Devang; Singh, Deepika; Pohl, Christian

2015-12-16

Quantitatively capturing developmental processes is crucial to derive mechanistic models and key to identify and describe mutant phenotypes. Here protocols are presented for preparing embryos and adult C. elegans animals for short- and long-term time-lapse microscopy and methods for tracking and quantification of developmental processes. The methods presented are all based on C. elegans strains available from the Caenorhabditis Genetics Center and on open-source software that can be easily implemented in any laboratory independently of the microscopy system used. A reconstruction of a 3D cell-shape model using the modelling software IMOD, manual tracking of fluorescently-labeled subcellular structures using the multi-purpose image analysis program Endrov, and an analysis of cortical contractile flow using PIVlab (Time-Resolved Digital Particle Image Velocimetry Tool for MATLAB) are shown. It is discussed how these methods can also be deployed to quantitatively capture other developmental processes in different models, e.g., cell tracking and lineage tracing, tracking of vesicle flow.

Early-Phase Studies of Biomarkers

DEFF Research Database (Denmark)

Pepe, Margaret S.; Janes, Holly; Li, Christopher I.

2016-01-01

of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average...... impact on patient outcomes of using the biomarker to make clinical decisions....

Mother-Child Interaction and Resilience in Children with Early Developmental Risk

Science.gov (United States)

Fenning, Rachel M.; Baker, Jason K.

2014-01-01

Although prenatal and genetic factors make strong contributions to the emergence of intellectual disability (ID), children's early environment may have the potential to alter developmental trajectories and to foster resilience in children with early risk. The present study examined mother-child interaction and the promotion of competence in 50 children with early developmental delays. Three related but distinct aspects of mother-child interaction were considered: maternal technical scaffolding, maternal positive-sensitivity, and mother-child dyadic pleasure. Children were classified as exhibiting undifferentiated delays at age three based upon performance on developmental assessments and the absence of known genetic syndromes. Mother-child interaction was assessed at age four through observational ratings of structured laboratory tasks and through naturalistic home observations. ID was identified at age five using the dual criteria of clinically significant delays in cognitive functioning and adaptive behavior. Maternal technical scaffolding and dyadic pleasure each uniquely predicted reduced likelihood of later ID, beyond the contributions of children's early developmental level and behavioral functioning. Follow-up analyses suggested that mother-child interaction was primarily important to resilience in the area of adaptive behavior, with scaffolding and dyadic pleasure differentially associated with particular sub-domains. Implications for theories of intellectual disability and for family-based early intervention and prevention efforts are discussed. PMID:22662771

Fluctuating asymmetry and developmental instability in Protoreaster nodosus (Chocolate Chip Sea Star as a biomarker for environmental stress

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D. J. V. Trono

2015-06-01

Full Text Available Fluctuating asymmetry (FA, pertains to small and random departures from perfect symmetry of an organism's bilateral traits and has been used as a measurement of developmental instability and as a potential indicator of stress in populations. It measures the variations from symmetry of a symmetrical structure whose sides are said to be genetically identical, with similar history of gene activity and experiencing the same environment. Symmetries are potentially the basis for studies on FA. Hence, this study assessed the potential of FA as a reliable developmental instability and environmental stress indicator in five-fold dihedral symmetrical Protoreaster nodosus (Chocolate chip sea fish from three (3 different sites (Linamon, Lanao del Norte; Initao, Misamis Oriental and Jasaan, Misamis Oriental. FA for each population from every site was measured for comparison. In this study, anatomical landmarks were subjected to Procrustes superimposition and Principal Component Analysis (PCA using "Symmetry and Asymmetry in Geometric Data" (SAGE program. Results showed highly significant FA and significant DA for population from Jasaan and Linamon where habitat disturbance due to anthropogenic activities were prevalent. Thus, experienced more stress compared to the other populations, suggesting that significant variation in size or left-right side of each individual could be a product of genotype-environment interaction. Moreover, insignificant FA and high DA was obtained from Initao (protected seascape area which indicated that variation among individual genotypes and asymmetry in phenotypes is mostly induced by genetics under less stressful environment. Significant FA and increase FA present inability of species to buffer stress in its developmental pathways and have implications on species fitness. Hypothesis assumes that fluctuating asymmetry has costs, reflects the quality of individuals and the level of genetic and environmental stress experienced by

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

International Nuclear Information System (INIS)

Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y.

2014-01-01

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

Energy Technology Data Exchange (ETDEWEB)

Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

2014-09-15

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

Novel Autoantibody Serum and Cerebrospinal Fluid Biomarkers in Veterans with Gulf War Illness

Science.gov (United States)

2017-10-01

using Western blot and ELISA assays. PURPOSE: Development of peripheral biomarkers for GWI. Scope of the Research: Serum and plasma from 250 Gulf War...basic protein (MBP), Myelin Associated Glycoprotein (MAG), CaMKII, alpha-synuclein, GFAP, S100B, Western Blot, ELISA , chronic fatigue syndrome (CFS...Milestone(s) Achieved: Site 1, 4 and 5 serum and CSF data collected and set up for laboratory assays ( ELISA , western blot). Autoantibody data shipped

Van de Graaff Laboratory progress report [1974

International Nuclear Information System (INIS)

Bhatia, M.S.

1977-01-01

Research and development work carried out in the Van de Graaff Laboratory of the Bhabha Atomic Research Centre, Bombay, India during 1974 has been reported. Research programmes in the field of nuclear reactions and activities of the Indian Nuclear Data Group are described. Progress of developmental work on the low energy horizontal tandem accelerator, Dumas mass separator and ion implantation facility is reported. (K.M.)

Biomarkers of PTSD: military applications and considerations.

Science.gov (United States)

Lehrner, Amy; Yehuda, Rachel

2014-01-01

Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

Implementation of proteomic biomarkers: making it work

Science.gov (United States)

Mischak, Harald; Ioannidis, John PA; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

2012-01-01

While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. PMID:22519700

DNA Methylation Biomarkers: Cancer and Beyond

Directory of Open Access Journals (Sweden)

Thomas Mikeska

2014-09-01

Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation.

Directory of Open Access Journals (Sweden)

Bibiana Bielekova

Full Text Available Diagnosis and management of the neuroinflammatory diseases of the central nervous system (CNS are hindered by the lack of reliable biomarkers of active intrathecal inflammation. We hypothesized that measuring several putative inflammatory biomarkers simultaneously will augment specificity and sensitivity of the biomarker to the clinically useful range. Based on our pilot experiment in which we measured 18 inflammatory biomarkers in 10-fold concentrated cerebrospinal fluid (CSF derived from 16 untreated patients with highly active multiple sclerosis (MS we selected a combination of three CSF biomarkers, IL-12p40, CXCL13 and IL-8, for further validation.Concentrations of IL-12p40, CXCL13 and IL-8 were determined in a blinded fashion in CSF samples from an initial cohort (n = 72 and a confirmatory cohort (n = 167 of prospectively collected, untreated subjects presenting for a diagnostic work-up of possible neuroimmunological disorder. Diagnostic conclusion was based on a thorough clinical workup, which included laboratory assessment of the blood and CSF, neuroimaging and longitudinal follow-up. Receiver operating characteristic (ROC curve analysis in conjunction with principal component analysis (PCA, which was used to combine information from all three biomarkers, assessed the diagnostic value of measured biomarkers.Each of the three biomarkers was significantly increased in MS and other inflammatory neurological disease (OIND in comparison to non-inflammatory neurological disorder patients (NIND at least in one cohort. However, considering all three biomarkers together improved accuracy of predicting the presence of intrathecal inflammation to the consistently good to excellent range (area under the ROC curve = 0.868-0.924.Future clinical studies will determine if a combinatorial biomarker consisting of CSF IL-12p40, CXCL13 and IL-8 provides utility in determining the presence of active intrathecal inflammation in diagnostically

Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia.

Science.gov (United States)

Key, Brian; Nurcombe, Victor

2003-01-01

This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was "student-oriented," ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experiencefirst-hand work in a research laboratory. Our philosophy is a "cradle-to-grave" approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research.

Developmental origins of metabolic disorders: The need for biomarker candidates and therapeutic targets from adequate preclinical models

Directory of Open Access Journals (Sweden)

Antonio Gonzalez-Bulnes

2016-03-01

Full Text Available The investigation on obesity and associated disorders have changed from an scenario in which genome drove the phenotype to a dynamic setup in which prenatal and early-postnatal conditions are determinant. However, research in human beings is difficult due to confounding factors (lifestyle and socioeconomic heterogeneity plus ethical issues. Hence, there is currently an intensive effort for developing adequate preclinical models, aiming for an adequate combination of basic studies in rodent models and specific preclinical studies in large animals. The results of these research strategies may increase the identification and development of contrasted biomarkers and therapeutic targets.

Serotonin Metabolites in the Cerebrospinal Fluid in the Sudden Infant Death Syndrome: In Search of a Biomarker of Risk

Science.gov (United States)

Rognum, Ingvar J.; Tran, Hoa; Haas, Elisabeth A.; Hyland, Keith; Paterson, David S.; Haynes, Robin L.; Broadbelt, Kevin G.; Harty, Brian J.; Mena, Othon; Krous, Henry F.; Kinney, Hannah C.

2015-01-01

Clinical biomarkers are urgently needed in the sudden infant death syndrome (SIDS) to identify living infants at risk because it because it occurs without occurs without clinical warning. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. Here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared to autopsy controls, as a first step towards their assessment as diagnostic biomarkers of medullary pathology. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high performance liquid chromatography in 57 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude use of 5-HIAA, HVA, Trp or Tyr measurements as CSF biomarkers of 5-HT medullary pathology in infants at risk. They provide, however, important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS. PMID:24423636

Implementation of proteomic biomarkers: making it work.

Science.gov (United States)

Mischak, Harald; Ioannidis, John P A; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

2012-09-01

While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

Biomarkers of PTSD: military applications and considerations

Directory of Open Access Journals (Sweden)

Amy Lehrner

2014-08-01

Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

Mining biomarker information in biomedical literature

Directory of Open Access Journals (Sweden)

Younesi Erfan

2012-12-01

Full Text Available Abstract Background For selection and evaluation of potential biomarkers, inclusion of already published information is of utmost importance. In spite of significant advancements in text- and data-mining techniques, the vast knowledge space of biomarkers in biomedical text has remained unexplored. Existing named entity recognition approaches are not sufficiently selective for the retrieval of biomarker information from the literature. The purpose of this study was to identify textual features that enhance the effectiveness of biomarker information retrieval for different indication areas and diverse end user perspectives. Methods A biomarker terminology was created and further organized into six concept classes. Performance of this terminology was optimized towards balanced selectivity and specificity. The information retrieval performance using the biomarker terminology was evaluated based on various combinations of the terminology's six classes. Further validation of these results was performed on two independent corpora representing two different neurodegenerative diseases. Results The current state of the biomarker terminology contains 119 entity classes supported by 1890 different synonyms. The result of information retrieval shows improved retrieval rate of informative abstracts, which is achieved by including clinical management terms and evidence of gene/protein alterations (e.g. gene/protein expression status or certain polymorphisms in combination with disease and gene name recognition. When additional filtering through other classes (e.g. diagnostic or prognostic methods is applied, the typical high number of unspecific search results is significantly reduced. The evaluation results suggest that this approach enables the automated identification of biomarker information in the literature. A demo version of the search engine SCAIView, including the biomarker retrieval, is made available to the public through http

Dietary and health biomarkers - time for an update

DEFF Research Database (Denmark)

Dragsted, Lars Ove; Gao, Qian; Pratico, Giulia

2017-01-01

for these biomarker classes, and no recent systematic review of all proposed biomarkers for food intake. While advanced databases exist for the human and food metabolomes, additional tools are needed to curate and evaluate current data on dietary and health biomarkers. The Food Biomarkers Alliance (FoodBAll) under......In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health...... much mechanistic insight into the effects of food components and diets. Although hundreds of papers in nutrition are published annually, there is no current ontology for the area, no generally accepted classification terminology for biomarkers in nutrition and health, no systematic validation scheme...

Developmental neurotoxicity of different pesticides in PC-12 cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132, Muttenz (Switzerland); Rusconi, Manuel; Crettaz, Pierre [Federal Office of Public Health, Division Chemical Products, 3003 Bern (Switzerland); Fent, Karl, E-mail: karl.fent@bluewin.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132, Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Environmental Systems Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich (Switzerland)

2017-06-15

The detection of developmental neurotoxicity (DNT) of chemicals has high relevance for protection of human health. However, DNT of many pesticides is only little known. Furthermore, validated in vitro systems for assessment of DNT are not well established. Here we employed the rat phaeochromocytoma cell line PC-12 to evaluate DNT of 18 frequently used pesticides of different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, as well as quaternary ammonium compounds, the organic compound used in pesticides, piperonyl butoxide, as well as the insect repellent diethyltoluamide (DEET). We determined the outgrowth of neurites in PC-12 cells co-treated with nerve growth factor and different concentrations of biocides for 5 days. Furthermore, we determined transcriptional alterations of selected genes that may be associated with DNT, such as camk2α and camk2β, gap-43, neurofilament-h, tubulin-α and tubulin-β. Strong and dose- dependent inhibition of neurite outgrowth was induced by azamethiphos and chlorpyrifos, and dieldrin and heptachlor, which was correlated with up-regulation of gap-43. No or only weak effects on neurite outgrowth and transcriptional alterations occurred for neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam, the pyrethroids λ-cyhalothrin, cyfluthrin, deltamethrin, and permethrin, the biocidal disinfectants C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride and barquat (dimethyl benzyl ammonium chloride), and piperonyl butoxide and DEET. Our study confirms potential developmental neurotoxicity of some pesticides and provides first evidence that azamethiphos has the potential to act as a developmental neurotoxic compound. We also demonstrate that inhibition of neurite outgrowth and transcriptional alterations of gap-43 expression correlate, which suggests the employment of gap-43 expression as a biomarker for detection and initial evaluation of potential DNT of chemicals

Developmental neurotoxicity of different pesticides in PC-12 cells in vitro

International Nuclear Information System (INIS)

Christen, Verena; Rusconi, Manuel; Crettaz, Pierre; Fent, Karl

2017-01-01

The detection of developmental neurotoxicity (DNT) of chemicals has high relevance for protection of human health. However, DNT of many pesticides is only little known. Furthermore, validated in vitro systems for assessment of DNT are not well established. Here we employed the rat phaeochromocytoma cell line PC-12 to evaluate DNT of 18 frequently used pesticides of different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, as well as quaternary ammonium compounds, the organic compound used in pesticides, piperonyl butoxide, as well as the insect repellent diethyltoluamide (DEET). We determined the outgrowth of neurites in PC-12 cells co-treated with nerve growth factor and different concentrations of biocides for 5 days. Furthermore, we determined transcriptional alterations of selected genes that may be associated with DNT, such as camk2α and camk2β, gap-43, neurofilament-h, tubulin-α and tubulin-β. Strong and dose- dependent inhibition of neurite outgrowth was induced by azamethiphos and chlorpyrifos, and dieldrin and heptachlor, which was correlated with up-regulation of gap-43. No or only weak effects on neurite outgrowth and transcriptional alterations occurred for neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam, the pyrethroids λ-cyhalothrin, cyfluthrin, deltamethrin, and permethrin, the biocidal disinfectants C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride and barquat (dimethyl benzyl ammonium chloride), and piperonyl butoxide and DEET. Our study confirms potential developmental neurotoxicity of some pesticides and provides first evidence that azamethiphos has the potential to act as a developmental neurotoxic compound. We also demonstrate that inhibition of neurite outgrowth and transcriptional alterations of gap-43 expression correlate, which suggests the employment of gap-43 expression as a biomarker for detection and initial evaluation of potential DNT of chemicals

Biomarkers of HIV-associated Cancer

OpenAIRE

Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd

2014-01-01

Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of can...

Molecular correlates of trait anxiety: expanding biomarker discovery from protein expression to turnover

OpenAIRE

Zhang, Yaoyang

2010-01-01

Depression and anxiety disorders affect a great number of people in the world. Although remarkable efforts have been devoted to understanding the clinical and biological basis of these disorders, progress has been relatively slow. Furthermore, no laboratory test currently is available for diagnosis of anxiety and depression. These disorders are mainly diagnosed empirically on the basis of a doctor’s personal observations and experiences. Hence, discovery of biomarkers for these psychiatric di...

Chasing the effects of Pre-analytical Confounders - a Multicentre Study on CSF-AD biomarkers

Directory of Open Access Journals (Sweden)

Maria Joao Leitao

2015-07-01

Full Text Available Core cerebrospinal fluid (CSF biomarkers-Aβ42, Tau and pTau–have been recently incorporated in the revised criteria for Alzheimer’s disease (AD. However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. In this study, we aim to surpass the efforts from previous studies, by employing a multicentre approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. Four different centres participated in this study and followed the same established protocol. CSF samples were analysed for three biomarkers (Aβ42, Tau and pTau and tested for different spinning conditions (temperature: Room temperature (RT vs. 4oC; speed: 500g vs. 2000g vs. 3000g, storage volume variations (25%, 50% and 75% of tube total volume as well as freezing-thaw cycles (up to 5 cyles. The influence of sample routine parameters, inter-centre variability and relative value of each biomarker (reported as normal/abnormal, was analysed. Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non centrifugation or centrifugation at RT, compared to 4ºC, led to higher Aβ42 levels. Reducing CSF storage volume from 75% to 50% of total tube capacity, decreased Aβ42 concentration (within analytical CV of the assay, whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to 5 freeze-thaw cycles, whereas Aβ42 levels decrease if CSF is freeze-thawed more than 3 times. This systematic study reinforces the need for CSF centrifugation at 4ºC prior to storage and highlights the influence of storage conditions in Aβ42 levels. This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-lab variability of CSF

Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability.

Science.gov (United States)

Fourier, Anthony; Portelius, Erik; Zetterberg, Henrik; Blennow, Kaj; Quadrio, Isabelle; Perret-Liaudet, Armand

2015-09-20

A panel of cerebrospinal fluid (CSF) biomarkers including total Tau (t-Tau), phosphorylated Tau protein at residue 181 (p-Tau) and β-amyloid peptides (Aβ42 and Aβ40), is frequently used as an aid in Alzheimer's disease (AD) diagnosis for young patients with cognitive impairment, for predicting prodromal AD in mild cognitive impairment (MCI) subjects, for AD discrimination in atypical clinical phenotypes and for inclusion/exclusion and stratification of patients in clinical trials. Due to variability in absolute levels between laboratories, there is no consensus on medical cut-off value for the CSF AD signature. Thus, for full implementation of this core AD biomarker panel in clinical routine, this issue has to be solved. Variability can be explained both by pre-analytical and analytical factors. For example, the plastic tubes used for CSF collection and storage, the lack of reference material and the variability of the analytical protocols were identified as important sources of variability. The aim of this review is to highlight these pre-analytical and analytical factors and describe efforts done to counteract them in order to establish cut-off values for core CSF AD biomarkers. This review will give the current state of recommendations. Copyright © 2015. Published by Elsevier B.V.

Evaluation of different biomarkers to predict individual radiosensitivity in an inter-laboratory comparison--lessons for future studies.

Directory of Open Access Journals (Sweden)

Burkhard Greve

Full Text Available Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs and derived lymphoblastoid cell lines (LCLs from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR-induced cell death (AnnexinV, induction and repair of DNA strand breaks (Comet assay, induction of yH2AX foci (as a result of DNA double strand breaks, and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the in vitro test systems investigated here seem not to be appropriate for a general prediction of clinical reactions during or after radiotherapy due to the experimental variability compared to the small effect of radiation sensitivity. Genome-wide expression analysis however revealed a set of 67 marker genes which were differentially induced 6 h after in vitro-irradiation in lymphocytes from radio-hypersensitive and non-radiosensitive patients. These results warrant future validation in larger

Analysis of biomarker data a practical guide

CERN Document Server

Looney, Stephen W

2015-01-01

A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

The Domain of Developmental Psychopathology.

Science.gov (United States)

Sroufe, L. Alan; Rutter, Michael

1984-01-01

Describes how developmental psychopathology differs from related disciplines, including abnormal psychology, psychiatry, clinical child psychology, and developmental psychology. Points out propositions underlying a developmental perspective and discusses implications for research in developmental psychopathology. (Author/RH)

Phthalate metabolites related to infertile biomarkers and infertility in Chinese men.

Science.gov (United States)

Liu, Liangpo; Wang, Heng; Tian, Meiping; Zhang, Jie; Panuwet, Parinya; D'Souza, Priya Esilda; Barr, Dana Boyd; Huang, Qingyu; Xia, Yankai; Shen, Heqing

2017-12-01

Although in vitro and in vivo laboratory studies have demonstrated androgen and anti-androgen effects on male reproduction from phthalate exposures, human studies still remain inconsistent. Therefore, a case-control study (n = 289) was conducted to evaluate the associations between phthalate exposures, male infertility risks, and changes in metabolomic biomarkers. Regional participants consisted of fertile (n = 150) and infertile (n = 139) males were recruited from Nanjing Medical University' affiliated hospitals. Seven urinary phthalate metabolites were measured using HPLC-MS/MS. Associations between levels of phthalate metabolites, infertility risks, and infertility-related biomarkers were statistically evaluated. MEHHP, one of the most abundant DEHP oxidative metabolites was significantly lower in cases than in controls (p = 0.039). When using the 1st quartile range as a reference, although statistically insignificant for odds ratios (ORs) of the 2nd, 3rd, and 4th quartiles (OR (95% CI) = 1.50 (0.34-6.48), 0.70 (0.14-3.52) and 0.42 (0.09-2.00), respectively), the MEHHP dose-dependent trend of infertility risk expressed as OR decreased significantly (p = 0.034). More interestingly, most of the phthalate metabolites, including MEHHP, were either positively associated with fertile prevention metabolic biomarkers or negatively associated with fertile hazard ones. Phthalate metabolism, along with their activated infertility-related biomarkers, may contribute to a decreased risk of male infertility at the subjects' ongoing exposure levels. Our results may be illustrated by the low-dose related androgen effect of phthalates and can improve our understanding of the controversial epidemiological results on this issue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Life Span Developmental Approach

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Ali Eryilmaz

2011-03-01

Full Text Available The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of individuals with respect to developmental stages. This developmental approach suggests that scientific disciplines should not explain developmental facts only with age changes. Along with aging, cognitive, biological, and socioemotional development throughout life should also be considered to provide a reasonable and acceptable context, guideposts, and reasonable expectations for the person. There are three important subjects whom life span developmental approach deals with. These are nature vs nurture, continuity vs discontinuity, and change vs stability. Researchers using life span developmental approach gather and produce knowledge on these three most important domains of individual development with their unique scientific methodology.

Automation on an Open-Access Platform of Alzheimer's Disease Biomarker Immunoassays.

Science.gov (United States)

Gille, Benjamin; Dedeene, Lieselot; Stoops, Erik; Demeyer, Leentje; Francois, Cindy; Lefever, Stefanie; De Schaepdryver, Maxim; Brix, Britta; Vandenberghe, Rik; Tournoy, Jos; Vanderstichele, Hugo; Poesen, Koen

2018-04-01

The lack of (inter-)laboratory standardization has hampered the application of universal cutoff values for Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and their transfer to general clinical practice. The automation of the AD biomarker immunoassays is suggested to generate more robust results than using manual testing. Open-access platforms will facilitate the integration of automation for novel biomarkers, allowing the introduction of the protein profiling concept. A feasibility study was performed on an automated open-access platform of the commercial immunoassays for the 42-amino-acid isoform of amyloid-β (Aβ 1-42 ), Aβ 1-40 , and total tau in CSF. Automated Aβ 1-42 , Aβ 1-40 , and tau immunoassays were performed within predefined acceptance criteria for bias and imprecision. Similar accuracy was obtained for ready-to-use calibrators as for reconstituted lyophilized kit calibrators. When compared with the addition of a standard curve in each test run, the use of a master calibrator curve, determined before and applied to each batch analysis as the standard curve, yielded an acceptable overall bias of -2.6% and -0.9% for Aβ 1-42 and Aβ 1-40 , respectively, with an imprecision profile of 6.2% and 8.4%, respectively. Our findings show that transfer of commercial manual immunoassays to fully automated open-access platforms is feasible, as it performs according to universal acceptance criteria.

Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration.

Science.gov (United States)

Khan, Gulafshana Hafeez; Galazis, Nicolas; Docheva, Nikolina; Layfield, Robert; Atiomo, William

2015-01-01

Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a

Proteomic and metabolomic approaches to biomarker discovery

CERN Document Server

Issaq, Haleem J

2013-01-01

Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

Biomarkers of latent TB infection

DEFF Research Database (Denmark)

Ruhwald, Morten; Ravn, Pernille

2009-01-01

For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

Road Transportable Analytical Laboratory system

International Nuclear Information System (INIS)

Finger, S.M.; Keith, V.F.; Spertzel, R.O.; De Avila, J.C.; O'Donnell, M.; Vann, R.L.

1993-09-01

This developmental effort clearly shows that a Road Transportable Analytical Laboratory System is a worthwhile and achievable goal. The RTAL is designed to fully analyze (radioanalytes, and organic and inorganic chemical analytes) 20 samples per day at the highest levels of quality assurance and quality control. It dramatically reduces the turnaround time for environmental sample analysis from 45 days (at a central commercial laboratory) to 1 day. At the same time each RTAL system will save the DOE over $12 million per year in sample analysis costs compared to the costs at a central commercial laboratory. If RTAL systems were used at the eight largest DOE facilities (at Hanford, Savannah River, Fernald, Oak Ridge, Idaho, Rocky Flats, Los Alamos, and the Nevada Test Site), the annual savings would be $96,589,000. The DOE's internal study of sample analysis needs projects 130,000 environmental samples requiring analysis in FY 1994, clearly supporting the need for the RTAL system. The cost and time savings achievable with the RTAL system will accelerate and improve the efficiency of cleanup and remediation operations throughout the DOE complex

MSU-DOE Plant Research Laboratory

Energy Technology Data Exchange (ETDEWEB)

1991-01-01

This document is the compiled progress reports of research funded through the Michigan State University/Department of Energy Plant Research Laboratory. Fourteen reports are included, covering the molecular basis of plant/microbe symbiosis, cell wall biosynthesis and proteins, gene expression, stress responses, plant hormone biosynthesis, interactions between the nuclear and organelle genomes, sensory transduction and tropisms, intracellular sorting and trafficking, regulation of lipid metabolism, molecular basis of disease resistance and plant pathogenesis, developmental biology of Cyanobacteria, and hormonal involvement in environmental control of plant growth. 320 refs., 26 figs., 3 tabs. (MHB)

Clinical laboratory technologist professional development in Camagüey

Directory of Open Access Journals (Sweden)

Mercedes Caridad García González

2015-05-01

Full Text Available The paper describes the results of research aimed at assessing the current conditions related to clinical laboratory technologist professional development. A descriptive cross study covering the period between November 2013 and January 2014 is presented. Several techniques for identifying and hierarchically arranging professional developmental related problems were used to study a sample at the Faculty of Health Technology of the Medical University “Carlos Juan Finlay”. The study involved heads of teaching departments and methodologists of health care technology specialties; moreover a survey and a content test were given graduate clinical laboratory technicians. The authors reached at the conclusion that clinical laboratory technologist professional development is limited and usually underestimate the necessities and interests of these graduates. Likewise, a lack of systematization and integration of the biomedical basic sciences contents and the laboratory diagnosis is noticeable.

Fluid biomarkers in multiple system atrophy

DEFF Research Database (Denmark)

Laurens, Brice; Constantinescu, Radu; Freeman, Roy

2015-01-01

Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

Effect of Developmental Stimulation Program on the Developmental Measures of Toddlers

Directory of Open Access Journals (Sweden)

Elahe Ghayebie

2018-04-01

Full Text Available Background: The variability in the developmental skills is reduced after the first three years of life; therefore, it is necessary to identify and manage early developmental delays. Aim: The aim of this study was to investigate the effect of developmental stimulation program on the developmental measures of the toddlers. Method: The present randomized controlled clinical trial was conducted on 31 toddlers aged 1-3 years residing at Ali Asghar Foster Care Center within 2016-2017. Developmental interventions were carried out based on the modified guidelines of West Virginia Early Learning Standards Framework for eight weeks (three 2-hour sessions a week. The interventions included a range of age- and developmental-specific activities described in the given guidelines. Child development age was measured based on motor dimensions (i.e., gross and fine and language development (i.e., receptive and expressive before and after the intervention. The data were analyzed in SPSS software (version 11 using independent t-test and Chi-square test. Results: The mean ages of the participants in the control and intervention groups were 19.9±5.5 and 20±6.02, respectively (P=0.62. The mean ages of receptive language development (P=0.003, expressive language development (P

Allergic asthma biomarkers using systems approaches

Directory of Open Access Journals (Sweden)

Gaurab eSircar

2014-01-01

Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

Urinary Biomarkers of Brain Diseases

Directory of Open Access Journals (Sweden)

Manxia An

2015-12-01

Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration.

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Galazis, Nicolas; Olaleye, Olalekan; Haoula, Zeina; Layfield, Robert; Atiomo, William

2012-12-01

To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. Academic department of obstetrics and gynecology in the United Kingdom. A total of 180 women identified in the six studies. Tissue samples from women with OC vs. tissue samples from women without OC. Proteomic biomarkers, proteomic technique used, and methodologic quality score. A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-γ, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Micro-computed tomography imaging and analysis in developmental biology and toxicology.

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Wise, L David; Winkelmann, Christopher T; Dogdas, Belma; Bagchi, Ansuman

2013-06-01

Micro-computed tomography (micro-CT) is a high resolution imaging technique that has expanded and strengthened in use since it was last reviewed in this journal in 2004. The technology has expanded to include more detailed analysis of bone, as well as soft tissues, by use of various contrast agents. It is increasingly applied to questions in developmental biology and developmental toxicology. Relatively high-throughput protocols now provide a powerful and efficient means to evaluate embryos and fetuses subjected to genetic manipulations or chemical exposures. This review provides an overview of the technology, including scanning, reconstruction, visualization, segmentation, and analysis of micro-CT generated images. This is followed by a review of more recent applications of the technology in some common laboratory species that highlight the diverse issues that can be addressed. Copyright © 2013 Wiley Periodicals, Inc.

Opinion paper on utility of point-of-care biomarkers in the emergency department pathways decision making.

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Di Somma, Salvatore; Zampini, Giorgio; Vetrone, Francesco; Soto-Ruiz, Karina M; Magrini, Laura; Cardelli, Patrizia; Ronco, Claudio; Maisel, Alan; Peacock, Frank W

2014-10-01

Overcrowding of the emergency department (ED) is rapidly becoming a global challenge and a major source of concern for emergency physicians. The evaluation of cardiac biomarkers is critical for confirming diagnoses and expediting treatment decisions to reduce overcrowding, however, physicians currently face the dilemma of choosing between slow and accurate central-based laboratory tests, or faster but imprecise assays. With improvements in technology, point-of-care testing (POCT) systems facilitate the efficient and high-throughput evaluation of biomarkers, such as troponin (cTn), brain natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL). In this context, POCT may help ED physicians to confirm a diagnosis of conditions, such as acute coronary syndrome, heart failure or kidney damage. Compared with classic laboratory methods, the use of cTn, BNP, and NGAL POCT has shown comparable sensitivity, specificity and failure rate, but with the potential to provide prompt and accurate diagnosis, shorten hospital stay, and alleviate the burden on the ED. Despite this potential, the full advantages of rapid delivery results will only be reached if POCT is implemented within hospital standardized procedures and ED staff receive appropriate training.

Cardiovascular biomarkers in clinical studies of type 2 diabetes

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Baldassarre, M P A; Andersen, A; Consoli, A

2018-01-01

biomarkers and 3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers). Within each category we present the currently best validated biomarkers with special focus on the population of interest (type 2 diabetes). For each individual biomarker, the physiological role, the validation...

Dietary and health biomarkers-time for an update

NARCIS (Netherlands)

Dragsted, L.O.; Gao Qizian,; Praticò, G.; Manach, Claudine; Wishart, D.S.; Scalbert, A.; Feskens, E.J.M.

2017-01-01

In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health.

Developmental competence of oocytes isolated from surplus medulla tissue in connection with cryopreservation of ovarian tissue for fertility preservation

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Wilken-Jensen, Helle N; Kristensen, Stine G; Jeppesen, Janni V

2014-01-01

OBJECTIVE: Evaluating the developmental competence of immature oocytes collected from surplus medulla tissue in connection with ovarian tissue cryopreservation for fertility preservation. DESIGN: Cohort comparative study. SETTING: University laboratory in Denmark from 2011-2012. POPULATION: 69...

Student-oriented learning: an inquiry-based developmental biology lecture course.

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Malacinski, George M

2003-01-01

In this junior-level undergraduate course, developmental life cycles exhibited by various organisms are reviewed, with special attention--where relevant--to the human embryo. Morphological features and processes are described and recent insights into the molecular biology of gene expression are discussed. Ways are studied in which model systems, including marine invertebrates, amphibia, fruit flies and other laboratory species are employed to elucidate general principles which apply to fertilization, cleavage, gastrulation and organogenesis. Special attention is given to insights into those topics which will soon be researched with data from the Human Genome Project. The learning experience is divided into three parts: Part I is a in which the Socratic (inquiry) method is employed by the instructor (GMM) to organize a review of classical developmental phenomena; Part II represents an in which students study the details related to the surveys included in Part I as they have been reported in research journals; Part III focuses on a class project--the preparation of a spiral bound on a topic of relevance to human developmental biology (e.g.,Textbook of Embryonal Stem Cells). Student response to the use of the Socratic method increases as the course progresses and represents the most successful aspect of the course.

Evaluating biomarkers for prognostic enrichment of clinical trials.

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Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

2017-12-01

A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

The current status of biomarkers for predicting toxicity

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Campion, Sarah; Aubrecht, Jiri; Boekelheide, Kim; Brewster, David W; Vaidya, Vishal S; Anderson, Linnea; Burt, Deborah; Dere, Edward; Hwang, Kathleen; Pacheco, Sara; Saikumar, Janani; Schomaker, Shelli; Sigman, Mark; Goodsaid, Federico

2013-01-01

Introduction There are significant rates of attrition in drug development. A number of compounds fail to progress past preclinical development due to limited tools that accurately monitor toxicity in preclinical studies and in the clinic. Research has focused on improving tools for the detection of organ-specific toxicity through the identification and characterization of biomarkers of toxicity. Areas covered This article reviews what we know about emerging biomarkers in toxicology, with a focus on the 2012 Northeast Society of Toxicology meeting titled ‘Translational Biomarkers in Toxicology.’ The areas covered in this meeting are summarized and include biomarkers of testicular injury and dysfunction, emerging biomarkers of kidney injury and translation of emerging biomarkers from preclinical species to human populations. The authors also provide a discussion about the biomarker qualification process and possible improvements to this process. Expert opinion There is currently a gap between the scientific work in the development and qualification of novel biomarkers for nonclinical drug safety assessment and how these biomarkers are actually used in drug safety assessment. A clear and efficient path to regulatory acceptance is needed so that breakthroughs in the biomarker toolkit for nonclinical drug safety assessment can be utilized to aid in the drug development process. PMID:23961847

Developmental neurotoxicity of different pesticides in PC-12 cells in vitro.

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Christen, Verena; Rusconi, Manuel; Crettaz, Pierre; Fent, Karl

2017-06-15

The detection of developmental neurotoxicity (DNT) of chemicals has high relevance for protection of human health. However, DNT of many pesticides is only little known. Furthermore, validated in vitro systems for assessment of DNT are not well established. Here we employed the rat phaeochromocytoma cell line PC-12 to evaluate DNT of 18 frequently used pesticides of different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, as well as quaternary ammonium compounds, the organic compound used in pesticides, piperonyl butoxide, as well as the insect repellent diethyltoluamide (DEET). We determined the outgrowth of neurites in PC-12 cells co-treated with nerve growth factor and different concentrations of biocides for 5days. Furthermore, we determined transcriptional alterations of selected genes that may be associated with DNT, such as camk2α and camk2β, gap-43, neurofilament-h, tubulin-α and tubulin-β. Strong and dose- dependent inhibition of neurite outgrowth was induced by azamethiphos and chlorpyrifos, and dieldrin and heptachlor, which was correlated with up-regulation of gap-43. No or only weak effects on neurite outgrowth and transcriptional alterations occurred for neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam, the pyrethroids λ-cyhalothrin, cyfluthrin, deltamethrin, and permethrin, the biocidal disinfectants C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride and barquat (dimethyl benzyl ammonium chloride), and piperonyl butoxide and DEET. Our study confirms potential developmental neurotoxicity of some pesticides and provides first evidence that azamethiphos has the potential to act as a developmental neurotoxic compound. We also demonstrate that inhibition of neurite outgrowth and transcriptional alterations of gap-43 expression correlate, which suggests the employment of gap-43 expression as a biomarker for detection and initial evaluation of potential DNT of chemicals

Discriminative capacity of biomarkers for acute stroke in the emergency department.

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Glickman, Seth W; Phillips, Samantha; Anstrom, Kevin J; Laskowitz, Daniel T; Cairns, Charles B

2011-09-01

Acute ischemic stroke remains largely a clinical diagnosis. To assess the potential of several biomarkers to distinguish acute ischemic stroke from mimics in the emergency department (ED). In this prospective study, 63 patients with suspected acute stroke were enrolled. Blood samples were collected at ED presentation and assayed for B-type natriuretic peptide, C-reactive protein (CRP), matrix metalloproteinase 9 (MMP-9), D-dimer, and protein S100B. Final diagnosis of stroke was rendered by blinded independent stroke experts after review of all clinical, imaging, and conventional laboratory data during admission. Logistic regression and bootstrapping models were used to evaluate the association between biomarker values and acute stroke. Thirty-four patients had a final diagnosis of stroke and 29 with mimics. The initial ED values of CRP, MMP-9, and S100B (C-indices of 0.808, 0.811, and 0.719, respectively) and the National Institutes of Health Stroke Scale (NIHSS) (C-index 0.887) predicted acute cerebral ischemia. CRP levels added discriminative value over clinical variables alone in the diagnosis of stroke. When the levels of CRP were added to the NIHSS, the combination was highly predictive of stroke (bootstrap mean C-index 0.951, 90% Confidence Interval 0.903-0.991, likelihood test p = 0.004). Biomarker testing with CRP and potentially MMP-9 and S100B, may add valuable and time-sensitive diagnostic information in the early evaluation of patients with suspected stroke in the ED. Future prospective evaluations are necessary to validate the diagnostic capability of these biomarkers for acute ischemic stroke in the ED before they should be considered for use in clinical practice. Copyright © 2011 Elsevier Inc. All rights reserved.

Building a developmental toxicity ontology.

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Baker, Nancy; Boobis, Alan; Burgoon, Lyle; Carney, Edward; Currie, Richard; Fritsche, Ellen; Knudsen, Thomas; Laffont, Madeleine; Piersma, Aldert H; Poole, Alan; Schneider, Steffen; Daston, George

2018-04-03

As more information is generated about modes of action for developmental toxicity and more data are generated using high-throughput and high-content technologies, it is becoming necessary to organize that information. This report discussed the need for a systematic representation of knowledge about developmental toxicity (i.e., an ontology) and proposes a method to build one based on knowledge of developmental biology and mode of action/ adverse outcome pathways in developmental toxicity. This report is the result of a consensus working group developing a plan to create an ontology for developmental toxicity that spans multiple levels of biological organization. This report provide a description of some of the challenges in building a developmental toxicity ontology and outlines a proposed methodology to meet those challenges. As the ontology is built on currently available web-based resources, a review of these resources is provided. Case studies on one of the most well-understood morphogens and developmental toxicants, retinoic acid, are presented as examples of how such an ontology might be developed. This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity. © 2018 Wiley Periodicals, Inc.

Breath Analysis Using Laser Spectroscopic Techniques: Breath Biomarkers, Spectral Fingerprints, and Detection Limits

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Peeyush Sahay

2009-10-01

Full Text Available Breath analysis, a promising new field of medicine and medical instrumentation, potentially offers noninvasive, real-time, and point-of-care (POC disease diagnostics and metabolic status monitoring. Numerous breath biomarkers have been detected and quantified so far by using the GC-MS technique. Recent advances in laser spectroscopic techniques and laser sources have driven breath analysis to new heights, moving from laboratory research to commercial reality. Laser spectroscopic detection techniques not only have high-sensitivity and high-selectivity, as equivalently offered by the MS-based techniques, but also have the advantageous features of near real-time response, low instrument costs, and POC function. Of the approximately 35 established breath biomarkers, such as acetone, ammonia, carbon dioxide, ethane, methane, and nitric oxide, 14 species in exhaled human breath have been analyzed by high-sensitivity laser spectroscopic techniques, namely, tunable diode laser absorption spectroscopy (TDLAS, cavity ringdown spectroscopy (CRDS, integrated cavity output spectroscopy (ICOS, cavity enhanced absorption spectroscopy (CEAS, cavity leak-out spectroscopy (CALOS, photoacoustic spectroscopy (PAS, quartz-enhanced photoacoustic spectroscopy (QEPAS, and optical frequency comb cavity-enhanced absorption spectroscopy (OFC-CEAS. Spectral fingerprints of the measured biomarkers span from the UV to the mid-IR spectral regions and the detection limits achieved by the laser techniques range from parts per million to parts per billion levels. Sensors using the laser spectroscopic techniques for a few breath biomarkers, e.g., carbon dioxide, nitric oxide, etc. are commercially available. This review presents an update on the latest developments in laser-based breath analysis.

Variation of Traditional Biomarkers of Liver Injury After an Ultramarathon at Altitude.

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Tirabassi, Jill N; Olewinski, Lucianne; Khodaee, Morteza

2018-03-01

Significant elevations of traditional biomarkers of liver injury can occur as a result of running an ultramarathon. Traditional serum biomarker levels of liver injury will significantly increase as the result of participating in this 161-km race at altitude. Prospective cross-sectional study. Level 3. A total of 64 (before) and 83 (after) volunteer runners participated in a prospective observational field-based study at the Leadville 100 ultramarathon race. Changes in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), and bilirubin levels were measured. Of 669 athletes who started the race, 352 successfully completed the race within the 30-hour cutoff (53%). Of 36 runners who had pre- and postrace blood samples taken, the mean ALT, AST, and bilirubin levels were increased from 23 ± 10 U/L, 23 ± 5 U/L, and 0.60 ± 0.29 mg/dL to 117 ± 106 U/L, 485 ± 500 U/L, and 1.60 ± 0.61 mg/dL, respectively (all P athletes' age, sex, body mass index, or finishing time. Significant positive linear correlations between AST, ALT, and LDH with CK were seen. Athletes in this study did not seek medical attention after the race based on an electronic survey (92% response rate). Significant elevations of traditional biomarkers of liver injury occurred as a result of running an ultramarathon at altitude. These correlated with CK, a marker of muscle injury. When reviewing laboratory studies of traditional biomarkers of liver injury in athletes after an ultramarathon, significant elevations may be seen from baseline but are likely to be of no clinical consequence.

Transgenerational developmental programming.

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Aiken, Catherine E; Ozanne, Susan E

2014-01-01

The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations

Biomarkers of the Dementia

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Mikio Shoji

2011-01-01

Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma.

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Sanna Neselius

Full Text Available BACKGROUND: Sports-related head trauma is common but still there is no established laboratory test used in the diagnostics of minimal or mild traumatic brain injuries. Further the effects of recurrent head trauma on brain injury markers are unknown. The purpose of this study was to investigate the relationship between Olympic (amateur boxing and cerebrospinal fluid (CSF brain injury biomarkers. METHODS: The study was designed as a prospective cohort study. Thirty Olympic boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in the study. CSF samples were collected by lumbar puncture 1-6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Biomarkers for acute and chronic brain injury were analysed. RESULTS: NFL (mean ± SD, 532±553 vs 135±51 ng/L p = 0.001, GFAP (496±238 vs 247±147 ng/L p80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. The lack of normalization of NFL and GFAP after the rest period in a subgroup of boxers may indicate ongoing degeneration. The recurrent head trauma in boxing may be associated with increased risk of chronic traumatic brain injury.

Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers.

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Yamada, Takashi; Hashimoto, Ryu-Ichiro; Yahata, Noriaki; Ichikawa, Naho; Yoshihara, Yujiro; Okamoto, Yasumasa; Kato, Nobumasa; Takahashi, Hidehiko; Kawato, Mitsuo

2017-10-01

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., "theranostic biomarker") is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Matching metal pollution with bioavailability, bioaccumulation and biomarkers response in fish (Centropomus parallelus) resident in neotropical estuaries

International Nuclear Information System (INIS)

Souza, Iara C.; Duarte, Ian D.; Pimentel, Natieli Q.; Rocha, Lívia D.; Morozesk, Mariana; Bonomo, Marina M.; Azevedo, Vinicius C.; Pereira, Camilo D.S.

2013-01-01

Two neotropical estuaries affected by different anthropogenic factors were studied. We report levels of metals and metalloids in water and sediment as well as their influence on genetic, biochemical and morphological biomarkers in the native fish Centropomus parallelus. Biomarkers reflected the fish health status. Multivariate statistics indicated both spatial and temporal changes in both water and sediment, which are linked to the elemental composition and health status of inhabitant fish, showing the biggest influence of surface water, followed by sediments and interstitial water. Bioaccumulation in fish muscle was useful to identify elements that were below detection limits in water, pointing out the risk of consuming fish exceeding allowance limits for some elements (As and Hg in this case). Multivariate statistics, including physical, chemical and biological issues, presents a suitable tool, integrating data from different origin allocated in the same estuary, which could be useful for future studies on estuarine systems. -- Highlights: •C. parallelus is a suitable bioindicator for assessing environmental quality in estuaries. •Biomarkers matched water quality pointing out different pollution scenarios. •Chemometrics allows extrapolating results from field and laboratory. •Chemometrics helps integrating biology and chemistry. -- Chemometrics allows matching pollution with bioaccumulation of metals and biomarkers responses in the fish Centropomus parallelus evidencing differences in estuaries quality

Plasma processing conditions substantially influence circulating microRNA biomarker levels.

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Cheng, Heather H; Yi, Hye Son; Kim, Yeonju; Kroh, Evan M; Chien, Jason W; Eaton, Keith D; Goodman, Marc T; Tait, Jonathan F; Tewari, Muneesh; Pritchard, Colin C

2013-01-01

Circulating, cell-free microRNAs (miRNAs) are promising candidate biomarkers, but optimal conditions for processing blood specimens for miRNA measurement remain to be established. Our previous work showed that the majority of plasma miRNAs are likely blood cell-derived. In the course of profiling lung cancer cases versus healthy controls, we observed a broad increase in circulating miRNA levels in cases compared to controls and that higher miRNA expression correlated with higher platelet and particle counts. We therefore hypothesized that the quantity of residual platelets and microparticles remaining after plasma processing might impact miRNA measurements. To systematically investigate this, we subjected matched plasma from healthy individuals to stepwise processing with differential centrifugation and 0.22 µm filtration and performed miRNA profiling. We found a major effect on circulating miRNAs, with the majority (72%) of detectable miRNAs substantially affected by processing alone. Specifically, 10% of miRNAs showed 4-30x variation, 46% showed 30-1,000x variation, and 15% showed >1,000x variation in expression solely from processing. This was predominantly due to platelet contamination, which persisted despite using standard laboratory protocols. Importantly, we show that platelet contamination in archived samples could largely be eliminated by additional centrifugation, even in frozen samples stored for six years. To minimize confounding effects in microRNA biomarker studies, additional steps to limit platelet contamination for circulating miRNA biomarker studies are necessary. We provide specific practical recommendations to help minimize confounding variation attributable to plasma processing and platelet contamination.

Diagnostic and prognostic epigenetic biomarkers in cancer.

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Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

2015-01-01

Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

MicroRNA biomarkers in glioblastoma

DEFF Research Database (Denmark)

Hermansen, Simon Kjær; Kristensen, Bjarne Winther

2013-01-01

tissues. Understanding these alterations is key to developing new biomarkers and intelligent treatment strategies. This review presents an overview of current knowledge about miRNA alterations in glioblastoma while focusing on the clinical future of miRNAs as biomarkers and discussing the strengths...

Biomarker discovery for colon cancer using a 761 gene RT-PCR assay

Directory of Open Access Journals (Sweden)

Hackett James R

2007-08-01

genes analyzed while maintaining the high specificity, sensitivity and reproducibility that are characteristics of RT-PCR. Biomarkers discovered using this approach can be transferred to a clinical reference laboratory setting without having to re-validate the assay on a second technology platform.

Comparative biomarker expression and RNA integrity in biospecimens derived from radical retropubic and robot-assisted laparoscopic prostatectomies.

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Ricciardelli, Carmela; Bianco-Miotto, Tina; Jindal, Shalini; Dodd, Thomas J; Cohen, Penelope A; Marshall, Villis R; Sutherland, Peter D; Samaratunga, Hemamali; Kench, James G; Dong, Ying; Wang, Hong; Clements, Judith A; Risbridger, Gail P; Sutherland, Robert L; Tilley, Wayne D; Horsfall, David J

2010-07-01

Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue sampling, handling, and storage might affect biomarker expression or invalidate tissue samples as analytes for some technologies. We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores. No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these samples into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue. Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear. Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided.

Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

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Namaste, Sorrel Ml; Aaron, Grant J; Varadhan, Ravi; Peerson, Janet M; Suchdev, Parminder S

2017-07-01

Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia. Objectives: The aims of the project were to 1 ) identify factors associated with inflammation, 2 ) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3 ) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA). Design: The BRINDA database inclusion criteria included surveys that 1 ) were conducted after 2004, 2 ) had target groups of PSC, WRA, or both, and 3 ) used a similar laboratory methodology for the measurement of ≥1 biomarker of iron [ferritin or soluble transferrin receptor or vitamin A status (retinol-binding protein or retinol)] and ≥1 biomarker of inflammation (α-1-acid glycoprotein or C-reactive protein). Individual data sets were standardized and merged into a BRINDA database comprising 16 nationally and regionally representative surveys from 14 countries. Collectively, the database covered all 6 WHO geographic regions and contained ∼30,000 PSC and 27,000 WRA. Data were analyzed individually and combined with the use of a meta-analysis. Results: The methods that were used to standardize the BRINDA database and the analytic approaches used to address the project's research questions are presented in this article. Three approaches to adjust micronutrient biomarker concentrations in the presence of inflammation and malaria infection are presented, along with an anemia conceptual framework that guided the BRINDA project's anemia analyses. Conclusions: The BRINDA project refines approaches to interpret iron and vitamin A biomarker values in settings of inflammation and malaria infection and suggests the use of a new regression approach as well as proposes an anemia framework to

How Nanotechnology and Biomedical Engineering Are Supporting the Identification of Predictive Biomarkers in Neuro-Oncology.

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Ganau, Mario; Paris, Marco; Syrmos, Nikolaos; Ganau, Laura; Ligarotti, Gianfranco K I; Moghaddamjou, Ali; Prisco, Lara; Ambu, Rossano; Chibbaro, Salvatore

2018-02-26

The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1) the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2) a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3) the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures.

How Nanotechnology and Biomedical Engineering Are Supporting the Identification of Predictive Biomarkers in Neuro-Oncology

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Mario Ganau

2018-02-01

Full Text Available The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1 the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2 a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3 the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures.

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

Energy Technology Data Exchange (ETDEWEB)

Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

2011-11-15

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

International Nuclear Information System (INIS)

Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.

2011-01-01

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: ► We tested 11 environmental compounds in a hESC metabolomics platform. ► Significant changes in secreted small molecule metabolites were observed. ► Perturbed mass features map to pathways critical for normal development and pregnancy. ► Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

Biomarkers in acute heart failure.

Science.gov (United States)

Mallick, Aditi; Januzzi, James L

2015-06-01

The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Inflammatory biomarkers and cancer

DEFF Research Database (Denmark)

Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

2017-01-01

and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

The path from biomarker discovery to regulatory qualification

CERN Document Server

Goodsaid, Federico

2013-01-01

The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

RECENT ADVANCES IN BIOMARKERS IN SEVERE BURNS.

Science.gov (United States)

Ruiz-Castilla, Mireia; Roca, Oriol; Masclans, Joan R; Barret, Joan P

2016-02-01

The pathophysiology of burn injuries is tremendously complex. A thorough understanding is essential for correct treatment of the burned area and also to limit the appearance of organ dysfunction, which, in fact, is a key determinant of morbidity and mortality. In this context, research into biomarkers may play a major role. Biomarkers have traditionally been considered an important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. Research into biomarkers may help to improve the prognosis of patients with severe burn injury. The aim of the present clinical review is to discuss new evidence of the value of biomarkers in this setting.

The Indian Consensus Document on cardiac biomarker

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I. Satyamurthy

2014-01-01

Full Text Available Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence, degree of severity and prognosis of the disease, they may be employed in combination with the present conventional clinical assessments. These make the biomarkers feasible options against the present expensive measurements and may provide clinical benefits.

Biomarkers in DILI: one more step forward

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Mercedes Robles-Díaz

2016-08-01

Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

Biomarkers for equine joint injury and osteoarthritis.

Science.gov (United States)

McIlwraith, C Wayne; Kawcak, Christopher E; Frisbie, David D; Little, Christopher B; Clegg, Peter D; Peffers, Mandy J; Karsdal, Morten A; Ekman, Stina; Laverty, Sheila; Slayden, Richard A; Sandell, Linda J; Lohmander, L S; Kraus, Virginia B

2018-03-01

We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of "wet" biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of equine and human OA were reviewed. The participants concluded that new information and studies in equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823-831, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Biology and Biomarkers for Wound Healing

Science.gov (United States)

Lindley, Linsey E.; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

2016-01-01

Background As the population grows older, the incidence and prevalence of conditions which lead to a predisposition for poor wound healing also increases. Ultimately, this increase in non-healing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has, and will continue to be the leading pathway to the discovery of therapeutic targets as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of non-healing patients for whom biomarker-guided approaches may aid in healing. Methods A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Results Currently, biomarkers are being identified using biomaterials sourced locally, from human wounds and/or systemically using systematic high-throughput “omics” modalities (genomic, proteomic, lipidomic, metabolomic analysis). In this review we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum including those measured in tissue specimens e.g. β-catenin and c-myc, wound fluid e.g. MMP’s and interleukins, swabs e.g. wound microbiota and serum e.g. procalcitonin and MMP’s. Conclusions Identification of numerous potential biomarkers utilizing different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity, and consistent implementation of these biomarkers as well as an emphasis on efficacious follow-up therapeutics is necessary for transition of this technology to clinically feasible point-of-care applications. PMID:27556760

Laboratory Medicine is Faced with the Evolution of Medical Practice

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Collinson Paul

2017-09-01

Full Text Available Laboratory medicine and clinical medicine are co-dependent components of medicine. Laboratory medicine functions most effectively when focused through a clinical lens. Me dical practice as a whole undergoes change. New drugs, treatments and changes in management strategies are introduced. New techniques, new technologies and new tests are developed. These changes may be either clinically or laboratory initiated, and so their introduction requires dialogue and interaction between clinical and laboratory medicine specialists. Treatment monitoring is integral to laboratory medicine, varying from direct drug measurement to monitoring cholesterol levels in response to treatment. The current trend to »personalised medicine« is an extension of this process with the development of companion diagnostics. Technological innovation forms part of modern laboratory practice. Introduction of new technology both facilitates standard laboratory approaches and permits introduction of new tests and testing strategies previously confined to the research laboratory only. The revolution in cardiac biomarker testing has been largely a laboratory led change. Flexibility in service provision in response to changing clinical practice or evolving technology provides a significant laboratory management challenge in the light of increasing expectations, shifts in population demographics and constraint in resource availability. Laboratory medicine practitioners are adept at meeting these challenges. One thing remains constant, that there will be a constant need laboratory medicine to meet the challenges of novel clinical challenges from infectious diseases to medical conditions developing from lifestyle and longevity.

Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26.

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Mary A Fletcher

2010-05-01

Full Text Available Chronic Fatigue Syndrome (CFS studies from our laboratory and others described decreased natural killer cell cytotoxicity (NKCC and elevated proportion of lymphocytes expressing the activation marker, dipeptidyl peptidase IV (DPPIV also known as CD26. However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS.Subjects included female and male CFS cases and healthy controls. NK cell function was measured with a bioassay, using K562 cells and (51Cr release. Lymphocyte associated DPPIV/CD26 was assayed by qualitative and quantitative flow cytometry. Serum DPPIV/CD26 was measured by ELISA. Analysis by receiver operating characteristic (ROC curve assessed biomarker potential. Cytotoxic function of NK cells for 176 CFS subjects was significantly lower than in the 230 controls. According to ROC analysis, NKCC was a good predictor of CFS status. There was no significant difference in NK cell counts between cases and controls. Percent CD2+ lymphocytes (T cells and NK cells positive for DPPIV/C26 was elevated in CFS cases, but there was a decrease in the number of molecules (rMol of DPPIV/C26 expressed on T cells and NK cells and a decrease in the soluble form of the enzyme in serum. Analyses by ROC curves indicated that all three measurements of DPPIV/CD26 demonstrated potential as biomarkers for CFS. None of the DPPIV/C26 assays were significantly correlated with NKCC.By ROC analysis, NKCC and three methods of measuring DPPIV/C26 examined in this study had potential as biomarkers for CFS. Of these, NKCC, %CD2+CD26+ lymphocytes and rMol CD26/CD2+ lymphocyte, required flow cytometry, fresh blood and access to a high complexity laboratory. Soluble DPPIV/C26 in serum is done with a standard ELISA assay, or with other soluble factors in a multiplex type of ELISA. Dipeptidyl peptidase IV on lymphocytes or in serum was

Biomarker monitoring in sports doping control.

Science.gov (United States)

Pottgiesser, Torben; Schumacher, Yorck Olaf

2012-06-01

Biomarker monitoring can be considered a new era in the effort against doping. Opposed to the old concept in doping control of direct detection of a prohibited substance in a biological sample such as urine or blood, the new paradigm allows a personalized longitudinal monitoring of biomarkers that indicate non-physiological responses independently of the used doping technique or substance, and may cause sanctioning of illicit practices. This review presents the development of biomarker monitoring in sports doping control and focuses on the implementation of the Athlete Biological Passport as the current concept of the World Anti Doping Agency for the detection of blood doping (hematological module). The scope of the article extends to the description of novel biomarkers and future concepts of application.

Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

Science.gov (United States)

Cooper, Christine A; Chahine, Lama M

2016-11-01

Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

Biomarkers of cancer cachexia.

Science.gov (United States)

Loumaye, Audrey; Thissen, Jean-Paul

2017-12-01

Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Imaging biomarkers as surrogate endpoints for drug development

International Nuclear Information System (INIS)

Richter, Wolf S.

2006-01-01

The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

Impact of biomarker development on drug safety assessment

International Nuclear Information System (INIS)

Marrer, Estelle; Dieterle, Frank

2010-01-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

Sputum biomarkers and the prediction of clinical outcomes in patients with cystic fibrosis.

Directory of Open Access Journals (Sweden)

Theodore G Liou

-CSF identifies patients with large acute declines in FEV(1%, possibly providing a laboratory-based objective decision-support tool for determination of an APE diagnosis. These biomarkers are potential CF reporting tools and treatment targets for slowing long-term progression and reducing short-term severity.

[A surveillance study on CRISPR/Cas molecular biomarker in Escherichia coli].

Science.gov (United States)

Liang, W J; Zhang, R G; Duan, G C; Hong, L J; Zhang, B; Xi, Y L; Yang, H Y; Chen, S Y; Lou, T Y; Zhao, Y X

2016-08-10

A new method related to molecular biomarker with CRISPR/Cas (clustered regularly interspaced short palindromic repeats-cas) in Escherichia (E.) coli was developed and used for surveillance programs. CRISPR/Cas sequence that containing 135 strains with complete sequence and 203 strains with whole genome shotgun sequence of E. coli in GenBank by BLAST and 361 strains of E. coli (including 38 strains of E. coli O157∶H7) in laboratory were identified by PCR and analyzed with the CRISPR Finder. Spacers were compared with DANMAN and the phylogenetic trees of cas gene were constructed under Clustal Ⅹ and Mega 5.1. With new perspective, a descriptive method was developed targeting on the position of CRISPR/cas in E. coli. The CRISPR1 was detected in 77.04%, 100.00% and 75.62% and the CRISPR2 was detected in 74.81%, 100.00% and 92.24% and the CRISPR3 and CRISPR4 were detected in 11.85%, 0 and 1.39% for 135 strains with complete sequence, 203 strains with whole genome shotgun sequence and 361 strains in the laboratory, respectively. One strain downloaded in GenBank with whole genome sequencing and 2 strains in the our laboratory were identified that containing four CRISPR locus. The other E. coli strain was with insertion sequence in downstream of the non-cas CRISPR1. The unique CRISPR was found in 8 strains of O55∶H7, in 180 strains of O157∶H7, in 8 strains of O157∶HNM, in 40 strains of O104∶H4, in 4 strains of O145∶H28, in all the 699 E. coli strains. The phylogenetic tree could be divided into two groups-cas with type I-E or type I-F. CRISPR/Cas might be used as a valuable molecular biomarker in epidemiological surveillance studies to identify the high virulent strains or new strains of E. coli. Phage night be related to the missing or obtaining of spacers.

More Accurate Oral Cancer Screening with Fewer Salivary Biomarkers

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James Michael Menke

2017-10-01

Full Text Available Signal detection and Bayesian inferential tools were applied to salivary biomarkers to improve screening accuracy and efficiency in detecting oral squamous cell carcinoma (OSCC. Potential cancer biomarkers are identified by significant differences in assay concentrations, receiver operating characteristic areas under the curve (AUCs, sensitivity, and specificity. However, the end goal is to report to individual patients their risk of having disease given positive or negative test results. Likelihood ratios (LRs and Bayes factors (BFs estimate evidential support and compile biomarker information to optimize screening accuracy. In total, 26 of 77 biomarkers were mentioned as having been tested at least twice in 137 studies and published in 16 summary papers through 2014. Studies represented 10 212 OSCC and 25 645 healthy patients. The measure of biomarker and panel information value was number of biomarkers needed to approximate 100% positive predictive value (PPV. As few as 5 biomarkers could achieve nearly 100% PPV for a disease prevalence of 0.2% when biomarkers were ordered from highest to lowest LR. When sequentially interpreting biomarker tests, high specificity was more important than test sensitivity in achieving rapid convergence toward a high PPV. Biomarkers ranked from highest to lowest LR were more informative and easier to interpret than AUC or Youden index. The proposed method should be applied to more recently published biomarker data to test its screening value.

Dehalococcoides as a Potential Biomarker Evidence for Uncharacterized Organohalides in Environmental Samples

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Qihong Lu

2017-09-01

Full Text Available The massive production and improper disposal of organohalides resulted in worldwide contamination in soil and water. However, their environmental survey based on chromatographic methods was hindered by challenges in testing the extremely wide variety of organohalides. Dehalococcoides as obligate organohalide-respiring bacteria exclusively use organohalides as electron acceptors to support their growth, of which the presence could be coupled with organohalides and, therefore, could be employed as a biomarker of the organohalide pollution. In this study, Dehalococcoides was screened in various samples of bioreactors and subsurface environments, showing the wide distribution of Dehalococcoides in sludge and sediment. Further laboratory cultivation confirmed the dechlorination activities of those Dehalococcoides. Among those samples, Dehalococcoides accounting for 1.8% of the total microbial community was found in an anaerobic granular sludge sample collected from a full-scale bioreactor treating petroleum wastewater. Experimental evidence suggested that the influent wastewater in the bioreactor contained bromomethane which support the growth of Dehalococcoides. This study demonstrated that Dehalococcoides could be employed as a promising biomarker to test the present of organohalides in wastestreams or other environmental samples.

Genome Transfer Prevents Fragmentation and Restores Developmental Potential of Developmentally Compromised Postovulatory Aged Mouse Oocytes

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Mitsutoshi Yamada

2017-03-01

Full Text Available Changes in oocyte quality can have great impact on the developmental potential of early embryos. Here we test whether nuclear genome transfer from a developmentally incompetent to a developmentally competent oocyte can restore developmental potential. Using in vitro oocyte aging as a model system we performed nuclear transfer in mouse oocytes at metaphase II or at the first interphase, and observed that development to the blastocyst stage and to term was as efficient as in control embryos. The increased developmental potential is explained primarily by correction of abnormal cytokinesis at anaphase of meiosis and mitosis, by a reduction in chromosome segregation errors, and by normalization of the localization of chromosome passenger complex components survivin and cyclin B1. These observations demonstrate that developmental decline is primarily due to abnormal function of cytoplasmic factors involved in cytokinesis, while the genome remains developmentally fully competent.

Developmental Science: Past, Present, and Future

Science.gov (United States)

Lerner, Richard M.

2012-01-01

The goal of developmental science is to describe, explain, and optimize intraindividual changes in adaptive developmental regulations and, as well, interindividual differences in such relations, across life. The history of developmental science is reviewed and its current foci, which are framed by relational developmental systems models that…

Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma

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Zhang ZG

2015-12-01

Full Text Available Zhiguo Zhang,1 Yanying Zhang,2 Yeying Wang,1 Lingling Xu,3 Wanju Xu3 1Department of Clinical Laboratory, Zhangqiu Maternity and Child Care Hospital, Zhangqiu, 2Department of Clinical Laboratory, Zaozhuang City Wangkai Infection Hospital, Zaozhuang, 3Department of Clinical Laboratory, Qianfoshan Hospital, Jinan, People’s Republic of China Abstract: Currently, there is no reliable biomarker for use in diagnosing alpha-fetoprotein (AFP-negative hepatocellular carcinoma (HCC. Such a biomarker would aid in making an early diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. This study examined AFP-L3 and Golgi protein 73 (GP73 as candidate biomarkers for AFP-negative HCC. The affinity adsorption method and enzyme-linked immunoassays were separately used to determine serum levels of AFP-L3 and GP73 in 50 patients with AFP-negative HCC, 30 non-HCC patients, and 50 healthy subjects. Fifty percent of patients with AFP-negative HCC tested positive for AFP-L3, while 3.33% of non-HCC patients and 2.00% of healthy subjects were AFP-L3 positive. Patients with AFP-negative HCC had significantly higher serum levels of AFP-L3 compared to non-HCC patients and healthy individuals; however, there was no significant difference in the AFP-L3 levels of non-HCC patients and healthy subjects. Sixty-six percent of patients with AFP-negative HCC tested positive for GP73, while 10% of non-HCC patients and 0% of healthy subjects were GP73-positive. Patients with AFP-negative HCC had significantly higher serum levels of GP73 compared to non-HCC patients and healthy subjects, but there was no significant difference between the GP73 levels of non-HCC patients and healthy individuals. Moreover, 20 patients with AFP-negative HCC were both AFP-L3- and GP73-positive, while no non-HCC patients or healthy subjects tested positive for both markers. Either AFP-L3 or GP73 may be used as a biomarker for diagnosing AFP-negative HCC, while their combined use

Recent advances in mathematical modeling of developmental abnormalities using mechanistic information.

Science.gov (United States)

Kavlock, R J

1997-01-01

During the last several years, significant changes in the risk assessment process for developmental toxicity of environmental contaminants have begun to emerge. The first of these changes is the development and beginning use of statistically based dose-response models [the benchmark dose (BMD) approach] that better utilize data derived from existing testing approaches. Accompanying this change is the greater emphasis placed on understanding and using mechanistic information to yield more accurate, reliable, and less uncertain risk assessments. The next stage in the evolution of risk assessment will be the use of biologically based dose-response (BBDR) models that begin to build into the statistically based models factors related to the underlying kinetic, biochemical, and/or physiologic processes perturbed by a toxicant. Such models are now emerging from several research laboratories. The introduction of quantitative models and the incorporation of biologic information into them has pointed to the need for even more sophisticated modifications for which we offer the term embryologically based dose-response (EBDR) models. Because these models would be based upon the understanding of normal morphogenesis, they represent a quantum leap in our thinking, but their complexity presents daunting challenges both to the developmental biologist and the developmental toxicologist. Implementation of these models will require extensive communication between developmental toxicologists, molecular embryologists, and biomathematicians. The remarkable progress in the understanding of mammalian embryonic development at the molecular level that has occurred over the last decade combined with advances in computing power and computational models should eventually enable these as yet hypothetical models to be brought into use.

Cardiovascular biomarkers and sex: the case for women.

Science.gov (United States)

Daniels, Lori B; Maisel, Alan S

2015-10-01

Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics

Science.gov (United States)

Molenaar, Peter C. M.

2015-01-01

The main theme of this paper concerns the persistent critique of Gilbert Gottlieb on developmental behavior genetics and my reactions to this critique, the latter changing from rejection to complete acceptation. Concise characterizations of developmental behavior genetics, developmental systems theory (to which Gottlieb made essential…

Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

Science.gov (United States)

Giglio, Anita; Brandmayr, Pietro

2017-08-01

Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection

KAUST Repository

Mansour, Hicham

2014-01-01

Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes.

Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection

KAUST Repository

Mansour, Hicham

2014-08-27

Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes.

Biomarkers in T cell therapy clinical trials

Directory of Open Access Journals (Sweden)

Kalos Michael

2011-08-01

Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

The development and applications of biomarkers

International Nuclear Information System (INIS)

Normandy, J.; Peeters, J.

1994-01-01

This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community

Biomarkers in psoriasis and psoriatic arthritis.

Science.gov (United States)

Villanova, Federica; Di Meglio, Paola; Nestle, Frank O

2013-04-01

Psoriasis is a common immune-mediated disease of the skin, which associates in 20-30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both conditions is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. At present there is no cure for psoriasis and there are no specific markers that can accurately predict disease progression and therapeutic response. Therefore, biomarkers for disease prognosis and response to treatment are urgently needed to help clinicians with objective indications to improve patient management and outcomes. Although many efforts have been made to identify psoriasis/PsA biomarkers none of them has yet been translated into routine clinical practice. In this review we summarise the different classes of possible biomarkers explored in psoriasis and PsA so far and discuss novel strategies for biomarker discovery.

The development and applications of biomarkers

Energy Technology Data Exchange (ETDEWEB)

Normandy, J.; Peeters, J. [eds.

1994-04-15

This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community.

Qualitative methodology in developmental psychology

DEFF Research Database (Denmark)

Demuth, Carolin; Mey, Günter

2015-01-01

Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing rec...... in qualitative research offers a promising avenue to advance the field in this direction.......Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

Biomarkers in spinal cord compression Ethics and perspectives

Directory of Open Access Journals (Sweden)

Iencean A.St.

2016-09-01

Full Text Available The phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H in serum or in cerebro-spinal fluid (CSF is a specific lesional biomarker for spinal cord injury. The lesional biomarkers and the reaction biomarkers are both presented after several hours post-injury. The specific predictive patterns of lesional biomarkers could be used to aid clinicians with making a diagnosis and establishing a prognosis, and evaluating therapeutic interventions. Diagnosis, prognosis, and treatment guidance based on biomarker used as a predictive indicator can determine ethical difficulties by differentiated therapies in patients with spinal cord compression. At this point based on studies until today we cannot take a decision based on biomarker limiting the treatment of neurological recovery in patients with complete spinal cord injury because we do not know the complexity of the biological response to spinal cord compression.

Attentional networks in developmental dyscalculia

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Henik Avishai

2010-01-01

Full Text Available Abstract Background Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Methods Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test - interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. Results The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. Conclusions These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

Attentional networks in developmental dyscalculia.

Science.gov (United States)

Askenazi, Sarit; Henik, Avishai

2010-01-07

Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test-interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

Biomarkers of intermediate endpoints in environmental and occupational health

DEFF Research Database (Denmark)

Knudsen, Lisbeth E; Hansen, Ase M

2007-01-01

The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

Developmental Scaffolding

DEFF Research Database (Denmark)

Giorgi, Franco; Bruni, Luis Emilio

2015-01-01

. Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. Awide range of genetic, cellular and morphological mechanisms allows the scaffolding to integrate these modular variations...... to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships selected amongst the ones...

Psychotherapy with people with developmental disabilities

Directory of Open Access Journals (Sweden)

Barbara Zafošnik

2011-08-01

Full Text Available People with developmental disabilities can experience any psychological abnormalitiy and psychiatric illness as do people without developmental disabilities. Due to different diagnostic criteria, assessment procedures and instruments, we lack definite prevalence rates for people with developmental disabilities, also suffering from mental health problems, eventhough most studies place the rate at 20 to 40%. One of the possible treatment alternatives for augmenting psychological well-being is psychotherapy, but is extremely rarely used for people with severe and profound disabilities, where speech cannot be the main therapeutic medium. So, those that are included in the psychotherapuetic process are predominantly clients with mild developmental disabilities, and they are mostly in cognitive-behavioral therapy. Recently, two models of (psychotherapy for persons with severe and profound developmental disabilities were developed: developmental-dynamic relationship therapy and attachment-based behaviour therapy for children. Conceptually, they both originate form developmental psychoanalytic theories.

CBD: a biomarker database for colorectal cancer.

Science.gov (United States)

Zhang, Xueli; Sun, Xiao-Feng; Cao, Yang; Ye, Benchen; Peng, Qiliang; Liu, Xingyun; Shen, Bairong; Zhang, Hong

2018-01-01

Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.Database URL: http://sysbio.suda.edu.cn/CBD/.

Emerging Concepts and Methodologies in Cancer Biomarker Discovery.

Science.gov (United States)

Lu, Meixia; Zhang, Jinxiang; Zhang, Lanjing

2017-01-01

Cancer biomarker discovery is a critical part of cancer prevention and treatment. Despite the decades of effort, only a small number of cancer biomarkers have been identified for and validated in clinical settings. Conceptual and methodological breakthroughs may help accelerate the discovery of additional cancer biomarkers, particularly their use for diagnostics. In this review, we have attempted to review the emerging concepts in cancer biomarker discovery, including real-world evidence, open access data, and data paucity in rare or uncommon cancers. We have also summarized the recent methodological progress in cancer biomarker discovery, such as high-throughput sequencing, liquid biopsy, big data, artificial intelligence (AI), and deep learning and neural networks. Much attention has been given to the methodological details and comparison of the methodologies. Notably, these concepts and methodologies interact with each other and will likely lead to synergistic effects when carefully combined. Newer, more innovative concepts and methodologies are emerging as the current emerging ones became mainstream and widely applied to the field. Some future challenges are also discussed. This review contributes to the development of future theoretical frameworks and technologies in cancer biomarker discovery and will contribute to the discovery of more useful cancer biomarkers.

Laboratory microfusion capability study

International Nuclear Information System (INIS)

1993-05-01

The purpose of this study is to elucidate the issues involved in developing a Laboratory Microfusion Capability (LMC) which is the major objective of the Inertial Confinement Fusion (ICF) program within the purview of the Department of Energy's Defense Programs. The study was initiated to support a number of DOE management needs: to provide insight for the evolution of the ICF program; to afford guidance to the ICF laboratories in planning their research and development programs; to inform Congress and others of the details and implications of the LMC; to identify criteria for selection of a concept for the Laboratory Microfusion Facility and to develop a coordinated plan for the realization of an LMC. As originally proposed, the LMC study was divided into two phases. The first phase identifies the purpose and potential utility of the LMC, the regime of its performance parameters, driver independent design issues and requirements, its development goals and requirements, and associated technical, management, staffing, environmental, and other developmental and operational issues. The second phase addresses driver-dependent issues such as specific design, range of performance capabilities, and cost. The study includes four driver options; the neodymium-glass solid state laser, the krypton fluoride excimer gas laser, the light-ion accelerator, and the heavy-ion induction linear accelerator. The results of the Phase II study are described in the present report

CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis.

Science.gov (United States)

Jia, Guiquan; Chandriani, Sanjay; Abbas, Alexander R; DePianto, Daryle J; N'Diaye, Elsa N; Yaylaoglu, Murat B; Moore, Heather M; Peng, Ivan; DeVoss, Jason; Collard, Harold R; Wolters, Paul J; Egen, Jackson G; Arron, Joseph R

2017-09-01

Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor. Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh was CXCL14 , which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib. CXCL14 expression was induced by SHh overexpression in mouse lung. Circulating CXCL14 protein levels were significantly higher in plasma from IPF patients than controls. In cancer patients, circulating CXCL14 levels were significantly reduced upon vismodegib treatment. CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF. Post-results, NCT00968981. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

Science.gov (United States)

Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

2016-05-01

Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Genetic Evaluation of Children with Global Developmental Delay—Current Status of Network Systems in Taiwan

Directory of Open Access Journals (Sweden)

Yong-Lin Foo

2015-08-01

Full Text Available This review article aims to introduce the screening and referral network of genetic evaluation for children with developmental delay in Taiwan. For these children, integrated systems provide services from the medical, educational, and social welfare sectors. All cities and counties in Taiwan have established a network for screening, detection, referral, evaluation, and intervention services. Increased awareness improves early detection and intervention. There remains a gap between supply and demand, especially with regard to financial resources and professional manpower. Genetic etiology has a major role in prenatal causes of developmental delay. A summary of reports on some related genetic disorders in the Taiwanese population is included in this review. Genetic diagnosis allows counseling with regard to recurrence risk and prevention. Networking with neonatal screening, laboratory diagnosis, genetic counseling, and orphan drugs logistics systems can provide effective treatment for patients. In Taiwan, several laboratories provide genetic tests for clinical diagnosis. Accessibility to advanced expensive tests such as gene chips or whole exome sequencing is limited because of funding problems; however, the service system in Taiwan can still operate in a relatively cost-effective manner. This experience in Taiwan may serve as a reference for other countries.

Biomarkers of Aging: From Function to Molecular Biology

Directory of Open Access Journals (Sweden)

Karl-Heinz Wagner

2016-06-01

Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

Biomarkers of PTSD: military applications and considerations

OpenAIRE

Amy Lehrner; Rachel Yehuda

2014-01-01

Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk fo...

WONOEP appraisal: Biomarkers of epilepsy-associated comorbidities.

Science.gov (United States)

Ravizza, Teresa; Onat, Filiz Y; Brooks-Kayal, Amy R; Depaulis, Antoine; Galanopoulou, Aristea S; Mazarati, Andrey; Numis, Adam L; Sankar, Raman; Friedman, Alon

2017-03-01

Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need. The objectives of the subgroup on biomarkers of comorbidities at the XIII Workshop on the Neurobiology of Epilepsy (WONOEP) were to present the state-of-the-art recent research findings in the field that highlighting potential biomarkers for comorbidities in epilepsy. We review recent progress in the field, including molecular, imaging, and genetic biomarkers of comorbidities as discussed during the WONOEP meeting on August 31-September 4, 2015, in Heybeliada Island (Istanbul, Turkey). We further highlight new directions and concepts from studies on comorbidities and potential new biomarkers for the prediction, diagnosis, and treatment of epilepsy-associated comorbidities. The activation of various molecular signaling pathways such as the "Janus Kinase/Signal Transducer and Activator of Transcription," "mammalian Target of Rapamycin," and oxidative stress have been shown to correlate with the presence and severity of subsequent cognitive abnormalities. Furthermore, dysfunction in serotonergic transmission, hyperactivity of the hypothalamic-pituitary-adrenocortical axis, the role of the inflammatory cytokines, and the contributions of genetic factors have all recently been regarded as relevant for understanding epilepsy-associated depression and cognitive deficits. Recent evidence supports the utility of imaging studies as potential biomarkers. The role of such biomarker may be far beyond the diagnosis of comorbidities, as accumulating clinical data indicate that comorbidities can predict epilepsy outcomes. Future research is required to reveal whether molecular changes in specific signaling pathways or advanced imaging techniques could be detected in the clinical settings and correlate

Proteomic Biomarkers for Spontaneous Preterm Birth

DEFF Research Database (Denmark)

Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

2014-01-01

This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

Imaging biomarker roadmap for cancer studies

NARCIS (Netherlands)

O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome.

Science.gov (United States)

McElroy, Anita K; Erickson, Bobbie R; Flietstra, Timothy D; Rollin, Pierre E; Nichol, Stuart T; Towner, Jonathan S; Spiropoulou, Christina F

2014-08-15

Ebola hemorrhagic fever (EHF) outbreaks occur sporadically in Africa and result in high rates of death. The 2000-2001 outbreak of Sudan virus-associated EHF in the Gulu district of Uganda led to 425 cases, of which 216 were laboratory confirmed, making it the largest EHF outbreak on record. Serum specimens from this outbreak had been preserved in liquid nitrogen from the time of collection and were available for analysis. Available samples were tested using a series of multiplex assays to measure the concentrations of 55 biomarkers. The data were analyzed to identify statistically significant associations between the tested biomarkers and hemorrhagic manifestations, viremia, and/or death. Death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines. Death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. Hemorrhage was also associated with elevated levels of soluble intracellular adhesion molecule. Viremia was independently associated with elevated levels of tissue factor and tissue plasminogen activator. Finally, samples from nonfatal cases had higher levels of sCD40L. These novel associations provide a better understanding of EHF pathophysiology and a starting point for researching new potential targets for therapeutic interventions. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Possible biomarkers modulating haloperidol efficacy and/or tolerability.

Science.gov (United States)

Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

2016-04-01

Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

Novel biomarkers for prediabetes, diabetes, and associated complications

Science.gov (United States)

Dorcely, Brenda; Katz, Karin; Jagannathan, Ram; Chiang, Stephanie S; Oluwadare, Babajide; Goldberg, Ira J; Bergman, Michael

2017-01-01

The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. PMID:28860833

Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention

Directory of Open Access Journals (Sweden)

Alaa Badawi

2010-05-01

Full Text Available Alaa Badawi1, Amira Klip2, Pierre Haddad3, David EC Cole4, Bibiana Garcia Bailo1,5, Ahmed El-Sohemy5, Mohamed Karmali11Office for Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, ON, Canada; 2Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; 3Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Montreal Diabetes Research Centre, Montreal, QC, Canada; 4Department of Laboratory Medicine and Pathobiology, 5Department of Nutritional Sciences, University of Toronto, Toronto, ON, CanadaAbstract: Obesity is a major risk factor for type 2 diabetes mellitus (T2DM, which is a significant health problem worldwide. Active disease is associated with low-grade chronic inflammation resulting in part from the activation of the innate immune system. In obesity, this activation leads to the release of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β and interleukin-6 that block major anabolic cascades downstream of insulin signaling and thus disrupt insulin homeostasis and action. Cytokines also trigger the production of acute-phase reactants such as C-reactive protein, plasminogen activator inhibitor-1, serum amyloid-A, and haptoglobin. The elevated synthesis of pro-inflammatory cytokines and acute-phase proteins (inflammatory network characterizes the early (or pre-clinical stages of T2DM and exhibits a graded increase with the disease progression. Current evidence suggests that understanding inflammatory networks can point to new biomarkers that may permit capturing the interaction between genetic and environmental risk factors in the pathogenesis of T2DM. Such biomarkers have a significant public health potential in the prediction of disease occurrence beyond risk factors presently monitored, such as family history, lifestyle assessment and standard clinical chemistry profiles. Furthermore, inflammatory markers may assist in the

Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions

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Radu M. Nanau

2015-06-01

Full Text Available Background: The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. Methods: A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010–2015. The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Findings: Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions.

Science.gov (United States)

Nanau, Radu M; Neuman, Manuela G

2015-06-29

The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010-2015). The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

Biomarkers: Delivering on the expectation of molecularly driven, quantitative health.

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Wilson, Jennifer L; Altman, Russ B

2018-02-01

Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health. Here we review themes of biomarker discovery, current implementations of biomarkers for precision health, and future opportunities and challenges for biomarker discovery. Impact statement Precision medicine evolved because of the understanding that human disease is molecularly driven and is highly variable across patients. This understanding has made biomarkers, a diverse class of biological measurements, more relevant for disease diagnosis, monitoring, and selection of treatment strategy. Biomarkers' impact on precision medicine can be seen in cancer, pharmacogenomics, and safety. The successes in these cases suggest many more applications for biomarkers and a greater impact for precision medicine across the spectrum of human disease. The authors assess the status of biomarker-guided medical practice by analyzing themes for biomarker discovery, reviewing the impact of these markers in the clinic, and highlight future and ongoing challenges for biomarker discovery. This work is timely and relevant, as the molecular, quantitative approach of precision medicine is spreading to many disease indications.

Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

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Betensky, Rebecca A.; Emerson, Sarah C.; Bonventre, Joseph V.

2012-01-01

Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies. PMID:22021710

Communication-Based Assessment of Developmental Age for Young Children with Developmental Disabilities

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DeVeney, Shari L.; Hoffman, Lesa; Cress, Cynthia J.

2012-01-01

Purpose: In this study, the authors compared a multiple-domain strategy for assessing developmental age of young children with developmental disabilities who were at risk for long-term reliance on augmentative and alternative communication (AAC) with a communication-based strategy composed of receptive language and communication indices that may…

Advances in Biomarkers in Critical Ill Polytrauma Patients.

Science.gov (United States)

Papurica, Marius; Rogobete, Alexandru F; Sandesc, Dorel; Dumache, Raluca; Cradigati, Carmen A; Sarandan, Mirela; Nartita, Radu; Popovici, Sonia E; Bedreag, Ovidiu H

2016-01-01

The complexity of the cases of critically ill polytrauma patients is given by both the primary, as well as the secondary, post-traumatic injuries. The severe injuries of organ systems, the major biochemical and physiological disequilibrium, and the molecular chaos lead to a high rate of morbidity and mortality in this type of patient. The 'gold goal' in the intensive therapy of such patients resides in the continuous evaluation and monitoring of their clinical status. Moreover, optimizing the therapy based on the expression of certain biomarkers with high specificity and sensitivity is extremely important because of the clinical course of the critically ill polytrauma patient. In this paper we wish to summarize the recent studies of biomarkers useful for the intensive care unit (ICU) physician. For this study the available literature on specific databases such as PubMed and Scopus was thoroughly analyzed. Each article was carefully reviewed and useful information for this study extracted. The keywords used to select the relevant articles were "sepsis biomarker", "traumatic brain injury biomarker" "spinal cord injury biomarker", "inflammation biomarker", "microRNAs biomarker", "trauma biomarker", and "critically ill patients". For this study to be carried out 556 original type articles were analyzed, as well as case reports and reviews. For this review, 89 articles with relevant topics for the present paper were selected. The critically ill polytrauma patient, because of the clinical complexity the case presents with, needs a series of evaluations and specific monitoring. Recent studies show a series of either tissue-specific or circulating biomarkers that are useful in the clinical status evaluation of these patients. The biomarkers existing today, with regard to the critically ill polytrauma patient, can bring a significant contribution to increasing the survival rate, by adapting the therapy according to their expressions. Nevertheless, the necessity remains to

Antibodies Against Complement Components: Relevance for the Antiphospholipid Syndrome-Biomarkers of the Disease and Biopharmaceuticals.

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Bećarević, Mirjana

2017-07-01

Laboratory criterion for the diagnosis of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPL Abs). Complement system has a role in mediating aPL Abs-induced thrombosis in animal models. The importance of antibodies against complement components (potential biomarkers of APS) and the importance of antibodies with beneficial anti-complement effects in APS (as biopharmaceuticals) are reviewed. Antibodies against complement components described in APS patients, so far, are anti-C1q and anti-factor H Abs, although anti-factor B Abs and anti-C5a Abs were described in animal models of APS. Clinical studies in APS patients are limited to a small number of case reports. Studies that would confirm potential role of Abs against complement components (as potential biomarkers of APS) are lacking. Lack of randomized clinical trials (that would provide complete data for confirmation of beneficial effects of biopharmaceuticals in complement inhibition) in APS is alarming.

The role of novel biomarkers in childhood idiopathic nephrotic syndrome: a narrative review of published evidence

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Uwaezuoke SN

2017-06-01

Full Text Available Samuel N Uwaezuoke Department of Pediatrics, Pediatric Nephrology Firm, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria Abstract: Two histological subtypes of idiopathic nephrotic syndrome are commonly recognized in children, namely minimal change nephropathy and focal segmental glomerulosclerosis. Children with minimal change nephropathy (the majority of whom are steroid-sensitive and focal segmental glomerulosclerosis (the majority of whom are steroid-resistant require early identification in order to ensure appropriate therapeutic intervention and better outcome. Although renal biopsy and histology remain the ideal diagnostic steps to identify these histological subtypes, reports indicate that serum and urinary biomarkers are now being utilized in the investigation of childhood idiopathic nephrotic syndrome. This paper aims to review the diagnostic and prognostic utility of novel biomarkers in childhood idiopathic nephrotic syndrome and to highlight their role in differentiating steroid-sensitive nephrotic syndrome (SRNS from steroid-resistant nephrotic syndrome (SSNS. Using the terms “idiopathic nephrotic syndrome,” “children,” and “biomarkers” the PubMed database was searched for relevant studies related to the topic. Biomarkers such as adiponectin, neopterin, β2-microglobulin, and N-acetyl-β-D glucosaminidase were reported as diagnostic markers. In addition to neopterin and N-acetyl-β-D glucosaminidase, urine vitamin D-binding protein and α1β-glycoprotein were shown to differentiate SRNS from SSNS while N-acetyl-β-D glucosaminidase and β2-microglobulin could predict steroid responsiveness and renal outcome in SRNS. Although progress has been made in demonstrating the diagnostic and prognostic utility of these biomarkers, their limited availability in most laboratories has precluded a complete paradigm shift from the conventional renal biopsy. Nevertheless, further longitudinal studies are required

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

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Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Biomarkers in inflammatory bowel diseases

DEFF Research Database (Denmark)

Bennike, Tue; Birkelund, Svend; Stensballe, Allan

2014-01-01

Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...

Establishment of post-harvest early-developmental categories for viability maintenance of Araucaria angustifolia seeds

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Cristhyane Garcia Araldi

2015-12-01

Full Text Available Araucaria angustifolia seeds are recalcitrant, and their metabolism remains high during storage. This research aimed to describe the initiation of germination in A. angustifolia seeds during storage in order to standardize the assessment of physiological quality and to promote seed conservation. Seeds were collected from two populations and stored for 270 days in the natural laboratory environment and cold chamber. Seeds were classified according to four early developmental stages: I - mature seeds; II - seeds with elongation along the embryonic axis; III - beginning of root protrusion; IV - advanced germination stage, with seedling shoots. After categorization, physical and physiological quality was assessed. In freshly collected seeds, only category I was observed. At 270 days, approximately 40% of seeds were in category III in laboratory conditions, while the maintenance in a cold chamber delayed germinative metabolism. Viability tests showed that seeds in categories III and IV were more susceptible to damage caused by storage. In conclusion, the percentage of viable A. angustifolia seeds depends on the development stage after collection. Seeds that have reached early developmental category III should be prioritized for propagation, while those remaining in categories I and II should be longer stored with periodic assessment for reduction in physiological quality.

Biomarkers of acute lung injury: worth their salt?

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Proudfoot Alastair G

2011-12-01

Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

Developmental plasticity: Friend or foe?

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Michels, Karin B

2017-01-01

Developmental plasticity - the concept that adaptation to changing and unfavorable environmental conditions are possible but may come at the price of compromised health potentials - has evolutionary grounding as it facilitates survival but dissents with fundamental evolutionary principles in that it may advance the lesser fit. It is an important cornerstone of the Developmental Origins of Health and Disease (DOHaD). Unlike evolutionary adaptation developmental plasticity may be short-lived and restricted to one or few generations and inheritance is uncertain. Potential mechanisms include epigenetic modifications adopted in utero which may not transmit to the next generation; future insights may allow adjustments of the outcomes of developmental plasticity.

Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: lnfluence of Gestation Length on Measurements of Offspring Body Weight and Puberty in Controls

Science.gov (United States)

Most laboratories conducting developmental and reproductive toxicity studies in rodents assign age by defining postnatal day (PND) 0 or 1 as the day of birth (DOB); i.e., gestation length affects PND and the timing of postnatal measurements. Some laboratories, however, define age...

Biomarkers in Diabetic Retinopathy.

Science.gov (United States)

Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

2015-01-01

There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

Biomarkers of carcinogen exposure and early effects.

OpenAIRE

2006-01-01

The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

Neural biomarkers for dyslexia, ADHD and ADD in the auditory cortex of children

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Bettina Serrallach

2016-07-01

Full Text Available Dyslexia, attention deficit hyperactivity disorder (ADHD, and attention deficit disorder (ADD show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N=147 using neuroimaging, magnet-encephalography and psychoacoustics. All disorder subgroups exhibited an oversized left planum temporale and an abnormal interhemispheric asynchrony (10-40 ms of the primary auditory evoked P1-response. Considering right auditory cortex morphology, bilateral P1 source waveform shapes, and auditory performance, the three disorder subgroups could be reliably differentiated with outstanding accuracies of 89-98%. We therefore for the first time provide differential biomarkers for a brain-based diagnosis of dyslexia, ADHD, and ADD. The method allowed not only a clear discrimination between two subtypes of attentional disorders (ADHD and ADD, a topic controversially discussed for decades in the scientific community, but also revealed the potential for objectively identifying comorbid cases. Noteworthy, in children playing a musical instrument, after three and a half years of training the observed interhemispheric asynchronies were reduced by about 2/3, thus suggesting a strong beneficial influence of music experience on brain development. These findings might have far-reaching implications for both research and practice and enable a profound understanding of the brain-related etiology, diagnosis, and musically based therapy of common auditory-related developmental disorders and learning disabilities.

Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

Science.gov (United States)

Zhao, Yang; Zheng, Wei; Zhuo, Daisy Y; Lu, Yuefeng; Ma, Xiwen; Liu, Hengchang; Zeng, Zhen; Laird, Glen

2017-10-11

Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

Use of biomarkers in ALS drug development and clinical trials.

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Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

2015-05-14

The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer's disease.

Science.gov (United States)

Kang, Ju-Hee; Vanderstichele, Hugo; Trojanowski, John Q; Shaw, Leslie M

2012-04-01

The xMAP-Luminex multiplex platform for measurement of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers using Innogenetics AlzBio3 immunoassay reagents that are for research use only has been shown to be an effective tool for early detection of an AD-like biomarker signature based on concentrations of CSF Aβ(1-42), t-tau and p-tau(181). Among the several advantages of the xMAP-Luminex platform for AD CSF biomarkers are: a wide dynamic range of ready-to-use calibrators, time savings for the simultaneous analyses of three biomarkers in one analytical run, reduction of human error, potential of reduced cost of reagents, and a modest reduction of sample volume as compared to conventional enzyme-linked immunosorbant assay (ELISA) methodology. Recent clinical studies support the use of CSF Aβ(1-42), t-tau and p-tau(181) measurement using the xMAP-Luminex platform for the early detection of AD pathology in cognitively normal individuals, and for prediction of progression to AD dementia in subjects with mild cognitive impairment (MCI). Studies that have shown the prediction of risk for progression to AD dementia by MCI patients provide the basis for the use of CSF Aβ(1-42), t-tau and p-tau(181) testing to assign risk for progression in patients enrolled in therapeutic trials. Furthermore emerging study data suggest that these pathologic changes occur in cognitively normal subjects 20 or more years before the onset of clinically detectable memory changes thus providing an objective measurement for use in the assessment of treatment effects in primary treatment trials. However, numerous previous ELISA and Luminex-based multiplex studies reported a wide range of absolute values of CSF Aβ(1-42), t-tau and p-tau(181) indicative of substantial inter-laboratory variability as well as varying degrees of intra-laboratory imprecision. In order to address these issues a recent inter-laboratory investigation that included a common set of CSF pool aliquots from

[Biomarkers of radiation-induced DNA repair processes].

Science.gov (United States)

Vallard, Alexis; Rancoule, Chloé; Guy, Jean-Baptiste; Espenel, Sophie; Sauvaigo, Sylvie; Rodriguez-Lafrasse, Claire; Magné, Nicolas

2017-11-01

The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death. The most important DNA repair biomarkers are DNA damage signaling proteins, with ATM, DNA-PKcs, 53BP1 and γ-H2AX. They can be analyzed either using immunostaining, or using lived cell imaging. However, to date, these techniques are still time and money consuming. The development of "omics" technologies should lead the way to new (and usable in daily routine) DNA repair biomarkers. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

Science.gov (United States)

Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E; Joshi, Lokesh; Kilcoyne, Michelle

2015-01-01

Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques.

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

Science.gov (United States)

Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-01-01

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

Biomarkers of exposure and dose: State of the art

International Nuclear Information System (INIS)

Brooks, A.L.

2001-01-01

Biomarkers provide methods to measure changes in biological systems and to relate them to environmental insults and disease processes. Biomarkers can be classified as markers of exposure and dose, markers of sensitivity, and markers of disease. It is important that the differences and applications of the various types of biomarkers be clearly understood. The military is primarily interested in early biomarkers of exposure and dose that do not require high levels of sensitivity but can be used to rapidly triage war fighters under combat or terrorist conditions and determine which, if any, require medical attention. Biomarkers of long-term radiation risk represent the second area of interest for the military. Biomarkers of risk require high sensitivity and specificity for the disease and insult but do not require rapid data turn around. Biomarkers will help provide information for quick command decisions in the field, characterise long-term troop risks and identify early stages of radiation-induced diseases. This information provides major positive reassurances about individual exposures and risk that will minimise the physical and psychological impact of wartime radiation exposures. (author)

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

Science.gov (United States)

Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-02-07

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

The New Digital Divide For Digital BioMarkers.

Science.gov (United States)

Torous, John; Rodriguez, Jorge; Powell, Adam

2017-09-01

As smartphone and sensors continue to become more ubiquitous across the world, digital biomarkers have emerged as a scalable and practical tool to explore disease states and advance health. But as the digital divide of access and ownership begins to fade, a new digital divide is emerging. Who are the types of people that own smartphones or smart watches, who are the types of people that download health apps or partake in digital biomarker studies, and who are the types of people that are actually active with digital biomarkers apps and sensors - the people providing the high quality and longitudinal data that this field is being founded upon? Understanding the people behind digital biomarkers, the very people this emerging field aims to help, may actually be the real challenge as well as opportunity for digital biomarkers.

Phase II cancer clinical trials for biomarker-guided treatments.

Science.gov (United States)

Jung, Sin-Ho

2018-01-01

The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

Systems biology and biomarker discovery

Energy Technology Data Exchange (ETDEWEB)

Rodland, Karin D.

2010-12-01

Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

A New Serum Biomarker for Lung Cancer - Transthyretin

Directory of Open Access Journals (Sweden)

Liyun LIU

2009-04-01

Full Text Available Background and objective Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI technique. Methods Serumsample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers were identified by ESI/MS-MS and database searching, and further confirmed by immunoprecipitation. The same sets of serum sample from all groups were re-measured by ELISA assay. Results Three protein peaks with the molecular weight 13.78 kDa, 13.90 kDa and 14.07 kDa were found significantlydecreased in lung cancer serum compared to the other groups and were all automatically selected as specific biomarkers by Biomarker Wizard software. The candidate biomarkers obtained from 1-D SDS gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin (nativeTTR, cysTTR and glutTTR, and the identity was further validated by immunoprecipitation using commercial TTR antibodies. Downregulated of TTR was found in both ELISA and SELDI analysis. Conclusion TTRs acted as the potentially useful biomarkers for lung cancer by SELDI technique.

Biomarkers of replicative senescence revisited

DEFF Research Database (Denmark)

Nehlin, Jan

2016-01-01

Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

Review of quantitative phase-digital holographic microscopy: promising novel imaging technique to resolve neuronal network activity and identify cellular biomarkers of psychiatric disorders

KAUST Repository

Marquet, Pierre

2014-09-22

Quantitative phase microscopy (QPM) has recently emerged as a new powerful quantitative imaging technique well suited to noninvasively explore a transparent specimen with a nanometric axial sensitivity. In this review, we expose the recent developments of quantitative phase-digital holographic microscopy (QP-DHM). Quantitative phase-digital holographic microscopy (QP-DHM) represents an important and efficient quantitative phase method to explore cell structure and dynamics. In a second part, the most relevant QPM applications in the field of cell biology are summarized. A particular emphasis is placed on the original biological information, which can be derived from the quantitative phase signal. In a third part, recent applications obtained, with QP-DHM in the field of cellular neuroscience, namely the possibility to optically resolve neuronal network activity and spine dynamics, are presented. Furthermore, potential applications of QPM related to psychiatry through the identification of new and original cell biomarkers that, when combined with a range of other biomarkers, could significantly contribute to the determination of high risk developmental trajectories for psychiatric disorders, are discussed.

DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

OpenAIRE

Jelena Kostić; Milkica Nešić; Jasminka Marković; Miodrag Stanković

2015-01-01

Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to c...

amphibian_biomarker_data

Data.gov (United States)

U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

Complex reference values for endocrine and special chemistry biomarkers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey.

Science.gov (United States)

Adeli, Khosrow; Higgins, Victoria; Nieuwesteeg, Michelle; Raizman, Joshua E; Chen, Yunqi; Wong, Suzy L; Blais, David

2015-08-01

Defining laboratory biomarker reference values in a healthy population and understanding the fluctuations in biomarker concentrations throughout life and between sexes are critical to clinical interpretation of laboratory test results in different disease states. The Canadian Health Measures Survey (CHMS) has collected blood samples and health information from the Canadian household population. In collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), the data have been analyzed to determine reference value distributions and reference intervals for several endocrine and special chemistry biomarkers in pediatric, adult, and geriatric age groups. CHMS collected data and blood samples from thousands of community participants aged 3 to 79 years. We used serum samples to measure 13 immunoassay-based special chemistry and endocrine markers. We assessed reference value distributions and, after excluding outliers, calculated age- and sex-specific reference intervals, along with corresponding 90% CIs, according to CLSI C28-A3 guidelines. We observed fluctuations in biomarker reference values across the pediatric, adult, and geriatric age range, with stratification required on the basis of age for all analytes. Additional sex partitions were required for apolipoprotein AI, homocysteine, ferritin, and high sensitivity C-reactive protein. The unique collaboration between CALIPER and CHMS has enabled, for the first time, a detailed examination of the changes in various immunochemical markers that occur in healthy individuals of different ages. The robust age- and sex-specific reference intervals established in this study provide insight into the complex biological changes that take place throughout development and aging and will contribute to improved clinical test interpretation. © 2015 American Association for Clinical Chemistry.

Challenging homeostasis to define biomarkers for nutrition related health

NARCIS (Netherlands)

Ommen, van B.; Keijer, J.; Heil, S.G.; Kaput, J.

2009-01-01

A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying normal homeostasis and developing validated biomarkers are formidable tasks because

Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

Science.gov (United States)

Tshering, Gyem; Dorji, Palden Wangyel; Chaijaroenkul, Wanna; Na-Bangchang, Kesara

2018-06-01

Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

A tuberculosis biomarker database: the key to novel TB diagnostics

Directory of Open Access Journals (Sweden)

Seda Yerlikaya

2017-03-01

Full Text Available New diagnostic innovations for tuberculosis (TB, including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this ‘biomarker pipeline problem’, FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools.

Biomarkers in pancreatic adenocarcinoma: current perspectives

Directory of Open Access Journals (Sweden)

Swords DS

2016-12-01

Full Text Available Douglas S Swords, Matthew A Firpo, Courtney L Scaife, Sean J Mulvihill Department of Surgery, University of Utah Health Sciences, Salt Lake City, UT, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9, which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA, CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. Keywords: pancreatic cancer, biomarkers, screening, CA 19-9, CEA

Crevicular fluid biomarkers and periodontal disease progression.

Science.gov (United States)

Kinney, Janet S; Morelli, Thiago; Oh, Min; Braun, Thomas M; Ramseier, Christoph A; Sugai, Jim V; Giannobile, William V

2014-02-01

Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biomarkers: in medicine, drug discovery, and environmental health

National Research Council Canada - National Science Library

Vaidya, Vishal S; Bonventre, Joseph V

2010-01-01

... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema.

Science.gov (United States)

Ptolemy, Adam S; Rifai, Nader

2010-01-01

A continual trend of annual growth can be seen within research devoted to the discovery and validation of disease biomarkers within both the natural and clinical sciences. This expansion of intellectual endeavours was quantified through database searches of (a) research grant awards provided by the various branches of the National Institutes of Health (NIH) and (b) academic publications. A search of awards presented between 1986 and 2009 revealed a total of 28,856 grants awarded by the NIH containing the term "biomarker". The total funds for these awards in 2008 and 2009 alone were over $2.5 billion. During the same respective time frames, searches of "biomarker" and either "discovery", "genomics", "proteomics" or "metabolomics" yielded a total of 4,928 NIH grants whose combined funding exceeded $1.2 billion. The derived trend in NIH awards paralleled the annual expansion in "biomarker" literature. A PubMed search for the term, between 1990 and 2009, revealed a total of 441,510 published articles, with 38,457 published in 2008. These enormous investments and academic outputs however have not translated into the expected integration of new biomarkers for patient care. For example no proteomics derived biomarkers are currently being utilized in routine clinical management. This translational chasm necessitates a review of the previously proposed biomarker definitions and evaluation schema. A subsequent discussion of both the analytical and pre-analytical considerations for such research is also presented within. This required knowledge should aid scientists in their pursuit and validation of new biological markers of disease.

Quality and future of clinical laboratories: the Vico's whole cyclical theory of the recurring cycles.

Science.gov (United States)

Plebani, Mario

2018-05-24

In the last few decades, laboratory medicine has undergone monumental changes, and laboratory technology, which has made enormous advances, now has new clinical applications thanks to the identification of a growing number of biomarkers and risk factors conducive to the promotion of predictive and preventive interventions that have enhanced the role of laboratory medicine in health care delivering. However, the paradigm shift in the past 50 years has led to a gap between laboratory and clinic, with an increased risk of inappropriateness in test request and interpretation, as well as the consolidation of analytical work in focused factories and megastructurers oriented only toward achieving greater volumes, decreasing cost per test and generating a vision of laboratory services as simple commodities. A careful historical revision of the changing models for delivering laboratory services in the United States leads to the prediction that there are several reasons for counteracting the vision of clinical laboratory as a commodity, and restoring the true nature of laboratory services as an integral part of the diagnosis and therapy process. The present study, which reports on internal and external drivers for change, proposes an integrated vision of quality in laboratory medicine.

Topographic processing in developmental prosopagnosia

DEFF Research Database (Denmark)

Klargaard, Solja K.; Starrfelt, Randi; Petersen, Anders

2016-01-01

deficit in visual processing or visual short-term memory. Interestingly, a classical dissociation could be demonstrated between impaired face memory and preserved topographic memory in two developmental prosopagnosics. We conclude that impairments in topographic memory tend to co-occur with developmental......Anecdotal evidence suggests a relation between impaired spatial (navigational) processing and developmental prosopagnosia. To address this formally, we tested two aspects of topographic processing – that is, perception and memory of mountain landscapes shown from different viewpoints. Participants...

Developmental stages of developmental screening: steps to implementation of a successful program.

Science.gov (United States)

Pinto-Martin, Jennifer A; Dunkle, Margaret; Earls, Marian; Fliedner, Dane; Landes, Cynthia

2005-11-01

Through the use of 2-stage screening strategies, research studies have shown that autism spectrum disorders and other developmental disabilities can now be detected reliably and with greater validity and in children as young as 18 months of age. Screening and diagnostic practices in the medical and educational arena lag far behind clinical research, however, with the average patient age at time of diagnosis being 3 to 6 years.We discuss the challenges of instituting universal developmental screening as part of pediatric care and present 2 models of existing or planned programs of early screening for autism spectrum disorder and developmental disability (1 in a community-based setting and 1 in a pediatric setting), and discuss the pros and cons of the different strategies.

Acute Coronary Syndromes: From The Laboratory Markers To The Coronary Vessels

Directory of Open Access Journals (Sweden)

Palazzuoli Alberto

2006-01-01

Full Text Available A number of "interesting" risk markers have been proposed as providing prognostic information in acute coronary syndromes (ACS. Elevation in plasma inflammatory and necrosis biomarkers have been related to future cardiovascular events in individuals with or without prior myocardial infarction. Recently BNP and pro-BNP are entered in clinical practice to recognize patients at major risk, providing incremental information respect to the traditional markers. Together with these laboratory indexes, a few of promising laboratory markers once easily available, could become useful in identification of patients at high risk. Several studies evaluated many markers of platelet aggregation, endothelial dysfunction and vascular thrombosis, but it is not yet clear whether each of the proposed markers may provide incremental predictive information. We describe, following the most studies reported in literature, the laboratory markers with potential clinical and prognostic power that could early help physicians in the identifi cation of patients with impaired coronary disease and more narrowed coronary arteries.

Genetic Evaluation of Children with Global Developmental Delay--Current Status of Network Systems in Taiwan.

Science.gov (United States)

Foo, Yong-Lin; Chow, Julie Chi; Lai, Ming-Chi; Tsai, Wen-Hui; Tung, Li-Chen; Kuo, Mei-Chin; Lin, Shio-Jean

2015-08-01

This review article aims to introduce the screening and referral network of genetic evaluation for children with developmental delay in Taiwan. For these children, integrated systems provide services from the medical, educational, and social welfare sectors. All cities and counties in Taiwan have established a network for screening, detection, referral, evaluation, and intervention services. Increased awareness improves early detection and intervention. There remains a gap between supply and demand, especially with regard to financial resources and professional manpower. Genetic etiology has a major role in prenatal causes of developmental delay. A summary of reports on some related genetic disorders in the Taiwanese population is included in this review. Genetic diagnosis allows counseling with regard to recurrence risk and prevention. Networking with neonatal screening, laboratory diagnosis, genetic counseling, and orphan drugs logistics systems can provide effective treatment for patients. In Taiwan, several laboratories provide genetic tests for clinical diagnosis. Accessibility to advanced expensive tests such as gene chips or whole exome sequencing is limited because of funding problems; however, the service system in Taiwan can still operate in a relatively cost-effective manner. This experience in Taiwan may serve as a reference for other countries. Copyright © 2014. Published by Elsevier B.V.

Biomarkers, Trauma, and Sepsis in Pediatrics: A Review

Directory of Open Access Journals (Sweden)

Marianne Frieri

2016-01-01

Full Text Available Context: There is a logical connection with biomarkers, trauma, and sepsis. This review paper provides new information and clinical practice implications. Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Stress management both in trauma is based upon the notion that stress causes an immune imbalance in susceptible individuals. Evidence Acquisition: Data sources included studies indexed in PubMed, a meta- analysis, predictive values, research strategies, and quality assessments. A recent paper by one of the authors stated marked increase in serum procalcitonin during the course of a septic process often indicates an exacerbation of the illness, and a decreasing level is a sign of improvement. A review of epidemiologic studies on pediatric soccer patients was also addressed. Keywords for searching included biomarkers, immunity, trauma, and sepsis. Results: Of 50 reviewed articles, 34 eligible articles were selected including biomarkers, predictive values for procalcitonin, identifying children at risk for intra-abdominal injuries, blunt trauma, and epidemiology, a meta-analysis. Of neonatal associated sepsis, the NF-kappa B pathway by inflammatory stimuli in human neutrophils, predictive value of gelsolin for the outcomes of preterm neonates, a meta-analysis interleukin-8 for neonatal sepsis diagnosis. Conclusions: Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms, and physiological functions of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Various topics were covered such as biomarkers, trauma, sepsis, inflammation, innate immunity, role of neutrophils and IL-8, reactive oxygen species

Biomarkers in Diabetic Retinopathy

Science.gov (United States)

Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

2015-01-01

There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

Diagnosing phenotypes of single-sample individuals by edge biomarkers.

Science.gov (United States)

Zhang, Wanwei; Zeng, Tao; Liu, Xiaoping; Chen, Luonan

2015-06-01

Network or edge biomarkers are a reliable form to characterize phenotypes or diseases. However, obtaining edges or correlations between molecules for an individual requires measurement of multiple samples of that individual, which are generally unavailable in clinical practice. Thus, it is strongly demanded to diagnose a disease by edge or network biomarkers in one-sample-for-one-individual context. Here, we developed a new computational framework, EdgeBiomarker, to integrate edge and node biomarkers to diagnose phenotype of each single test sample. By applying the method to datasets of lung and breast cancer, it reveals new marker genes/gene-pairs and related sub-networks for distinguishing earlier and advanced cancer stages. Our method shows advantages over traditional methods: (i) edge biomarkers extracted from non-differentially expressed genes achieve better cross-validation accuracy of diagnosis than molecule or node biomarkers from differentially expressed genes, suggesting that certain pathogenic information is only present at the level of network and under-estimated by traditional methods; (ii) edge biomarkers categorize patients into low/high survival rate in a more reliable manner; (iii) edge biomarkers are significantly enriched in relevant biological functions or pathways, implying that the association changes in a network, rather than expression changes in individual molecules, tend to be causally related to cancer development. The new framework of edge biomarkers paves the way for diagnosing diseases and analyzing their molecular mechanisms by edges or networks in one-sample-for-one-individual basis. This also provides a powerful tool for precision medicine or big-data medicine. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

[Biomarkers of Alzheimer disease].

Science.gov (United States)

Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

2014-01-01

Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

Metabolomics as a tool in the identification of dietary biomarkers.

Science.gov (United States)

Gibbons, Helena; Brennan, Lorraine

2017-02-01

Current dietary assessment methods including FFQ, 24-h recalls and weighed food diaries are associated with many measurement errors. In an attempt to overcome some of these errors, dietary biomarkers have emerged as a complementary approach to these traditional methods. Metabolomics has developed as a key technology for the identification of new dietary biomarkers and to date, metabolomic-based approaches have led to the identification of a number of putative biomarkers. The three approaches generally employed when using metabolomics in dietary biomarker discovery are: (i) acute interventions where participants consume specific amounts of a test food, (ii) cohort studies where metabolic profiles are compared between consumers and non-consumers of a specific food and (iii) the analysis of dietary patterns and metabolic profiles to identify nutritypes and biomarkers. The present review critiques the current literature in terms of the approaches used for dietary biomarker discovery and gives a detailed overview of the currently proposed biomarkers, highlighting steps needed for their full validation. Furthermore, the present review also evaluates areas such as current databases and software tools, which are needed to advance the interpretation of results and therefore enhance the utility of dietary biomarkers in nutrition research.

Road Transportable Analytical Laboratory system. Phase 1

Energy Technology Data Exchange (ETDEWEB)

Finger, S.M.; Keith, V.F.; Spertzel, R.O.; De Avila, J.C.; O`Donnell, M.; Vann, R.L.

1993-09-01

This developmental effort clearly shows that a Road Transportable Analytical Laboratory System is a worthwhile and achievable goal. The RTAL is designed to fully analyze (radioanalytes, and organic and inorganic chemical analytes) 20 samples per day at the highest levels of quality assurance and quality control. It dramatically reduces the turnaround time for environmental sample analysis from 45 days (at a central commercial laboratory) to 1 day. At the same time each RTAL system will save the DOE over $12 million per year in sample analysis costs compared to the costs at a central commercial laboratory. If RTAL systems were used at the eight largest DOE facilities (at Hanford, Savannah River, Fernald, Oak Ridge, Idaho, Rocky Flats, Los Alamos, and the Nevada Test Site), the annual savings would be $96,589,000. The DOE`s internal study of sample analysis needs projects 130,000 environmental samples requiring analysis in FY 1994, clearly supporting the need for the RTAL system. The cost and time savings achievable with the RTAL system will accelerate and improve the efficiency of cleanup and remediation operations throughout the DOE complex.

Implementation of proteomic biomarkers : Making it work

NARCIS (Netherlands)

Mischak, Harald; Ioannidis, John P. A.; Argiles, Angel; Attwood, Teresa K.; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P.; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W.; Julien, Bruce A.; Lankisch, Tim; Leung, Hing Y.; Maahs, David; Magni, Fulvio; Manns, Michael P.; Manolis, Efthymios; Mayer, Gert; Navis, Gerarda; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H.; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P.; Vlahou, Antonia

Eur J Clin Invest 2012; 42 (9): 10271036 Abstract While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe

Novel biomarkers for prediabetes, diabetes, and associated complications

Directory of Open Access Journals (Sweden)

Dorcely B

2017-08-01

Full Text Available Brenda Dorcely,1 Karin Katz,1 Ram Jagannathan,2 Stephanie S Chiang,1 Babajide Oluwadare,1 Ira J Goldberg,1 Michael Bergman1 1New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY, 2Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA Abstract: The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c, fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recogni­zing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. Keywords: prediabetes, biomarkers, inflammatory markers, diabetes, diabetes complications

Using Aptamers for Cancer Biomarker Discovery

Directory of Open Access Journals (Sweden)

Yun Min Chang

2013-01-01

Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

Biomarkers of threat and reward sensitivity demonstrate unique associations with risk for psychopathology.

Science.gov (United States)

Nelson, Brady D; McGowan, Sarah Kate; Sarapas, Casey; Robison-Andrew, E Jenna; Altman, Sarah E; Campbell, Miranda L; Gorka, Stephanie M; Katz, Andrea C; Shankman, Stewart A

2013-08-01

Two emotional/motivational constructs that have been posited to underlie anxiety and depressive disorders are heightened sensitivity to threat and reduced sensitivity to reward, respectively. It is unclear, though, whether these constructs are only epiphenomena or also connote risk for these disorders (and relatedly, whether they connote risk for separate disorders). Using family history of psychopathology as an indicator of risk, the present study examined whether biomarkers of sensitivity to threat (startle potentiation) and reward (frontal EEG asymmetry) were associated with similar or different familial liabilities. In addition, the present study examined whether these biomarkers were associated with risk independent of proband DSM-IV diagnosis. One-hundred and seventy-three individuals diagnosed with panic disorder (PD), early onset major depressive disorder (MDD), both (comorbids), or controls completed two laboratory paradigms assessing sensitivity to predictable/unpredictable threat (measured via startle response) and reward (measured via frontal EEG asymmetry during a gambling task). Results indicated that across all participants: (a) startle potentiation to unpredictable threat was associated with family history of PD (but not MDD); and (b) frontal EEG asymmetry while anticipating reward was associated with family history of MDD (but not PD). Additionally, both measures continued to be associated with family history of psychopathology after controlling for proband DSM-IV diagnosis. Results suggest that the proposed biomarkers of sensitivity to unpredictable threat and reward exhibit discriminant validity and may add to the predictive validity of the DSM-IV defined constructs of PD and MDD, respectively. PsycINFO Database Record (c) 2013 APA, all rights reserved.

The role of novel biomarkers in predicting diabetic nephropathy: a review

Directory of Open Access Journals (Sweden)

Uwaezuoke SN

2017-08-01

Full Text Available Samuel N Uwaezuoke Pediatric Nephrology Firm, Department of Pediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria Abstract: Diabetic nephropathy (DN is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM, and occasionally from type 2 diabetes mellitus (T2DM. Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN. Keywords: type 1 diabetes mellitus, renal microvascular complication, microalbuminuria, end-stage kidney disease, biomarker panel

The use of mass spectrometry for analysing metabolite biomarkers in epidemiology

DEFF Research Database (Denmark)

Lind, Mads Vendelbo; Savolainen, Otto I; Ross, Alastair B

2016-01-01

measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many...... biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses...

CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma.

Science.gov (United States)

Neselius, Sanna; Brisby, Helena; Theodorsson, Annette; Blennow, Kaj; Zetterberg, Henrik; Marcusson, Jan

2012-01-01

Sports-related head trauma is common but still there is no established laboratory test used in the diagnostics of minimal or mild traumatic brain injuries. Further the effects of recurrent head trauma on brain injury markers are unknown. The purpose of this study was to investigate the relationship between Olympic (amateur) boxing and cerebrospinal fluid (CSF) brain injury biomarkers. The study was designed as a prospective cohort study. Thirty Olympic boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in the study. CSF samples were collected by lumbar puncture 1-6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Biomarkers for acute and chronic brain injury were analysed. NFL (mean ± SD, 532±553 vs 135±51 ng/L p = 0.001), GFAP (496±238 vs 247±147 ng/L pboxing compared to controls. NFL (402±434 ng/L p = 0.004) and GFAP (369±113 ng/L p = 0.001) concentrations remained elevated after the rest period. Increased CSF levels of T-tau, NFL, GFAP, and S-100B in >80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. The lack of normalization of NFL and GFAP after the rest period in a subgroup of boxers may indicate ongoing degeneration. The recurrent head trauma in boxing may be associated with increased risk of chronic traumatic brain injury.

Biomarkers of Renal Function : Towards Clinical Actionability

NARCIS (Netherlands)

Binnenmars, S Heleen; Hijmans, R S; Navis, G; de Borst, M H

This review provides an overview of the clinical value of themost relevant renal biomarkers, focusing on two main clinical conditions: acute kidney injury and chronic kidney disease. We categorize biomarkers according to their actionability, in terms of a documented response to treatment in relation

Biomarker Detection using PS2-Thioaptamers, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a system to detect and quantify bone demineralization biomarkers as outlined in SBIR Topic "Technologies to Detect Biomarkers"....

Guidelines for Biomarker of Food Intake Reviews (BFIRev: how to conduct an extensive literature search for biomarker of food intake discovery

Directory of Open Access Journals (Sweden)

Giulia Praticò

2018-02-01

Full Text Available Abstract Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs. However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

Guidelines for Biomarker of Food Intake Reviews (BFIRev): how to conduct an extensive literature search for biomarker of food intake discovery.

Science.gov (United States)

Praticò, Giulia; Gao, Qian; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Pedapati, Sri Harsha; Afman, Lydia A; Wishart, David S; Vázquez-Fresno, Rosa; Lacueva, Cristina Andres; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J M; Dragsted, Lars O

2018-01-01

Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

Institute of Scientific and Technical Information of China (English)

Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

2017-01-01

Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Seema Patel

2011-01-01

Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

Improving accuracy of breast cancer biomarker testing in India

Directory of Open Access Journals (Sweden)

Tanuja Shet

2017-01-01

Full Text Available There is a global mandate even in countries with low resources to improve the accuracy of testing biomarkers in breast cancer viz. oestrogen receptor (ER, progesterone receptor (PR and human epidermal growth factor receptor 2 (HER2neu given their critical impact in the management of patients. The steps taken include compulsory participation in an external quality assurance (EQA programme, centralized testing, and regular performance audits for laboratories. This review addresses the status of ER/PR and HER2neu testing in India and possible reasons for the delay in development of guidelines and mandate for testing in the country. The chief cause of erroneous ER and PR testing in India continues to be easily correctable issues such as fixation and antigen retrieval, while for HER2neu testing, it is the use of low-cost non-validated antibodies and interpretative errors. These deficiencies can however, be rectified by (i distributing the accountability and responsibility to surgeons and oncologist, (ii certification of centres for testing in oncology, and (iii initiation of a national EQA system (EQAS programme that will help with economical solutions and identifying the centres of excellence and instill a system for reprimand of poorly performing laboratories.

Geomorphic and geochemical controls on leaf wax biomarker transport and preservation in alluvial river systems: Rio Bermejo, Argentina

Science.gov (United States)

Repasch, M. N.; Sachse, D.; Hovius, N.; Scheingross, J. S.; Szupiany, R. N.

2017-12-01

Rivers are the primary conduits for organic carbon (OC) transfer from vegetation-rich uplands to long-term sinks, and thus are responsible for significant fluxes among different reservoirs of the carbon cycle. Fluxes of terrestrial OC out of river systems are generally less than fluxes into the systems, indicating loss of OC either during active fluvial transport, during residence in the active channel belt, or in older deposits outside of the active channel belt. Sedimentary biomarkers can be used to elucidate the mechanisms of transport, preservation, and/or transformation of OC during its passage from source to sink. In this study we evaluate the influence of fluvial sediment transport on preservation of terrestrial leaf wax n-alkanes. Our natural laboratory is the Rio Bermejo in northern Argentina, which transports sediment and organic matter from the central Andes over 700 km across the foreland basin without input of foreign material from tributaries. Rapid channel migration rates in a region of flexural foreland basin uplift (the forebulge) are responsible for remobilization of floodplain sediment and terrestrial OC. By sampling suspended sediment, river bank sediment, and soil from several locations along the length of the Rio Bermejo, and analyzing the dissolved chemistry, biomarker composition, and compound-specific stable isotopes, we can evaluate the geomorphic and geochemical processes that act to influence the preservation of terrestrial biomarkers through the river system. Data suggest that concentrations of long-chain terrestrial (C25-C33) alkanes decrease downstream, while concentrations of short-chain (C15-C19) alkanes increase. This trend is corroborated by a downstream increase in suspended sediment δ13C values, suggesting a replacement of terrestrial OC by microbial OC. It is likely that microbial degradation is responsible for loss of terrestrial biomarkers as their residence time in the river system increases. Controlled laboratory

Time-dependent efficacy of longitudinal biomarker for clinical endpoint.

Science.gov (United States)

Kolamunnage-Dona, Ruwanthi; Williamson, Paula R

2018-06-01

Joint modelling of longitudinal biomarker and event-time processes has gained its popularity in recent years as they yield more accurate and precise estimates. Considering this modelling framework, a new methodology for evaluating the time-dependent efficacy of a longitudinal biomarker for clinical endpoint is proposed in this article. In particular, the proposed model assesses how well longitudinally repeated measurements of a biomarker over various time periods (0,t) distinguish between individuals who developed the disease by time t and individuals who remain disease-free beyond time t. The receiver operating characteristic curve is used to provide the corresponding efficacy summaries at various t based on the association between longitudinal biomarker trajectory and risk of clinical endpoint prior to each time point. The model also allows detecting the time period over which a biomarker should be monitored for its best discriminatory value. The proposed approach is evaluated through simulation and illustrated on the motivating dataset from a prospective observational study of biomarkers to diagnose the onset of sepsis.

Mass spectrometry-based proteomic quest for diabetes biomarkers.

Science.gov (United States)

Shao, Shiying; Guo, Tiannan; Aebersold, Ruedi

2015-06-01

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia, which affects hundreds of millions of individuals worldwide. Early diagnosis and complication prevention of DM are helpful for disease treatment. However, currently available DM diagnostic markers fail to achieve the goals. Identification of new diabetic biomarkers assisted by mass spectrometry (MS)-based proteomics may offer solution for the clinical challenges. Here, we review the current status of biomarker discovery in DM, and describe the pressure cycling technology (PCT)-Sequential Window Acquisition of all Theoretical fragment-ion (SWATH) workflow for sample-processing, biomarker discovery and validation, which may accelerate the current quest for DM biomarkers. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2014 Elsevier B.V. All rights reserved.

Guppy sexual behavior as an effect biomarker of estrogen mimics

DEFF Research Database (Denmark)

Bayley, M; Nielsen, J R; Baatrup, E

1999-01-01

There is widespread concern that some environmental chemicals can reduce the reproductive capability of humans and wildlife by mimicking natural estrogens and disrupting endocrine function. This potential threat to animal populations posed by xenoestrogens has, hardly surprisingly, been met...... strongly on the ability to perform the appropriate sexual behavior. The sexual display of the male guppy is strongly linked to reproductive success and is readily quantified under laboratory conditions. This preliminary study demonstrates that exposure of adult male guppies to water weakly contaminated...... with either natural estrogen (17beta-estradiol) or the xenoestrogen (4-tert-octylphenol) causes a dramatic decrease in the rate and intensity of sexual display. It is concluded that quantitative analysis of the sexual display of male guppies holds great promise as a biomarker at the organismal level...

An overview of children as a special population-Relevance to predictive biomarkers

International Nuclear Information System (INIS)

Kimmel, Gary L.

2005-01-01

There has been an increasing focus on children as a special population in the fields of toxicology and epidemiology. At the same time, there has been considerable improvement in the technology for defining normal development and pathways of pathogenesis. Increased support of these areas has culminated in stronger research programs and greater professional involvement in addressing the specific challenges of applying new techniques and data to the improvement of children's health. Part of these challenges relates to the ever changing environment of the child. Not only does a child's anatomy, physiology, and metabolism change with time, but their lifestyle and awareness change as well. All of these can have a significant impact on a child's exposure and the potential of that exposure to have an effect on health and development. This paper will provide a brief overview of the susceptibility of the child relative to sensitive developmental life stages, the changing nature of exposure parameters during development, and how these factors can impact the relevance of predictive biomarkers of chemical toxicity in children

Stable isotopes and biomarkers in microbial ecology

NARCIS (Netherlands)

Boschker, H.T.S.; Middelburg, J.J.

2002-01-01

The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

Bias in emerging biomarkers for bipolar disorder

DEFF Research Database (Denmark)

Carvalho, A F; Köhler, C A; Fernandes, B S

2016-01-01

BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, E...

Reading in developmental prosopagnosia

DEFF Research Database (Denmark)

Starrfelt, Randi; Klargaard, Solja K; Petersen, Anders

2018-01-01

exposure durations (targeting the word superiority effect), and d) text reading. RESULTS: Participants with developmental prosopagnosia performed strikingly similar to controls across the four reading tasks. Formal analysis revealed a significant dissociation between word and face recognition......, that is, impaired reading in developmental prosopagnosia. METHOD: We tested 10 adults with developmental prosopagnosia and 20 matched controls. All participants completed the Cambridge Face Memory Test, the Cambridge Face Perception test and a Face recognition questionnaire used to quantify everyday face...... recognition experience. Reading was measured in four experimental tasks, testing different levels of letter, word, and text reading: (a) single word reading with words of varying length,(b) vocal response times in single letter and short word naming, (c) recognition of single letters and short words at brief...

Management of water hyacinth. Report from India (Regional Research Laboratory, Jorhat, Assam)

International Nuclear Information System (INIS)

Baruah, J.N.

1981-01-01

The main objective of the project is the development of an environmentally sound management scheme for water hyacinth infestation through its various utilization potentials. Such an approach is considered desirable from the point ov view of economic viability and environmental protection. Accordingly various aspects of the problem have been studied in India in three different laboratories. Regional Research Laboratory, Jorhat, which is the lead laboratory, is concerned with the study of various factors involved in the growth of this weed, production of biogas, paper and board from water hyacinth, screening of compounds and organisms with commercial potential in this plant and utilization of this weed for mushroom cultivation. Developmental and engineering aspects of biogas production from water hyacinth are studied at Central Mechanical Engineering Research Institute, Durgapur, and Nagarjuna Sagar Engineering College, J N Technological University, Hyderabad. Pilot plant investigation on the production of handmade paper and board is being investigated at Regional Research Laboratory, Hyderabad

Biomarkers in critical illness: have we made progress?

Directory of Open Access Journals (Sweden)

Honore PM

2016-10-01

Full Text Available Patrick M Honore,1 Rita Jacobs,1 Inne Hendrickx,1 Elisabeth De Waele,1 Viola Van Gorp,1 Olivier Joannes-Boyau,2 Jouke De Regt,1 Willem Boer,3 Herbert D Spapen1 1Intensive Care Unit, Universitair Ziekenhuis Brussel, VUB University, Brussels, Belgium; 2Intensive Care Unit, Hopital Haut Leveque, University of Bordeaux 2, Bordeaux, France; 3Intensive Care Unit, Ziekenhuis Oost-Limburg, Genk, Belgium Abstract: Biomarkers have emerged as exemplary key players in translational medicine. Many have been assessed for timely recognition, early treatment, and adequate follow-up for a variety of pathologies. Biomarker sensitivity has improved considerably over the last years but specificity remains poor, in particular when two “marker-sensitive” conditions overlap in one patient. Biomarker research holds an enormous potential for diagnostic and prognostic purposes in postoperative and critically ill patients who present varying degrees of inflammation, infection, and concomitant (subacute organ dysfunction or failure. Despite a remarkable progress in development and testing, biomarkers are not yet ready for routine use at the bedside. Keywords: biomarkers, acute kidney injury, sepsis, ARDS

Clinical, functional, behavioural and epigenomic biomarkers of obesity.

Science.gov (United States)

Lafortuna, Claudio L; Tovar, Armando R; Rastelli, Fabio; Tabozzi, Sarah A; Caramenti, Martina; Orozco-Ruiz, Ximena; Aguilar-Lopez, Miriam; Guevara-Cruz, Martha; Avila-Nava, Azalia; Torres, Nimbe; Bertoli, Gloria

2017-06-01

Overweight and obesity are highly prevalent conditions worldwide, linked to an increased risk for death, disability and disease due to metabolic and biochemical abnormalities affecting the biological human system throughout different domains. Biomarkers, defined as indicators of biological processes in health and disease, relevant for body mass excess management have been identified according to different criteria, including anthropometric and molecular indexes, as well as physiological and behavioural aspects. Analysing these different biomarkers, we identified their potential role in diagnosis, prognosis and treatment. Epigenetic biomarkers, cellular mediators of inflammation and factors related to microbiota-host interactions may be considered to have a theranostic value. Though, the molecular processes responsible for the biological phenomenology detected by the other analysed markers, is not clear yet. Nevertheless, these biomarkers possess valuable diagnostic and prognostic power. A new frontier for theranostic biomarkers can be foreseen in the exploitation of parameters defining behaviours and lifestyles linked to the risk of obesity, capable to describe the effects of interventions for obesity prevention and treatment which include also behaviour change strategies.

Oral Metagenomic Biomarkers in Rheumatoid Arthritis

Science.gov (United States)

2017-09-01

individuals with rheumatoid arthritis (RA). The goal is to test the  hypothesis that oral microbiome and metagenomic analyses will allow  us  to identify new...biomarkers  that are  useful  for the diagnosis of early RA and/or biomarkers that help to predict the efficacy of  specific therapeutic interventions... RNA  microbiome analysis as well as whole genome shotgun sequencing.  Upon completion of these aims, any identified bacterial biomarkers may be

Biomarkers in pancreatic adenocarcinoma: current perspectives.

Science.gov (United States)

Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Science.gov (United States)

Tahara, Hideaki; Sato, Marimo; Thurin, Magdalena; Wang, Ena; Butterfield, Lisa H; Disis, Mary L; Fox, Bernard A; Lee, Peter P; Khleif, Samir N; Wigginton, Jon M; Ambs, Stefan; Akutsu, Yasunori; Chaussabel, Damien; Doki, Yuichiro; Eremin, Oleg; Fridman, Wolf Hervé; Hirohashi, Yoshihiko; Imai, Kohzoh; Jacobson, James; Jinushi, Masahisa; Kanamoto, Akira; Kashani-Sabet, Mohammed; Kato, Kazunori; Kawakami, Yutaka; Kirkwood, John M; Kleen, Thomas O; Lehmann, Paul V; Liotta, Lance; Lotze, Michael T; Maio, Michele; Malyguine, Anatoli; Masucci, Giuseppe; Matsubara, Hisahiro; Mayrand-Chung, Shawmarie; Nakamura, Kiminori; Nishikawa, Hiroyoshi; Palucka, A Karolina; Petricoin, Emanuel F; Pos, Zoltan; Ribas, Antoni; Rivoltini, Licia; Sato, Noriyuki; Shiku, Hiroshi; Slingluff, Craig L; Streicher, Howard; Stroncek, David F; Takeuchi, Hiroya; Toyota, Minoru; Wada, Hisashi; Wu, Xifeng; Wulfkuhle, Julia; Yaguchi, Tomonori; Zeskind, Benjamin; Zhao, Yingdong; Zocca, Mai-Britt; Marincola, Francesco M

2009-01-01

might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions. PMID:19534815

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Directory of Open Access Journals (Sweden)

Rivoltini Licia

2009-06-01

were recognized that might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions.

Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

Science.gov (United States)

Chauhan, Ranjit; Lahiri, Nivedita

2016-01-01

Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Ranjit Chauhan

2016-01-01

Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

Novel ageing-biomarker discovery using data-intensive technologies.

Science.gov (United States)

Griffiths, H R; Augustyniak, E M; Bennett, S J; Debacq-Chainiaux, F; Dunston, C R; Kristensen, P; Melchjorsen, C J; Navarrete, Santos A; Simm, A; Toussaint, O

2015-11-01

Ageing is accompanied by many visible characteristics. Other biological and physiological markers are also well-described e.g. loss of circulating sex hormones and increased inflammatory cytokines. Biomarkers for healthy ageing studies are presently predicated on existing knowledge of ageing traits. The increasing availability of data-intensive methods enables deep-analysis of biological samples for novel biomarkers. We have adopted two discrete approaches in MARK-AGE Work Package 7 for biomarker discovery; (1) microarray analyses and/or proteomics in cell systems e.g. endothelial progenitor cells or T cell ageing including a stress model; and (2) investigation of cellular material and plasma directly from tightly-defined proband subsets of different ages using proteomic, transcriptomic and miR array. The first approach provided longitudinal insight into endothelial progenitor and T cell ageing. This review describes the strategy and use of hypothesis-free, data-intensive approaches to explore cellular proteins, miR, mRNA and plasma proteins as healthy ageing biomarkers, using ageing models and directly within samples from adults of different ages. It considers the challenges associated with integrating multiple models and pilot studies as rational biomarkers for a large cohort study. From this approach, a number of high-throughput methods were developed to evaluate novel, putative biomarkers of ageing in the MARK-AGE cohort. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Comparison of biomarker based Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and conventional methods in the identification of clinically relevant bacteria and yeast.

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Kassim, Ali; Pflüger, Valentin; Premji, Zul; Daubenberger, Claudia; Revathi, Gunturu

2017-05-25

MALDI-TOF MS is an analytical method that has recently become integral in the identification of microorganisms in clinical laboratories. It relies on databases that majorly employ pattern recognition or fingerprinting. Biomarker based databases have also been developed and there is optimism that these may be superior to pattern recognition based databases. This study compared the performance of ribosomal biomarker based MALDI-TOF MS and conventional methods in the identification of selected bacteria and yeast. The study was a cross sectional study identifying clinically relevant bacteria and yeast isolated from varied clinical specimens submitted to a clinical laboratory. The identification of bacteria using conventional Vitek 2™ automated system, serotyping and MALDI-TOF MS was performed as per standard operating procedures. Comparison of sensitivities were then carried out using Pearson Chi-Square test and p-value of bacteria and Gram positive bacteria to the species level. For the Gram positive bacteria, significant difference was observed in the identification of Coagulase negative Staphylococci (p = 0.000) and Enterococcus (p = 0.008). Significant difference was also observed between serotyping and MALDI-TOF MS (p = 0.005) and this was attributed to the lack of identification of Shigella species by MALDI-TOF MS. There was no significant difference observed in the identification of yeast however some species of Candida were unidentified by MALDI-TOF MS. Biomarker based MALDI-TOF MS had good performance in a clinical laboratory setting with high sensitivities in the identification of clinically relevant microorganisms.

Biomarkers of nanomaterial exposure and effect: current status

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Iavicoli, Ivo; Leso, Veruscka; Manno, Maurizio; Schulte, Paul A.

2014-03-01

Recent advances in nanotechnology have induced a widespread production and application of nanomaterials. As a consequence, an increasing number of workers are expected to undergo exposure to these xenobiotics, while the possible hazards to their health remain not being completely understood. In this context, biological monitoring may play a key role not only to identify potential hazards from and to evaluate occupational exposure to nanomaterials, but also to detect their early biological effects to better assess and manage risks of exposure in respect of the health of workers. Therefore, the aim of this review is to provide a critical evaluation of potential biomarkers of nanomaterial exposure and effect investigated in human and animal studies. Concerning exposure biomarkers, internal dose of metallic or metal oxide nanoparticle exposure may be assessed measuring the elemental metallic content in blood or urine or other biological materials, whereas specific molecules may be carefully evaluated in target tissues as possible biomarkers of biologically effective dose. Oxidative stress biomarkers, such as 8-hydroxy-deoxy-guanosine, genotoxicity biomarkers, and inflammatory response indicators may also be useful, although not specific, as biomarkers of nanomaterial early adverse health effects. Finally, potential biomarkers from "omic" technologies appear to be quite innovative and greatly relevant, although mechanistic, ethical, and practical issues should all be resolved before their routine application in occupational settings could be implemented. Although all these findings are interesting, they point out the need for further research to identify and possibly validate sensitive and specific biomarkers of exposure and effect, suitable for future use in occupational biomonitoring programs. A valuable contribution may derive from the studies investigating the biological behavior of nanomaterials and the factors influencing their toxicokinetics and reactivity. In

Developmental toxicity of engineered nanomaterials in rodents

Energy Technology Data Exchange (ETDEWEB)

Ema, Makoto, E-mail: ema-makoto@aist.go.jp; Gamo, Masashi; Honda, Kazumasa

2016-05-15

We summarized significant effects reported in the literature on the developmental toxicity of engineered nanomaterials (ENMs) in rodents. The developmental toxicity of ENMs included not only structural abnormalities, but also death, growth retardation, and behavioral and functional abnormalities. Most studies were performed on mice using an injection route of exposure. Teratogenic effects were indicated when multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), and TiO{sub 2}-nanoparticles were administered to mice during early gestation. Reactive oxygen species levels were increased in placentas and malformed fetuses and their placentas after prenatal exposure to MWCNTs and SWCNTs, respectively. The pre- and postnatal mortalities and growth retardation in offspring increased after prenatal exposure to ENMs. Histopathological and functional abnormalities were also induced in placentas after prenatal exposure to ENMs. Maternal exposure to ENMs induced behavioral alterations, histopathological and biochemical changes in the central nervous system, increased susceptibility to allergy, transplacental genotoxicity, and vascular, immunological, and reproductive effects in offspring. The size- and developmental stage-dependent placental transfer of ENMs was noted after maternal exposure. Silver accumulated in the visceral yolk sac after being injected with Ag-NPs during early gestation. Although currently available data has provided initial information on the potential developmental toxicity of ENMs, that on the developmental toxicity of ENMs is still very limited. Further studies using well-characterized ENMs, state-of the-art study protocols, and appropriate routes of exposure are required in order to clarify these developmental effects and provide information suitable for risk assessments of ENMs. - Highlights: • We review the developmental toxicity studies of engineered nanomaterials (ENMs). • Various developmental endpoints have been

Developmental origins of health and disease--global public health implications.

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Hanson, M A; Gluckman, P D

2015-01-01

The rapidly rising prevalence of non-communicable diseases (NCDs) represents a major challenge to public health and clinical medicine globally. NCDs are increasing rapidly in high-income countries, but even more rapidly in some low-middle-income countries with insufficient resources to meet the challenge. Whilst not identified in the Millennium Development Goals, there is much attention paid to NCDs in the discussions at many levels on the Sustainable Development Goals, as they underpin economic, social and environmental development in the post-2015 era. In this article, we discuss how a life-course approach to health, commencing of necessity in early development, can provide new opportunities for addressing this challenge. The approach can leverage human health capital throughout life and across generations. New insights into mechanisms, especially those processes by which the developmental environment affects epigenetic processes in the developing offspring, offer the prospect of identifying biomarkers of future risks. New interventions to promote health literacy, lifestyle and physical fitness in adolescents, young adults and their children hold great promise. In this respect, health-care professionals concerned with preconceptional, pregnancy and newborn care will have a vital role to play. Copyright © 2014 Elsevier Ltd. All rights reserved.

YKL-40: a new biomarker in cardiovascular disease?

DEFF Research Database (Denmark)

Mathiasen, Anders Bruun; Henningsen, Kristoffer Mads Aaris; Harutyunyan, Marina Jurjevna

2010-01-01

Cardiovascular disease in the form of coronary artery disease is the most common cause of death in western countries. Early treatment with stabilizing drugs and mechanical revascularization by percutaneous coronary intervention or coronary bypass surgery has reduced the mortality significantly....... But in spite of improved treatments, many patients are still plagued by a high frequency of angina symptoms, hospitalizations and a poor prognosis. There is a need for new independent or supplementary biomarkers that can help to predict cardiovascular disease and cardiovascular events earlier and more...... precisely, and thus accompany existing biomarkers in both primary and secondary cardiovascular prevention. One such potential new biomarker is the protein YKL-40. As an independent biomarker in both cardiovascular diseases and noncardiovascular diseases, current evidence suggests YKL-40 to be most useful...

Telomere Length – a New Biomarker in Medicine

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Agnieszka Kozłowska

2015-12-01

Full Text Available A number of xenobiotics in the environment and workplace influences on our health and life. Biomarkers are tools for measuring such exposures and their effects in the organism. Nowadays, telomere length, epigenetic changes, mutations and changes in gene expression pattern have become new molecular biomarkers. Telomeres play the role of molecular clock, which influences on expectancy of cell life and thus aging, the formation of damages, development diseases and carcinogenesis. The telomere length depends on mechanisms of replication and the activity of telomerase. Telomere length is currently used as a biomarker of susceptibility and/or exposure. This paper describes the role of telomere length as a biomarker of aging cells, oxidative stress, a marker of many diseases including cancer, and as a marker of environmental and occupational exposure.

The Wide and Complex Field of NAFLD Biomarker Research: Trends.

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Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

2014-01-01

Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression and prognosis of obesity related liver diseases. Methodology. We analyzed finally 62 articles accounting for 157 cohorts and 45,288 subjects. Results. Despite the various approaches, most cohorts were considerably small and rarely comparable. Also, we found that the same standard parameters were measured rather than novel biomarkers. Diagnostics approaches appeared incomparable. Conclusions. Further collaborative investigations on harmonizing ways of data acquisition and identifying such biomarkers for clinical use are necessary to yield sufficient significant results of potential biomarkers.

A brief review and evaluation of earthworm biomarkers in soil pollution assessment.

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Shi, Zhiming; Tang, Zhiwen; Wang, Congying

2017-05-01

Earthworm biomarker response to pollutants has been widely investigated in the assessment of soil pollution. However, whether and how the earthworm biomarker-approach can be actually applied to soil pollution assessment is still a controversial issue. This review is concerned about the following points: 1. Despite much debate, biomarker is valuable to ecotoxicology and biomarker approach has been properly used in different fields. Earthworm biomarker might be used in different scenarios such as large-scale soil pollution survey and soil pollution risk assessment. Compared with physicochemical analysis, they can provide more comprehensive and straightforward information about soil pollution at low cost. 2. Although many earthworm species from different ecological categories have been tested, Eisenia fetida/andrei is commonly used. Many earthworm biomarkers have been screened from the molecular to the individual level, while only a few biomarkers, such as avoidance behavior and lysosomal membrane stability, have been focused on. Other aspects of the experimental design were critically reviewed. 3. More studies should focus on determining the reliability of various earthworm biomarkers in soil pollution assessment in future research. Besides, establishing a database of a basal level of each biomarker, exploring biomarker response in different region/section/part of earthworm, and other issues are also proposed. 4. A set of research guideline for earthworm biomarker studies was recommended, and the suitability of several earthworm biomarkers was briefly evaluated with respect to their application in soil pollution assessment. This review will help to promote further studies and practical application of earthworm biomarker in soil pollution assessment.

Towards biomarker-based tests that can facilitate decisions about prevention and management of preeclampsia in low-resource settings.

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Acestor, Nathalie; Goett, Jane; Lee, Arthur; Herrick, Tara M; Engelbrecht, Susheela M; Harner-Jay, Claudia M; Howell, Bonnie J; Weigl, Bernhard H

2016-01-01

In recent years, an increasing amount of literature is emerging on candidate urine and blood-based biomarkers associated with incidence and severity of preeclampsia (PE) in pregnant women. While enthusiasm on the usefulness of several of these markers in predicting PE is evolving, essentially all work so far has focused on the needs of high-resource settings and high-income countries, resulting primarily in multi-parameter laboratory assays based on proteomic and metabolomics analysis techniques. These highly complex methods, however, require laboratory capabilities that are rarely available or affordable in low-resource settings (LRS). The importance of quantifying maternal and perinatal risks and identifying which pregnancies can be safely prolonged is also much greater in LRS, where intensive care facilities that can rapidly respond to PE-related health threats for women and infants are limited. For these reasons, simple, low cost, sensitive, and specific point-of-care (POC) tests are needed that can be performed by antenatal health care providers in LRS and that can facilitate decisions about detection and management of PE. Our study aims to provide a comprehensive systematic review of current and emerging blood and urine biomarkers for PE, not only on the basis of their clinical performance, but also of their suitability to be used in LRS-compatible test formats, such as lateral flow and other variants of POC rapid assays.

Metabolomics for laboratory diagnostics.

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Bujak, Renata; Struck-Lewicka, Wiktoria; Markuszewski, Michał J; Kaliszan, Roman

2015-09-10

Metabolomics is an emerging approach in a systems biology field. Due to continuous development in advanced analytical techniques and in bioinformatics, metabolomics has been extensively applied as a novel, holistic diagnostic tool in clinical and biomedical studies. Metabolome's measurement, as a chemical reflection of a current phenotype of a particular biological system, is nowadays frequently implemented to understand pathophysiological processes involved in disease progression as well as to search for new diagnostic or prognostic biomarkers of various organism's disorders. In this review, we discussed the research strategies and analytical platforms commonly applied in the metabolomics studies. The applications of the metabolomics in laboratory diagnostics in the last 5 years were also reviewed according to the type of biological sample used in the metabolome's analysis. We also discussed some limitations and further improvements which should be considered taking in mind potential applications of metabolomic research and practice. Copyright © 2014 Elsevier B.V. All rights reserved.

Early Intervention in Children with Developmental Disabilities

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Beena Johnson

2016-01-01

Full Text Available Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth of young children in developing countries are at risk for or have developmental delay or disabilities. Inadequate stimulation has significant negative impact on physical, socioemotional and cognitive development of children. Hence early scientific intervention programs are necessary in the management of children at risk for developmental delay.

The economics of cardiac biomarker testing in suspected myocardial infarction.

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Goodacre, Steve; Thokala, Praveen

2015-03-01

Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Distinguishing prognostic and predictive biomarkers: An information theoretic approach.

Science.gov (United States)

Sechidis, Konstantinos; Papangelou, Konstantinos; Metcalfe, Paul D; Svensson, David; Weatherall, James; Brown, Gavin

2018-05-02

The identification of biomarkers to support decision-making is central to personalised medicine, in both clinical and research scenarios. The challenge can be seen in two halves: identifying predictive markers, which guide the development/use of tailored therapies; and identifying prognostic markers, which guide other aspects of care and clinical trial planning, i.e. prognostic markers can be considered as covariates for stratification. Mistakenly assuming a biomarker to be predictive, when it is in fact largely prognostic (and vice-versa) is highly undesirable, and can result in financial, ethical and personal consequences. We present a framework for data-driven ranking of biomarkers on their prognostic/predictive strength, using a novel information theoretic method. This approach provides a natural algebra to discuss and quantify the individual predictive and prognostic strength, in a self-consistent mathematical framework. Our contribution is a novel procedure, INFO+, which naturally distinguishes the prognostic vs predictive role of each biomarker and handles higher order interactions. In a comprehensive empirical evaluation INFO+ outperforms more complex methods, most notably when noise factors dominate, and biomarkers are likely to be falsely identified as predictive, when in fact they are just strongly prognostic. Furthermore, we show that our methods can be 1-3 orders of magnitude faster than competitors, making it useful for biomarker discovery in 'big data' scenarios. Finally, we apply our methods to identify predictive biomarkers on two real clinical trials, and introduce a new graphical representation that provides greater insight into the prognostic and predictive strength of each biomarker. R implementations of the suggested methods are available at https://github.com/sechidis. konstantinos.sechidis@manchester.ac.uk. Supplementary data are available at Bioinformatics online.

Potential biomarkers for bipolar disorder: Where do we stand?

Directory of Open Access Journals (Sweden)

Rajesh Sagar

2017-01-01

Full Text Available Bipolar disorder (BD is a severe, recurrent mood disorder, associated with a significant morbidity and mortality, with high rates of suicides and medical comorbidities. There is a high risk of mood disorders among the first-degree relatives of patients with BD. In the current clinical practice, the diagnosis of BD is made by history taking, interview and behavioural observations, thereby lacking an objective, biological validation. This approach may result in underdiagnosis, misdiagnosis and eventually poorer outcomes. Due to the heterogeneity of BD, the possibility of developing a single, specific biomarker is still remote; however, there is a set of promising biomarkers which may serve as predictive, prognostic or treatment markers in the future. The review presents a critical appraisal and update on some of the most promising candidates for biomarkers, namely, neuroimaging markers, peripheral biomarkers and genetic markers, including a brief discussion on cognitive endophenotypes as indicative of genetic risk. The lessons learnt from other fields and specialties in medicine need to be applied to psychiatry to translate the knowledge from 'bench to bedside' by means of clinically useful biomarkers. Overall, the biomarkers may help in pushing the shift towards personalized medicine for psychiatric patients.

Progression in sensing cardiac troponin biomarker charge transductions on semiconducting nanomaterials

Energy Technology Data Exchange (ETDEWEB)

Fathil, M.F.M., E-mail: faris.fathil@gmail.com [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Md Arshad, M.K., E-mail: mohd.khairuddin@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Microelectronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Ruslinda, A.R., E-mail: ruslinda@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Nuzaihan, M.N.M., E-mail: m.nuzaihan@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Gopinath, Subash C.B., E-mail: subash@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Bioprocess Engineering, Universiti Malaysia Perlis, 02600, Arau, Perlis (Malaysia); Adzhri, R., E-mail: adzhri@gmail.com [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Hashim, U., E-mail: uda@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Microelectronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia)

2016-09-07

A real-time ability to interpret the interaction between targeted biomolecules and the surface of semiconductors (metal transducers) into readable electrical signals, without biomolecular modification involving fluorescence dyes, redox enzymes, and radioactive labels, created by label-free biosensors has been extensively researched. Field-effect transistor (FET)- and capacitor-based biosensors are among the diverse electrical charge biosensing architectures that have drawn much attention for having charge transduction; thus, enabling the early and rapid diagnosis of the appropriate cardiac biomarkers at lower concentrations. These semiconducting material-based transducers are very suitable to be integrated with portable electronic devices for future online collection, transmission, reception, analysis, and reporting. This overview elucidates and clarifies two major electrical label-free systems (FET- and capacitor-based biosensors) with cardiac troponin (cTn) biomarker-mediated charge transduction for acute myocardial infarction (AMI) diagnosis. Advances in these systems are highlighted by their progression in bridging the laboratory and industry; the foremost technologies have made the transition from benchtop to bedside and beyond. - Highlights: • The progression of cardiac troponin detection from past to future are presented. • Electrical label-free biosensors for cardiac troponin are discussed. • The discussion focused on field-effect transistor-and capacitor-based devices. • Surface functionalization, sensitivity, and innovation of devices are highlighted. • They presented high sensitivity and specificity of real-time AMI determination.

Developmental effects of mercury on Etheostoma caeruleum and E. spectabile: Predictable biomarkers of stress

Energy Technology Data Exchange (ETDEWEB)

Sharp, J.R. [Southeast Missouri State Univ., Cape Girardeau, MO (United States). Dept. of Biology

1995-12-31

Etheostoma caeruleum and E. spectabile are sympatric teleostean species of the Family Percidae. The ova diameters and incubation times are different: E. caeruleum (1.9mm and 12-d), E. spectabile (1.2mm and 8-d). For both species, cleavage stage (4--8 cell), mid-blastula, mid-neurula, and early-eye stage embryos were exposed to + {minus}1 a 24-h static-renewal test of 0, 10, 20, 40, 60, 80, 100 {micro}gHg {sup ++}L{sup {minus}1} to assess the effects of stage-specific initial mercury exposure on the embryo-larval responses. In addition, cleavage stage embryos were exposed to a 1-d, 2-d, and 4-d static-renewal toxicity test to determine the influence that exposure duration to mercury has on embryolarval responses. Five replicates of 10 embryos each were incubated at 18 C for each concentration and exposure variation. Embryos were allowed to develop until all had hatched or died. Four embryonic responses were assessed for each species and exposure protocol: 96-h LC50, AB50, SH50 and VH50. The typical nonstressor specific terata were noted for each species with an increase in percent of embryos expressing abnormal developmental patterns with increase mercury concentrations and severity of exposure. These included dwarfism, cephalic complications, ophthalmic abnormalities, cardiovascular abnormalities, various edema, and haemorrhagia. Hatching success and viability of hatch were likewise reduced with increasing severity of exposure and mercury concentration. Previously undetected terata that were observed in the first hatch included scoliosis, lordosis, kyphosis, synarthrodic jaws, and grossly enlarged yolk sacs.

Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.

Directory of Open Access Journals (Sweden)

Bas C T van Bussel

Full Text Available BACKGROUND: In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. METHODS: We measured, in a large ongoing cohort study (n = 574, by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD and single-biomarker techniques (ELISA or immunoturbidimetric assay, the following biomarkers of low-grade inflammation: C-reactive protein (CRP, serum amyloid A (SAA, soluble intercellular adhesion molecule 1 (sICAM-1 and soluble vascular cell adhesion molecule 1 (sVCAM-1. These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA. RESULTS: Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all≥0.755 absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP, 0.711 (SAA, 0.895 (sICAM-1 and 0.858 (sVCAM-1. Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. CONCLUSIONS: Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.

Identification of cancer protein biomarkers using proteomic techniques

Energy Technology Data Exchange (ETDEWEB)

Mor, Gil G.; Ward, David C.; Bray-Ward, Patricia

2016-10-18

The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

Science.gov (United States)

Pinho, Rosa T; Waghabi, Mariana C; Cardillo, Fabíola; Mengel, José; Antas, Paulo R Z

2016-01-01

Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials.

Plasma biomarker of dietary phytosterol intake.

Directory of Open Access Journals (Sweden)

Xiaobo Lin

Full Text Available Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI. Therefore, we sought to identify a plasma biomarker of DPI.Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P < 0.01.The ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

Imaging biomarkers in primary brain tumours

Energy Technology Data Exchange (ETDEWEB)

Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

2015-04-01

We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

[Contemporary cognitive theories about developmental dyscalculia].

Science.gov (United States)

Castro-Cañizares, D; Estévez-Pérez, N; Reigosa-Crespo, V

To analyze the current theories describing the cognitive mechanisms underlying developmental dyscalculia. The four most researched hypotheses concerning the cognitive deficits related to developmental dyscalculia, as well as experimental evidences supporting or refusing them are presented. The first hypothesis states that developmental dyscalculia is consequence of domain general cognitive deficits. The second hypothesis suggests that it is due to a failure in the development of specialized brain systems dedicated to numerosity processing. The third hypothesis asserts the disorder is caused by a deficit in accessing quantity representation through numerical symbols. The last hypothesis states developmental dyscalculia appears as a consequence of impairments in a generalized magnitude system dedicated to the processing of continuous and discrete magnitudes. None of the hypotheses has been proven more plausible than the rest. Relevant issues rose by them need to be revisited and answered in the light of new experimental designs. In the last years the understanding of cognitive disorders involved in developmental dyscalculia has remarkably increased, but it is nonetheless insufficient. Additional research is required in order to achieve a comprehensive cognitive model of numerical processing development and its disorders. This will improve the diagnostic precision and the effectiveness of developmental dyscalculia intervention strategies.

Molecular biomarkers in idiopathic pulmonary fibrosis

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Ley, Brett; Brown, Kevin K.

2014-01-01

Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

Biomarkers in adult posthemorrhagic hydrocephalus.

Science.gov (United States)

Hua, Cong; Zhao, Gang

2017-08-01

Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.

Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects

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Toledo, Jon B.; Zetterberg, Henrik; van Harten, Argonde C.; Glodzik, Lidia; Martinez-Lage, Pablo; Bocchio-Chiavetto, Luisella; Rami, Lorena; Hansson, Oskar; Sperling, Reisa; Engelborghs, Sebastiaan; Osorio, Ricardo S.; Vanderstichele, Hugo; Vandijck, Manu; Hampel, Harald; Teipl, Stefan; Moghekar, Abhay; Albert, Marilyn; Hu, William T.; Monge Argilés, Jose A.; Gorostidi, Ana; Teunissen, Charlotte E.; De Deyn, Peter P.; Hyman, Bradley T.; Molinuevo, Jose L.; Frisoni, Giovanni B.; Linazasoro, Gurutz; de Leon, Mony J.; van der Flier, Wiesje M.; Scheltens, Philip; Blennow, Kaj; Shaw, Leslie M.

2015-01-01

In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer’s disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40–84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer’s disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype

[Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified

NARCIS (Netherlands)

Mercadante, M.T.; Gaag, R.J. van der; Schwartzman, J.S.

2006-01-01

The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett's syndrome and childhood disintegrative

Life Span Developmental Approach

OpenAIRE

Ali Eryilmaz

2011-01-01

The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of...

Parents' and Teachers' Reflections on the Process of Daily Transitions in an Infant and Toddler Laboratory School

Science.gov (United States)

Traum, Linda C.; Moran, Mary Jane

2016-01-01

This qualitative study considered values, beliefs, perspectives, and meanings of 7 parents and 3 teachers within the context of daily home-to-child care transitions in one infant-toddler center in an early childhood laboratory school. Sociocultural and attachment theories anchored the study and the developmental niche framework informed…

What Is a Developmental-Behavioral Pediatrician?

Science.gov (United States)

... social worker. Developmental-behavioral pediatricians work closely with parents, families, and schools. Developmental-behavioral pediatricians understand that children’s development and behavior happen first and foremost in the ...

Developmental adjustments of house sparrow (Passer domesticus) nestlings to diet composition.

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Brzek, Paweł; Kohl, Kevin; Caviedes-Vidal, Enrique; Karasov, William H

2009-05-01

House sparrow nestlings are fed primarily on insects during the first 3 days of their life, and seeds become gradually more important afterwards. We tested whether developmental changes in size and functional capacity of the digestive tract in young house sparrows are genetically hard-wired and independent of diet, or can be modified by food type. Under laboratory conditions, we hand-fed young house sparrows with either a starch-free insect-like diet, based mainly on protein and fat, or a starch-containing diet with a mix of substrates similar to that offered to older nestlings in natural nests when they are gradually weaned from an insect to a seed diet. Patterns of overall development in body size and thermoregulatory ability, and in alimentary organ size increase, were relatively similar in house sparrow nestlings developing on both diets. However, total intestinal maltase activity, important in carbohydrate breakdown, was at least twice as high in house sparrow nestlings fed the starch-containing diet (PFuture studies must test whether the diet-dependent increase in maltase activity during development is irreversible or reversible, reflecting, respectively, a developmental plasticity or a phenotypic flexibility.

Characterization of a genotoxicity biomarker in three-spined stickleback (Gasterosteus aculeatus L.): Biotic variability and integration in a battery of biomarkers for environmental monitoring.

Science.gov (United States)

Santos, Raphael; Joyeux, Aude; Palluel, Olivier; Palos-Ladeiro, Mélissa; Besnard, Aurélien; Blanchard, Christophe; Porcher, Jean Marc; Bony, Sylvie; Devaux, Alain; Sanchez, Wilfried

2016-04-01

As a large array of hazardous substances exhibiting genotoxicity are discharged into surface water, this work aimed at assessing the relevance of adding a genotoxicity biomarker in a battery of biomarkers recently developed in the model fish three-spined stickleback (Gasterosteus aculeatus). First the confounding influence of gender, body length, and season (used as a proxy of age and of the fish reproductive status, respectively) on the level of primary DNA damage in erythrocytes was investigated in wild sticklebacks. Then, the genotoxity biomarker was included in a large battery of biomarkers assessing xenobiotic biotransformation, oxidative stress and neurotoxicity, and implemented in five sites. Gender, age and reproductive status did not influence DNA damage level in fish from the reference site. A significant relationship between the level of primary DNA damage and fish length (as a proxy of age also correlated to the season) was highlighted in the contaminated site. Among all biomarkers investigated in the field, the level of DNA damage was one of the four most discriminating biomarkers with EROD, catalase activity and the level of lipid peroxidation representing together 75.40% of the discriminating power in sampled fish. The level of DNA damage was correlated to the EROD activity and to the level of peroxidation, which mainly discriminated fish from sites under urban pressure. Finally, Integrated Biomarker Response indexes (IBRv2), which were calculated with the whole biomarker response dataset exhibited higher values in the Reveillon (9.62), the Scarpe and Rhonelle contaminated sites (5.11 and 4.90) compared with the two reference sites (2.38 and 2.55). The present work highlights that integration of a genotoxicity biomarker in a multiparametric approach is relevant to assess ecotoxicological risk in freshwater aquatic organisms. © 2014 Wiley Periodicals, Inc.

Trisomy 21 and facial developmental instability.

Science.gov (United States)

Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T

2013-05-01

The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. Copyright © 2013 Wiley Periodicals, Inc.

Association between a biomarker of exposure to polycyclic aromatic hydrocarbons and semen quality

Directory of Open Access Journals (Sweden)

Joanna Jurewicz

2013-10-01

Full Text Available Objectives: Growing evidence supports the reproductive and developmental toxicity of polycyclic aromatic hydrocarbons (PAHs from prenatal and postnatal exposure, but the results of epidemiological studies regarding harmful effects of PAHs exposure on male reproductive system still remain limited and inconclusive. The aim of the present study was to investigate the relationship between 1-hydroxypyrene, a biomarker of polycyclic aromatic hydrocarbons exposure and semen quality. Materials and Methods: The study population consisted of 277 men attending an infertility clinic for diagnostic purposes and having normal semen concentration of 20-300 mln/ml or slight oligozoospermia (semen concentration: 15-20 mln/ml (WHO 1999. All the men were healthy and under 45 years of age. All participants were interviewed and provided a semen sample. The interview included questions concerning demographics, socio-economic status, medical history related to past diseases which may have an impact on semen quality, lifestyle factors and occupational information. Concentrations of 1-hydroxypyrene (1-OHP in the urine samples were analyzed using high performance liquid chromatography (HPLC. Results: A positive association was found between the level of 1-OHP in urine and sperm neck abnormalities as well as the percentage of static sperm cells (p = 0.001, p = 0.018, respectively. Additionally, exposure to PAHs measured by 1-OHP in urine decreased semen volume and the percentage of motile sperm cells (p = 0.014, p = 0.0001, respectively. Conclusions: Presented findings indicate that the environmental level of PAHs exposure adversely affects male semen quality. The future large-scale studies should incorporate different biomarkers to generate a more accurate and full assessment of the effects of PAHs exposure on male fertility.

Bio-markers and the search for extinct life on Mars

Science.gov (United States)

Schwartz, D. E.; Mancinelli, R. L.

1989-01-01

In order to predict what biomarkers could be used on Mars, several biomarkers, or key signatures, of extinct life on earth are identified. Some of these biomarkers which may be applicable to Mars include reduced carbon and nitrogen compounds, CO3(2-), SO4(2-), NO3(-), Mg, Mn, Fe, and the isotopic ratios of C, N, and S. It is suggested that a fully equipped Mars rover might be able to perform analyses to measure most of these biomarkers while on the Martian surface.

Developmental Kindergarten Program Evaluation Report.

Science.gov (United States)

Blois, George T.; Cushing, Katherine S.

The evaluation of the Developmental Kindergarten (DK) Program at the Harrison School District #2, Colorado Springs, Colorado, involved pre- and post-testing of student academic gains and interviewing of principals and teachers. The program aimed to provide developmentally appropriate activities for students believed to be "at risk" of…

Developmentally Appropriate Peace Education Curricula

Science.gov (United States)

Lewsader, Joellen; Myers-Walls, Judith A.

2017-01-01

Peace education has been offered to children for decades, but those curricula have been only minimally guided by children's developmental stages and needs. In this article, the authors apply their research on children's developmental understanding of peace along with peace education principles and Vygotsky's sociocultural theory to present…

Risk Factors and Biomarkers of Age-Related Macular Degeneration

Science.gov (United States)

Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

2016-01-01

A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

Developmental biology, the stem cell of biological disciplines.

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Gilbert, Scott F

2017-12-01

Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated. In many disciplines, especially in evolutionary biology and oncology, the developmental perspective is being reasserted as an important research program.

An early-biomarker algorithm predicts lethal graft-versus-host disease and survival.

Science.gov (United States)

Hartwell, Matthew J; Özbek, Umut; Holler, Ernst; Renteria, Anne S; Major-Monfried, Hannah; Reddy, Pavan; Aziz, Mina; Hogan, William J; Ayuk, Francis; Efebera, Yvonne A; Hexner, Elizabeth O; Bunworasate, Udomsak; Qayed, Muna; Ordemann, Rainer; Wölfl, Matthias; Mielke, Stephan; Pawarode, Attaphol; Chen, Yi-Bin; Devine, Steven; Harris, Andrew C; Jagasia, Madan; Kitko, Carrie L; Litzow, Mark R; Kröger, Nicolaus; Locatelli, Franco; Morales, George; Nakamura, Ryotaro; Reshef, Ran; Rösler, Wolf; Weber, Daniela; Wudhikarn, Kitsada; Yanik, Gregory A; Levine, John E; Ferrara, James L M

2017-02-09

BACKGROUND. No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. METHODS. Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups. We then applied the final algorithm in an independent test set ( n = 309) and validation set ( n = 358). RESULTS. A 2-biomarker model using ST2 and REG3α concentrations identified patients with a cumulative incidence of 6-month NRM of 28% in the high-risk group and 7% in the low-risk group ( P < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, P < 0.001) and the multicenter validation set (26% vs. 10%, P < 0.001). Sixteen percent, 17%, and 20% of patients were at high risk in the training, test, and validation sets, respectively. GVHD-related mortality was greater in high-risk patients (18% vs. 4%, P < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, P < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. CONCLUSION. A biomarker algorithm based on a blood sample taken 7 days after HCT can consistently identify a group of patients at high risk for lethal GVHD and NRM. FUNDING. The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation.

Developmental toxicology: adequacy of current methods.

Science.gov (United States)

Peters, P W

1998-01-01

Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and reproductive toxicity. Reproductive toxicology is concerned with possible effects of substances on the reproductive process, i.e. on sexual organs and their functions, endocrine regulation, fertilization, transport of the fertilized ovum, implantation, and embryonic, fetal and postnatal development, until the end-differentiation of the organs is achieved. Reproductive toxicology is divided into areas related to male and female fertility, and developmental toxicology. Developmental toxicology can be further broken down into prenatal and postnatal toxicology. Today, much new information is available about the origins of developmental disorders resulting from chemical exposure. While these findings seem to promise important new developments in methodology and research, there is a danger of losing sight of the precepts and principles established in the light of existing knowledge. There is also a danger that we may fail to correct shortcomings in our existing procedures and practice. The aim of this presentation is to emphasize the importance of testing substances for their impact in advance of their use and to underline that we must use the best existing tools for carrying out risk assessments. Moreover, it needs to be stressed that there are many substances that are never assessed with respect to reproductive and developmental toxicity. Similarly, our programmes for post-marketing surveillance with respect to developmental toxicology are grossly inadequate. Our ability to identify risks to normal development and reproduction would be much improved, first if a number of straightforward precepts were always followed and second, if we had a clearer understanding of what we mean by risk and acceptable levels of risk in the context of development. Other aims of this paper are: to stress the complexity of the different stages of normal prenatal development; to note the principles that are

Biomarkers in scleroderma: Current status

Directory of Open Access Journals (Sweden)

Latika Gupta

2017-01-01

Full Text Available Scleroderma is an autoimmune disease characterized by indolent obliterative vasculopathy and widespread fibrosis. The two main morphological manifestations of the disease overlap and may make it difficult to separate activity from damage. Many patients, especially those with the limited subset of the disease, have an indolent course without clear-cut inflammatory manifestations. There is a felt need for validated biomarkers, which can differentiate activity from damage, and yet be sensitive to change with therapy. Multiplex arrays of biomarkers have ushered an era of targeted or personalized medicine based on phenotypic characteristics in an individual.

Multiomics Data Triangulation for Asthma Candidate Biomarkers and Precision Medicine.

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Pecak, Matija; Korošec, Peter; Kunej, Tanja

2018-06-01

Asthma is a common complex disorder and has been subject to intensive omics research for disease susceptibility and therapeutic innovation. Candidate biomarkers of asthma and its precision treatment demand that they stand the test of multiomics data triangulation before they can be prioritized for clinical applications. We classified the biomarkers of asthma after a search of the literature and based on whether or not a given biomarker candidate is reported in multiple omics platforms and methodologies, using PubMed and Web of Science, we identified omics studies of asthma conducted on diverse platforms using keywords, such as asthma, genomics, metabolomics, and epigenomics. We extracted data about asthma candidate biomarkers from 73 articles and developed a catalog of 190 potential asthma biomarkers (167 human, 23 animal data), comprising DNA loci, transcripts, proteins, metabolites, epimutations, and noncoding RNAs. The data were sorted according to 13 omics types: genomics, epigenomics, transcriptomics, proteomics, interactomics, metabolomics, ncRNAomics, glycomics, lipidomics, environmental omics, pharmacogenomics, phenomics, and integrative omics. Importantly, we found that 10 candidate biomarkers were apparent in at least two or more omics levels, thus promising potential for further biomarker research and development and precision medicine applications. This multiomics catalog reported herein for the first time contributes to future decision-making on prioritization of biomarkers and validation efforts for precision medicine in asthma. The findings may also facilitate meta-analyses and integrative omics studies in the future.

Biomarker responses of Peromyscus leucopus exposed to lead and cadmium in the Southeast Missouri Lead Mining District.

Science.gov (United States)

Beyer, W Nelson; Casteel, Stan W; Friedrichs, Kristen R; Gramlich, Eric; Houseright, Ruth A; Nichols, John R; Karouna-Renier, Natalie K; Kim, Dae Young; Rangen, Kathleen L; Rattner, Barnett A; Schultz, Sandra L

2018-01-29

Biomarker responses and histopathological lesions have been documented in laboratory mammals exposed to elevated concentrations of lead and cadmium. The exposure of white-footed mice (Peromyscus leucopus) to these metals and the potential associated toxic effects were examined at three contaminated sites in the Southeast Missouri Lead Mining District and at a reference site in MO, USA. Mice from the contaminated sites showed evidence of oxidative stress and reduced activity of red blood cell δ-aminolevulinic acid dehydratase (ALAD). Histological examinations of the liver and kidney, cytologic examination of blood smears, and biomarkers of lipid peroxidation and DNA damage failed to show indications of toxic effects from lead. The biomagnification factor of cadmium (hepatic concentration/soil concentration) at a site with a strongly acid soil was 44 times the average of the biomagnification factors at two sites with slightly alkaline soils. The elevated concentrations of cadmium in the mice did not cause observable toxicity, but were associated with about a 50% decrease in expected tissue lead concentrations and greater ALAD activity compared to the activity at the reference site. Lead was associated with a decrease in concentrations of hepatic glutathione and thiols, whereas cadmium was associated with an increase. In addition, to support risk assessment efforts, we developed linear regression models relating both tissue lead dosages (based on a previously published a laboratory study) and tissue lead concentrations in Peromyscus to soil lead concentrations.

Biomarker responses of Peromyscus leucopus exposed to lead and cadmium in the Southeast Missouri Lead Mining District

Science.gov (United States)

Beyer, W. Nelson; Casteel, Stan W.; Friedrichs, Kristen R.; Gramlich, Eric; Houseright, Ruth A.; Nichols, John W.; Karouna-Renier, Natalie; Kim, Dae Young; Rangen, Kathleen; Rattner, Barnett A.; Schultz, Sandra

2018-01-01

Biomarker responses and histopathological lesions have been documented in laboratory mammals exposed to elevated concentrations of lead and cadmium. The exposure of white-footed mice (Peromyscus leucopus) to these metals and the potential associated toxic effects were examined at three contaminated sites in the Southeast Missouri Lead Mining District and at a reference site in MO, USA. Mice from the contaminated sites showed evidence of oxidative stress and reduced activity of red blood cell δ-aminolevulinic acid dehydratase (ALAD). Histological examinations of the liver and kidney, cytologic examination of blood smears, and biomarkers of lipid peroxidation and DNA damage failed to show indications of toxic effects from lead. The biomagnification factor of cadmium (hepatic concentration/soil concentration) at a site with a strongly acid soil was 44 times the average of the biomagnification factors at two sites with slightly alkaline soils. The elevated concentrations of cadmium in the mice did not cause observable toxicity, but were associated with about a 50% decrease in expected tissue lead concentrations and greater ALAD activity compared to the activity at the reference site. Lead was associated with a decrease in concentrations of hepatic glutathione and thiols, whereas cadmium was associated with an increase. In addition, to support risk assessment efforts, we developed linear regression models relating both tissue lead dosages (based on a previously published a laboratory study) and tissue lead concentrations in Peromyscus to soil lead concentrations.

Effects of metal pollution on earthworm communities in a contaminated floodplain area: Linking biomarker, community and functional responses

International Nuclear Information System (INIS)

Gestel, Cornelis A.M. van; Koolhaas, Josee E.; Hamers, Timo; Hoppe, Maarten van; Roovert, Martijn van; Korsman, Cora; Reinecke, Sophie A.

2009-01-01

Effects on earthworms in the contaminated floodplain area the Biesbosch, the Netherlands, were determined at different levels of organization using a combination of field and laboratory tests. The species Lumbricus rubellus, collected from different polluted sites in the Biesbosch, showed reduced values for the biomarker neutral red retention time (NRRT), mainly explained by high metal concentrations in the soil and the resulting high internal copper concentrations in the earthworms. Organic pollutant levels in earthworms were low and did not explain reduced NRRTs. Earthworm abundance and biomass were not correlated with pollutant levels in the soil. Litterbag decomposition and bait-lamina feeding activity, measures of the functional role of earthworms, were not affected by metal pollution and did not show any correlation with metal concentrations in soil or earthworms nor with NRRT. Effects at the biochemical level therefore did not result in a reduced functioning of earthworm communities. - Metal pollution in floodplain soils does affect earthworm biomarker response but not their activity in decomposition processes

Effects of metal pollution on earthworm communities in a contaminated floodplain area: Linking biomarker, community and functional responses

Energy Technology Data Exchange (ETDEWEB)

Gestel, Cornelis A.M. van [Institute of Ecological Science, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)], E-mail: kees.van.gestel@falw.vu.nl; Koolhaas, Josee E. [Institute of Ecological Science, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Hamers, Timo [Institute of Environmental Studies, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Hoppe, Maarten van; Roovert, Martijn van; Korsman, Cora [Institute of Ecological Science, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Reinecke, Sophie A. [Department of Botany and Zoology, University of Stellenbosch, Private bag X1, Matieland 7602 (South Africa)

2009-03-15

Effects on earthworms in the contaminated floodplain area the Biesbosch, the Netherlands, were determined at different levels of organization using a combination of field and laboratory tests. The species Lumbricus rubellus, collected from different polluted sites in the Biesbosch, showed reduced values for the biomarker neutral red retention time (NRRT), mainly explained by high metal concentrations in the soil and the resulting high internal copper concentrations in the earthworms. Organic pollutant levels in earthworms were low and did not explain reduced NRRTs. Earthworm abundance and biomass were not correlated with pollutant levels in the soil. Litterbag decomposition and bait-lamina feeding activity, measures of the functional role of earthworms, were not affected by metal pollution and did not show any correlation with metal concentrations in soil or earthworms nor with NRRT. Effects at the biochemical level therefore did not result in a reduced functioning of earthworm communities. - Metal pollution in floodplain soils does affect earthworm biomarker response but not their activity in decomposition processes.

A scheme for a flexible classification of dietary and health biomarkers

DEFF Research Database (Denmark)

Gao, Qian; Pratico, Giulia; Scalbert, Augustin

2017-01-01

to have a solid scheme for biomarker classification that will provide a well-defined ontology for the field. In this manuscript, we provide an improved scheme for biomarker classification based on their intended use rather than the technology or outcomes (six subclasses are suggested: food compound intake...... in the scientific literature. However, the existing concepts for classification of biomarkers in the dietary and health area may be ambiguous, leading to uncertainty about their application. In order to better understand the potential of biomarkers and to communicate their use and application, it is imperative...... with previous biomarker classification for this field of research....

Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

Science.gov (United States)

Al Shweiki, Mhd Rami; Oeckl, Patrick; Steinacker, Petra; Hengerer, Bastian; Schönfeldt-Lecuona, Carlos; Otto, Markus

2017-06-01

Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

Developmentalism: An Obscure but Pervasive Restriction

Directory of Open Access Journals (Sweden)

J. E. Stone

1996-04-01

Full Text Available Despite continuing criticism of public education, experimentally demonstrated and field tested teaching methods have been ignored, rejected, and abandoned. Instead of a stable consensus regarding best teaching practices, there seems only an unending succession of innovations. A longstanding educational doctrine appears to underlie this anomalous state of affairs. Termed developmentalism, it presumes "natural" ontogenesis to be optimal and it requires experimentally demonstrated teaching practices to overcome a presumption that they interfere with an optimal developmental trajectory. It also discourages teachers and parents from asserting themselves with children. Instead of effective interventions, it seeks the preservation of a postulated natural perfection. Developmentalism's rich history is expressed in a literature extending over 400 years. Its notable exponents include Jean Jacques Rousseau, John Dewey, and Jean Piaget; and its most recent expressions include "developmentally appropriate practice" and "constructivism." In the years during which it gained ascendance, developmentalism served as a basis for rejecting harsh and inhumane teaching methods. Today it impedes efforts to hold schools accountable for student academic achievement.

Comparison of the effects of intensive insulin treatment modalities on cardiovascular biomarkers in type 1 diabetes mellitus.

Science.gov (United States)

Cetinkalp, Sevki; Felekoglu, Canan; Karadeniz, Muammer; Boyacıoglu, Hayal; Delen, Yasemin; Yildirim, Eser; Yilmaz, Candeger

2015-01-01

To evaluate effects of intensive insulin treatment modalities on cardiovascular biomarkers in patients with type 1 diabetes mellitus (T1DM). A total of 25 patients with T1DM receiving intensive insulin therapy either in the form of continuous insulin pump (IP group; n=13) or as multiple daily injections (MDI group; n=12) and 13 controls (control group, n=13) were included. Data on demographics, anthropometrics, diabetes history, and laboratory findings including glycemic and lipid parameters, and cardiovascular biomarkers [C-reactive protein (mg/dL), homocysteine (μmol/L), fibrinogen (mg/dL), oxidized LDL (ng/dL), PAI-1 (ng/mL), MCP-1 (pg/mL) and VEGF (pg/mL)] were recorded in each group. Correlation of cardiovascular biomarkers to other parameters was also evaluated in T1DM patients. Apart from significantly higher mean (SD) values for HbA1c [6.1 (0.3) vs. 5.6 (0.5)% (43 (3) vs. 38 (5) mmol/mol), p1.5 (13.6) vs. 58.2 (10.8), p1) in the IP than in the MDI group, no significance difference was noted between insulin treatment modalities as well as between patient and control groups in terms of demographic, anthropometric and laboratory parameters. Negative correlation of MCP-1 to treatment duration (r=-0.615, p=0.025), and HDL-c to CRP (r=-0.685, p=0.010) and VEGF (r=-0.678, p=0.011) was noted in IP group, whereas positive correlation of PAI-1 to diabetes age (r=0.805, p=0.002) and treatment duration was noted in MDI group. Our findings in a cohort of T1DM patients with optimal glycemic control revealed that intensive insulin therapy was not associated with an increase in atherosclerotic markers in T1DM, regardless of whether continuous IP infusion or MDIs was administered. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy.

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Forker, L J; Choudhury, A; Kiltie, A E

2015-10-01

Radiotherapy is an essential component of treatment for more than half of newly diagnosed cancer patients. The response to radiotherapy varies widely between individuals and although advances in technology have allowed the adaptation of radiotherapy fields to tumour anatomy, it is still not possible to tailor radiotherapy based on tumour biology. A biomarker of intrinsic radiosensitivity would be extremely valuable for individual dosing, aiding decision making between radical treatment options and avoiding toxicity of neoadjuvant or adjuvant radiotherapy in those unlikely to benefit. This systematic review summarises the current evidence for biomarkers under investigation as predictors of radiotherapy benefit. Only 10 biomarkers were identified as having been evaluated for their radiotherapy-specific predictive value in over 100 patients in a clinical setting, highlighting that despite a rich literature there were few high-quality studies for inclusion. The most extensively studied radiotherapy predictive biomarkers were the radiosensitivity index and MRE11; however, neither has been evaluated in a randomised controlled trial. Although these biomarkers show promise, there is not enough evidence to justify their use in routine practice. Further validation is needed before biomarkers can fulfil their potential and predict treatment outcomes for large numbers of patients. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

An epigenetic biomarker of aging for lifespan and healthspan

Science.gov (United States)

Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Chen, Brian H.; Assimes, Themistocles L.; Bandinelli, Stefania; Hou, Lifang; Baccarelli, Andrea A.; Stewart, James D.; Li, Yun; Whitsel, Eric A.; Wilson, James G; Reiner, Alex P; Aviv, Abraham; Lohman, Kurt; Liu, Yongmei; Ferrucci, Luigi

2018-01-01

Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging. PMID:29676998

Human movement stochastic variability leads to diagnostic biomarkers In Autism Spectrum Disorders (ASD)

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Wu, Di; Torres, Elizabeth B.; Jose, Jorge V.

2015-03-01

ASD is a spectrum of neurodevelopmental disorders. The high heterogeneity of the symptoms associated with the disorder impedes efficient diagnoses based on human observations. Recent advances with high-resolution MEM wearable sensors enable accurate movement measurements that may escape the naked eye. It calls for objective metrics to extract physiological relevant information from the rapidly accumulating data. In this talk we'll discuss the statistical analysis of movement data continuously collected with high-resolution sensors at 240Hz. We calculated statistical properties of speed fluctuations within the millisecond time range that closely correlate with the subjects' cognitive abilities. We computed the periodicity and synchronicity of the speed fluctuations' from their power spectrum and ensemble averaged two-point cross-correlation function. We built a two-parameter phase space from the temporal statistical analyses of the nearest neighbor fluctuations that provided a quantitative biomarker for ASD and adult normal subjects and further classified ASD severity. We also found age related developmental statistical signatures and potential ASD parental links in our movement dynamical studies. Our results may have direct clinical applications.

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

LENUS (Irish Health Repository)

Mc Ardle, Angela

2015-01-01

Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate

Ambient temperature and cardiovascular biomarkers in a repeated-measure study in healthy adults: A novel biomarker index approach.

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Wu, Shaowei; Yang, Di; Pan, Lu; Shan, Jiao; Li, Hongyu; Wei, Hongying; Wang, Bin; Huang, Jing; Baccarelli, Andrea A; Shima, Masayuki; Deng, Furong; Guo, Xinbiao

2017-07-01

Associations of ambient temperature with cardiovascular morbidity and mortality have been well documented in numerous epidemiological studies, but the underlying pathways remain unclear. We investigated whether systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function may be the mechanistic pathways associated with ambient temperature. Forty study participants underwent repeated blood collections for 12 times in Beijing, China in 2010-2011. Ambient temperature and air pollution data were measured in central monitors close to student residences. We created five indices as the sum of weighted biomarker percentiles to represent the overall levels of 15 cardiovascular biomarkers in five pathways (systemic inflammation: hs-CRP, TNF-α and fibrinogen; coagulation: fibrinogen, PAI-1, tPA, vWF and sP-selectin; systemic oxidative stress: Ox-LDL and sCD36: antioxidant activity: EC-SOD and GPX1; and endothelial function: ET-1, E-selectin, ICAM-1 and VCAM-1). We used generalized mixed-effects models to estimate temperature effects controlling for air pollution and other covariates. There were significant decreasing trends in the adjusted means of biomarker indices over the lowest to the highest quartiles of daily temperatures before blood collection. A 10°C decrease at 2-d average daily temperature were associated with increases of 2.5% [95% confidence interval (CI): 0.7, 4.2], 1.6% (95% CI: 0.1, 3.1), 2.7% (95% CI: 0.5, 4.8), 5.5% (95% CI: 3.8, 7.3) and 2.0% (95% CI: 0.3, 3.8) in the indices for systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function, respectively. In contrast, the associations between ambient temperature and individual biomarkers had substantial variation in magnitude and strength. The altered cardiovascular biomarker profiles in healthy adults associated with ambient temperature changes may help explain the temperature-related cardiovascular morbidity

Developmental Systems Theory and the Person-Oriented Approach. Commentary on: "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics"

Science.gov (United States)

Bergman, Lars R.

2015-01-01

Molenaar's (2015) article concerns Developmental Systems Theory (DST) in relation to behavior genetics and he presents implications of DST for empirical research, especially the need for subject-specific studies. In this commentary, the article is discussed from a broader developmental science perspective, particularly regarded through the lens of…

Developmental plasticity: re-conceiving the genotype.

Science.gov (United States)

Sultan, Sonia E

2017-10-06

In recent decades, the phenotype of an organism (i.e. its traits and behaviour) has been studied as the outcome of a developmental 'programme' coded in its genotype. This deterministic view is implicit in the Modern Synthesis approach to adaptive evolution as a sorting process among genetic variants. Studies of developmental pathways have revealed that genotypes are in fact differently expressed depending on environmental conditions. Accordingly, the genotype can be understood as a repertoire of potential developmental outcomes or norm of reaction. Reconceiving the genotype as an environmental response repertoire rather than a fixed developmental programme leads to three critical evolutionary insights. First, plastic responses to specific conditions often comprise functionally appropriate trait adjustments, resulting in an individual-level, developmental mode of adaptive variation. Second, because genotypes are differently expressed depending on the environment, the genetic diversity available to natural selection is itself environmentally contingent. Finally, environmental influences on development can extend across multiple generations via cytoplasmic and epigenetic factors transmitted to progeny individuals, altering their responses to their own, immediate environmental conditions and, in some cases, leading to inherited but non-genetic adaptations. Together, these insights suggest a more nuanced understanding of the genotype and its evolutionary role, as well as a shift in research focus to investigating the complex developmental interactions among genotypes, environments and previous environments.

Estimating HAPs and radionuclide emissions from a laboratory complex at a nuclear processing site

International Nuclear Information System (INIS)

Paul, R.A.; Faugl, T.

1993-01-01

A unique methodology was developed for conducting an air emission inventory (AEI) at a DOE nuclear processing facility. This methodology involved the use of computer-assisted design (CAD) drawings to document emission points, computerized process drawings to document industrial processes leading to emissions, and a computerized data base of AEI forms to document emission estimates and related process data. A detailed air emissions inventory for operating years 1985--1991 was recently implemented for the entire site using this methodology. One industrial area at the DOE Site is comprised of laboratory facilities that provide direct support to the nuclear reactor and recovery operations, developmental studies to support reactor and separation operations, and developmental studies to support waste handling and storage. The majority of the functions are conducted in a single large building complex wherein bench scale and pilot scale experiments are carried out involving radionuclides, hazardous air pollutants (HAP), and other chemicals reportable under the Clean Air Act Amendments (CAAA) and Superfund Amendments and Re-authorization Act (SARA) Title 111. The results of the inventory showed that HAP and radionuclide emissions from the laboratory complex were relatively minor

Family Life and Developmental Idealism in Yazd, Iran

Directory of Open Access Journals (Sweden)

Mohammad Jalal Abbasi-Shavazi

2012-03-01

Full Text Available BACKGROUND This paper is motivated by the theory that developmental idealism has been disseminated globally and has become an international force for family and demographic change. Developmental idealism is a set of cultural beliefs and values about development and how development relates to family and demographic behavior. It holds that modern societies are causal forces producing modern families, that modern families help to produce modern societies, and that modern family change is to be expected. OBJECTIVE We examine the extent to which developmental idealism has been disseminated in Iran. We also investigate predictors of the dissemination of developmental idealism. METHODS We use survey data collected in 2007 from a sample of women in Yazd, a city in Iran. We examine the distribution of developmental idealism in the sample and the multivariate predictors of developmental idealism. RESULTS We find considerable support for the expectation that many elements of developmental idealism have been widely disseminated. Statistically significant majorities associate development with particular family attributes, believe that development causes change in families, believe that fertility reductions and age-at-marriage increases help foster development, and perceive family trends in Iran headed toward modernity. As predicted, parental education, respondent education, and income affect adherence to developmental idealism. CONCLUSIONS Developmental idealism has been widely disseminated in Yazd, Iran and is related to social and demographic factors in predicted ways. COMMENTS Although our data come from only one city, we expect that developmental idealism has been widely distributed in Iran, with important implications for family and demographic behavior.

29 CFR 1902.33 - Developmental period.

Science.gov (United States)

2010-07-01

... consideration of developmental changes by OSHA. Generally, whenever a State completes a developmental step, it must submit the resulting plan change as a supplement to its plan to OSHA for approval. OSHA's approval...

Relationship between biomarkers of inflammation, oxidative stress and endothelial/microcirculatory function in successful aging versus healthy youth: a transversal study.

Science.gov (United States)

Bottino, Daniel Alexandre; Lopes, Flávia Gomes; de Oliveira, Francisco José; Mecenas, Anete de Souza; Clapauch, Ruth; Bouskela, Eliete

2015-04-08

There is a functional decline of endothelial- dependent vasodilatation in the aging process. The aims of this study were to investigate if various microcirculatory parameters could correlate to anthropometrical variables, oxidative stress and inflammatory biomarkers in successful aging and compare the results to young healthy controls. Healthy elderly women (HE, 74.0 ± 8.7 years, n = 11) and young controls (YC, 23.1 ± 3.6 years, n = 24) were evaluated through nailfold videocapillaroscopy (NVC), venous occlusion plethysmography (VOP) and laboratorial analysis. Functional capillary density (FCD) and diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min arterial occlusion at the finger base, time to reach RBCVmax were determined by NVC, peak increment of forearm blood flow (FBF) during the reactive hyperemia response (%Hyper) and after 0.4 mg sublingual nitroglycerin (%Nitro) by VOP and lipidogram, fibrinogen, fasting and postload glucose, oxidized LDL-cholesterol (oxLDL), sICAM, sVCAM, sE-Selectin, interleukines 1 and 6 and TNF-α by laboratorial analysis. Correlations and linear multiple regression (LMR) between %Hyper, %Nitro, microcirculatory parameters, oxidative stress and inflammatory biomarkers were investigated. sVCAM, sE-Selectin and oxLDL were higher and RBCVmax/RBCVbaseline and %Hyper lower in HE, while %Nitro and FCD remained unchanged. Fibrinogen, LDL-cholesterol, oxLDL correlated negatively to %Hyper while sVCAM correlated negatively to %Hyper and RBCVmax/RBCVbaseline. Healthy aged women presented dilated capillaries with sustained perfusion and endothelial dysfunction with preserved vascular smooth muscle reactivity. Fibrinogen, LDL-cholesterol, oxidized-LDL and sVCAM correlated negatively to endothelial function but not to microcirculatory parameters. Oxidized-LDL and sVCAM could determine %Hyper through LMR. Oxidized-LDL and sVCAM might be used as endothelial

An integrative multi-platform analysis for discovering biomarkers of osteosarcoma

International Nuclear Information System (INIS)

Li, Guodong; Zhang, Wenjuan; Zeng, Huazong; Chen, Lei; Wang, Wenjing; Liu, Jilong; Zhang, Zhiyu; Cai, Zhengdong

2009-01-01

SELDI-TOF-MS (Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry) has become an attractive approach for cancer biomarker discovery due to its ability to resolve low mass proteins and high-throughput capability. However, the analytes from mass spectrometry are described only by their mass-to-charge ratio (m/z) values without further identification and annotation. To discover potential biomarkers for early diagnosis of osteosarcoma, we designed an integrative workflow combining data sets from both SELDI-TOF-MS and gene microarray analysis. After extracting the information for potential biomarkers from SELDI data and microarray analysis, their associations were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. Immuno-blot analysis was then performed to examine whether the expression of the putative biomarkers were indeed altered in serum from patients with osteosarcoma. Six differentially expressed protein peaks with strong statistical significances were detected by SELDI-TOF-MS. Four of the proteins were up-regulated and two of them were down-regulated. Microarray analysis showed that, compared with an osteoblastic cell line, the expression of 653 genes was changed more than 2 folds in three osteosarcoma cell lines. While expression of 310 genes was increased, expression of the other 343 genes was decreased. The two sets of biomarkers candidates were combined by the link-test statistics, indicating that 13 genes were potential biomarkers for early diagnosis of osteosarcoma. Among these genes, cytochrome c1 (CYC-1) was selected for further experimental validation. Link-test on datasets from both SELDI-TOF-MS and microarray high-throughput analysis can accelerate the identification of tumor biomarkers. The result confirmed that CYC-1 may be a promising biomarker for early diagnosis of osteosarcoma

Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome.

Science.gov (United States)

Hoxha, Ariela; Mattia, Elena; Tonello, Marta; Grava, Chiara; Pengo, Vittorio; Ruffatti, Amelia

2017-05-01

Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies have begun to be considered potentional biomarkers for antiphospholipid syndrome (APS). This cohort study investigate the role of aPS/PT antibodies as a risk factor for severe APS by evaluating the association between those antibodies and clinical/laboratory profiles of APS. Plasma/serum samples from 197 APS patients, 100 healthy subjects and 106 patients with autoimmune diseases were collected. IgG/IgM aPS/PT antibodies were assayed using commercial ELISA kit. Prevalences of IgG and IgM aPS/PT (pantiphospholipid antibody patients than in double and single positivity ones (p<0.0001 for all). APS/PT antibodies were associated to severe thrombosis, severe pregnancy complications inducing prematurity, and vascular microangiopathy, all generally associated to high risk APS forms requiring strong therapy.

The Knowledge-Integrated Network Biomarkers Discovery for Major Adverse Cardiac Events

Science.gov (United States)

Jin, Guangxu; Zhou, Xiaobo; Wang, Honghui; Zhao, Hong; Cui, Kemi; Zhang, Xiang-Sun; Chen, Luonan; Hazen, Stanley L.; Li, King; Wong, Stephen T. C.

2010-01-01

The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein–protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein–protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction. PMID:18665624

ALS Biomarkers for Therapy Development: State of the Field & Future Directions

Science.gov (United States)

Benatar, Michael; Boylan, Kevin; Jeromin, Andreas; Rutkove, Seward B.; Berry, James; Atassi, Nazem; Bruijn, Lucie

2015-01-01

Biomarkers have become the focus of intense research in the field of amyotrophic lateral sclerosis (ALS), with the hope that they might aid therapy development efforts. Notwithstanding the discovery of many candidate biomarkers, none have yet emerged as validated tools for drug development. In this review we present a nuanced view of biomarkers based on the perspective of the FDA; highlight the distinction between discovery and validation; describe existing and emerging resources; review leading biological fluid-based, electrophysiological and neuroimaging candidates relevant to therapy development efforts; discuss lessons learned from biomarker initiatives in related neurodegenerative diseases; and outline specific steps that we, as a field, might take in order to hasten the development and validation of biomarkers that will prove useful in enhancing efforts to develop effective treatments for ALS patients. Most important among these perhaps is the proposal to establish a federated ALS Biomarker Consortium (ABC) in which all interested and willing stakeholders may participate with equal opportunity to contribute to the broader mission of biomarker development and validation. PMID:26574709

Biomarkers in the evolution of multiple sclerosis.

Science.gov (United States)

Berger, Thomas

2017-11-01

Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown. Currently, there are no individualized biomarkers suitable to track disease progression. Neutralizing antibodies against IFN-β, natalizumab and daclizumab arise with variable frequency and reduce treatment efficacy. The anti-John Cunningham virus antibody index has potential as a biomarker for risk of progressive multifocal leukoencephalopathy.

Biomarkers for CNS involvement in pediatric lupus

Science.gov (United States)

Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

2015-01-01

CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

Eye Tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an Autism Spectrum Disorder Subtype Associated With Increased Symptom Severity.

Science.gov (United States)

Pierce, Karen; Marinero, Steven; Hazin, Roxana; McKenna, Benjamin; Barnes, Cynthia Carter; Malige, Ajith

2016-04-15

Clinically and biologically, autism spectrum disorder (ASD) is heterogeneous. Unusual patterns of visual preference as indexed by eye tracking are hallmarks; however, whether they can be used to define an early biomarker of ASD as a whole or leveraged to define a subtype is unclear. To begin to examine this issue, large cohorts are required. A sample of 334 toddlers from six distinct groups (115 toddlers with ASD, 20 toddlers with ASD features, 57 toddlers with developmental delay, 53 toddlers with other conditions [e.g., premature birth, prenatal drug exposure], 64 toddlers with typical development, and 25 unaffected toddlers with siblings with ASD) was studied. Toddlers watched a movie containing geometric and social images. Fixation duration and number of saccades within each area of interest and validation statistics for this independent sample were computed. Next, to maximize power, data from our previous study (n = 110) were added for a total of 444 subjects. A subset of toddlers repeated the eye-tracking procedure. As in the original study, a subset of toddlers with ASD fixated on geometric images >69% of the time. Using this cutoff, sensitivity for ASD was 21%, specificity was 98%, and positive predictive value was 86%. Toddlers with ASD who strongly preferred geometric images had 1) worse cognitive, language, and social skills relative to toddlers with ASD who strongly preferred social images and 2) fewer saccades when viewing geometric images. Unaffected siblings of ASD probands did not show evidence of heightened preference for geometric images. Test-retest reliability was good. Examination of age effects suggested that this test may not be appropriate with children >4 years old. Enhanced visual preference for geometric repetition may be an early developmental biomarker of an ASD subtype with more severe symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Biomarkers of tolerance: searching for the hidden phenotype.

Science.gov (United States)

Perucha, Esperanza; Rebollo-Mesa, Irene; Sagoo, Pervinder; Hernandez-Fuentes, Maria P

2011-08-01

Induction of transplantation tolerance remains the ideal long-term clinical and logistic solution to the current challenges facing the management of renal allograft recipients. In this review, we describe the recent studies and advances made in identifying biomarkers of renal transplant tolerance, from study inceptions, to the lessons learned and their implications for current and future studies with the same goal. With the age of biomarker discovery entering a new dimension of high-throughput technologies, here we also review the current approaches, developments, and pitfalls faced in the subsequent statistical analysis required to identify valid biomarker candidates.

Biomarkers specific to densely-ionising (high LET) radiations

International Nuclear Information System (INIS)

Brenner, D.J.; Okladnikova, N.; Hande, P.; Burak, L.; Geard, C.R.; Azizova, T.

2001-01-01

There have been several suggestions of biomarkers that are specific to high LET radiation. Such a biomarker could significantly increase the power of epidemiological studies of individuals exposed to densely-ionising radiations such as alpha particles (e.g. radon, plutonium workers, individuals exposed to depleted uranium) or neutrons (e.g. radiation workers, airline personnel). We discuss here a potentially powerful high LET biomarker (the H value) which is the ratio of induced inter-chromosomal aberrations to intra-arm aberrations. Both theoretical and experimental studies have suggested that this ratio should differ by a factor of about three between high LET radiation and any other likely clastogen, and will yield more discrimination than the previously suggested F value (ratio of inter-chromosomal aberrations to intra-chromosomal inter-arm aberrations). Evidence of the long-term stability of such chromosomal biomarkers has also been generated. Because these stable intra-arm and inter-chromosomal aberrations are (1) frequent and (2) measurable at long times after exposure, this H value appears to be a practical biomarker of high LET exposure, and several in vitro studies have confirmed the approach for unstable aberrations. The approach is currently being tested in a population of Russian radiation workers exposed several decades ago to high- or low LET radiation. (author)

Biomarkers of acute kidney injury in neonatal encephalopathy.

LENUS (Irish Health Repository)

Sweetman, D U

2013-03-01

Acute kidney injury (AKI) is a common complication of neonatal encephalopathy (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies on suboptimal methods such as identification of rising serum creatinine, decreased urinary output and glomerular filtration rate. Studies of AKI biomarkers in adults and children have shown that biomarkers can improve the early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and serum NGAL all show good ability to predict early AKI in a heterogeneous critically ill neonatal population including infants post-CPB. Moreover, serum and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE. These findings are promising and open up the possibility of biomarkers playing a significant role in the early diagnosis and treatment of NE-related AKI. There is an urgent need to explore the role of AKI biomarkers in infants with NE as establishing the diagnosis of AKI earlier may allow more timely intervention with potential for improving long-term outcome.

Developmental principles: fact or fiction.

Science.gov (United States)

Durston, A J

2012-01-01

While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, "whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm". We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level?) adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

Biomarkers for personalized oncology: recent advances and future challenges.

Science.gov (United States)

Kalia, Madhu

2015-03-01

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and

Salivary pH: A diagnostic biomarker

OpenAIRE

Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

2013-01-01

Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study D...

The Developmental Work

DEFF Research Database (Denmark)

Møller, Niels; Hvid, Helge

2001-01-01

AbstractIn the nineties, the concept of the developmental work (DW) has become a significant point of orientation for the actors on Danish labour market. The DW has moved the focus of the labour market from wages and working time towards work and production. For employees, the DW promises...... developmental possibilities, influence and responsibility, but also greater social responsibility for the firm. For firms, the DW promises increased competitiveness and better products. In this paper we present the concept of the DW as one which encourages the development of work, production and organisation...... of the firm and show that the DW is different from mainstream management concepts, as the DW...

Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

Energy Technology Data Exchange (ETDEWEB)

Krishnan, A

2006-08-30

The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improving our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study

OpenAIRE

Mastrangelo, Giuseppe; Carta, Angela; Arici, Cecilia; Pavanello, Sofia; Porru, Stefano

2017-01-01

Background No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. Methods Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; th...

Future Directions in Sleep and Developmental Psychopathology.

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Meltzer, Lisa J

2017-01-01

It is critical for psychologists to gain a better understanding about the intersection between sleep and developmental psychopathology. However, while many strive to answer the question of whether sleep causes developmental psychopathology, or vice versa, ultimately the relationship between sleep and developmental psychopathology is complex and dynamic. This article considers future directions in the field of clinical child and adolescent psychology that go beyond this mechanistic question, highlighting areas important to address for clinicians and researchers who strive to better understand how best to serve children and adolescents with developmental psychopathology. Questions are presented about what is normal in terms of sleep across development, the role of individual variability in terms of sleep needs and vulnerability to sleep loss, and how sleep may serve as a risk or resilience factor for developmental psychopathology, concluding with considerations for interventions.

Author's Response to Commentaries on: "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics"

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Molenaar, Peter C. M.

2015-01-01

In this article, Peter Molenaar responds to three commentaries (this issue) on his article, "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics." He addresses aspects of relational developmental systems (RDS) mentioned and questions raised in each of the…

Urine biomarkers in the early stages of diseases: current status and perspective.

Science.gov (United States)

Jing, Jian; Gao, Youhe

2018-02-01

As a noninvasive and easily available biological fluid, the urine is becoming an important source for disease biomarker study. Change is essential for the usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate more changes, especially in the early stages of diseases. In this review, we summarize current status and discuss perspectives on the discovery of urine biomarkers in the early stages of diseases. We emphasize the advantages of urine biomarkers compared to plasma biomarkers for the diagnosis of diseases at early stages, propose a urine biomarker research roadmap, and highlight a novel membrane storage technique that enables large-scale urine sample collection and storage efficiently and economically. It is anticipated that urine biomarker studies will greatly promote early diagnosis, prevention, treatment, and prognosis of a variety of diseases, and provide strong support for translational and precision medicine.

Novel biomarkers for sepsis

DEFF Research Database (Denmark)

Larsen, Frederik Fruergaard; Petersen, J Asger

2017-01-01

BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

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Jelena Kostić

2015-12-01

Full Text Available Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to conduct disorder which have different causes and serve as the basis for the current typology of conduct disorders in the classification systems. Such a typology of conduct disorders in the diagnostic classification allows better understanding, prognosis and choice of treatment.

The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints.

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Lassere, Marissa N

2008-06-01

There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Section 2 is a systematic, historical review of the biomarker-surrogate endpoint literature with special reference to the nomenclature, the systems of classification and statistical methods developed for their evaluation. In Section 3 an explicit, criterion-based, quantitative, multidimensional hierarchical levels of evidence schema - Biomarker-Surrogacy Evaluation Schema - is proposed to evaluate and co-ordinate the multiple dimensions (biological, epidemiological, statistical, clinical trial and risk-benefit evidence) of the biomarker clinical endpoint relationships. The schema systematically evaluates and ranks the surrogacy status of biomarkers and surrogate endpoints using defined levels of evidence. The schema incorporates the three independent domains: Study Design, Target Outcome and Statistical Evaluation. Each domain has items ranked from zero to five. An additional category called Penalties incorporates additional considerations of biological plausibility, risk-benefit and generalizability. The total score (0-15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. The term ;surrogate' is restricted to markers attaining Levels 1 or 2 only. Surrogacy status of markers can then be directly compared within and across different areas of medicine to guide individual, trial-based or drug-development decisions. This schema would facilitate communication between clinical, researcher, regulatory, industry and consumer participants necessary for evaluation of the biomarker-surrogate-clinical endpoint relationship in their different settings.

Functional MRI and CT biomarkers in oncology

Energy Technology Data Exchange (ETDEWEB)

Winfield, J.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Sutton (United Kingdom); Payne, G.S.; DeSouza, N.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom)

2015-04-01

Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T{sub 1} relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R{sub 2}*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives. (orig.)

Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

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Martha V. Douglas-Escobar

2012-11-01

Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

Target biomarker profile for the clinical management of paracetamol overdose

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Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

2015-01-01

Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

Oxidative stress biomarkers in Oreochromis niloticus as early ...

African Journals Online (AJOL)

2018-04-10

Apr 10, 2018 ... warning signals in assessing pollution from acid mine drainage and ... fish species Oreochromis niloticus as a bio-indicator organism in active ... Key water quality parameters, including ... Biomarkers can provide early warning of potential higher- ...... CT (2001) The use of biomarkers in Ecological Risk.

Language used in interaction during developmental science instruction

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Avenia-Tapper, Brianna

The coordination of theory and evidence is an important part of scientific practice. Developmental approaches to instruction, which make the relationship between the abstract and the concrete a central focus of students' learning activity, provide educators with a unique opportunity to strengthen students' coordination of theory and evidence. Therefore, developmental approaches may be a useful instructional response to documented science achievement gaps for linguistically diverse students. However, if we are to leverage the potential of developmental instruction to improve the science achievement of linguistically diverse students, we need more information on the intersection of developmental science instruction and linguistically diverse learning contexts. This manuscript style dissertation uses discourse analysis to investigate the language used in interaction during developmental teaching-learning in three linguistically diverse third grade classrooms. The first manuscript asks how language was used to construct ascension from the abstract to the concrete. The second manuscript asks how students' non-English home languages were useful (or not) for meeting the learning goals of the developmental instructional program. The third manuscript asks how students' interlocutors may influence student choice to use an important discourse practice--justification--during the developmental teaching-learning activity. All three manuscripts report findings relevant to the instructional decisions that teachers need to make when implementing developmental instruction in linguistically diverse contexts.

Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

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Htun, Nay Min; Peter, Karlheinz

2014-10-01

Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Other biomarkers for detecting prostate cancer.

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Nogueira, Lucas; Corradi, Renato; Eastham, James A

2010-01-01

Prostate-specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase-type plasminogen activator receptor, prostate-specific membrane antigen, early prostate cancer antigen, PCA3, alpha-methylacyl-CoA racemase and glutathione S-transferase pi hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.

HCC Biomarkers in China and Taiwan

Directory of Open Access Journals (Sweden)

Regina M. Santella

2007-02-01

Full Text Available

A number of different types of biomarkers have been used to understand the etiology and progression of hepatocellular cancer (HCC. Perhaps the most well known are the serum/ plasma markers of HBV or HCV infection. These markers include analysis of viral DNA or proteins or antibodies produced against the viral proteins. HBV surface antigen (HBsAg is most frequently used to determine chronic infection with high or low viral replication, while HBeAg is a measure of chronic infection with high viral replication. Analysis of antibodies includes measurement of anti-HBV core antigen, anti-HBV e antigen and anti-HBsAg. The response to immunization can be monitored by analysis of anti-HBsAg. The other major classes of biomarkers used in studies of HCC are biomarkers of exposure to environmental, lifestyle or dietary carcinogens, biomarkers of oxidative stress and early biologic response. In addition, studies of genetic susceptibility have studied polymorphisms in a number of pathways and their role in HCC risk. The biomarkers of exposure include the measurement of carcinogens in urine and carcinogen-DNA and protein adducts. Examples are measurement of aflatoxin and polycyclic aromatic hydrocarbon metabolites, and DNA and protein adducts.

Biomarkers of oxidative stress include urinary isoprostanes and 8-oxodeoxyguanosine and oxidized plasma proteins. Most of these assays are immunologic although the use of high performance liquid chromatograph (HPLC as well as gas chromatography/mass spectroscopy (GC/MS have been utilized. In nested case-control studies, many of these markers are associated with elevated risk. For example, elevated aflatoxin and polycyclic aromatic hydrocarbon-albumin adducts, aflatoxin metabolites in urine and urinary isoprostanes were observed in baseline samples from

Biomarker discovery in mass spectrometry-based urinary proteomics.

Science.gov (United States)

Thomas, Samuel; Hao, Ling; Ricke, William A; Li, Lingjun

2016-04-01

Urinary proteomics has become one of the most attractive topics in disease biomarker discovery. MS-based proteomic analysis has advanced continuously and emerged as a prominent tool in the field of clinical bioanalysis. However, only few protein biomarkers have made their way to validation and clinical practice. Biomarker discovery is challenged by many clinical and analytical factors including, but not limited to, the complexity of urine and the wide dynamic range of endogenous proteins in the sample. This article highlights promising technologies and strategies in the MS-based biomarker discovery process, including study design, sample preparation, protein quantification, instrumental platforms, and bioinformatics. Different proteomics approaches are discussed, and progresses in maximizing urinary proteome coverage and standardization are emphasized in this review. MS-based urinary proteomics has great potential in the development of noninvasive diagnostic assays in the future, which will require collaborative efforts between analytical scientists, systems biologists, and clinicians. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developmental Immunotoxicity

Science.gov (United States)

Animal models suggest that the immature immune system is more susceptible to xenobiotics than the fully mature system, and sequelae of developmental immunotoxicant exposure may be persistent well into adulthood. Immune maturation may be delayed by xenobiotic exposure and recover...

Developmental Work

DEFF Research Database (Denmark)

Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard

2003-01-01

Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

Managing hypertension: relevant biomarkers and combating bioactive compounds

Directory of Open Access Journals (Sweden)

Bryan Singharaj

2017-06-01

Full Text Available Hypertension is one of the most common chronic diseases which affects many people who belong to a higher age range. The standard definition that is offered to the general public has a minimum age of 18 years to be diagnosed with hypertension. Many studies have been conducted in the hopes of finding consistent data that provides information on the biomarkers of hypertension and effective forms of treatment. However, there is a tendency for skewed data due to the ineffectiveness of diagnosing hypertension, due to variability in technique or even negligence. Interestingly, research has indicated that there are connections to certain biomarkers of hypertension. However,the results have been deemed inconclusive. Moreover, the results provide promising data for future studies that have an emphasis on biomarkers. The biomarkers that have been consistently brought to researchers’ attention include the following: circulating C-reactive protein (CRP, plasminogen activator inhibitor-1 (PAI-1, urinary albumin:creatinine ratio (UACR, and aldosterone:renin ratio (ARR. These four biomarkers have become the foundation of multiple hypertension studies, even though the only formal conclusion drawn from these studies is that there is a wide range of variables that have some kind of influence on hypertension. More recently, treatment options for hypertension have increasingly become an emphasis for studies, with research predicting that nutrition plays a key role in the managing of diseases. Furthermore, the role of bioactive compounds has gained traction in hypertension research, being loosely correlated to managing specific biomarkers. Ultimately, these correlations to bioactive compounds like antioxidants would demonstrate that certain functional foods have the capacity to help treat hypertension. The modality is to find an alternative option for managing or treating hypertension through natural sources of food or food products fortified with ingredients to

COPD association and repeatability of blood biomarkers in the ECLIPSE cohort

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Dickens Jennifer A

2011-11-01

Full Text Available Abstract Background There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE cohort. Methods Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients. Results Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201 of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201 reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved. Conclusions Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD. Further analysis of more promising biomarkers may reveal

Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

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Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

2017-09-01

Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association.

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Chow, Sheryl L; Maisel, Alan S; Anand, Inder; Bozkurt, Biykem; de Boer, Rudolf A; Felker, G Michael; Fonarow, Gregg C; Greenberg, Barry; Januzzi, James L; Kiernan, Michael S; Liu, Peter P; Wang, Thomas J; Yancy, Clyde W; Zile, Michael R

2017-05-30

Natriuretic peptides have led the way as a diagnostic and prognostic tool for the diagnosis and management of heart failure (HF). More recent evidence suggests that natriuretic peptides along with the next generation of biomarkers may provide added value to medical management, which could potentially lower risk of mortality and readmissions. The purpose of this scientific statement is to summarize the existing literature and to provide guidance for the utility of currently available biomarkers. The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through December 2016. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or contemporary clinical practice recommendations. A number of biomarkers associated with HF are well recognized, and measuring their concentrations in circulation can be a convenient and noninvasive approach to provide important information about disease severity and helps in the detection, diagnosis, prognosis, and management of HF. These include natriuretic peptides, soluble suppressor of tumorgenicity 2, highly sensitive troponin, galectin-3, midregional proadrenomedullin, cystatin-C, interleukin-6, procalcitonin, and others. There is a need to further evaluate existing and novel markers for guiding therapy and to summarize their data in a standardized format to improve communication among researchers and practitioners. HF is a complex syndrome involving diverse pathways and pathological processes that can manifest in circulation as biomarkers. A number of such biomarkers are now clinically available, and monitoring their

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

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Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Assessing the Developmental Neurotoxicity of 27 ...

Science.gov (United States)

Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay, Waalkes, M., Hunter, D.L., Jarema, K., Mundy, W., and S. Padilla. The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for developmental neurotoxicity. As such, we are exploring a behavioral testing paradigm that can assess the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants on zebrafish (Danio rerio). This in vivo assay quantifies the locomotor response to light stimuli under tandem light and dark conditions in a 96-well plate using a video tracking system on 6 day post fertilization zebrafish larvae. Each of twenty-seven organophosphorus pesticides was tested for their developmental neurotoxic potential by exposing zebrafish embryos/larvae to the pesticide at several concentrations (≤ 100 μM nominal concentration) during the first five days of development, followed by 24 hours of depuration and then behavioral testing. Approximately 22% of the chemicals (Acephate, Dichlorvos, Diazoxon, Bensulide,Tribufos, Tebupirimfos) did not produce any behavioral changes after developmental exposure, while many (Malaoxon Fosthiazate, Dimethoate, Dicrotophos, Ethoprop, Malathion, Naled, Diazinon, Methamidophos, Terbufos, Trichlorfon, Phorate, Pirimiphos-methyl, Profenofos, Z-Tetrachlorvinphos, Chlorpyrifos, Coumaphos, Phosmet, Omethoate) produced changes in swi

Inflammatory biomarkers in asthma-COPD overlap syndrome

Directory of Open Access Journals (Sweden)

Kobayashi S

2016-09-01

Full Text Available Seiichi Kobayashi, Masakazu Hanagama, Shinsuke Yamanda, Masatsugu Ishida, Masaru YanaiDepartment of Respiratory Medicine, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, JapanBackground: The clinical phenotypes and underlying mechanisms of asthma-COPD overlap syndrome (ACOS remain elusive. This study aimed to investigate a comparison of COPD patients with and without ACOS, focusing on inflammatory biomarkers, in an outpatient COPD cohort.Methods: We conducted a cross-sectional study analyzing prospectively collected data from the Ishinomaki COPD Network registry. All participants were diagnosed with COPD, confirmed by using spirometry, and were aged 40–90 years and former smokers. Patients with features of asthma including both variable respiratory symptoms and variable expiratory airflow limitation were identified and defined as having ACOS. Then, the inflammatory biomarkers such as fractional exhaled nitric oxide level, blood eosinophil count and percentage, total immunoglobulin E (IgE level, and presence of antigen-specific IgE were evaluated.Results: A total of 257 patients with COPD were identified, including 37 (14.4% with ACOS. Patients with ACOS tended to be younger, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids and theophylline. Mean fractional exhaled nitric oxide level was significantly higher in those with ACOS than in those without ACOS (38.5 parts per billion [ppb] vs 20.3 ppb, P<0.001. Blood eosinophil count and percentage were significantly increased in those with ACOS (295/mm3 vs 212/mm3, P=0.032; 4.7% vs 3.2%, P=0.003, respectively. Total IgE level was also significantly higher, and presence of antigen-specific IgE was observed more frequently in patients with ACOS. Receiver operating characteristic curve analysis indicated that the sensitivity and specificity of these biomarkers were relatively low, but combinations of these biomarkers showed high specificity for

Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.

Science.gov (United States)

Mundt, Filip; Johansson, Henrik J; Forshed, Jenny; Arslan, Sertaç; Metintas, Muzaffer; Dobra, Katalin; Lehtiö, Janne; Hjerpe, Anders

2014-03-01

Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome

Plasma proteomics to identify biomarkers - Application to cardiovascular diseases

DEFF Research Database (Denmark)

Beck, Hans Christian; Overgaard, Martin; Melholt Rasmussen, Lars

2015-01-01

There is an unmet need for new cardiovascular biomarkers. Despite this only few biomarkers for the diagnosis or screening of cardiovascular diseases have been implemented in the clinic. Thousands of proteins can be analysed in plasma by mass spectrometry-based proteomics technologies. Therefore......, this technology may therefore identify new biomarkers that previously have not been associated with cardiovascular diseases. In this review, we summarize the key challenges and considerations, including strategies, recent discoveries and clinical applications in cardiovascular proteomics that may lead...

A novel biomarker in patients with knee osteoarthritis: adropin.

Science.gov (United States)

Gundogdu, Gulsah; Gundogdu, Koksal

2018-03-16

Adropin is newly discovered peptide hormone. Osteoarthritis (OA) is a kind of joint disease characterized by progressive joint cartilage loss and joint pain. The present study was carried out to investigate adropin and tumor necrosis factor alpha (TNF-α) levels and the relationship between adropin in patients with knee OA classified by Kellgren-Lawrence (KL). A total of 60 knee OA patients and 30 healthy controls were included in this study. KL grading was carried out using the radiographic findings. Demographic characteristics and laboratory parameters were recorded. Adropin and TNF-α levels were determined by using enzyme-linked immunosorbent assay (ELISA). Adropin level was lower in the knee OA patients compared with the healthy controls (p  30 (p < 0.01). Mean NLR of KL grade 4 was significantly increased compared with other grades (p < 0.05). The consequence of the present study suggested that serum adropin level could be used as a new biomarker indicating the early grade of knee OA.

Evolutionary and developmental modules.

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Lacquaniti, Francesco; Ivanenko, Yuri P; d'Avella, Andrea; Zelik, Karl E; Zago, Myrka

2013-01-01

The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates.

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

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Kimberly B. Hoang

2017-10-01

Full Text Available The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs, and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs, and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms.

Sexual dysfunction within an adult developmental perspective.

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Fagan, P J; Meyer, J K; Schmidt, C W

1986-01-01

The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

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Bălănescu, Paul; Lădaru, Anca; Bălănescu, Eugenia; Băicuş, Cristian; Dan, Gheorghe Andrei

2014-08-01

Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. Medline and Embase databases were searched in February 2014. Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

Emerging biomarkers for cancer immunotherapy in melanoma.

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Axelrod, Margaret L; Johnson, Douglas B; Balko, Justin M

2017-09-14

The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature. Due to the ability of ICIs to illicit dramatic and durable responses, well-validated biomarkers that can be effectively implemented in the clinic will require strong negative predictive values that do not limit patients with who may benefit from ICI therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Testing of the OMERACT 8 draft validation criteria for a soluble biomarker reflecting structural damage in rheumatoid arthritis: a systematic literature search on 5 candidate biomarkers

DEFF Research Database (Denmark)

Syversen, Silje W; Landewe, Robert; van der Heijde, Désirée

2009-01-01

OBJECTIVE: To test the OMERACT 8 draft validation criteria for soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers. METHODS: A systematic literature search was conducted on the 5 soluble biomarkers RANKL, osteoprotegerin (OPG), matrix...... metalloprotease (MMP-3), urine C-telopeptide of types I and II collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT 8 criteria. Two electronic voting exercises were conducted to address: (1) strength of evidence for each biomarker as reflecting structural damage according to each individual criterion...

Biomarkers in Alzheimer’s Disease Analysis by Mass Spectrometry-Based Proteomics

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Yahui Liu

2014-05-01

Full Text Available Alzheimer’s disease (AD is a common chronic and destructive disease. The early diagnosis of AD is difficult, thus the need for clinically applicable biomarkers development is growing rapidly. There are many methods to biomarker discovery and identification. In this review, we aim to summarize Mass spectrometry (MS-based proteomics studies on AD and discuss thoroughly the methods to identify candidate biomarkers in cerebrospinal fluid (CSF and blood. This review will also discuss the potential research areas on biomarkers.

UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A single center pilot study

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Martha V. Douglas-Escobar

2014-12-01

Full Text Available Objective - We examined two potential biomarkers of brain damage in HIE neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury. We hypothesized the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. Further, we hypothesized that serum samples of HIE neonates would have higher levels and would correlate with brain damage on MRI and later developmental outcomes.Study Design - Serum UCH - L1 and GFAP concentrations from HIE neonates(n = 16 were compared with controls(n = 11.Pearson correlation coefficients and a mixed model design examined the relationship between biomarker concentrations of HIE neonates and brain damage(MRI and developmental outcomes(Bayley - III.Result– Both biomarkers were detected in cord blood from control subjects.UCH - L1 concentrations were higher in HIE neonates(p < 0.001 and associated with cortical injury(p < 0.055 and later motor and cognitive developmental outcomes(p < 0.05.The temporal change in GFAP concentrations from birth to 96 hours of age predicted motor developmental outcomes(p < 0.05 and injury to the basal ganglia and white matter.Conclusion– UCH - L1 concentrations correlated with cortical injury and developmental delays and GFAP concentrations correlated with basal ganglia and white matter injury and motor delay in HIE affected patients.Researchers should continue to explore UCH - L1 and GFAP as promising serum biomarkers of brain damage and predictors of neurodevelopmental outcomes in neonates with HIE.