A Biomonitoring Framework to Support Exposure and Risk Assessments

EPA Science Inventory

Background - Biomonitoring is used in exposure and risk assessments to reduce uncertainties along the source-to-outcome continuum. Specifically, biomarkers can help identify exposure sources, routes, and distributions, and reflect kinetic and dynamic processes following exposure ...

A TASER conducted electrical weapon with cardiac biomonitoring capability: Proof of concept and initial human trial.

PubMed

Stopyra, Jason P; Ritter, Samuel I; Beatty, Jennifer; Johnson, James C; Kleiner, Douglas M; Winslow, James E; Gardner, Alison R; Bozeman, William P

2016-10-01

Despite research demonstrating the overall safety of Conducted Electrical Weapons (CEWs), commonly known by the brand name TASER(®), concerns remain regarding cardiac safety. The addition of cardiac biomonitoring capability to a CEW could prove useful and even lifesaving in the rare event of a medical crisis by detecting and analyzing cardiac rhythms during the period immediately after CEW discharge. To combine an electrocardiogram (ECG) device with a CEW to detect and store ECG signals while still allowing the CEW to perform its primary function of delivering an incapacitating electrical discharge. This work was performed in three phases. In Phase 1 standard law enforcement issue CEW cartridges were modified to demonstrate transmission of ECG signals. In Phase 2, a miniaturized ECG recorder was combined with a standard issue CEW and tested. In Phase 3, a prototype CEW with on-board cardiac biomonitoring was tested on human volunteers to assess its ability to perform its primary function of electrical incapacitation. Bench testing demonstrated that slightly modified CEW cartridge wires transmitted simulated ECG signals produced by an ECG rhythm generator and from a human volunteer. Ultimately, a modified CEW incorporating ECG monitoring successfully delivered incapacitating current to human volunteers and successfully recorded ECG signals from subcutaneous CEW probes after firing. An ECG recording device was successfully incorporated into a standard issue CEW without impeding the functioning of the device. This serves as proof-of-concept that safety measures such as cardiac biomonitoring can be incorporated into CEWs and possibly other law enforcement devices. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Review of genotoxicity biomonitoring studies of glyphosate-based formulations

PubMed Central

Kier, Larry D.

2015-01-01

Abstract Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs. The environmental and most of the human biomonitoring studies were not informative because there was either a very low frequency of GBF exposure or exposure to a large number of pesticides without analysis of specific pesticide effects. One pesticide sprayer biomonitoring study indicated there was not a statistically significant relationship between frequency of GBF exposure reported for the last spraying season and oxidative DNA damage. There were three studies of human populations in regions of GBF aerial spraying. One study found increases for the cytokinesis-block micronucleus endpoint but these increases did not show statistically significant associations with self-reported spray exposure and were not consistent with application rates. A second study found increases for the blood cell comet endpoint at high exposures causing toxicity. However, a follow-up to this study 2 years after spraying did not indicate chromosomal effects. The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures. PMID:25687244

Noninvasive Biomonitoring Approaches to Determine Dosimetry and Risk Following Acute Chemical Exposure: Analysis of Lead or Organophosphate Insecticide in Saliva

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

2004-04-01

There is a need to develop approaches for assessing risk associated with acute exposures to a broad-range of chemical agents and to rapidly determine the potential implications to human health. Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants including heavy metals and pesticides. To advance the application of non-invasive biomonitoring a microfluidic/ electrochemical device has also been developed for the analysis of lead (Pb), using square wave anodic stripping voltammetry. Themore » system demonstrates a linear response over a broad concentration range (1 2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb-acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for non-invasive biomonitoring can provide a sensitive, and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these non-invasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for accessing acute exposure and health risk.« less

Using Spot Biomarker Data to Inform Chronic Exposure and Health Risk

EPA Science Inventory

The U.S. NHANES and other health surveys frequently collect and analyze spot biological specimens to inform chemical exposures. These spot measurements can be compared to biomarker-based reference levels, such as “Biomonitoring Equivalents” (BEs), to evaluate health r...

The role of toxicology to characterize biomarkers for agrochemicals with potential endocrine activities.

PubMed

Mantovani, Alberto; Maranghi, Francesca; La Rocca, Cinzia; Tiboni, Gian Mario; Clementi, Maurizio

2008-09-01

The paper discusses current knowledge and possible research priorities on biomarkers of exposure, effect and susceptibility for potential endocrine activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates, triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals highlights the need to assess internal exposure of animals or humans, which is the most relevant exposure measure for hazard and risk estimation; however, exposure data should be integrated by early indicators predictive of possible health effects, particularly for vulnerable groups such as mother-child pairs. Research need include: non-invasive biomarkers for children biomonitoring; novel biomarkers of total exposure to measure whole endocrine disrupter-related burden; characterization of biomarkers of susceptibility, including the role of markers of nutritional status; anchoring early molecular markers to established toxicological endpoints to support their predictivity; integrating "omics"-based approaches in a system-toxicology framework. As biomonitoring becomes increasingly important in the environment-and-health scenario, toxicologists can substantially contribute both to the characterization of new biomarkers and to the predictivity assessment and improvement of the existing ones.

Biomonitoring Data for 2,4-Dichlorophenoxyacetic Acid in the United States and Canada: Interpretation in a Public Health Risk Assessment Context Using Biomonitoring Equivalents

PubMed Central

Aylward, Lesa L.; Morgan, Marsha K.; Arbuckle, Tye E.; Barr, Dana B.; Burns, Carol J.; Alexander, Bruce H.; Hays, Sean M.

2010-01-01

Background Several extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents (BEs; concentrations in urine or plasma that are consistent with those RfDs) for 2,4-D have recently been derived and published. Objective We reviewed the available biomonitoring data for 2,4-D from the United States and Canada and compared them with BE values to draw conclusions regarding the margin of safety for 2,4-D exposures within each population group. Data sources Data on urinary 2,4-D excretion in general and target populations from recent published studies are tabulated and the derivation of BE values for 2,4-D summarized. Data synthesis The biomonitoring data indicate margins of safety (ratio of BE value to biomarker concentration) of approximately 200 at the central tendency and 50 at the extremes in the general population. Median exposures for applicators and their family members during periods of use appear to be well within acute exposure guidance values. Conclusions Biomonitoring data from these studies indicate that current exposures to 2,4-D are below applicable exposure guidance values. This review demonstrates the value of biomonitoring data in assessing population exposures in the context of existing risk assessments using the BE approach. Risk managers can use this approach to integrate the available biomonitoring data into an overall assessment of current risk management practices for 2,4-D. PMID:20123603

Biomonitoring our streams

USGS Publications Warehouse

Byl, Thomas Duane; Smith, George F.

1994-01-01

Biomonitoring is often used to enhance or replace chemical monitoring when evaluating water quality in our streams. This report is intended to introduce the theories behind biomonitoring and some of the techniques used in a biomonitoring study. It also lists some of the advantages and limitations of biomonitoring.

[Air pollution biomonitoring with plants and fungi: concepts and uses].

PubMed

Cuny, D

2012-07-01

Air pollution remains a major environmental concern of the French. Since about 30 years, due to evolution and diversification of sources, pollution became more and more complex, constituting a true "cocktail". Today, it is very important to know environmental and health effects of this cocktail. In this context air biomonitoring using plants and fungi can bring a lot of information. Biomonitoring includes four concepts: the use of biomarkers, bioindication biointegration and bioaccumulation. These four concepts are articulated according to the levels of biological organization, what links up biosurveillance on fundamental plan with ecotoxicology. It is a complementary approach of the physicochemical techniques of air pollution measurements. The main objectives of biomonitoring studies are the monitoring of the space and temporal distribution of pollutants effect; the monitoring of local sources; participation in the health risks assessment; the information of people and the help to decision in public policies. Biomonitoring of air quality is a method, which made its proof in numerous domains of application and brings fundamental information on the impacts of the quality of air. Recent evolution of low concerning biggest industries allows us to envisage the increase of air quality biomonitoring with plants and fungi applications in the field of the valuation of environmental and health risks. The recent normalization (French and European) of different methods will also allow the development of uses. Copyright © 2012. Published by Elsevier Masson SAS.

Analytical methods for human biomonitoring of pesticides. A review.

PubMed

Yusa, Vicent; Millet, Maurice; Coscolla, Clara; Roca, Marta

2015-09-03

Biomonitoring of both currently-used and banned-persistent pesticides is a very useful tool for assessing human exposure to these chemicals. In this review, we present current approaches and recent advances in the analytical methods for determining the biomarkers of exposure to pesticides in the most commonly used specimens, such as blood, urine, and breast milk, and in emerging non-invasive matrices such as hair and meconium. We critically discuss the main applications for sample treatment, and the instrumental techniques currently used to determine the most relevant pesticide biomarkers. We finally look at the future trends in this field. Copyright © 2015 Elsevier B.V. All rights reserved.

Pilot study testing a European human biomonitoring framework for biomarkers of chemical exposure in children and their mothers: experiences in the UK.

PubMed

Exley, Karen; Aerts, Dominique; Biot, Pierre; Casteleyn, Ludwine; Kolossa-Gehring, Marike; Schwedler, Gerda; Castaño, Argelia; Angerer, Jürgen; Koch, Holger M; Esteban, Marta; Schindler, Birgit K; Schoeters, Greet; Den Hond, Elly; Horvat, Milena; Bloemen, Louis; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Sepai, Ovnair

2015-10-01

Exposure to a number of environmental chemicals in UK mothers and children has been assessed as part of the European biomonitoring pilot study, Demonstration of a Study to Coordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES). For the European-funded project, 17 countries tested the biomonitoring guidelines and protocols developed by COPHES. The results from the pilot study in the UK are presented; 21 school children aged 6-11 years old and their mothers provided hair samples to measure mercury and urine samples, to measure cadmium, cotinine and several phthalate metabolites: mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP), mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP). Questionnaire data was collected on environment, health and lifestyle. Mercury in hair was higher in children who reported frequent consumption of fish (geometric mean 0.35 μg/g) compared to those that ate fish less frequently (0.13 μg/g, p = 0.002). Cadmium accumulates with age as demonstrated by higher levels of urinary cadmium in the mothers (geometric mean 0.24 μg/L) than in the children(0.14 μg/L). None of the mothers reported being regular smokers, and this was evident with extremely low levels of cotinine measured (maximum value 3.6 μg/L in mothers, 2.4 μg/L in children). Very low levels of the phthalate metabolites were also measured in both mothers and children (geometric means in mothers: 5OH-MEHP 8.6 μg/L, 5oxo-MEHP 5.1 μg/L, MEHP 1.2 μg/L, MEP 26.8 μg/L, MiBP 17.0 μg/L, MBzP 1.6 μg/L and MnBP 13.5 μg/L; and in children: 5OH-MEHP 18.4 μg/L, 5oxo-MEHP 11.4 μg/L, MEHP 1.4 μg/L, MEP 14.3 μg/L, MiBP 25.8 μg/L, MBzP 3.5 μg/L and MnBP 22.6 μg/L). All measured biomarker levels were similar to or below population-based reference values published by the US National Health and Nutrition

Human biomonitoring reference values for metals and trace elements in blood and urine derived from the Canadian Health Measures Survey 2007-2013.

PubMed

Saravanabhavan, Gurusankar; Werry, Kate; Walker, Mike; Haines, Douglas; Malowany, Morie; Khoury, Cheryl

2017-03-01

Human biomonitoring reference values are statistical estimates that indicate the upper margin of background exposure to a given chemical at a given time. Nationally representative human biomonitoring data on 176 chemicals, including several metals and trace elements, are available in Canada from 2007 to 2013 through the Canadian Health Measures Survey (CHMS). In this work, we used a systematic approach based on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry to derive reference values (RV 95 s) for metals and trace elements. These RV 95 s were derived for blood and urine matrices in the general Canadian population based on the latest biomonitoring data from the CHMS. Biomarkers were chosen based on specific selection criteria, including widespread detection in Canadians (≥66% detection rate). Reference populations were created for each biomarker by applying appropriate exclusion criteria. Age and sex were evaluated as possible partitioning criteria and separate RV 95 s were derived for the sub-populations in cases where partitioning was deemed necessary. The RV 95 s for metals and trace elements in blood ranged from 0.18μg/L for cadmium in young children aged 3-5 years to 7900μg/L for zinc in males aged 20-79 years. In the case of urinary biomarkers, the RV 95 s ranged from 0.17μg/L for antimony in the total population aged 3-79 years to 1400mg/L for fluoride in adults aged 20-79 years. These RV 95 s represent the first set of reference values for metals and trace elements in the general Canadian population. We compare the RV 95 s from other countries where available and discuss factors that could influence such comparisons. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Reconstruction of Exposure to m-Xylene from Human Biomonitoring Data Using PBPK Modelling, Bayesian Inference, and Markov Chain Monte Carlo Simulation

PubMed Central

McNally, Kevin; Cotton, Richard; Cocker, John; Jones, Kate; Bartels, Mike; Rick, David; Price, Paul; Loizou, George

2012-01-01

There are numerous biomonitoring programs, both recent and ongoing, to evaluate environmental exposure of humans to chemicals. Due to the lack of exposure and kinetic data, the correlation of biomarker levels with exposure concentrations leads to difficulty in utilizing biomonitoring data for biological guidance values. Exposure reconstruction or reverse dosimetry is the retrospective interpretation of external exposure consistent with biomonitoring data. We investigated the integration of physiologically based pharmacokinetic modelling, global sensitivity analysis, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of inhalation exposure to m-xylene. We used exhaled breath and venous blood m-xylene and urinary 3-methylhippuric acid measurements from a controlled human volunteer study in order to evaluate the ability of our computational framework to predict known inhalation exposures. We also investigated the importance of model structure and dimensionality with respect to its ability to reconstruct exposure. PMID:22719759

A proposal for assessing study quality: Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument.

PubMed

LaKind, Judy S; Sobus, Jon R; Goodman, Michael; Barr, Dana Boyd; Fürst, Peter; Albertini, Richard J; Arbuckle, Tye E; Schoeters, Greet; Tan, Yu-Mei; Teeguarden, Justin; Tornero-Velez, Rogelio; Weisel, Clifford P

2014-12-01

The quality of exposure assessment is a major determinant of the overall quality of any environmental epidemiology study. The use of biomonitoring as a tool for assessing exposure to ubiquitous chemicals with short physiologic half-lives began relatively recently. These chemicals present several challenges, including their presence in analytical laboratories and sampling equipment, difficulty in establishing temporal order in cross-sectional studies, short- and long-term variability in exposures and biomarker concentrations, and a paucity of information on the number of measurements required for proper exposure classification. To date, the scientific community has not developed a set of systematic guidelines for designing, implementing and interpreting studies of short-lived chemicals that use biomonitoring as the exposure metric or for evaluating the quality of this type of research for WOE assessments or for peer review of grants or publications. We describe key issues that affect epidemiology studies using biomonitoring data on short-lived chemicals and propose a systematic instrument--the Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument--for evaluating the quality of research proposals and studies that incorporate biomonitoring data on short-lived chemicals. Quality criteria for three areas considered fundamental to the evaluation of epidemiology studies that include biological measurements of short-lived chemicals are described: 1) biomarker selection and measurement, 2) study design and execution, and 3) general epidemiological study design considerations. We recognize that the development of an evaluative tool such as BEES-C is neither simple nor non-controversial. We hope and anticipate that the instrument will initiate further discussion/debate on this topic. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A proposal for assessing study quality: Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument

PubMed Central

LaKind, Judy S.; Sobus, Jon R.; Goodman, Michael; Barr, Dana Boyd; Fürst, Peter; Albertini, Richard J.; Arbuckle, Tye E.; Schoeters, Greet; Tan, Yu-Mei; Teeguarden, Justin; Tornero-Velez, Rogelio; Weisel, Clifford P.

2015-01-01

The quality of exposure assessment is a major determinant of the overall quality of any environmental epidemiology study. The use of biomonitoring as a tool for assessing exposure to ubiquitous chemicals with short physiologic half-lives began relatively recently. These chemicals present several challenges, including their presence in analytical laboratories and sampling equipment, difficulty in establishing temporal order in cross-sectional studies, short- and long-term variability in exposures and biomarker concentrations, and a paucity of information on the number of measurements required for proper exposure classification. To date, the scientific community has not developed a set of systematic guidelines for designing, implementing and interpreting studies of short-lived chemicals that use biomonitoring as the exposure metric or for evaluating the quality of this type of research for WOE assessments or for peer review of grants or publications. We describe key issues that affect epidemiology studies using biomonitoring data on short-lived chemicals and propose a systematic instrument – the Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument – for evaluating the quality of research proposals and studies that incorporate biomonitoring data on short-lived chemicals. Quality criteria for three areas considered fundamental to the evaluation of epidemiology studies that include biological measurements of short-lived chemicals are described: 1) biomarker selection and measurement, 2) study design and execution, and 3) general epidemiological study design considerations. We recognize that the development of an evaluative tool such as BEES-C is neither simple nor non-controversial. We hope and anticipate that the instrument will initiate further discussion/debate on this topic. PMID:25137624

A New Method for Generating Distribution of Biomonitoring Equivalents to Support Exposure Assessment and Prioritization

EPA Science Inventory

Biomonitoring data are now available for hundreds of chemicals through state and national health surveys. Exposure guidance values also exist for many of these chemicals. Several methods are frequently used to evaluate biomarker data with respect to a guidance value. The “biomoni...

INTERPRETATION OF BENZENE URINARY BIOMARKER DATA FOR RISK ASSESSMENT: A CASE STUDY

EPA Science Inventory

Human biomonitoring is an effective tool in assessing exposure to hundreds of chemicals. Too often, however, biomarkers such as parent or metabolite concentrations in blood or urine are reported without information on doses associated with the biomarkers and implications for hum...

Foreword: Biomonitoring Equivalents special issue.

PubMed

Meek, M E; Sonawane, B; Becker, R A

2008-08-01

The challenge of interpreting results of biomonitoring for environmental chemicals in humans is highlighted in this Foreword to the Biomonitoring Equivalents (BEs) special issue of Regulatory Toxicology and Pharmacology. There is a pressing need to develop risk-based tools in order to empower scientists and health professionals to interpret and communicate the significance of human biomonitoring data. The BE approach, which integrates dosimetry and risk assessment methods, represents an important advancement on the path toward achieving this objective. The articles in this issue, developed as a result of an expert panel meeting, present guidelines for derivation of BEs, guidelines for communication using BEs and several case studies illustrating application of the BE approach for specific substances.

Uses and issues of biomonitoring.

PubMed

Needham, Larry L; Calafat, Antonia M; Barr, Dana B

2007-05-01

In the last two decades, an explosion in information and literature on human biomonitoring data has occurred. Symposia, workshops, and workgroups have been formed to discuss all issues surrounding biomonitoring. One such workgroup, formed by the International Life Sciences Institute's Health and Environmental Sciences Institute (HESI), developed a wheel which has biomonitoring at its hub; its spokes depict the uses of biomonitoring. As it rolls and picks up speed, the biomonitoring wheel will no doubt gain additional spokes. In this manuscript, we describe and give examples of these biomonitoring uses and some of their further applications as well as some of the issues surrounding biomonitoring. Special emphasis is placed on the uses and limitations of large-scale representative cross sectional studies such as the National Health and Nutrition Examination Surveys in the United States. Priority setting, improved modeling methods for interpreting the biomonitoring data, and an increase in studies designed to associate health indicators and health risks to selected environmental chemicals are needed to increase the power of biomonitoring.

The French human biomonitoring program: First lessons from the perinatal component and future needs.

PubMed

Dereumeaux, Clémentine; Fillol, Clémence; Charles, Marie-Aline; Denys, Sébastien

2017-03-01

This paper presents a progress report of the French human biomonitoring (HBM) program established in 2010. This program has been designed to provide a national representative estimation of the French population's exposure to various environmental chemicals and to study the determinants of exposure. This program currently consists in two surveys: a perinatal component related to a selection of 4145 pregnant women who have been enrolled in the Elfe cohort (the French Longitudinal Study since Childhood) in 2011, and a general population survey related to adults aged 18-74 years and children as from 6 years (Esteban). The aim of this manuscript is to present highlights of the French human biomonitoring program with particular focus on the prioritization of biomarkers to be analyzed in the program and the selection of biomarkers applied to both program components. The Delphi method was used to establish a consensual list of prioritized biomarkers in 2011. First results of the perinatal component of the French HBM program have shown that the biomarkers prioritized were relevant, as almost all pregnant women were exposed to them. However, for some biomarkers, levels' decreases have been observed which may partly be explained by measures taken to prohibit some of these chemicals (e.g. atrazine) and by industrial processes evolutions leading to the substitution of others (e.g. bisphenol A, di-2-ethylhexyl phthalate/DEHP, dialkyl phosphates). Therefore, the list of biomarkers to be monitored in the French HBM program has been implemented to include some substitutes of biomarkers prioritized in the first instance (e.g. bisphenol S, F). Finally, this method combines rigor and flexibility and helped us to build a prioritized list that will be shared and supported by many if not all actors. Copyright © 2016 Elsevier GmbH. All rights reserved.

Monitoring population exposure to pesticides based on liquid chromatography-tandem mass spectrometry measurement of their urinary metabolites in urban wastewater: A novel biomonitoring approach.

PubMed

Rousis, Nikolaos I; Zuccato, Ettore; Castiglioni, Sara

2016-11-15

Biomonitoring studies have documented the high exposure of the population to pesticides which are widely used for crop protection, industrial and household purposes. This is the first study which has measured human urinary metabolites of pesticides in urban wastewater as biomarkers of population exposure. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure fifteen urinary metabolites selected from the major classes of pesticides. Raw wastewater samples were processed by solid phase extraction (SPE) or direct injection into the LC-MS/MS system. Recoveries ranged from 75 to 115% and the limits of quantification were 1-15ng/L for the SPE method and 40-800ng/L for direct injection. The method was employed for the analysis of 44 composite 24-h wastewater samples collected in seven Italian cities. Most of the target substances were detected at concentrations ranging from 1.1ng/L to 1.6μg/L. The highest concentrations were for some common metabolites of alkyl phosphates and pyrethroids and the specific metabolite of chlorpyrifos and chlorpyrifos-methyl (3,5,6-trichloro-2-pyridinol). The frequency of detection and abundance of most of the measured metabolites were in line with the profiles reported in urine biomonitoring studies. This method is therefore proposed as a novel "biomonitoring approach" for obtaining objective, direct information on the levels of exposure of a specific population to pesticides, and current research is addressed to validate the method identifying the most reliable biomarkers. Copyright © 2016 Elsevier B.V. All rights reserved.

Green garden snail, Cantareus apertus, as biomonitor and sentinel for integrative metal pollution assessment in roadside soils.

PubMed

Mleiki, Anwar; Marigómez, Ionan; El Menif, Najoua Trigui

2017-11-01

The present investigation was conceived to study, in a small scale field study, the potential of the green garden snail, Cantareus apertus, as biomonitor and sentinel for integrative metal pollution assessment in soils. For this purpose, we investigated the association between the trace metal (Cd, Pb, As, Fe, Cr, Cu, Ni, and Zn) concentrations in soil, plants (Trifolium repens), and C. apertus depending on the distance (20, 150, and 700 m) from a main roadside in Tunisia as well as between metal concentrations and biomarkers of oxidative stress, oxidative damage, and neurotoxicity in C. apertus. Results revealed a clear association between the concentration of metals such as Ni, Cu, and Zn in snail digestive gland, both amongst them and with oxidative stress and neurotoxicity biomarkers recorded in the same organ. Interestingly, Ni, Pb, and Zn occurred at the highest concentration in soil, plant, and snails and the association appeared related to the immediacy of the roadside and the concentration of these three metals tended to decrease with distance from the roadside in the soil-plant-snail system. Conversely, Cd and Cu were bioaccumulated in plants and snails but their concentrations in soil were not high and did not show a decline in concentration with distance from the roadside. After PCA analysis, PC-01 (56% of the variance) represented metal bioaccumulation and associated toxic effects in snails in the presence of high levels of metal pollution (nearby the roadside) while PC-02 (35% of the variance) represented stress induced by moderate levels of metal pollution (at intermediate distances from the roadside). The four studied sites were clearly discriminated one from each other, depending on how they are affected by traffic pollution. In summary, this field study reveals that (a) C. apertus can be used as biomonitor for metal pollution in roadside soils and as sentinel for pollution effects assessment based on biochemical biomarkers; and (b) that oxidative

A pilot study on the feasibility of European harmonized human biomonitoring: Strategies towards a common approach, challenges and opportunities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casteleyn, L., E-mail: Ludwine.Casteleyn@med.kuleuven.be; Dumez, B.; Becker, K.

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother–child pairs in the frame of DEMOnstration of amore » study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES). Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to

Biomonitoring of airborne particulate matter emitted from a cement plant and comparison with dispersion modelling results

NASA Astrophysics Data System (ADS)

Abril, Gabriela A.; Wannaz, Eduardo D.; Mateos, Ana C.; Pignata, María L.

2014-01-01

The influence of a cement plant that incinerates industrial waste on the air quality of a region in the province of Córdoba, Argentina, was assessed by means of biomonitoring studies (effects of immission) and atmospheric dispersion (effects of emission) of PM10 with the application of the ISC3 model (Industrial Source Complex) developed by the USEPA (Environmental Protection Agency). For the biomonitoring studies, samples from the epiphyte plant Tillandsia capillaris Ruíz & Pav. f. capillaris were transplanted to the vicinities of the cement plant in order to determine the physiological damage and heavy metal accumulation (Ca, Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb). For the application of the ISC3 model, point and area sources from the cement plant were considered to obtain average PM10 concentration results from the biomonitoring exposure period. This model permitted it to be determined that the emissions from the cement plant (point and area sources) were confined to the vicinities, without significant dispersion in the study area. This was also observed in the biomonitoring study, which identified Ca, Cd and Pb, pH and electric conductivity (EC) as biomarkers of this cement plant. Vehicular traffic emissions and soil re-suspension could be observed in the biomonitors, giving a more complete scenario. In this study, biomonitoring studies along with the application of atmospheric dispersion models, allowed the atmospheric pollution to be assessed in more detail.

Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Aiqiong; Du, Dan; Lin, Yuehe

Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detectionmore » of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.« less

Interpretation of benzene biomarkers of exposure for risk assessment

EPA Science Inventory

Human biomarkers of exposure such as parent or metabolite concentrations in blood or urine are often reported without any context to the sources of exposure or the implications for human risk. The Biomonitoring Technical Committee of the International Life Sciences Institute/Huma...

The comet assay in human biomonitoring.

PubMed

Anderson, Diana; Dhawan, Alok; Laubenthal, Julian

2013-01-01

Human biomonitoring studies aim to identify potential exposures to environmental, occupational, or lifestyle toxicants in human populations and are commonly used by public health decision makers to predict disease risk. The Comet assay measures changes in genomic stability and is one of the most reliable biomarkers to indicate early biological effects, and therefore accepted by various governmental regulatory agencies. The appeal of the Comet assay lies in its relative simplicity, rapidity, sensitivity, and economic efficiency. Furthermore, the assay is known for its broad versatility, as it can be applied to virtually any human cell and easily adapted in order to detect particular biomarkers of interest, such as DNA repair capacity or single- and double-strand breaks. In a standard experiment, isolated single cells are first embedded in agarose, and then lysed in high-salt solutions in order to remove all cellular contents except the DNA attached to a nuclear scaffold. Subsequent electrophoresis results in accumulation of undamaged DNA sequences at the proximity of the nuclear scaffold, while damaged sequences migrate towards the anode. When visualized with fluorochromes, these migrated DNA fragments resemble a comet tail and can be quantified for their intensity and shape according to internationally drafted guidelines.

Biomarkers of oxidative damage and antioxidant defense capacity in Caiman latirostris blood.

PubMed

Poletta, Gisela L; Simoniello, María Fernanda; Mudry, Marta D

2016-01-01

Several xenobiotics, and among them pesticides, can produce oxidative stress, providing a mechanistic basis for their observed toxicity. Chronic oxidative stress induces deleterious modifications to DNA, lipids and proteins that are used as effective biomarkers to study pollutant-mediated oxidative stress. No previous report existed on the application of oxidative damage and antioxidant defense biomarkers in Caiman latirostris blood, while few studies reported in other crocodilians were done in organs or muscles of dead animals. The aim of this study was to characterize a new set of oxidative stress biomarkers in C. latirostris blood, through the modification of conventional techniques: 1) damage to lipids by thiobarbituric acid reactive substances (TBARS), 2) damage to DNA by comet assay modified with the enzymes FPG and Endo III, and 3) antioxidant defenses: catalase, superoxide dismutase and glutathione; in order to apply them in future biomonitoring studies. We successfully adapted standard procedures for CAT, SOD, GSH and TBARS determination in C. latirostris blood. Calibration curves for FPG and Endo III showed that the three dilutions tested were appropriate to conduct the modified comet assay for the detection of oxidized bases in C. latirostris erythrocytes. One hour of incubation allowed a complete repair of the damage generated. The incorporation of these biomarkers in biomonitoring studies of caiman populations exposed to xenobiotics is highly important considering that this species has recovered from a serious endangered state through the implementation of sustainable use programs in Argentina, and represents nowadays a relevant economic resource for many human communities. Copyright © 2015 Elsevier Inc. All rights reserved.

Mass Spectrometry-based Assay for High Throughput and High Sensitivity Biomarker Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Xuejiang; Tang, Keqi

Searching for disease specific biomarkers has become a major undertaking in the biomedical research field as the effective diagnosis, prognosis and treatment of many complex human diseases are largely determined by the availability and the quality of the biomarkers. A successful biomarker as an indicator to a specific biological or pathological process is usually selected from a large group of candidates by a strict verification and validation process. To be clinically useful, the validated biomarkers must be detectable and quantifiable by the selected testing techniques in their related tissues or body fluids. Due to its easy accessibility, protein biomarkers wouldmore » ideally be identified in blood plasma or serum. However, most disease related protein biomarkers in blood exist at very low concentrations (<1ng/mL) and are “masked” by many none significant species at orders of magnitude higher concentrations. The extreme requirements of measurement sensitivity, dynamic range and specificity make the method development extremely challenging. The current clinical protein biomarker measurement primarily relies on antibody based immunoassays, such as ELISA. Although the technique is sensitive and highly specific, the development of high quality protein antibody is both expensive and time consuming. The limited capability of assay multiplexing also makes the measurement an extremely low throughput one rendering it impractical when hundreds to thousands potential biomarkers need to be quantitatively measured across multiple samples. Mass spectrometry (MS)-based assays have recently shown to be a viable alternative for high throughput and quantitative candidate protein biomarker verification. Among them, the triple quadrupole MS based assay is the most promising one. When it is coupled with liquid chromatography (LC) separation and electrospray ionization (ESI) source, a triple quadrupole mass spectrometer operating in a special selected reaction monitoring (SRM

An overview of human biomonitoring of environmental chemicals in the Canadian Health Measures Survey: 2007-2019.

PubMed

Haines, Douglas A; Saravanabhavan, Gurusankar; Werry, Kate; Khoury, Cheryl

2017-03-01

Human biomonitoring (HBM) is used to indicate and quantify exposure by measuring environmental chemicals, their metabolites or reaction products in biological specimens. The biomonitoring component of the Canadian Health Measures Survey (CHMS) is the most comprehensive initiative providing general population HBM data in Canada. The CHMS is an ongoing cross-sectional direct measures survey implemented in 2-year cycles. It provides nationally-representative data on health, nutritional status, environmental exposures, and related risks and protective characteristics. The survey follows a robust planning, design and sampling protocol as well as a comprehensive quality assurance and quality control regime implemented for all aspect of the survey to ensure the validity of the HBM results. HBM blood and urine data are available for CHMS cycles 1 (2007-2009), 2 (2009-2011) and 3 (2012-2013). Field collection has been completed for cycle 4 (2014-2015), with cycle 5 (2016-2017) in progress and cycle 6 planning (2018-2019) being finalized. Biomonitoring results for 279 chemicals are expected over the six cycles of the CHMS (220 in individual blood, urine or hair samples, and 59 in pooled serum samples). The chemicals include metals and trace elements, polychlorinated biphenyls (PCBs), organochlorines, flame retardants, perfluoroalkyl substances, volatile organic compounds (VOCs) and metabolites, environmental phenols, triclocarban, acrylamide, pesticides (e.g., triazines, carbamates, organophosphates, phenoxy, pyrethroids) and/or their metabolites, chlorophenols, polycyclic aromatic hydrocarbon (PAH) metabolites, phthalates and alternate plasticizer metabolites, and tobacco biomarkers. Approximately one half of the chemicals measured in individual blood and urine samples over the first three cycles were detected in more than 60% of samples. CHMS biomonitoring data have been used to establish baseline HBM concentrations in Canadians; inform public health, regulatory risk

A pilot study on the feasibility of European harmonized human biomonitoring: Strategies towards a common approach, challenges and opportunities.

PubMed

Casteleyn, L; Dumez, B; Becker, K; Kolossa-Gehring, M; Den Hond, E; Schoeters, G; Castaño, A; Koch, H M; Angerer, J; Esteban, M; Exley, K; Sepai, O; Bloemen, L; Horvat, M; Knudsen, L E; Joas, A; Joas, R; Biot, P; Koppen, G; Dewolf, M-C; Katsonouri, A; Hadjipanayis, A; Cerná, M; Krsková, A; Schwedler, G; Fiddicke, U; Nielsen, J K S; Jensen, J F; Rudnai, P; Közepésy, S; Mulcahy, M; Mannion, R; Gutleb, A C; Fischer, M E; Ligocka, D; Jakubowski, M; Reis, M F; Namorado, S; Lupsa, I-R; Gurzau, A E; Halzlova, K; Jajcaj, M; Mazej, D; Tratnik Snoj, J; Posada, M; López, E; Berglund, M; Larsson, K; Lehmann, A; Crettaz, P; Aerts, D

2015-08-01

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother-child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).(1) Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop

Human biomonitoring in Israel: Recent results and lessons learned.

PubMed

Berman, Tamar; Goldsmith, Rebecca; Levine, Hagai; Grotto, Itamar

2017-03-01

The use of human biomonitoring (HBM) as a tool for environmental health policy and research is developing rapidly in Israel. Despite challenges in securing political and financial support for HBM, the Ministry of Health has initiated national HBM studies and has utilized HBM data in environmental health policy decision making. Currently, the Ministry of Health is collecting urine samples from children and adults in the framework of the National Health and Nutrition Study (MABAT), with the goal of ongoing surveillance of population exposure to pesticides and environmental tobacco smoke, and of combining HBM data with data on diet and health behavior. In academic research studies in Israel, biomarkers are used increasingly in environmental epidemiology, including in three active birth cohort studies on adverse health effects of phthalates, brominated flame retardants, and organophosphate pesticides. Future Ministry of Health goals include establishing HBM analytical capabilities, developing a long term national HBM plan for Israel and participating in the proposed HBM4EU project in order to improve data harmonization. One of the lessons learned in Israel is that even in the absence of a formal HBM program, it is possible to collect meaningful HBM data and use it in an ad hoc fashion to support environmental health policy. Copyright © 2016 Elsevier GmbH. All rights reserved.

Correcting for the influence of sampling conditions on biomarkers of exposure to phenols and phthalates: a 2-step standardization method based on regression residuals.

PubMed

Mortamais, Marion; Chevrier, Cécile; Philippat, Claire; Petit, Claire; Calafat, Antonia M; Ye, Xiaoyun; Silva, Manori J; Brambilla, Christian; Eijkemans, Marinus J C; Charles, Marie-Aline; Cordier, Sylvaine; Slama, Rémy

2012-04-26

Environmental epidemiology and biomonitoring studies typically rely on biological samples to assay the concentration of non-persistent exposure biomarkers. Between-participant variations in sampling conditions of these biological samples constitute a potential source of exposure misclassification. Few studies attempted to correct biomarker levels for this error. We aimed to assess the influence of sampling conditions on concentrations of urinary biomarkers of select phenols and phthalates, two widely-produced families of chemicals, and to standardize biomarker concentrations on sampling conditions. Urine samples were collected between 2002 and 2006 among 287 pregnant women from Eden and Pélagie cohorts, from which phthalates and phenols metabolites levels were assayed. We applied a 2-step standardization method based on regression residuals. First, the influence of sampling conditions (including sampling hour, duration of storage before freezing) and of creatinine levels on biomarker concentrations were characterized using adjusted linear regression models. In the second step, the model estimates were used to remove the variability in biomarker concentrations due to sampling conditions and to standardize concentrations as if all samples had been collected under the same conditions (e.g., same hour of urine collection). Sampling hour was associated with concentrations of several exposure biomarkers. After standardization for sampling conditions, median concentrations differed by--38% for 2,5-dichlorophenol to +80 % for a metabolite of diisodecyl phthalate. However, at the individual level, standardized biomarker levels were strongly correlated (correlation coefficients above 0.80) with unstandardized measures. Sampling conditions, such as sampling hour, should be systematically collected in biomarker-based studies, in particular when the biomarker half-life is short. The 2-step standardization method based on regression residuals that we proposed in order to

Biomarkers of benzene exposure and their interpretation for human health risk assessment

EPA Science Inventory

Human biomarkers of exposure such as parent or metabolite concentrations in blood or urine are often reported without any context to the sources of exposure or the implications for human risk. The Biomonitoring Technical Committee of the International Life Sciences Institute/Huma...

A proposed framework for the interpretation of biomonitoring data

PubMed Central

Boogaard, Peter J; Money, Chris D

2008-01-01

Biomonitoring, the determination of chemical substances in human body fluids or tissues, is more and more frequently applied. At the same time detection limits are decreasing steadily. As a consequence, many data with potential relevance for public health are generated although they need not necessarily allow interpretation in term of health relevance. The European Centre of Ecotoxicology and Toxicology of Chemicals (ECETOC) formed a dedicated task force to build a framework for the interpretation of biomonitoring data. The framework that was developed evaluates biomonitoring data based on their analytical integrity, their ability to describe dose (toxicokinetics), their ability to relate to effects, and an overall evaluation and weight of evidence analysis. This framework was subsequently evaluated with a number of case studies and was shown to provide a rational basis to advance discussions on human biomonitoring allowing better use and application of this type of data in human health risk assessment. PMID:18541066

Screening of seaweeds in the East China Sea as potential bio-monitors of heavy metals.

PubMed

Pan, Yaoru; Wernberg, Thomas; de Bettignies, Thibaut; Holmer, Marianne; Li, Ke; Wu, Jiaping; Lin, Fang; Yu, Yan; Xu, Jiang; Zhou, Chaosheng; Huang, Zhixing; Xiao, Xi

2018-06-01

Seaweeds are good bio-monitors of heavy metal pollution and have been included in European coastal monitoring programs. However, data for seaweed species in China are scarce or missing. In this study, we explored the potential of seaweeds as bio-monitor by screening the natural occurring seaweeds in the "Kingdom of seaweed and shellfish" at Dongtou Islands, the East China Sea. Totally, 12 seaweed species were collected from six sites, with richness following the sequence of Rhodophyta > Phaeophyta > Chlorophyta. The concentration of heavy metals (Cu, Cr, Ni, Zn, Pb, Cd, As) in the seaweeds was determined, and the bioaccumulation coefficient was calculated. A combination of four seaweeds, Pachydictyon coriaceum, Gelidium divaricatum, Sargassum thunbergii, and Pterocladiella capillacea, were proposed as bio-monitors due to their high bioaccumulation capabilities of specific heavy metals in the East China Sea and hence hinted the importance of using seaweed community for monitoring of pollution rather than single species. Our results provide first-hand data for the selection of bio-monitor species for heavy metals in the East China Sea and contribute to selection of cosmopolitan bio-monitor communities over geographical large area, which will benefit the establishment of monitoring programs for coastal heavy metal contamination.

Advancing environmental health surveillance in the US through a national human biomonitoring network.

PubMed

Latshaw, Megan Weil; Degeberg, Ruhiyyih; Patel, Surili Sutaria; Rhodes, Blaine; King, Ewa; Chaudhuri, Sanwat; Nassif, Julianne

2017-03-01

The United States lacks a comprehensive, nationally-coordinated, state-based environmental health surveillance system. This lack of infrastructure leads to: • varying levels of understanding of chemical exposures at the state & local levels • often inefficient public health responses to chemical exposure emergencies (such as those that occurred in the Flint drinking water crisis, the Gold King mine spill, the Elk river spill and the Gulf Coast oil spill) • reduced ability to measure the impact of public health interventions or environmental policies • less efficient use of resources for cleaning up environmental contamination Establishing the National Biomonitoring Network serves as a step toward building a national, state-based environmental health surveillance system. The Network builds upon CDC investments in emergency preparedness and environmental public health tracking, which have created advanced chemical analysis and information sharing capabilities in the state public health systems. The short-term goal of the network is to harmonize approaches to human biomonitoring in the US, thus increasing the comparability of human biomonitoring data across states and communities. The long-term goal is to compile baseline data on exposures at the state level, similar to data found in CDC's National Report on Human Exposure to Environmental Chemicals. Barriers to success for this network include: available resources, effective risk communication strategies, data comparability & sharing, and political will. Anticipated benefits include high quality data on which to base public health and environmental decisions, data with which to assess the success of public health interventions, improved risk assessments for chemicals, and new ways to prioritize environmental health research. Copyright © 2016 Elsevier GmbH. All rights reserved.

Seasonal variations of gene expression biomarkers in Mytilus galloprovincialis cultured populations: temperature, oxidative stress and reproductive cycle as major modulators.

PubMed

Jarque, Sergio; Prats, Eva; Olivares, Alba; Casado, Marta; Ramón, Montserrat; Piña, Benjamin

2014-11-15

The blue mussel Mytilus galloprovincialis has been used as monitoring organism in many biomonitoring programs because of its broad distribution in South European sea waters and its physiological characteristics. Different pollution-stress biomarkers, including gene expression biomarkers, have been developed to determine its physiological response to the presence of different pollutants. However, the existing information about basal expression profiles is very limited, as very few biomarker-based studies were designed to reflect the natural seasonal variations. In the present study, we analyzed the natural expression patterns of several genes commonly used in biomonitoring, namely ferritin, metallothionein, cytochrome P450, glutathione S-transferase, heat shock protein and the kinase responsive to stress KRS, during an annual life cycle. Analysis of mantle-gonad samples of cultured populations of M. galloprovincialis from the Delta del Ebro (North East Spain) showed natural seasonal variability of these biomarkers, pointing to temperature and oxidative stress as major abiotic modulators. In turn, the reproductive cycle, a process that can be tracked by VCLM7 expression, and known to be influenced by temperature, seems to be the major biotic factor involved in seasonality. Our results illustrate the influence of environmental factors in the physiology of mussels through their annual cycle, a crucial information for the correct interpretation of responses under stress conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Environmental health and justice and the right to research: institutional review board denials of community-based chemical biomonitoring of breast milk.

PubMed

Saxton, Dvera I; Brown, Phil; Seguinot-Medina, Samarys; Eckstein, Lorraine; Carpenter, David O; Miller, Pamela; Waghiyi, Vi

2015-11-25

Recently, conflicts and challenges have emerged regarding environmental justice and research ethics for some indigenous communities. Alaska Community Action on Toxics (ACAT) responded to community requests for breast milk biomonitoring and conceived the Breast Milk Pilot Study (BMPS). Despite having community support and federal and private funding, the BMPS remains incomplete due to repeated disapprovals by the Alaska Area IRB (Institutional Review Board). In this commentary, we explore the consequences of years of IRB denials, in terms of health inequalities, environmental justice, and research ethics. We highlight the greater significance of this story with respect to research in Alaska Native communities, biomonitoring, and global toxics regulation. We offer suggestions to community-based researchers conducting biomonitoring projects on how to engage with IRBs in order to cultivate reflective, context-based research ethics that better consider the needs and concerns of communities.

Biological Matrix Effects in Quantitative Tandem Mass Spectrometry-Based Analytical Methods: Advancing Biomonitoring

PubMed Central

Panuwet, Parinya; Hunter, Ronald E.; D’Souza, Priya E.; Chen, Xianyu; Radford, Samantha A.; Cohen, Jordan R.; Marder, M. Elizabeth; Kartavenka, Kostya; Ryan, P. Barry; Barr, Dana Boyd

2015-01-01

The ability to quantify levels of target analytes in biological samples accurately and precisely, in biomonitoring, involves the use of highly sensitive and selective instrumentation such as tandem mass spectrometers and a thorough understanding of highly variable matrix effects. Typically, matrix effects are caused by co-eluting matrix components that alter the ionization of target analytes as well as the chromatographic response of target analytes, leading to reduced or increased sensitivity of the analysis. Thus, before the desired accuracy and precision standards of laboratory data are achieved, these effects must be characterized and controlled. Here we present our review and observations of matrix effects encountered during the validation and implementation of tandem mass spectrometry-based analytical methods. We also provide systematic, comprehensive laboratory strategies needed to control challenges posed by matrix effects in order to ensure delivery of the most accurate data for biomonitoring studies assessing exposure to environmental toxicants. PMID:25562585

Identifying Chemical Groups for Biomonitoring

PubMed Central

Krowech, Gail; Hoover, Sara; Plummer, Laurel; Sandy, Martha; Zeise, Lauren; Solomon, Gina

2016-01-01

Summary: Regulatory agencies face daunting challenges identifying emerging chemical hazards because of the large number of chemicals in commerce and limited data on exposure and toxicology. Evaluating one chemical at a time is inefficient and can lead to replacement with uncharacterized chemicals or chemicals with structural features already linked to toxicity. The Office of Environmental Health Hazard Assessment (OEHHA) has developed a process for constructing and assessing chemical groups for potential biomonitoring in California. We screen for chemicals with significant exposure potential and propose possible chemical groups, based on structure and function. To support formal consideration of these groups by Biomonitoring California’s Scientific Guidance Panel, we conduct a detailed review of exposure and toxicity data and examine the likelihood of detection in biological samples. To date, 12 chemical groups have been constructed and added to the pool of chemicals that can be selected for Biomonitoring California studies, including p,p´-bisphenols, brominated and chlorinated organic compounds used as flame retardants, non-halogenated aromatic phosphates, and synthetic polycyclic musks. Evaluating chemical groups, rather than individual chemicals, is an efficient way to respond to shifts in chemical use and the emergence of new chemicals. This strategy can enable earlier identification of important chemicals for monitoring and intervention. PMID:27905275

II. Species sensitivity distributions based on biomarkers and whole organism responses for integrated impact and risk assessment criteria.

PubMed

Sanni, Steinar; Lyng, Emily; Pampanin, Daniela M; Smit, Mathijs G D

2017-06-01

The aim of this paper is to bridge gaps between biomarker and whole organism responses related to oil based offshore discharges. These biomarker bridges will facilitate acceptance criteria for biomarker data linked to environmental risk assessment and translate biomarker results to higher order effects. Biomarker based species sensitivity distributions (SSD biomarkers ) have been constructed for relevant groups of biomarkers based on laboratory data from oil exposures. SSD curves express the fraction of species responding to different types of biomarkers. They have been connected to SSDs for whole organism responses (WORs) constructed in order to relate the SSD biomarkers to animal fitness parameters that are commonly used in environmental risk assessment. The resulting SSD curves show that biomarkers and WORs can be linked through their potentially affected fraction of species (PAF) distributions, enhancing the capability to monitor field parameters with better correlation to impact and risk assessment criteria and providing improved chemical/biological integration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomonitoring of air pollution as exemplified by recent IAEA programs.

PubMed

Smodis, B; Parr, R M

1999-01-01

Biomonitoring is an appropriate tool for assessing the levels of atmospheric pollution, having several advantages compared with the use of direct measurements of contaminants (e.g., in airborne particulate matter, atmospheric deposition, precipitation), related primarily to the permanent and common occurrence of the chosen organisms in the field, the ease of sampling, and trace element accumulation. Furthermore, biomonitors may provide a measure of integrated exposure over an extended period of time and are present in remote areas and no expensive technical equipment is involved in collecting them. They accumulate contaminants over the exposure time and concentrate them, thus facilitating analytical measurements. Based on large-scale biomonitoring surveys, polluted areas can be identified, and by applying appropriate statistical tools, information can be obtained on the type of pollution sources and on the transboundary transport of atmospheric pollutants. The International Atomic Energy Agency is including the research on biomonitors in its projects on health-related environmental studies. Biomonitoring activities from several coordinated research projects on air pollution are presented, and results from an international workshop are discussed. In addition, activities in supporting improvement quality in the participating laboratories are outlined.

The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications

PubMed Central

Sonner, Z.; Wilder, E.; Heikenfeld, J.; Kasting, G.; Beyette, F.; Swaile, D.; Sherman, F.; Joyce, J.; Hagen, J.; Kelley-Loughnane, N.; Naik, R.

2015-01-01

Non-invasive and accurate access of biomarkers remains a holy grail of the biomedical community. Human eccrine sweat is a surprisingly biomarker-rich fluid which is gaining increasing attention. This is especially true in applications of continuous bio-monitoring where other biofluids prove more challenging, if not impossible. However, much confusion on the topic exists as the microfluidics of the eccrine sweat gland has never been comprehensively presented and models of biomarker partitioning into sweat are either underdeveloped and/or highly scattered across literature. Reported here are microfluidic models for eccrine sweat generation and flow which are coupled with review of blood-to-sweat biomarker partition pathways, therefore providing insights such as how biomarker concentration changes with sweat flow rate. Additionally, it is shown that both flow rate and biomarker diffusion determine the effective sampling rate of biomarkers at the skin surface (chronological resolution). The discussion covers a broad class of biomarkers including ions (Na+, Cl−, K+, NH4+), small molecules (ethanol, cortisol, urea, and lactate), and even peptides or small proteins (neuropeptides and cytokines). The models are not meant to be exhaustive for all biomarkers, yet collectively serve as a foundational guide for further development of sweat-based diagnostics and for those beginning exploration of new biomarker opportunities in sweat. PMID:26045728

Pollution gets personal! A first population-based human biomonitoring study in Austria.

PubMed

Hohenblum, Philipp; Steinbichl, Philipp; Raffesberg, Wolfgang; Weiss, Stefan; Moche, Wolfgang; Vallant, Birgit; Scharf, Sigrid; Haluza, Daniela; Moshammer, Hanns; Kundi, Michael; Piegler, Brigitte; Wallner, Peter; Hutter, Hans-Peter

2012-02-01

Humans are exposed to a broad variety of man-made chemicals. Human biomonitoring (HBM) data reveal the individual body burden irrespective of sources and routes of uptake. A first population-based study was started in Austria in 2008 and was finished at the end of May 2011. This cross sectional study aims at documenting the extent, the distribution and the determinants of human exposure to industrial chemicals as well as proving the feasibility of a representative HBM study. Overall, 150 volunteers (50 families) were selected by stratified random sampling. Exposure to phthalates, trisphosphates, polybrominated diphenyl ethers (PBDE), bisphenol A (along with nonyl- and octyl phenol) and methyl mercury was assessed. Sixteen of 18 PBDE determined were detected above the limit of quantification (LOQ) in blood samples with #153 and #197 the most abundant species. Bisphenol A in urine was measured in a subsample of 25 with only 4 samples found above the LOQ. In 3 of 100 urine samples at least one of 8 trisphosphate compounds assessed was above the LOQ. These first analytical results of the human biomonitoring data show that the body burden of the Austrian population with respect to the assessed compounds is comparable to or even lower than in other European countries. Overall, the study revealed that in order to develop a feasible protocol for representative human biomonitoring studies procedures have to be optimized to allow for non-invasive sampling of body tissues in accordance with the main metabolic pathways. Procedures of participants' recruitment were, however, labor intensive and have to be improved. Copyright © 2011 Elsevier GmbH. All rights reserved.

BIOMONITORING OF EXPOSURE IN FARMWORKER STUDIES

EPA Science Inventory

Though biomonitoring has been used in many occupational and environmental health and exposure studies, we are only beginning to understand the complexities and uncertainties involved with the biomonitoring process -- from study design, to sample collection, to chemical analysis -...

The Ontario Benthos Biomonitoring Network

Treesearch

Chris Jones; Brian Craig; Nicole Dmytrow

2006-01-01

Canada’s Ontario Ministry of the Environment and Environment Canada (Ecological Monitoring and Assessment Network) are developing an aquatic macroinvertebrate biomonitoring network for Ontario’s lakes, streams, and wetlands. We are building the program, called the Ontario Benthos Biomonitoring Network (OBBN), on the principles of partnership, free data sharing, and...

Design of a novel class of protein-based magnetic resonance imaging contrast agents for the molecular imaging of cancer biomarkers

PubMed Central

Xue, Shenghui; Qiao, Jingjuan; Pu, Fan; Cameron, Mathew; Yang, Jenny J.

2014-01-01

Magnetic resonance imaging (MRI) of disease biomarkers, especially cancer biomarkers, could potentially improve our understanding of the disease and drug activity during preclinical and clinical drug treatment and patient stratification. MRI contrast agents with high relaxivity and targeting capability to tumor biomarkers are highly required. Extensive work has been done to develop MRI contrast agents. However, only a few limited literatures report that protein residues can function as ligands to bind Gd3+ with high binding affinity, selectivity, and relaxivity. In this paper, we focus on reporting our current progress on designing a novel class of protein-based Gd3+ MRI contrast agents (ProCAs) equipped with several desirable capabilities for in vivo application of MRI of tumor biomarkers. We will first discuss our strategy for improving the relaxivity by a novel protein-based design. We then discuss the effect of increased relaxivity of ProCAs on improving the detection limits for MRI contrast agent, especially for in vivo application. We will further report our efforts to improve in vivo imaging capability and our achievement in molecular imaging of cancer biomarkers with potential preclinical and clinical applications. PMID:23335551

Societal and ethical issues in human biomonitoring--a view from science studies.

PubMed

Bauer, Susanne

2008-06-05

Human biomonitoring (HBM) has rapidly gained importance. In some epidemiological studies, the measurement and use of biomarkers of exposure, susceptibility and disease have replaced traditional environmental indicators. While in HBM, ethical issues have mostly been addressed in terms of informed consent and confidentiality, this paper maps out a larger array of societal issues from an epistemological perspective, i.e. bringing into focus the conditions of how and what is known in environmental health science. In order to analyse the effects of HBM and the shift towards biomarker research in the assessment of environmental pollution in a broader societal context, selected analytical frameworks of science studies are introduced. To develop the epistemological perspective, concepts from "biomedical platform sociology" and the notion of "epistemic cultures" and "thought styles" are applied to the research infrastructures of HBM. Further, concepts of "biocitizenship" and "civic epistemologies" are drawn upon as analytical tools to discuss the visions and promises of HBM as well as related ethical problematisations. In human biomonitoring, two different epistemological cultures meet; these are environmental science with for instance pollution surveys and toxicological assessments on the one hand, and analytical epidemiology investigating the association between exposure and disease in probabilistic risk estimation on the other hand. The surveillance of exposure and dose via biomarkers as envisioned in HBM is shifting the site of exposure monitoring to the human body. Establishing an HBM platform faces not only the need to consider individual decision autonomy as an ethics issue, but also larger epistemological and societal questions, such as the mode of evidence demanded in science, policy and regulation. The shift of exposure monitoring towards the biosurveillance of human populations involves fundamental changes in the ways environment, health and disease are

Integrated pipeline for mass spectrometry-based discovery and confirmation of biomarkers demonstrated in a mouse model of breast cancer.

PubMed

Whiteaker, Jeffrey R; Zhang, Heidi; Zhao, Lei; Wang, Pei; Kelly-Spratt, Karen S; Ivey, Richard G; Piening, Brian D; Feng, Li-Chia; Kasarda, Erik; Gurley, Kay E; Eng, Jimmy K; Chodosh, Lewis A; Kemp, Christopher J; McIntosh, Martin W; Paulovich, Amanda G

2007-10-01

Despite their potential to impact diagnosis and treatment of cancer, few protein biomarkers are in clinical use. Biomarker discovery is plagued with difficulties ranging from technological (inability to globally interrogate proteomes) to biological (genetic and environmental differences among patients and their tumors). We urgently need paradigms for biomarker discovery. To minimize biological variation and facilitate testing of proteomic approaches, we employed a mouse model of breast cancer. Specifically, we performed LC-MS/MS of tumor and normal mammary tissue from a conditional HER2/Neu-driven mouse model of breast cancer, identifying 6758 peptides representing >700 proteins. We developed a novel statistical approach (SASPECT) for prioritizing proteins differentially represented in LC-MS/MS datasets and identified proteins over- or under-represented in tumors. Using a combination of antibody-based approaches and multiple reaction monitoring-mass spectrometry (MRM-MS), we confirmed the overproduction of multiple proteins at the tissue level, identified fibulin-2 as a plasma biomarker, and extensively characterized osteopontin as a plasma biomarker capable of early disease detection in the mouse. Our results show that a staged pipeline employing shotgun-based comparative proteomics for biomarker discovery and multiple reaction monitoring for confirmation of biomarker candidates is capable of finding novel tissue and plasma biomarkers in a mouse model of breast cancer. Furthermore, the approach can be extended to find biomarkers relevant to human disease.

Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery

PubMed Central

Gold, Larry; Ayers, Deborah; Bertino, Jennifer; Bock, Christopher; Bock, Ashley; Brody, Edward N.; Carter, Jeff; Dalby, Andrew B.; Eaton, Bruce E.; Fitzwater, Tim; Flather, Dylan; Forbes, Ashley; Foreman, Trudi; Fowler, Cate; Gawande, Bharat; Goss, Meredith; Gunn, Magda; Gupta, Shashi; Halladay, Dennis; Heil, Jim; Heilig, Joe; Hicke, Brian; Husar, Gregory; Janjic, Nebojsa; Jarvis, Thale; Jennings, Susan; Katilius, Evaldas; Keeney, Tracy R.; Kim, Nancy; Koch, Tad H.; Kraemer, Stephan; Kroiss, Luke; Le, Ngan; Levine, Daniel; Lindsey, Wes; Lollo, Bridget; Mayfield, Wes; Mehan, Mike; Mehler, Robert; Nelson, Sally K.; Nelson, Michele; Nieuwlandt, Dan; Nikrad, Malti; Ochsner, Urs; Ostroff, Rachel M.; Otis, Matt; Parker, Thomas; Pietrasiewicz, Steve; Resnicow, Daniel I.; Rohloff, John; Sanders, Glenn; Sattin, Sarah; Schneider, Daniel; Singer, Britta; Stanton, Martin; Sterkel, Alana; Stewart, Alex; Stratford, Suzanne; Vaught, Jonathan D.; Vrkljan, Mike; Walker, Jeffrey J.; Watrobka, Mike; Waugh, Sheela; Weiss, Allison; Wilcox, Sheri K.; Wolfson, Alexey; Wolk, Steven K.; Zhang, Chi; Zichi, Dom

2010-01-01

Background The interrogation of proteomes (“proteomics”) in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine. Methodology/Principal Findings We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (∼100 fM–1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states. Conclusions/Significance We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of

Aptamer-based multiplexed proteomic technology for biomarker discovery.

PubMed

Gold, Larry; Ayers, Deborah; Bertino, Jennifer; Bock, Christopher; Bock, Ashley; Brody, Edward N; Carter, Jeff; Dalby, Andrew B; Eaton, Bruce E; Fitzwater, Tim; Flather, Dylan; Forbes, Ashley; Foreman, Trudi; Fowler, Cate; Gawande, Bharat; Goss, Meredith; Gunn, Magda; Gupta, Shashi; Halladay, Dennis; Heil, Jim; Heilig, Joe; Hicke, Brian; Husar, Gregory; Janjic, Nebojsa; Jarvis, Thale; Jennings, Susan; Katilius, Evaldas; Keeney, Tracy R; Kim, Nancy; Koch, Tad H; Kraemer, Stephan; Kroiss, Luke; Le, Ngan; Levine, Daniel; Lindsey, Wes; Lollo, Bridget; Mayfield, Wes; Mehan, Mike; Mehler, Robert; Nelson, Sally K; Nelson, Michele; Nieuwlandt, Dan; Nikrad, Malti; Ochsner, Urs; Ostroff, Rachel M; Otis, Matt; Parker, Thomas; Pietrasiewicz, Steve; Resnicow, Daniel I; Rohloff, John; Sanders, Glenn; Sattin, Sarah; Schneider, Daniel; Singer, Britta; Stanton, Martin; Sterkel, Alana; Stewart, Alex; Stratford, Suzanne; Vaught, Jonathan D; Vrkljan, Mike; Walker, Jeffrey J; Watrobka, Mike; Waugh, Sheela; Weiss, Allison; Wilcox, Sheri K; Wolfson, Alexey; Wolk, Steven K; Zhang, Chi; Zichi, Dom

2010-12-07

The interrogation of proteomes ("proteomics") in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (~100 fM-1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states. We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.

Policy recommendations and cost implications for a more sustainable framework for European human biomonitoring surveys.

PubMed

Joas, Anke; Knudsen, Lisbeth E; Kolossa-Gehring, Marike; Sepai, Ovnair; Casteleyn, Ludwine; Schoeters, Greet; Angerer, Jürgen; Castaño, Argelia; Aerts, Dominique; Biot, Pierre; Horvat, Milena; Bloemen, Louis; Reis, M Fátima; Lupsa, Ioana-Rodica; Katsonouri, Andromachi; Cerna, Milena; Berglund, Marika; Crettaz, Pierre; Rudnai, Peter; Halzlova, Katarina; Mulcahy, Maurice; Gutleb, Arno C; Fischer, Marc E; Becher, Georg; Fréry, Nadine; Jensen, Genon; Van Vliet, Lisette; Koch, Holger M; Den Hond, Elly; Fiddicke, Ulrike; Esteban, Marta; Exley, Karen; Schwedler, Gerda; Seiwert, Margarete; Ligocka, Danuta; Hohenblum, Philipp; Kyrtopoulos, Soterios; Botsivali, Maria; DeFelip, Elena; Guillou, Claude; Reniero, Fabiano; Grazuleviciene, Regina; Veidebaum, Toomas; Mørck, Thit A; Nielsen, Jeanette K S; Jensen, Janne F; Rivas, Teresa C; Sanchez, Jinny; Koppen, Gudrun; Smolders, Roel; Kozepesy, Szilvia; Hadjipanayis, Adamos; Krskova, Andrea; Mannion, Rory; Jakubowski, Marek; Fucic, J Aleksandra; Pereira-Miguel, Jose; Gurzau, Anca E; Jajcaj, Michal; Mazej, Darja; Tratnik, Janja Snoj; Lehmann, Andrea; Larsson, Kristin; Dumez, Birgit; Joas, Reinhard

2015-08-01

The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES. Copyright © 2014 Elsevier Inc. All rights reserved.

I: Biomarker quantification in fish exposed to crude oil as input to species sensitivity distributions and threshold values for environmental monitoring.

PubMed

Sanni, Steinar; Björkblom, Carina; Jonsson, Henrik; Godal, Brit F; Liewenborg, Birgitta; Lyng, Emily; Pampanin, Daniela M

2017-04-01

The aim of this study was to determine a suitable set of biomarker based methods for environmental monitoring in sub-arctic and temperate offshore areas using scientific knowledge on the sensitivity of fish species to dispersed crude oil. Threshold values for environmental monitoring and risk assessment were obtained based on a quantitative comparison of biomarker responses. Turbot, halibut, salmon and sprat were exposed for up to 8 weeks to five different sub-lethal concentrations of dispersed crude oil. Biomarkers assessing PAH metabolites, oxidative stress, detoxification system I activity, genotoxicity, immunotoxicity, endocrine disruption, general cellular stress and histological changes were measured. Results showed that PAH metabolites, CYP1A/EROD, DNA adducts and histopathology rendered the most robust results across the different fish species, both in terms of sensitivity and dose-responsiveness. The reported results contributed to forming links between biomonitoring and risk assessment procedures by using biomarker species sensitivity distributions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Owls as biomonitors of environmental contamination

Treesearch

Steven R. Sheffield

1997-01-01

Much like the caged canary used by miners, a plethora of wildlife species have been promoted as biomonitors of environmental contamination. These species provide an "early warning system" for toxic contaminants in the environment. Species promoted as useful biomonitors share many common life history characters, such as wide distribution, territorial, non-...

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

PubMed

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.

Mass spectrometry-assisted gel-based proteomics in cancer biomarker discovery: approaches and application

PubMed Central

Huang, Rongrong; Chen, Zhongsi; He, Lei; He, Nongyue; Xi, Zhijiang; Li, Zhiyang; Deng, Yan; Zeng, Xin

2017-01-01

There is a critical need for the discovery of novel biomarkers for early detection and targeted therapy of cancer, a major cause of deaths worldwide. In this respect, proteomic technologies, such as mass spectrometry (MS), enable the identification of pathologically significant proteins in various types of samples. MS is capable of high-throughput profiling of complex biological samples including blood, tissues, urine, milk, and cells. MS-assisted proteomics has contributed to the development of cancer biomarkers that may form the foundation for new clinical tests. It can also aid in elucidating the molecular mechanisms underlying cancer. In this review, we discuss MS principles and instrumentation as well as approaches in MS-based proteomics, which have been employed in the development of potential biomarkers. Furthermore, the challenges in validation of MS biomarkers for their use in clinical practice are also reviewed. PMID:28912895

Societal and ethical issues in human biomonitoring – a view from science studies

PubMed Central

Bauer, Susanne

2008-01-01

Background Human biomonitoring (HBM) has rapidly gained importance. In some epidemiological studies, the measurement and use of biomarkers of exposure, susceptibility and disease have replaced traditional environmental indicators. While in HBM, ethical issues have mostly been addressed in terms of informed consent and confidentiality, this paper maps out a larger array of societal issues from an epistemological perspective, i.e. bringing into focus the conditions of how and what is known in environmental health science. Methods In order to analyse the effects of HBM and the shift towards biomarker research in the assessment of environmental pollution in a broader societal context, selected analytical frameworks of science studies are introduced. To develop the epistemological perspective, concepts from "biomedical platform sociology" and the notion of "epistemic cultures" and "thought styles" are applied to the research infrastructures of HBM. Further, concepts of "biocitizenship" and "civic epistemologies" are drawn upon as analytical tools to discuss the visions and promises of HBM as well as related ethical problematisations. Results In human biomonitoring, two different epistemological cultures meet; these are environmental science with for instance pollution surveys and toxicological assessments on the one hand, and analytical epidemiology investigating the association between exposure and disease in probabilistic risk estimation on the other hand. The surveillance of exposure and dose via biomarkers as envisioned in HBM is shifting the site of exposure monitoring to the human body. Establishing an HBM platform faces not only the need to consider individual decision autonomy as an ethics issue, but also larger epistemological and societal questions, such as the mode of evidence demanded in science, policy and regulation. Conclusion The shift of exposure monitoring towards the biosurveillance of human populations involves fundamental changes in the ways

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

PubMed Central

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

2017-01-01

Abstract 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. PMID:28977523

Tissue-based biomarkers in prostate cancer

PubMed Central

Clinton, Timothy N.; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Raj, Ganesh V; Woldu, Solomon L

2017-01-01

Introduction Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas Covered The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy. Additionally, some of the obstacles to the widespread adoption of these biomarkers and discuss several investigational sources of new biomarkers are discussed. Expert Commentary Work is ongoing to answer pertinent clinical questions in prostate cancer management including which patients should undergo biopsy, active surveillance, receive adjuvant therapy, and what systemic therapy is best in the first-line. Incorporation into novel biomarkers may allow for the incorporation of a ‘personalized’ approach to management. Further validation will be required and questions of cost must be considered before wide scale adoption of these biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques. PMID:29226251

Surface-Enhanced Raman Scattering-Based Immunoassay Technologies for Detection of Disease Biomarkers

PubMed Central

Smolsky, Joseph; Kaur, Sukhwinder; Hayashi, Chihiro; Batra, Surinder K.; Krasnoslobodtsev, Alexey V.

2017-01-01

Detection of biomarkers is of vital importance in disease detection, management, and monitoring of therapeutic efficacy. Extensive efforts have been devoted to the development of novel diagnostic methods that detect and quantify biomarkers with higher sensitivity and reliability, contributing to better disease diagnosis and prognosis. When it comes to such devastating diseases as cancer, these novel powerful methods allow for disease staging as well as detection of cancer at very early stages. Over the past decade, there have been some advances in the development of platforms for biomarker detection of diseases. The main focus has recently shifted to the development of simple and reliable diagnostic tests that are inexpensive, accurate, and can follow a patient’s disease progression and therapy response. The individualized approach in biomarker detection has been also emphasized with detection of multiple biomarkers in body fluids such as blood and urine. This review article covers the developments in Surface-Enhanced Raman Scattering (SERS) and related technologies with the primary focus on immunoassays. Limitations and advantages of the SERS-based immunoassay platform are discussed. The article thoroughly describes all components of the SERS immunoassay and highlights the superior capabilities of SERS readout strategy such as high sensitivity and simultaneous detection of a multitude of biomarkers. Finally, it introduces recently developed strategies for in vivo biomarker detection using SERS. PMID:28085088

Pathway mapping and development of disease-specific biomarkers: protein-based network biomarkers

PubMed Central

Chen, Hao; Zhu, Zhitu; Zhu, Yichun; Wang, Jian; Mei, Yunqing; Cheng, Yunfeng

2015-01-01

It is known that a disease is rarely a consequence of an abnormality of a single gene, but reflects the interactions of various processes in a complex network. Annotated molecular networks offer new opportunities to understand diseases within a systems biology framework and provide an excellent substrate for network-based identification of biomarkers. The network biomarkers and dynamic network biomarkers (DNBs) represent new types of biomarkers with protein–protein or gene–gene interactions that can be monitored and evaluated at different stages and time-points during development of disease. Clinical bioinformatics as a new way to combine clinical measurements and signs with human tissue-generated bioinformatics is crucial to translate biomarkers into clinical application, validate the disease specificity, and understand the role of biomarkers in clinical settings. In this article, the recent advances and developments on network biomarkers and DNBs are comprehensively reviewed. How network biomarkers help a better understanding of molecular mechanism of diseases, the advantages and constraints of network biomarkers for clinical application, clinical bioinformatics as a bridge to the development of diseases-specific, stage-specific, severity-specific and therapy predictive biomarkers, and the potentials of network biomarkers are also discussed. PMID:25560835

Fish bioaccumulation and biomarkers in environmental risk assessment: a review.

PubMed

van der Oost, Ron; Beyer, Jonny; Vermeulen, Nico P E

2003-02-01

. All fish biomarkers are evaluated for their potential use in ERA programs, based upon six criteria that have been proposed in the present paper. This evaluation demonstrates that phase I enzymes (e.g. hepatic EROD and CYP1A), biotransformation products (e.g. biliary PAH metabolites), reproductive parameters (e.g. plasma VTG) and genotoxic parameters (e.g. hepatic DNA adducts) are currently the most valuable fish biomarkers for ERA. The use of biomonitoring methods in the control strategies for chemical pollution has several advantages over chemical monitoring. Many of the biological measurements form the only way of integrating effects on a large number of individual and interactive processes in aquatic organisms. Moreover, biological and biochemical effects may link the bioavailability of the compounds of interest with their concentration at target organs and intrinsic toxicity. The limitations of biomonitoring, such as confounding factors that are not related to pollution, should be carefully considered when interpreting biomarker data. Based upon this overview there is little doubt that measurements of bioaccumulation and biomarker responses in fish from contaminated sites offer great promises for providing information that can contribute to environmental monitoring programs designed for various aspects of ERA.

Development of biomonitoring equivalents for barium in urine and plasma for interpreting human biomonitoring data.

PubMed

Poddalgoda, Devika; Macey, Kristin; Assad, Henry; Krishnan, Kannan

2017-06-01

The objectives of the present work were: (1) to assemble population-level biomonitoring data to identify the concentrations of urinary and plasma barium across the general population; and (2) to derive biomonitoring equivalents (BEs) for barium in urine and plasma in order to facilitate the interpretation of barium concentrations in the biological matrices. In population level biomonitoring studies, barium has been measured in urine in the U.S. (NHANES study), but no such data on plasma barium levels were identified. The BE values for plasma and urine were derived from U.S. EPA's reference dose (RfD) of 0.2 mg/kg bw/d, based on a lower confidence limit on the benchmark dose (BMDL 05 ) of 63 mg/kg bw/d. The plasma BE (9 μg Ba/L) was derived by regression analysis of the near-steady-state plasma concentrations associated with the administered doses in animals exposed to barium chloride dihydrate in drinking water for 2-years in a NTP study. Using a human urinary excretion fraction of 0.023, a BE for urinary barium (0.19 mg/L or 0.25 mg/g creatinine) was derived for US EPA's RfD. The median and the 95 th percentile barium urine concentrations of the general population in U.S. are below the BE determined in this study, indicating that the population exposure to inorganic barium is expected to be below the exposure guidance value of 0.2 mg/kg bw/d. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Bio-Monitoring of Ozone by Young Students

ERIC Educational Resources Information Center

Lorenzini, Giacomo; Nali, Cristina

2004-01-01

An educational pilot project on the bio-monitoring of air quality was carried out in the Umbria Region of Central Italy. It involved about 1000 young students (ages 4 to 16) from 42 schools of 16 municipalities in active biomonitoring of tropospheric ozone with bio-indicator sensitive tobacco seedlings. Some 6500 raw biological readings were used…

[New perspectives in monitoring of exposures to carcinogens].

PubMed

Pavanello, Sofia; Lotti, Marcello

2011-01-01

Biomonitoring occupational and environmental exposures to carcinogens is a common practice and several biomarkers have been developed for risk assessment. However, in particular, because of the lack of prospective studies, the place of these biomarkers within the complex scenario of the gene-environment interactions leading to cancer cannot be defined. New opportunities and suggestions for biomonitoring exposures to carcinogens could derive from exploring the exposome, from the results of genomewide association and omic studies. Based on these premises it is possible to envisage personalized biomonitoring procedures, as those already actuated in nutrition and clinical oncology, allowing a better predictivity of biomarkers in the preventive settings.

Cross-sectional biomonitoring study of pesticide exposures in Queensland, Australia, using pooled urine samples.

PubMed

Heffernan, A L; English, K; Toms, Lml; Calafat, A M; Valentin-Blasini, L; Hobson, P; Broomhall, S; Ware, R S; Jagals, P; Sly, P D; Mueller, J F

2016-12-01

A range of pesticides are available in Australia for use in agricultural and domestic settings to control pests, including organophosphate and pyrethroid insecticides, herbicides, and insect repellents, such as N,N-diethyl-meta-toluamide (DEET). The aim of this study was to provide a cost-effective preliminary assessment of background exposure to a range of pesticides among a convenience sample of Australian residents. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n = 24 pools of 100 specimens). Concentrations of urinary pesticide biomarkers were quantified using solid-phase extraction coupled with isotope dilution high-performance liquid chromatography-tandem mass spectrometry. Geometric mean biomarker concentrations ranged from <0.1 to 36.8 ng/mL for organophosphate insecticides, <0.1 to 5.5 ng/mL for pyrethroid insecticides, and <0.1 to 8.51 ng/mL for all other biomarkers with the exception of the DEET metabolite 3-diethylcarbamoyl benzoic acid (4.23 to 850 ng/mL). We observed no association between age and concentration for most biomarkers measured but noted a "U-shaped" trend for five organophosphate metabolites, with the highest concentrations observed in the youngest and oldest age strata, perhaps related to age-specific differences in behavior or physiology. The fact that concentrations of specific and non-specific metabolites of the organophosphate insecticide chlorpyrifos were higher than reported in USA and Canada may relate to differences in registered applications among countries. Additional biomonitoring programs of the general population and focusing on vulnerable populations would improve the exposure assessment and the monitoring of temporal exposure trends as usage patterns of pesticide products in Australia change over time.

Rapid toxicity detection in water quality control utilizing automated multispecies biomonitoring for permanent space stations

NASA Technical Reports Server (NTRS)

Morgan, E. L.; Young, R. C.; Smith, M. D.; Eagleson, K. W.

1986-01-01

The objective of this study was to evaluate proposed design characteristics and applications of automated biomonitoring devices for real-time toxicity detection in water quality control on-board permanent space stations. Simulated tests in downlinking transmissions of automated biomonitoring data to Earth-receiving stations were simulated using satellite data transmissions from remote Earth-based stations.

A real-time biomonitoring system to detect arsenic toxicity by valve movement in freshwater clam Corbicula fluminea.

PubMed

Chen, Wei-Yu; Jou, Li-John; Chen, Suz-Hsin; Liao, Chung-Min

2012-05-01

Arsenic (As) is the element of greatest ecotoxicological concern in aquatic environments. Effective monitoring and diagnosis of As pollution via a biological early warning system is a great challenge for As-affected regions. The purpose of this study was to synthesize water chemistry-based bioavailability and valve daily rhythm in Corbicula fluminea to design a biomonitoring system for detecting waterborne As. We integrated valve daily rhythm dynamic patterns and water chemistry-based Hill dose-response model to build into a programmatic mechanism of inductance-based valvometry technique for providing a rapid and cost-effective dynamic detection system. A LabVIEW graphic control program in a personal computer was employed to demonstrate completely the functional presentation of the present dynamic system. We verified the simulated dissolved As concentrations based on the valve daily rhythm behavior with published experimental data. Generally, the performance of this proposed biomonitoring system demonstrates fairly good applicability to detect waterborne As concentrations when the field As concentrations are less than 1 mg L(-1). We also revealed that the detection times were dependent on As exposure concentrations. This biomonitoring system could particularly provide real-time transmitted information on the waterborne As activity under various aquatic environments. This parsimonious C. fluminea valve rhythm behavior-based real-time biomonitoring system presents a valuable effort to promote the automated biomonitoring and offers early warnings on potential ecotoxicological risks in regions with elevated As exposure concentrations.

Human biomonitoring reference values for some non-persistent chemicals in blood and urine derived from the Canadian Health Measures Survey 2009-2013.

PubMed

Khoury, Cheryl; Werry, Kate; Haines, Douglas; Walker, Mike; Malowany, Morie

2018-05-01

The Canadian Health Measures Survey collects nationally representative human biomonitoring data on a suite of chemicals and their metabolites, including many non-persistent chemicals. Data has been collected on non-persistent chemicals, including acrylamide, chlorophenols, environmental phenols and triclocarban, organophosphate insecticides, phthalates, polycyclic aromatic hydrocarbon, pyrethroid insecticides, and volatile organic compounds from 2009 to 2013. Using a systematic approach building on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry, we derive human biomonitoring reference values (RV 95 s) for these classes of non-persistent chemicals in blood and urine for the general Canadian population. RV 95 s were derived for biomarkers of non-persistent chemicals with widespread detection in Canadians (>66% detection rate). Samples with urinary creatinine levels outside the recommended range of 0.3-3.0 μg/L were excluded. Reference populations were constructed by applying smoking and fasting as exclusion criteria where appropriate. Age and sex were evaluated as possible partitioning criteria and separate RV 95 s were derived for sub-populations in cases where partitioning was deemed necessary. Reference values were derived for 40 biomarkers and represent the first set of RV 95 s for non-persistent chemicals in the general Canadian population. These values provide a measure of the upper margin of background exposure in the general population and can be compared against individual and population human biomonitoring data. RV 95 s can be used to by public health officials to identify individuals with high exposures, and by risk assessors and risk managers to identify atypical exposures or subpopulations with elevated exposures. Crown Copyright © 2018. Published by Elsevier GmbH. All rights reserved.

Newborns health in the Danube Region: Environment, biomonitoring, interventions and economic benefits in a large prospective birth cohort study.

PubMed

Andersen, Zorana J; Sram, Radim J; Ščasný, Milan; Gurzau, Eugen S; Fucic, Aleksandra; Gribaldo, Laura; Rossner, Pavel; Rossnerova, Andrea; Kohlová, Markéta Braun; Máca, Vojtěch; Zvěřinová, Iva; Gajdosova, Dagmar; Moshammer, Hanns; Rudnai, Peter; Knudsen, Lisbeth E

2016-03-01

The EU strategy for the Danube Region addresses numerous challenges including environment, health and socioeconomic disparities. Many old environmental burdens and heavily polluted areas in Europe are located in the Danube Region, consisting of 14 countries, with over 100 million people. Estimating the burden of environmental exposures on early-life health is a growing research area in Europe which has major public health implications, but the data from the Danube Region are largely missing. This review presents an inventory of current environmental challenges, related early-life health risks, and knowledge gaps in the Danube Region, based on publicly available databases, registers, and literature, as a rationale and incentive for a new integrated project. The review also proposes the concept for the project aiming to characterize in utero exposures to multiple environmental factors and estimate their effect on early-life health, evaluate economic impact, as well as identify interventions with a potential to harness social norms to reduce emissions, exposures and health risks in the Danube Region. Experts in environmental epidemiology, human biomonitoring and social science in collaboration with clinicians propose to establish a new large multi-center birth cohort of mother-child pairs from Danube countries, measure biomarkers of exposure and health in biological samples at birth, collect centrally measured climate, air and water pollution data, conduct pre- and postnatal surveys on lifestyle, indoor exposures, noise, occupation, socio-economic status, risk-averting behavior, and preferences; and undertake clinical examinations of children at and after birth. Birth cohort will include at least 2000 newborns per site, and a subset of at least 200 mother-child pairs per site for biomonitoring. Novel biomarkers of exposure, susceptibility, and effect will be applied, to gain better mechanistic insight. Effects of multiple environmental exposures on fetal and child

Reconstructing population exposures to environmental chemicals from biomarkers: challenges and opportunities.

PubMed

Georgopoulos, Panos G; Sasso, Alan F; Isukapalli, Sastry S; Lioy, Paul J; Vallero, Daniel A; Okino, Miles; Reiter, Larry

2009-02-01

A conceptual/computational framework for exposure reconstruction from biomarker data combined with auxiliary exposure-related data is presented, evaluated with example applications, and examined in the context of future needs and opportunities. This framework employs physiologically based toxicokinetic (PBTK) modeling in conjunction with numerical "inversion" techniques. To quantify the value of different types of exposure data "accompanying" biomarker data, a study was conducted focusing on reconstructing exposures to chlorpyrifos, from measurements of its metabolite levels in urine. The study employed biomarker data as well as supporting exposure-related information from the National Human Exposure Assessment Survey (NHEXAS), Maryland, while the MENTOR-3P system (Modeling ENvironment for TOtal Risk with Physiologically based Pharmacokinetic modeling for Populations) was used for PBTK modeling. Recently proposed, simple numerical reconstruction methods were applied in this study, in conjunction with PBTK models. Two types of reconstructions were studied using (a) just the available biomarker and supporting exposure data and (b) synthetic data developed via augmenting available observations. Reconstruction using only available data resulted in a wide range of variation in estimated exposures. Reconstruction using synthetic data facilitated evaluation of numerical inversion methods and characterization of the value of additional information, such as study-specific data that can be collected in conjunction with the biomarker data. Although the NHEXAS data set provides a significant amount of supporting exposure-related information, especially when compared to national studies such as the National Health and Nutrition Examination Survey (NHANES), this information is still not adequate for detailed reconstruction of exposures under several conditions, as demonstrated here. The analysis presented here provides a starting point for introducing improved designs for future

Capsaicinoids, Chloropicrin and Sulfur Mustard: Possibilities for Exposure Biomarkers

PubMed Central

Pesonen, Maija; Vähäkangas, Kirsi; Halme, Mia; Vanninen, Paula; Seulanto, Heikki; Hemmilä, Matti; Pasanen, Markku; Kuitunen, Tapio

2010-01-01

Incapacitating and irritating agents produce temporary disability persisting for hours to days after the exposure. One can be exposed to these agents occupationally in industrial or other working environments. Also general public can be exposed in special circumstances, like industrial accidents or riots. Incapacitating and irritating agents discussed in this review are chloropicrin and capsaicinoids. In addition, we include sulfur mustard, which is an old chemical warfare agent and known to cause severe long-lasting injuries or even death. Chloropicrin that was used as a warfare agent in the World War I is currently used mainly as a pesticide. Capsaicinoids, components of hot pepper plants, are used by police and other law enforcement personnel as riot control agents. Toxicity of these chemicals is associated particularly with the respiratory tract, eyes, and skin. Their acute effects are relatively well known but the knowledge of putative long-term effects is almost non-existent. Also, mechanisms of effects at cellular level are not fully understood. There is a need for further research to get better idea of health risks, particularly of long-term and low-level exposures to these chemicals. For this, exposure biomarkers are essential. Validated exposure biomarkers for capsaicinoids, chloropicrin, and sulfur mustard do not exist so far. Metabolites and macromolecular adducts have been suggested biomarkers for sulfur mustard and these can already be measured qualitatively, but quantitative biomarkers await further development and validation. The purpose of this review is, based on the existing mechanistic and toxicokinetic information, to shed light on the possibilities for developing biomarkers for exposure biomonitoring of these compounds. It is also of interest to find ideas for early effect biomarkers considering the need for studies on subchronic and chronic toxicity. PMID:21833179

Biomonitoring of perfluorinated compounds in a drop of blood.

PubMed

Mao, Pan; Wang, Daojing

2015-06-02

Biomonitoring of pollutants and their metabolites and derivatives using biofluids provides new opportunities for spatiotemporal assessment of human risks to environmental exposures. Perfluorinated compounds (PFCs) have been used widely in industry and pose significant environmental concerns due to their stability and bioaccumulation in humans and animals. However, current methods for extraction and measurement of PFCs require relatively large volumes (over one hundred microliters) of blood samples, and therefore, are not suitable for frequent blood sampling and longitudinal biomonitoring of PFCs. We have developed a new microassay, enabled by our silicon microfluidic chip platform, for analyzing PFCs in small volumes (less than five microliters) of blood. Our assay integrates on-chip solid-phase extraction (SPE) with online nanoflow liquid chromatography-electrospray ionization-mass spectrometry (nanoLC-ESI-MS) detection. We demonstrated high sample recovery, excellent interday and intraday accuracy and precision, and a limit of detection down to 50 femtogram of PFCs, in one microliter of human plasma. We validated our assay performance using pooled human plasma and NIST SRM 1950 samples. Our microfluidic chip-based assay may enable frequent longitudinal biomonitoring of PFCs and other environmental toxins using a finger prick of blood, thereby providing new insights into their bioaccumulation, bioavailability, and toxicity.

Environmental Barcoding: A Next-Generation Sequencing Approach for Biomonitoring Applications Using River Benthos

PubMed Central

Hajibabaei, Mehrdad; Shokralla, Shadi; Zhou, Xin; Singer, Gregory A. C.; Baird, Donald J.

2011-01-01

Timely and accurate biodiversity analysis poses an ongoing challenge for the success of biomonitoring programs. Morphology-based identification of bioindicator taxa is time consuming, and rarely supports species-level resolution especially for immature life stages. Much work has been done in the past decade to develop alternative approaches for biodiversity analysis using DNA sequence-based approaches such as molecular phylogenetics and DNA barcoding. On-going assembly of DNA barcode reference libraries will provide the basis for a DNA-based identification system. The use of recently introduced next-generation sequencing (NGS) approaches in biodiversity science has the potential to further extend the application of DNA information for routine biomonitoring applications to an unprecedented scale. Here we demonstrate the feasibility of using 454 massively parallel pyrosequencing for species-level analysis of freshwater benthic macroinvertebrate taxa commonly used for biomonitoring. We designed our experiments in order to directly compare morphology-based, Sanger sequencing DNA barcoding, and next-generation environmental barcoding approaches. Our results show the ability of 454 pyrosequencing of mini-barcodes to accurately identify all species with more than 1% abundance in the pooled mixture. Although the approach failed to identify 6 rare species in the mixture, the presence of sequences from 9 species that were not represented by individuals in the mixture provides evidence that DNA based analysis may yet provide a valuable approach in finding rare species in bulk environmental samples. We further demonstrate the application of the environmental barcoding approach by comparing benthic macroinvertebrates from an urban region to those obtained from a conservation area. Although considerable effort will be required to robustly optimize NGS tools to identify species from bulk environmental samples, our results indicate the potential of an environmental barcoding

Manila clam Venerupis philippinarum as a biomonitor to metal pollution

NASA Astrophysics Data System (ADS)

Wu, Huifeng; Ji, Chenglong; Wang, Qing; Liu, Xiaoli; Zhao, Jianmin; Feng, Jianghua

2013-01-01

The Manila clam Venerupis philippinarum is a good biomonitor/bioindicator to marine metal pollution and is frequently used in aquatic toxicology. Two dominant pedigrees (white and zebra) of clam are distributed in the Bohai Sea; however, little attention has been paid to potential biological differences between these two pedigrees. In this study, we tested the sensitivity of both pedigrees to marine metal (cadmium and zinc) pollution biomonitoring and marine environmental toxicology. Results demonstrate significant biological differences in gills of white and zebra clams based on metabolic profiles and antioxidant enzyme activities. In addition, we found that hypotaurine, malonate and homarine were relatively high in white clam gills, while alanine, arginine, glutamate, succinate, 4-aminobutyrate, taurine and betaine were high in zebra clam gills. Zebra clam gills were also more sensitive to a mixture of Cd and Zn, as shown by antioxidant enzyme activities and metabolic profiles, but white clam gills could accumulate more Zn. Therefore, we suggest that the white pedigree can be used as a biomonitor to marine Zn pollution, whereas the zebra pedigree can be used for toxicology studies on Cd and Zn mixed pollution.

Environmental epigenetics: A promising venue for developing next-generation pollution biomonitoring tools in marine invertebrates.

PubMed

Suarez-Ulloa, Victoria; Gonzalez-Romero, Rodrigo; Eirin-Lopez, Jose M

2015-09-15

Environmental epigenetics investigates the cause-effect relationships between specific environmental factors and the subsequent epigenetic modifications triggering adaptive responses in the cell. Given the dynamic and potentially reversible nature of the different types of epigenetic marks, environmental epigenetics constitutes a promising venue for developing fast and sensible biomonitoring programs. Indeed, several epigenetic biomarkers have been successfully developed and applied in traditional model organisms (e.g., human and mouse). Nevertheless, the lack of epigenetic knowledge in other ecologically and environmentally relevant organisms has hampered the application of these tools in a broader range of ecosystems, most notably in the marine environment. Fortunately, that scenario is now changing thanks to the growing availability of complete reference genome sequences along with the development of high-throughput DNA sequencing and bioinformatic methods. Altogether, these resources make the epigenetic study of marine organisms (and more specifically marine invertebrates) a reality. By building on this knowledge, the present work provides a timely perspective highlighting the extraordinary potential of environmental epigenetic analyses as a promising source of rapid and sensible tools for pollution biomonitoring, using marine invertebrates as sentinel organisms. This strategy represents an innovative, groundbreaking approach, improving the conservation and management of natural resources in the oceans. Copyright © 2015 Elsevier Ltd. All rights reserved.

US Fish and Wildlife Service lands biomonitoring operations manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rope, R.C.; Breckenridge, R.P.

1993-08-01

This is Volume 1 of an operations manual designed to facilitate the development of biomonitoring strategies for U.S. Fish and Wildlife Service Lands. It is one component of the U.S. Fish and Wildlife Service Lands Biomonitoring Operations Manual. The Volume contains the Introduction to the Manual, background information on monitoring, and procedures for developing a biomonitoring strategy for Service lands. The purpose of the Biomonitoring Operations Manual is to provide an approach to develop and implement biomonitoring activities to assess the status and trends of U.S. Fish and Wildlife Service trust resources. It also provides field sampline methods and documentationmore » protocols for contaminant monitoring activities. The strategy described in the Manual has been designed as a stand alone process to characterize the presence of contaminants on lands managed by the Service. This process can be sued to develop a monitoring program for any tract of real estate with potential threats from on- or off-site contaminants. Because the process was designed to address concerns for Service lands that span the United States from Alaska to the Tropical Islands, it has a generic format that can be used in al types of ecosystems, however, significant site specific informtion is required to complete the Workbook and make the process work successfully.« less

Biomarkers of susceptibility following benzene exposure: influence of genetic polymorphisms on benzene metabolism and health effects.

PubMed

Carbonari, Damiano; Chiarella, Pieranna; Mansi, Antonella; Pigini, Daniela; Iavicoli, Sergio; Tranfo, Giovanna

2016-01-01

Benzene is a ubiquitous occupational and environmental pollutant. Improved industrial hygiene allowed airborne concentrations close to the environmental context (1-1000 µg/m(3)). Conversely, new limits for benzene levels in urban air were set (5 µg/m(3)). The biomonitoring of exposure to such low benzene concentrations are performed measuring specific and sensitive biomarkers such as S-phenylmercapturic acid, trans, trans-muconic acid and urinary benzene: many studies referred high variability in the levels of these biomarkers, suggesting the involvement of polymorphic metabolic genes in the individual susceptibility to benzene toxicity. We reviewed the influence of metabolic polymorphisms on the biomarkers levels of benzene exposure and effect, in order to understand the real impact of benzene exposure on subjects with increased susceptibility.

Aquatic biomonitoring of reclaimed water for potable use: the San Diego Health Effects Study.

PubMed

de Peyster, A; Donohoe, R; Slymen, D J; Froines, J R; Olivieri, A W; Eisenberg, D M

1993-05-01

Highly treated reclaimed wastewater was evaluated as a possible supplement to raw water sources required to meet San Diego's growing need for potable water. Biomonitoring experiments employing fathead minnows (Pimephales promelas) were used to compare reclaimed water with the city's current raw water supply. Juvenile fish were exposed in flow-through aquaria in field laboratories located at the reclamation plant (AQUA II) and at a municipal potable water treatment facility (Miramar). Biomonitoring measurements were survival and growth, swimming performance, and trace amounts of 68 base/neutral/acid extractable organics, 27 pesticides, and 27 inorganic chemicals found in fish tissues after exposure. Biomonitoring revealed differences in survival, growth, and swimming performance only after 90- and 180-d exposure. Reclaimed water and raw water were not readily distinguishable in 28-d chemical bioaccumulation tests in terms of organic chemical contaminants in fish tissue except for pesticide levels, which tended to be higher in raw water. Similar inorganic species were found in samples from both waters, although there was greater evidence of bioaccumulation of certain contaminants from raw water. Based on biomonitoring parameters included in these experiments, the use of reclaimed water to supplement raw water supplies would appear to pose no major public health threats. The results of these studies will be combined with additional health effects information before final conclusions are reached about the suitability of reclaimed water for human consumption.

Metabolism and Biomarkers of Heterocyclic Aromatic Amines in Molecular Epidemiology Studies: Lessons Learned from Aromatic Amines

PubMed Central

2011-01-01

Aromatic amines and heterocyclic aromatic amines (HAAs) are structurally related classes of carcinogens that are formed during the combustion of tobacco or during the high-temperature cooking of meats. Both classes of procarcinogens undergo metabolic activation by N-hydroxylation of the exocyclic amine group, to produce a common proposed intermediate, the arylnitrenium ion, which is the critical metabolite implicated in toxicity and DNA damage. However, the biochemistry and chemical properties of these compounds are distinct and different biomarkers of aromatic amines and HAAs have been developed for human biomonitoring studies. Hemoglobin adducts have been extensively used as biomarkers to monitor occupational and environmental exposures to a number of aromatic amines; however, HAAs do not form hemoglobin adducts at appreciable levels and other biomarkers have been sought. A number of epidemiologic studies that have investigated dietary consumption of well-done meat in relation to various tumor sites reported a positive association between cancer risk and well-done meat consumption, although some studies have shown no associations between well-done meat and cancer risk. A major limiting factor in most epidemiological studies is the uncertainty in quantitative estimates of chronic exposure to HAAs and, thus, the association of HAAs formed in cooked meat and cancer risk has been difficult to establish. There is a critical need to establish long-term biomarkers of HAAs that can be implemented in molecular epidemioIogy studies. In this review article, we highlight and contrast the biochemistry of several prototypical carcinogenic aromatic amines and HAAs to which humans are chronically exposed. The biochemical properties and the impact of polymorphisms of the major xenobiotic-metabolizing enzymes on the biological effects of these chemicals are examined. Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and

INTEGRATION OF BIOMONITORING EXPOSURE DATA INTO THE RISK ASSESSMENT PROCESS

EPA Science Inventory

Improved biomonitoring techniques are being used to measure very low levels of environmental chemicals in the tissues of adults and children. Public and private demand for biomonitoring data are on the increase worldwide. In the United States alone, government-sponsored programs...

[New perspectives in biomonitoring of metallic elements: the example of hexavalent chromium].

PubMed

Mutti, A; De Palma, G; Goldoni, M

2012-01-01

Plating industry is an important productive sector in all the national territory, because of its contribution to a high number of industrial products and crafts. In the chrome plating sector there is a specific chemical risk due to the exposure to compounds containing hexavalent Chromium [Cr(VI)]. Exhaled breath condensate (EBC) has been used to study both acute and long term exposure to Cr(VI) in chrome plating workers. Cr-EBC correlates with specific oxidative stress biomarkers. Moreover, both total Cr and its hexavalent fraction can be measured in EBC, which therefore is a promising biological fluid to assess the absorbed dose at the target organ level, the pulmonary reduction kinetics of Cr(VI) and in general its local pneumotoxic effects. EBC collection and analysis could give additional information to the traditional measures performed during biomonitoring.

Analysis of Moms Across America report suggesting bioaccumulation of glyphosate in U.S. mother's breast milk: Implausibility based on inconsistency with available body of glyphosate animal toxicokinetic, human biomonitoring, and physico-chemical data.

PubMed

Bus, James S

2015-12-01

The non-peer-reviewed biomonitoring report published online by Moms Across America (MAA; Honeycutt and Rowlands, 2014) does not support the conclusion that glyphosate concentrations detected in a limited number of urine samples from women, men and children, or breast milk from nursing mothers, pose a health risk to the public, including nursing children. Systemically absorbed doses of glyphosate estimated from the MAA urine biomonitoring data and from other published biomonitoring studies indicate that daily glyphosate doses are substantially below health protective reference standards (ADIs; RfDs) established by regulatory agencies. The MAA report also suggested that detection of relatively high glyphosate concentrations in breast milk in 3 of 10 sampled women raised a concern for bioaccumulation in breast milk. However, the breast milk concentrations reported by MAA are highly implausible when considered in context to low daily systemic doses of glyphosate estimated from human urine biomonitoring data, and also are inconsistent with animal toxicokinetic data demonstrating no evidence of retention in tissues or milk after single- or multiple-dose glyphosate treatment. In addition, toxicokinetic studies in lactating goats have shown that glyphosate does not partition into milk at concentrations greater than blood, and that only a very small percentage of the total administered dose (<0.03%) is ultimately excreted into milk. The toxicokinetic studies also indicate that human glyphosate exposures estimated from urine biomonitoring fall thousands-of-fold short of external doses capable of producing blood concentrations sufficient to result in the breast milk concentrations described in the MAA report. Finally, in contrast to highly lipophilic compounds with bioaccumulation potential in breast milk, the physico-chemical properties of glyphosate indicate that it is highly hydrophilic (ionized) at physiological pH and unlikely to preferentially distribute into breast

Miniaturized video-microscopy system for near real-time water quality biomonitoring using microfluidic chip-based devices

NASA Astrophysics Data System (ADS)

Huang, Yushi; Nigam, Abhimanyu; Campana, Olivia; Nugegoda, Dayanthi; Wlodkowic, Donald

2016-12-01

Biomonitoring studies apply biological responses of sensitive biomonitor organisms to rapidly detect adverse environmental changes such as presence of physic-chemical stressors and toxins. Behavioral responses such as changes in swimming patterns of small aquatic invertebrates are emerging as sensitive endpoints to monitor aquatic pollution. Although behavioral responses do not deliver information on an exact type or the intensity of toxicants present in water samples, they could provide orders of magnitude higher sensitivity than lethal endpoints such as mortality. Despite the advantages of behavioral biotests performed on sentinel organisms, their wider application in real-time and near realtime biomonitoring of water quality is limited by the lack of dedicated and automated video-microscopy systems. Current behavioral analysis systems rely mostly on static test conditions and manual procedures that are time-consuming and labor intensive. Tracking and precise quantification of locomotory activities of multiple small aquatic organisms requires high-resolution optical data recording. This is often problematic due to small size of fast moving animals and limitations of culture vessels that are not specially designed for video data recording. In this work, we capitalized on recent advances in miniaturized CMOS cameras, high resolution optics and biomicrofluidic technologies to develop near real-time water quality sensing using locomotory activities of small marine invertebrates. We present proof-of-concept integration of high-resolution time-resolved video recording system and high-throughput miniaturized perfusion biomicrofluidic platform for optical tracking of nauplii of marine crustacean Artemia franciscana. Preliminary data demonstrate that Artemia sp. exhibits rapid alterations of swimming patterns in response to toxicant exposure. The combination of video-microscopy and biomicrofluidic platform facilitated straightforward recording of fast moving objects. We

A new spin on research translation: the Boston Consensus Conference on Human Biomonitoring.

PubMed

Nelson, Jessica W; Scammell, Madeleine Kangsen; Altman, Rebecca Gasior; Webster, Thomas F; Ozonoff, David M

2009-04-01

Translating research to make it more understandable and effective (research translation) has been declared a priority in environmental health but does not always include communication to the public or residents of communities affected by environmental hazards. Their unique perspectives are also commonly missing from discussions about science and technology policy. The consensus conference process, developed in Denmark, offers a way to address this gap. The Boston Consensus Conference on Human Biomonitoring, held in Boston, Massachusetts, in the fall of 2006, was designed to educate and elicit input from 15 Boston-area residents on the scientifically complex topic of human biomonitoring for environmental chemicals. This lay panel considered the many ethical, legal, and scientific issues surrounding biomonitoring and prepared a report expressing their views. The lay panel's findings provide a distinct and important voice on the expanding use of biomonitoring. In some cases, such as a call for opt-in reporting of biomonitoring results to study participants, they mirror recommendations raised elsewhere. Other conclusions have not been heard previously, including the recommendation that an individual's results should be statutorily exempted from the medical record unless permission is granted, and the opportunity to use biomonitoring data to stimulate green chemistry. The consensus conference model addresses both aspects of a broader conception of research translation: engaging the public in scientific questions, and bringing their unique perspectives to bear on public health research, practice, and policy. In this specific application, a lay panel's recommendations on biomonitoring surveillance, communication, and ethics have practical implications for the conduct of biomonitoring studies and surveillance programs.

Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis

PubMed Central

Saad, Mohamed N.; Mabrouk, Mai S.; Eldeib, Ayman M.; Shaker, Olfat G.

2015-01-01

Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field. PMID:26843965

Toxicological importance of human biomonitoring of metallic and metalloid elements in different biological samples.

PubMed

Gil, F; Hernández, A F

2015-06-01

Human biomonitoring has become an important tool for the assessment of internal doses of metallic and metalloid elements. These elements are of great significance because of their toxic properties and wide distribution in environmental compartments. Although blood and urine are the most used and accepted matrices for human biomonitoring, other non-conventional samples (saliva, placenta, meconium, hair, nails, teeth, breast milk) may have practical advantages and would provide additional information on health risk. Nevertheless, the analysis of these compounds in biological matrices other than blood and urine has not yet been accepted as a useful tool for biomonitoring. The validation of analytical procedures is absolutely necessary for a proper implementation of non-conventional samples in biomonitoring programs. However, the lack of reliable and useful analytical methodologies to assess exposure to metallic elements, and the potential interference of external contamination and variation in biological features of non-conventional samples are important limitations for setting health-based reference values. The influence of potential confounding factors on metallic concentration should always be considered. More research is needed to ascertain whether or not non-conventional matrices offer definitive advantages over the traditional samples and to broaden the available database for establishing worldwide accepted reference values in non-exposed populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

BIOMONITORING OF SOURCE WATER QUALITY

EPA Science Inventory

Living organisms are commonly used to determine the toxicity of environmental samples but are usually limited to survival, growth, or reproduction. With advances in electronic and computer technology, biomonitors are being developed that can assess the toxicity of water by monit...

Mass spectrometric based approaches in urine metabolomics and biomarker discovery.

PubMed

Khamis, Mona M; Adamko, Darryl J; El-Aneed, Anas

2017-03-01

Urine metabolomics has recently emerged as a prominent field for the discovery of non-invasive biomarkers that can detect subtle metabolic discrepancies in response to a specific disease or therapeutic intervention. Urine, compared to other biofluids, is characterized by its ease of collection, richness in metabolites and its ability to reflect imbalances of all biochemical pathways within the body. Following urine collection for metabolomic analysis, samples must be immediately frozen to quench any biogenic and/or non-biogenic chemical reactions. According to the aim of the experiment; sample preparation can vary from simple procedures such as filtration to more specific extraction protocols such as liquid-liquid extraction. Due to the lack of comprehensive studies on urine metabolome stability, higher storage temperatures (i.e. 4°C) and repetitive freeze-thaw cycles should be avoided. To date, among all analytical techniques, mass spectrometry (MS) provides the best sensitivity, selectivity and identification capabilities to analyze the majority of the metabolite composition in the urine. Combined with the qualitative and quantitative capabilities of MS, and due to the continuous improvements in its related technologies (i.e. ultra high-performance liquid chromatography [UPLC] and hydrophilic interaction liquid chromatography [HILIC]), liquid chromatography (LC)-MS is unequivocally the most utilized and the most informative analytical tool employed in urine metabolomics. Furthermore, differential isotope tagging techniques has provided a solution to ion suppression from urine matrix thus allowing for quantitative analysis. In addition to LC-MS, other MS-based technologies have been utilized in urine metabolomics. These include direct injection (infusion)-MS, capillary electrophoresis-MS and gas chromatography-MS. In this article, the current progresses of different MS-based techniques in exploring the urine metabolome as well as the recent findings in providing

Biomonitoring of Environmental Status and Trends (BEST) Program: selected methods for monitoring chemical contaminants and their effects in aquatic ecosystems

USGS Publications Warehouse

Schmitt, Christopher J.; Dethloff, Gail M.

2000-01-01

This document describes the suite of biological methods of the U.S. Geological Survey- Biomonitoring of Environmental Status and Trends program for monitoring chemical contaminants and their effects on fish. The methods, which were selected by panels of experts, are being field-tested in rivers of the Mississippi River, Columbia River, and Rio Grande basins. General health biomarkers include a health assessment index based on gross observation; histopathological examination of selected organs and tissues; condition factor; and the heptosomatic and splenosomatic indices. Immune system indicators are plasma lysozyme activity and measures of splenic macrophage aggregates. Reproductive biomarkers include plasma concentrations of sex steroid hormones (17b-estradiol and 11-ketotestosterone) and vitellogenin, gonadal histopathology (including reproductive stage and, in females, gonadal atresia), and the gonadosomatic index. Indicators of exposure to polycyclic aromatic and polyhalogenated hydrocarbons are the H4IIE rat hepatoma cell bioassay (performed on solvent extracts of composite fish samples) and hepatic ethoxyresorufin-O-deethylase activity. Stable nitrogen isotope ratios are used to assess the trophic position of the fish and their exposure to sewage and other animal wastes. For each indicator we describe endpoint(s) and methods, and discuss the indicator?s value and limitations for contaminant monitoring and assessment.

Toxic ignorance and right-to-know in biomonitoring results communication: a survey of scientists and study participants.

PubMed

Morello-Frosch, Rachel; Brody, Julia Green; Brown, Phil; Altman, Rebecca Gasior; Rudel, Ruthann A; Pérez, Carla

2009-02-28

Exposure assessment has shifted from pollutant monitoring in air, soil, and water toward personal exposure measurements and biomonitoring. This trend along with the paucity of health effect data for many of the pollutants studied raise ethical and scientific challenges for reporting results to study participants. We interviewed 26 individuals involved in biomonitoring studies, including academic scientists, scientists from environmental advocacy organizations, IRB officials, and study participants; observed meetings where stakeholders discussed these issues; and reviewed the relevant literature to assess emerging ethical, scientific, and policy debates about personal exposure assessment and biomonitoring, including public demand for information on the human health effects of chemical body burdens. We identify three frameworks for report-back in personal exposure studies: clinical ethics; community-based participatory research; and citizen science 'data judo.' The first approach emphasizes reporting results only when the health significance of exposures is known, while the latter two represent new communication strategies where study participants play a role in interpreting, disseminating, and leveraging results to promote community health. We identify five critical areas to consider in planning future biomonitoring studies. Public deliberation about communication in personal exposure assessment research suggests that new forms of community-based research ethics and participatory scientific practice are emerging.

Biomonitors of atmospheric nitrogen deposition: potential uses and limitations.

PubMed

Díaz-Álvarez, Edison A; Lindig-Cisneros, Roberto; de la Barrera, Erick

2018-01-01

Atmospheric nitrogen deposition is the third largest cause of global biodiversity loss, with rates that have more than doubled over the past century. This is especially threatening for tropical regions where the deposition may soon exceed 25 kg of N ha -1 year -1 , well above the threshold for physiological damage of 12-20 kg of N ha -1 year -1 , depending on plant species and nitrogenous compound. It is thus urgent to monitor these regions where the most diverse biotas occur. However, most studies have been conducted in Europe, the USA and recently in China. This review presents the case for the potential use of biological organisms to monitor nitrogen deposition, with emphasis on tropical plants. We first present an overview of atmospheric chemistry and the nitrogen metabolism of potential biomonitors, followed by a framework for monitoring nitrogen deposition based on the simultaneous use of various functional groups. In particular, the tissue nitrogen content responds to the rate of deposition, especially for mosses, whose nitrogen content increases by 1‰ per kilogram of N ha -1 year -1 . The isotopic signature, δ 15 N, is a useful indicator of the nitrogen source, as the slightly negative values (e.g. 5‰) of plants from natural environments can become very negative (-11.2‰) in sites with agricultural and husbandry activities, but very positive (13.3‰) in urban environments with high vehicular activity. Mosses are good biomonitors for wet deposition and atmospheric epiphytes for dry deposition. In turn, the nitrogen saturation of ecosystems can be monitored with trees whose isotopic values increase with saturation. Although given ecophysiological limitations of different organisms, particular studies should be conducted in each area of interest to determine the most suitable biomonitors. Overall, biomonitors can provide an integrative approach for characterizing nitrogen deposition in regions where the deployment of automated instruments or passive

Biomonitors of atmospheric nitrogen deposition: potential uses and limitations

PubMed Central

Díaz-Álvarez, Edison A; Lindig-Cisneros, Roberto

2018-01-01

Abstract Atmospheric nitrogen deposition is the third largest cause of global biodiversity loss, with rates that have more than doubled over the past century. This is especially threatening for tropical regions where the deposition may soon exceed 25 kg of N ha−1 year−1, well above the threshold for physiological damage of 12–20 kg of N ha−1 year−1, depending on plant species and nitrogenous compound. It is thus urgent to monitor these regions where the most diverse biotas occur. However, most studies have been conducted in Europe, the USA and recently in China. This review presents the case for the potential use of biological organisms to monitor nitrogen deposition, with emphasis on tropical plants. We first present an overview of atmospheric chemistry and the nitrogen metabolism of potential biomonitors, followed by a framework for monitoring nitrogen deposition based on the simultaneous use of various functional groups. In particular, the tissue nitrogen content responds to the rate of deposition, especially for mosses, whose nitrogen content increases by 1‰ per kilogram of N ha−1 year−1. The isotopic signature, δ15N, is a useful indicator of the nitrogen source, as the slightly negative values (e.g. 5‰) of plants from natural environments can become very negative (−11.2‰) in sites with agricultural and husbandry activities, but very positive (13.3‰) in urban environments with high vehicular activity. Mosses are good biomonitors for wet deposition and atmospheric epiphytes for dry deposition. In turn, the nitrogen saturation of ecosystems can be monitored with trees whose isotopic values increase with saturation. Although given ecophysiological limitations of different organisms, particular studies should be conducted in each area of interest to determine the most suitable biomonitors. Overall, biomonitors can provide an integrative approach for characterizing nitrogen deposition in regions where the deployment of automated instruments

Seasonal changes in stress biomarkers of an exotic coastal species - Chaetopleura angulata (Polyplacophora) - Implications for biomonitoring.

PubMed

Madeira, Diana; Vinagre, Catarina; Mendonça, Vanessa; Diniz, Mário Sousa

2017-07-15

Knowledge on baseline values of stress biomarkers in natural conditions is urgent due to the need of reference values for monitoring purposes. Here we assessed the cellular stress response of the chiton Chaetopleura angulata in situ. Biomarkers commonly used in environmental monitoring (heat shock protein 70kDa, total ubiquitin, catalase, glutathione-S-transferase, superoxide-dismutase, lipid peroxidation) were analyzed in the digestive system, gills and muscle of C. angulata, under spring and summer conditions in order to assess seasonal tissue-specific responses. Season had an effect on all targeted organs, especially affecting the digestive system which displayed clear seasonal clusters. The respective Integrated Biomarker Response (IBR) showed a 7.2-fold seasonal difference. Muscle and gills showed similar IBRs between seasons making them appropriate organs to monitor chemical pollution as they were less responsive to seasonal variation. The most stable biomarkers in these organs were ubiquitin and superoxide-dismutase thus being reliable for monitoring purposes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sparse representation based biomarker selection for schizophrenia with integrated analysis of fMRI and SNPs.

PubMed

Cao, Hongbao; Duan, Junbo; Lin, Dongdong; Shugart, Yin Yao; Calhoun, Vince; Wang, Yu-Ping

2014-11-15

Integrative analysis of multiple data types can take advantage of their complementary information and therefore may provide higher power to identify potential biomarkers that would be missed using individual data analysis. Due to different natures of diverse data modality, data integration is challenging. Here we address the data integration problem by developing a generalized sparse model (GSM) using weighting factors to integrate multi-modality data for biomarker selection. As an example, we applied the GSM model to a joint analysis of two types of schizophrenia data sets: 759,075 SNPs and 153,594 functional magnetic resonance imaging (fMRI) voxels in 208 subjects (92 cases/116 controls). To solve this small-sample-large-variable problem, we developed a novel sparse representation based variable selection (SRVS) algorithm, with the primary aim to identify biomarkers associated with schizophrenia. To validate the effectiveness of the selected variables, we performed multivariate classification followed by a ten-fold cross validation. We compared our proposed SRVS algorithm with an earlier sparse model based variable selection algorithm for integrated analysis. In addition, we compared with the traditional statistics method for uni-variant data analysis (Chi-squared test for SNP data and ANOVA for fMRI data). Results showed that our proposed SRVS method can identify novel biomarkers that show stronger capability in distinguishing schizophrenia patients from healthy controls. Moreover, better classification ratios were achieved using biomarkers from both types of data, suggesting the importance of integrative analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

Biomarkers of Aging: From Function to Molecular Biology

PubMed Central

Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

2016-01-01

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. PMID:27271660

MAKING SENSE OF HUMAN BIOMONITORING DATA: FINDINGS AND RECOMMENDATIONS OF A WORKSHOP

EPA Science Inventory

The ability to measure chemicals in humans (often termed biomonitoring) is far outpacing the ability to reliably interpret these data for public health purposes, creating a major knowledge gap. Until this gap is filled, the great promise of routinely using biomonitoring data to s...

A multi-biomarker approach in cross-transplanted mussels Mytilus galloprovincialis.

PubMed

Serafim, Angela; Lopes, Belisandra; Company, Rui; Cravo, Alexandra; Gomes, Tânia; Sousa, Vânia; Bebianno, Maria João

2011-11-01

The present work integrates the active biomonitoring (ABM) concept in mussels Mytilus galloprovincialis from the South coast of Portugal transplanted during 28 days between two sites with different sources of contamination, and vice versa, in order to assess biological effects in these mussels. For that purpose a multibiomarker approach was used. The suit of biomarkers indicative of metal contamination were metallothioneins (MT) and the enzyme δ-aminolevulinic acid dehydratase (ALAD), for organic contamination mixed function oxidase system (MFO), glutathione-S-transferase (GST) and acetylcholinesterase (AChE), as oxidative stress biomarkers superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation (LPO). These biomarkers were used to determine an index to evaluate the stress levels in these two sites. Site A is strongly influenced by metallic contamination, with higher Cu, Cr and Pb in M. galloprovincialis, as well as higher MT levels, antioxidant enzymes activities and LPO concentrations, and lower ALAD activity. In site B organic compounds (PAHs) are prevalent and native mussels show higher activities of the MFO system components and GST. Transplanted mussels had significant alterations in some biomarkers that reflect the type of contaminants present in each site, which demonstrates the primary role of the environment in determining the physiological characteristics of resident mussels. Therefore the application of ABM using a battery of biomarkers turns out to be a useful approach in sites where usually complex mixtures of contaminants occurs. In this study the biomarkers that better differentiate the impact of different contaminants at each site were MT, CYP450, SOD and CAT.

Multiplexed MRM-based quantitation of candidate cancer biomarker proteins in undepleted and non-enriched human plasma.

PubMed

Percy, Andrew J; Chambers, Andrew G; Yang, Juncong; Borchers, Christoph H

2013-07-01

An emerging approach for multiplexed targeted proteomics involves bottom-up LC-MRM-MS, with stable isotope-labeled internal standard peptides, to accurately quantitate panels of putative disease biomarkers in biofluids. In this paper, we used this approach to quantitate 27 candidate cancer-biomarker proteins in human plasma that had not been treated by immunoaffinity depletion or enrichment techniques. These proteins have been reported as biomarkers for a variety of human cancers, from laryngeal to ovarian, with breast cancer having the highest correlation. We implemented measures to minimize the analytical variability, improve the quantitative accuracy, and increase the feasibility and applicability of this MRM-based method. We have demonstrated excellent retention time reproducibility (median interday CV: 0.08%) and signal stability (median interday CV: 4.5% for the analytical platform and 6.1% for the bottom-up workflow) for the 27 biomarker proteins (represented by 57 interference-free peptides). The linear dynamic range for the MRM assays spanned four orders-of-magnitude, with 25 assays covering a 10(3) -10(4) range in protein concentration. The lowest abundance quantifiable protein in our biomarker panel was insulin-like growth factor 1 (calculated concentration: 127 ng/mL). Overall, the analytical performance of this assay demonstrates high robustness and sensitivity, and provides the necessary throughput and multiplexing capabilities required to verify and validate cancer-associated protein biomarker panels in human plasma, prior to clinical use. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new scheme for biomonitoring heavy metal concentrations in semi-natural wetlands.

PubMed

Batzias, A F; Siontorou, C G

2008-10-30

This work introduces a semi-natural wetland biomonitoring framework for heavy metal concentrations based on a robust dynamic integration between biological assemblages and relevant biosensors. The cooperative/synergistic scheme developed minimizes uncertainty and monitoring costs and increases reliability of pollution control and abatement. Attention is given to establishing a fully functioning and reliable network approach for monitoring inflows and achieving dose-response relations and calibration of biomonitoring species. The biomonitoring network initially consists of both, biosensors and species, as a validation phase in each wetland of the surveillance area; once the species monitoring efficiency is verified by the biosensors, the biosensor network moves to the next wetland and so on, following a circular pattern until all area wetlands have a fully functional natural monitoring scheme. By means of species recalibration with periodic revisiting of the biosensors, the scheme progressively reaches a quasi steady-state (including seasonality), thus ensuring reliability and robustness. This framework, currently pilot-tested in Voiotia, Greece, for assessing chromium levels, has been built to cover short-, medium- and long-term monitoring requirements. The results gathered so far, support the employment of the proposed scheme in heavy metal monitoring, and, further, arise the need for volunteer involvement to achieve long-term viability.

Evaluating ethanol-based sample preservation to facilitate use of DNA barcoding in routine freshwater biomonitoring programs using benthic macroinvertebrates.

PubMed

Stein, Eric D; White, Bryan P; Mazor, Raphael D; Miller, Peter E; Pilgrim, Erik M

2013-01-01

Molecular methods, such as DNA barcoding, have the potential to enhance biomonitoring programs worldwide. Altering routinely used sample preservation methods to protect DNA from degradation may pose a potential impediment to application of DNA barcoding and metagenomics for biomonitoring using benthic macroinvertebrates. Using higher volumes or concentrations of ethanol, requirements for shorter holding times, or the need to include additional filtering may increase cost and logistical constraints to existing biomonitoring programs. To address this issue we evaluated the efficacy of various ethanol-based sample preservation methods at maintaining DNA integrity. We evaluated a series of methods that were minimally modified from typical field protocols in order to identify an approach that can be readily incorporated into existing monitoring programs. Benthic macroinvertebrates were collected from a minimally disturbed stream in southern California, USA and subjected to one of six preservation treatments. Ten individuals from five taxa were selected from each treatment and processed to produce DNA barcodes from the mitochondrial gene cytochrome c oxidase I (COI). On average, we obtained successful COI sequences (i.e. either full or partial barcodes) for between 93-99% of all specimens across all six treatments. As long as samples were initially preserved in 95% ethanol, successful sequencing of COI barcodes was not affected by a low dilution ratio of 2∶1, transfer to 70% ethanol, presence of abundant organic matter, or holding times of up to six months. Barcoding success varied by taxa, with Leptohyphidae (Ephemeroptera) producing the lowest barcode success rate, most likely due to poor PCR primer efficiency. Differential barcoding success rates have the potential to introduce spurious results. However, routine preservation methods can largely be used without adverse effects on DNA integrity.

Evaluating Ethanol-based Sample Preservation to Facilitate Use of DNA Barcoding in Routine Freshwater Biomonitoring Programs Using Benthic Macroinvertebrates

PubMed Central

Stein, Eric D.; White, Bryan P.; Mazor, Raphael D.; Miller, Peter E.; Pilgrim, Erik M.

2013-01-01

Molecular methods, such as DNA barcoding, have the potential to enhance biomonitoring programs worldwide. Altering routinely used sample preservation methods to protect DNA from degradation may pose a potential impediment to application of DNA barcoding and metagenomics for biomonitoring using benthic macroinvertebrates. Using higher volumes or concentrations of ethanol, requirements for shorter holding times, or the need to include additional filtering may increase cost and logistical constraints to existing biomonitoring programs. To address this issue we evaluated the efficacy of various ethanol-based sample preservation methods at maintaining DNA integrity. We evaluated a series of methods that were minimally modified from typical field protocols in order to identify an approach that can be readily incorporated into existing monitoring programs. Benthic macroinvertebrates were collected from a minimally disturbed stream in southern California, USA and subjected to one of six preservation treatments. Ten individuals from five taxa were selected from each treatment and processed to produce DNA barcodes from the mitochondrial gene cytochrome c oxidase I (COI). On average, we obtained successful COI sequences (i.e. either full or partial barcodes) for between 93–99% of all specimens across all six treatments. As long as samples were initially preserved in 95% ethanol, successful sequencing of COI barcodes was not affected by a low dilution ratio of 2∶1, transfer to 70% ethanol, presence of abundant organic matter, or holding times of up to six months. Barcoding success varied by taxa, with Leptohyphidae (Ephemeroptera) producing the lowest barcode success rate, most likely due to poor PCR primer efficiency. Differential barcoding success rates have the potential to introduce spurious results. However, routine preservation methods can largely be used without adverse effects on DNA integrity. PMID:23308097

Biomarkers of nanomaterial exposure and effect: current status

NASA Astrophysics Data System (ADS)

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

Response Characteristics of an Aquatic Biomonitor Used for Rapid Toxicity Detection

DTIC Science & Technology

2004-05-15

for drinking water protection. 14. SUBJECT TERMS 15. NUMBER OF PAGES biological early warning system; Lepomis macrochirus; bluegill; aquatic toxicity...Fort Detrick, MD 21702-5010, USA Key words: biomonitor; biological early warning system; Lepomis macrochirus; bluegill; aquatic toxicity; water ...narcosis are most likely to cause rapid aquatic biomonitor depth related to variations in water quality (primarily responses. Other modes of action may

Differential blood-based biomarkers of psychopathological dimensions of schizophrenia.

PubMed

Garcia-Alvarez, Leticia; Garcia-Portilla, Maria Paz; Gonzalez-Blanco, Leticia; Saiz Martinez, Pilar Alejandra; de la Fuente-Tomas, Lorena; Menendez-Miranda, Isabel; Iglesias, Celso; Bobes, Julio

Symptomatology of schizophrenia is heterogeneous, there is not any pathognomonic symptom. Moreover, the diagnosis is difficult, since it is based on subjective information, instead of markers. The purpose of this study is to provide a review of the current status of blood-based biomarkers of psychopathological dimensions of schizophrenia. Inflammatory, hormonal or metabolic dysfunctions have been identified in patients with schizophrenia and it has attempted to establish biomarkers responsible for these dysfunctions. The identification of these biomarkers could contribute to the diagnosis and treatment of schizophrenia. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

A novel immunochromatographic electrochemical biosensor for highly sensitive and selective detection of trichloropyridinol, a biomarker of exposure to chlorpyrifos.

PubMed

Wang, Limin; Lu, Donglai; Wang, Jun; Du, Dan; Zou, Zhexiang; Wang, Hua; Smith, Jordan N; Timchalk, Charles; Liu, Fengquan; Lin, Yuehe

2011-02-15

We present a novel portable immunochromatographic electrochemical biosensor (IEB) for simple, rapid, and sensitive biomonitoring of trichloropyridinol (TCP), a metabolite biomarker of exposure to organophosphorus insecticides. Our new approach takes the advantage of immunochromatographic test strip for a rapid competitive immunoreaction and a disposable screen-printed carbon electrode for a rapid and sensitive electrochemical analysis of captured HRP labeling. Several key experimental parameters (e.g. immunoreaction time, the amount of HRP labeled TCP, concentration of the substrate for electrochemical measurements, and the blocking agents for the nitrocellulose membrane) were optimized to achieve a high sensitivity, selectivity and stability. Under optimal conditions, the IEB has demonstrated a wide linear range (0.1-100 ng/ml) with a detection limit as low as 0.1 ng/ml TCP. Furthermore, the IEB has been successfully applied for biomonitoring of TCP in the rat plasma samples with in vivo exposure to organophosphorus insecticides like Chlorpyrifos-oxon (CPF-oxon). The IEB thus opens up new pathways for designing a simple, rapid, clinically accurate, and quantitative tool for TCP detection, as well as holds a great promise for in-field screening of metabolite biomarkers, e.g., TCP, for humans exposed to organophosphorus insecticides. Copyright © 2010 Elsevier B.V. All rights reserved.

Acetylcholinesterase as a Biomarker in Environmental and Occupational Medicine: New Insights and Future Perspectives

PubMed Central

Caricato, Roberto; Calisi, Antonio; Giordano, Maria Elena; Schettino, Trifone

2013-01-01

Acetylcholinesterase (AChE) is a key enzyme in the nervous system. It terminates nerve impulses by catalysing the hydrolysis of neurotransmitter acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, acetylcholinesterase activity and its inhibition has been early recognized to be a human biological marker of pesticide poisoning. Measurement of AChE inhibition has been increasingly used in the last two decades as a biomarker of effect on nervous system following exposure to organophosphate and carbamate pesticides in occupational and environmental medicine. The success of this biomarker arises from the fact that it meets a number of characteristics necessary for the successful application of a biological response as biomarker in human biomonitoring: the response is easy to measure, it shows a dose-dependent behavior to pollutant exposure, it is sensitive, and it exhibits a link to health adverse effects. The aim of this work is to review and discuss the recent findings about acetylcholinesterase, including its sensitivity to other pollutants and the expression of different splice variants. These insights open new perspective for the future use of this biomarker in environmental and occupational human health monitoring. PMID:23936791

Biomarker Discovery by Novel Sensors Based on Nanoproteomics Approaches

PubMed Central

Dasilva, Noelia; Díez, Paula; Matarraz, Sergio; González-González, María; Paradinas, Sara; Orfao, Alberto; Fuentes, Manuel

2012-01-01

During the last years, proteomics has facilitated biomarker discovery by coupling high-throughput techniques with novel nanosensors. In the present review, we focus on the study of label-based and label-free detection systems, as well as nanotechnology approaches, indicating their advantages and applications in biomarker discovery. In addition, several disease biomarkers are shown in order to display the clinical importance of the improvement of sensitivity and selectivity by using nanoproteomics approaches as novel sensors. PMID:22438764

Citizens' Guide to Biomonitoring in the Great Lakes and St. Lawrence River.

ERIC Educational Resources Information Center

Great Lakes United, Buffalo, NY.

The purpose of this report is to present the issues surrounding biomonitoring of wastewaters discharged into the Great Lakes Basin. Biomonitoring is the process of using organisms to monitor the toxicity of a substance. The report reflects an interest in seeing zero discharge of toxic pollutants in the Great Lakes region. The report is organized…

US Fish and Wildlife Service biomonitoring operations manual, Appendices A--K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gianotto, D.F.; Rope, R.C.; Mondecar, M.

1993-04-01

Volume 2 contains Appendices and Summary Sheets for the following areas: A-Legislative Background and Key to Relevant Legislation, B- Biomonitoring Operations Workbook, C-Air Monitoring, D-Introduction to the Flora and Fauna for Biomonitoring, E-Decontamination Guidance Reference Field Methods, F-Documentation Guidance, Sample Handling, and Quality Assurance/Quality Control Standard Operating Procedures, G-Field Instrument Measurements Reference Field Methods, H-Ground Water Sampling Reference Field Methods, I-Sediment Sampling Reference Field Methods, J-Soil Sampling Reference Field Methods, K-Surface Water Reference Field Methods. Appendix B explains how to set up strategy to enter information on the ``disk workbook``. Appendix B is enhanced by DE97006389, an on-line workbook formore » users to be able to make revisions to their own biomonitoring data.« less

Lessons learnt on recruitment and fieldwork from a pilot European human biomonitoring survey.

PubMed

Fiddicke, Ulrike; Becker, Kerstin; Schwedler, Gerda; Seiwert, Margarete; Joas, Reinhard; Joas, Anke; Biot, Pierre; Aerts, Dominique; Casteleyn, Ludwine; Dumez, Birgit; Castaño, Argelia; Esteban, Marta; Angerer, Jürgen; Koch, Holger M; Schoeters, Greet; Den Hond, Elly; Sepai, Ovnair; Exley, Karen; Knudsen, Lisbeth E; Horvat, Milena; Bloemen, Louis; Katsonouri, Andromachi; Hadjipanayis, Adamos; Cerna, Milena; Krsková, Andrea; Jensen, Janne Fangel; Nielsen, Jeanette K S; Rudnai, Peter; Közepésy, Szilvia; Gutleb, Arno C; Fischer, Marc E; Ligocka, Danuta; Kamińska, Joanna; Reis, M Fátima; Namorado, Sónia; Lupsa, Ioana-Rodica; Gurzau, Anca E; Halzlová, Katarína; Mazej, Darja; Tratnik, Janja Snoj; Rivas, Teresa C; Gómez, Silvia; Berglund, Marika; Larsson, Kristin; Lehmann, Andrea; Crettaz, Pierre; Dewolf, Marie-Christine; Burns, Damien; Kellegher, Anne; Kolossa-Gehring, Marike

2015-08-01

Within the European Environment and Health Action Plan an initiative to establish a coherent human biomonitoring approach in Europe was started. The project COPHES (COnsortium to Perform Human biomonitoring on a European Scale ) developed recommendations for a harmonized conduct of a human biomonitoring (HBM) survey which came into action as the pilot study DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale). Seventeen European countries conducted a survey with harmonized instruments for, inter alia, recruitment, fieldwork and sampling, in autumn/winter 2011/2012. Based on the countries' experiences of conducting the pilot study, following lessons learnt were compiled: the harmonized fieldwork instruments (basic questionnaire, urine and hair sampling) turned out to be very valuable for future HBM surveys on the European scale. A school approach was favoured by most of the countries to recruit school-aged children according to the established guidelines and country specific experiences. To avoid a low participation rate, intensive communication with the involved institutions and possible participants proved to be necessary. The communication material should also include information on exclusion criteria and offered incentives. Telephone contact to the participants the day before fieldwork during the survey can prevent the forgetting of appointments and first morning urine samples. To achieve comparable results on the European scale, training of interviewers in all issues of recruitment, fieldwork and sampling through information material and training sessions is crucial. A survey involving many European countries needs time for preparation and conduct. Materials for quality control prepared for all steps of recruitment, fieldwork and sampling proved to be important to warrant reliable results. Copyright © 2014 Elsevier Inc. All rights reserved.

Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers

PubMed Central

Riahi, Reza; Shaegh, Seyed Ali Mousavi; Ghaderi, Masoumeh; Zhang, Yu Shrike; Shin, Su Ryon; Aleman, Julio; Massa, Solange; Kim, Duckjin; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

2016-01-01

There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips. PMID:27098564

Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers

NASA Astrophysics Data System (ADS)

Riahi, Reza; Shaegh, Seyed Ali Mousavi; Ghaderi, Masoumeh; Zhang, Yu Shrike; Shin, Su Ryon; Aleman, Julio; Massa, Solange; Kim, Duckjin; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

2016-04-01

There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips.

Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

PubMed

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.

Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics

PubMed Central

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

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. PMID:26509158

USEPA BIOMONITORING AND BIOINDICATORS CONCEPTS NEEDED TO EVALUATE THE BIOLOGICAL INTEGRITY OF AQUATIC SYSTEMS

EPA Science Inventory

This chapter presents the current uses, concepts and anticipated future directions of biomonitoring and bioindicators in the regulatory and research programs of the United States Environmental Protection Agency (USEPA). The chapter provides a historical look on how biomonitoring ...

USEPA BIOMONITORING AND BIOINDICATOR CONCEPTS NEEDED TO EVALUATE THE BIOLOGICAL INTEGRITY OF AQUATIC SYSTEMS

EPA Science Inventory

This chapter presents the current uses, concepts and anticipated future directions of biomonitoring and bioindicators in the regulatory and research programs of the United States Environmental Protection Agency (USEPA). The chapter provides a historical look on how biomonitoring...

Proteomic Workflows for Biomarker Identification Using Mass Spectrometry — Technical and Statistical Considerations during Initial Discovery

PubMed Central

Orton, Dennis J.; Doucette, Alan A.

2013-01-01

Identification of biomarkers capable of differentiating between pathophysiological states of an individual is a laudable goal in the field of proteomics. Protein biomarker discovery generally employs high throughput sample characterization by mass spectrometry (MS), being capable of identifying and quantifying thousands of proteins per sample. While MS-based technologies have rapidly matured, the identification of truly informative biomarkers remains elusive, with only a handful of clinically applicable tests stemming from proteomic workflows. This underlying lack of progress is attributed in large part to erroneous experimental design, biased sample handling, as well as improper statistical analysis of the resulting data. This review will discuss in detail the importance of experimental design and provide some insight into the overall workflow required for biomarker identification experiments. Proper balance between the degree of biological vs. technical replication is required for confident biomarker identification. PMID:28250400

Prediction of Chemical Respiratory Sensitizers Using GARD, a Novel In Vitro Assay Based on a Genomic Biomarker Signature

PubMed Central

Albrekt, Ann-Sofie; Borrebaeck, Carl A. K.; Lindstedt, Malin

2015-01-01

Background Repeated exposure to certain low molecular weight (LMW) chemical compounds may result in development of allergic reactions in the skin or in the respiratory tract. In most cases, a certain LMW compound selectively sensitize the skin, giving rise to allergic contact dermatitis (ACD), or the respiratory tract, giving rise to occupational asthma (OA). To limit occurrence of allergic diseases, efforts are currently being made to develop predictive assays that accurately identify chemicals capable of inducing such reactions. However, while a few promising methods for prediction of skin sensitization have been described, to date no validated method, in vitro or in vivo, exists that is able to accurately classify chemicals as respiratory sensitizers. Results Recently, we presented the in vitro based Genomic Allergen Rapid Detection (GARD) assay as a novel testing strategy for classification of skin sensitizing chemicals based on measurement of a genomic biomarker signature. We have expanded the applicability domain of the GARD assay to classify also respiratory sensitizers by identifying a separate biomarker signature containing 389 differentially regulated genes for respiratory sensitizers in comparison to non-respiratory sensitizers. By using an independent data set in combination with supervised machine learning, we validated the assay, showing that the identified genomic biomarker is able to accurately classify respiratory sensitizers. Conclusions We have identified a genomic biomarker signature for classification of respiratory sensitizers. Combining this newly identified biomarker signature with our previously identified biomarker signature for classification of skin sensitizers, we have developed a novel in vitro testing strategy with a potent ability to predict both skin and respiratory sensitization in the same sample. PMID:25760038

Laser and biological methods of biomonitoring of surrounding waters

NASA Astrophysics Data System (ADS)

Posudin, Yuri I.

1994-02-01

Three main methods are proposed for the biomonitoring of chemicals in water medium: laser spectrofluorometry, which is based on the excitation and recording of the spectra of fluorescence; laser scattering, which is connected with measurement of the Doppler shifts of the scattered light from the motile cells; videomicrography, which provides the analysis of parameters of photomovement of motile cells via microscope and video system. Such chemicals as surface-active substances, heavy metals and pesticides were determined in water medium due to these methods.

Pilot biomonitoring of adults and children following use of chlorpyrifos shampoo and flea collars on dogs.

PubMed

Dyk, Melinda Bigelow; Chen, Zhenshan; Mosadeghi, Sasan; Vega, Helen; Krieger, Robert

2011-01-01

Pesticide handlers and pet owners who use products such as shampoos and dips and insecticide-impregnated collars to treat and control fleas on companion animals are exposed to a variety of active ingredients. Chlorpyrifos exposures of adults and children were measured using urine biomonitoring following use of over-the-counter products on dogs. Age and gender-specific measurements of urinary 3, 5, 6-trichloro-2-pyridinol (TCPy) revealed modest elevations of biomarker excretion following shampoo/dips. Smaller TCPy increments were measured following application of impregnated dog collars. The extent of indoor activity and potential pet contact were important determinants of urine biomarker level. Children without direct pet contact excreted more TCPy following collar application. Pet collars may be a source of indoor surface contamination and human exposure. Children excreted up to 4 times more TCPy than adults when urine volumes were adjusted using age-specific creatinine excretion levels. Although chlorpyrifos is no longer used in the United States in pet care products, results of this research provide perspective on the extent of human exposure from similar pet care products. These pilot studies demonstrated that pet care products such as insecticidal shampoos and dips and impregnated collars may expose family members to low levels of insecticide relative to toxic levels of concern.

The future of blood-based biomarkers for Alzheimer’s disease

PubMed Central

Henriksen, Kim; O’Bryant, Sid E.; Hampel, Harald; Trojanowski, John Q.; Montine, Thomas J.; Jeromin, Andreas; Blennow, Kaj; Lönneborg, Anders; Wyss-Coray, Tony; Soares, Holly; Bazenet, Chantal; Sjögren, Magnus; Hu, William; Lovestone, Simon; Karsdal, Morten A.; Weiner, Michael W.

2014-01-01

Treatment of Alzheimer’s disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the “right” control population, and the blood– brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field. PMID:23850333

Deriving Biomonitoring Equivalents for selected E- and P-series glycol ethers for public health risk assessment.

PubMed

Poet, Torka; Ball, Nicholas; Hays, Sean M

2016-01-01

Glycol ethers are a widely used class of solvents that may lead to both workplace and general population exposures. Biomonitoring studies are available that have quantified glycol ethers or their metabolites in blood and/or urine amongst exposed populations. These biomonitoring levels indicate exposures to the glycol ethers, but do not by themselves indicate a health hazard risk. Biomonitoring Equivalents (BEs) have been created to provide the ability to interpret human biomonitoring data in a public health risk context. The BE is defined as the concentration of a chemical or metabolite in a biological fluid (blood or urine) that is consistent with exposures at a regulatory derived safe exposure limit, such as a tolerable daily intake (TDI). In this exercise, we derived BEs for general population exposures for selected E- and P-series glycol ethers based on their respective derived no effect levels (DNELs). Selected DNELs have been derived as part of respective Registration, Evaluation, Authorisation and Regulation of Chemicals (REACh) regulation dossiers in the EU. The BEs derived here are unique in the sense that they are the first BEs derived for urinary excretion of compounds following inhalation exposures. The urinary mass excretion fractions (Fue) of the acetic acid metabolites for the E-series GEs range from approximately 0.2 to 0.7. The Fues for the excretion of the parent P-series GEs range from approximately 0.1 to 0.2, with the exception of propylene glycol methyl ether and its acetate (Fue = 0.004). Despite the narrow range of Fues, the BEs exhibit a larger range, resulting from the larger range in DNELs across GEs. The BEs derived here can be used to interpret human biomonitoring data for inhalation exposures to GEs amongst the general population. Copyright © 2015 Elsevier GmbH. All rights reserved.

Topic model-based mass spectrometric data analysis in cancer biomarker discovery studies.

PubMed

Wang, Minkun; Tsai, Tsung-Heng; Di Poto, Cristina; Ferrarini, Alessia; Yu, Guoqiang; Ressom, Habtom W

2016-08-18

A fundamental challenge in quantitation of biomolecules for cancer biomarker discovery is owing to the heterogeneous nature of human biospecimens. Although this issue has been a subject of discussion in cancer genomic studies, it has not yet been rigorously investigated in mass spectrometry based proteomic and metabolomic studies. Purification of mass spectometric data is highly desired prior to subsequent analysis, e.g., quantitative comparison of the abundance of biomolecules in biological samples. We investigated topic models to computationally analyze mass spectrometric data considering both integrated peak intensities and scan-level features, i.e., extracted ion chromatograms (EICs). Probabilistic generative models enable flexible representation in data structure and infer sample-specific pure resources. Scan-level modeling helps alleviate information loss during data preprocessing. We evaluated the capability of the proposed models in capturing mixture proportions of contaminants and cancer profiles on LC-MS based serum proteomic and GC-MS based tissue metabolomic datasets acquired from patients with hepatocellular carcinoma (HCC) and liver cirrhosis as well as synthetic data we generated based on the serum proteomic data. The results we obtained by analysis of the synthetic data demonstrated that both intensity-level and scan-level purification models can accurately infer the mixture proportions and the underlying true cancerous sources with small average error ratios (<7 %) between estimation and ground truth. By applying the topic model-based purification to mass spectrometric data, we found more proteins and metabolites with significant changes between HCC cases and cirrhotic controls. Candidate biomarkers selected after purification yielded biologically meaningful pathway analysis results and improved disease discrimination power in terms of the area under ROC curve compared to the results found prior to purification. We investigated topic model-based

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

PubMed Central

Vandenberg, Laura N.; Chahoud, Ibrahim; Heindel, Jerrold J.; Padmanabhan, Vasantha; Paumgartten, Francisco J.R.; Schoenfelder, Gilbert

2010-01-01

Background Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. Importantly, results from a large number of biomonitoring studies are at odds with the results from two toxicokinetic studies. Objective We examined several possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. Data sources We examined > 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism. Data extraction and synthesis The > 80 biomonitoring studies examined included measurements in thousands of individuals from several different countries, and these studies overwhelmingly detected BPA in individual adults, adolescents, and children. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Some regulatory agencies have relied solely on these toxicokinetic models in their risk assessments. Conclusions Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes. PMID:20338858

Biomonitoring: Measuring Toxins in Our Bodies as a Tool in Protecting Children's Health

ERIC Educational Resources Information Center

Patton, Sharyle

2005-01-01

Biomonitoring is a public health tool that has been used by scientists and researchers for decades to test blood, bone, urine, hair, human milk, adipose tissue, and other body substances for the presence of toxic chemicals, in order to assess what is called the "chemical body burden." Biomonitoring helps to: (1) identify which chemicals…

Expanding Genomic Biomonitoring to Regional & National Scale Projects

EPA Science Inventory

This presentation provides a summary of ORD/NERL/SED research efforts applying DNA metabarcoding to questions related to biomonitoring and invasive species detection, along with development of sensitive indicators of nutrient condition.

Big-data-based edge biomarkers: study on dynamical drug sensitivity and resistance in individuals.

PubMed

Zeng, Tao; Zhang, Wanwei; Yu, Xiangtian; Liu, Xiaoping; Li, Meiyi; Chen, Luonan

2016-07-01

Big-data-based edge biomarker is a new concept to characterize disease features based on biomedical big data in a dynamical and network manner, which also provides alternative strategies to indicate disease status in single samples. This article gives a comprehensive review on big-data-based edge biomarkers for complex diseases in an individual patient, which are defined as biomarkers based on network information and high-dimensional data. Specifically, we firstly introduce the sources and structures of biomedical big data accessible in public for edge biomarker and disease study. We show that biomedical big data are typically 'small-sample size in high-dimension space', i.e. small samples but with high dimensions on features (e.g. omics data) for each individual, in contrast to traditional big data in many other fields characterized as 'large-sample size in low-dimension space', i.e. big samples but with low dimensions on features. Then, we demonstrate the concept, model and algorithm for edge biomarkers and further big-data-based edge biomarkers. Dissimilar to conventional biomarkers, edge biomarkers, e.g. module biomarkers in module network rewiring-analysis, are able to predict the disease state by learning differential associations between molecules rather than differential expressions of molecules during disease progression or treatment in individual patients. In particular, in contrast to using the information of the common molecules or edges (i.e.molecule-pairs) across a population in traditional biomarkers including network and edge biomarkers, big-data-based edge biomarkers are specific for each individual and thus can accurately evaluate the disease state by considering the individual heterogeneity. Therefore, the measurement of big data in a high-dimensional space is required not only in the learning process but also in the diagnosing or predicting process of the tested individual. Finally, we provide a case study on analyzing the temporal expression

APPLICATIONS OF AUTOMATED BIOMONITORING FOR WATERSHED MANAGEMENT

EPA Science Inventory

Over three decades of progress have been made since John Cairns and his associates first coined a new scientific endeavor known as automated biomonitoring. Implementations have ranged from designs for early warning of toxicity in wastewater discharges using fish as sensors, to co...

[The biomonitoring of toxic substances in biological samples of general population].

PubMed

Ibarluzea, Jesús; Aurrekoetxea, Juan José; Porta, Miquel; Sunyer, Jordi; Ballester, Ferran

2016-11-01

Many of the world's most developed countries have adopted biomonitoring of toxic substances in order to ascertain their levels in biological samples. These substances get into the body through different environmental exposures. Monitoring toxic substances in biological samples should allow us to ascertain their levels in vulnerable groups, assess their evolution over time, make comparisons with levels observed in other countries, identify groups at risk or with high toxic levels and promote research. The main objective of biomonitoring is to act as a policy design tool to facilitate the implementation of particular measures in various sectors: health, environmental, agricultural and livestock or food industry sectors. In Spain, information on levels of toxic substances of environmental origin is provided by specific studies on health effects from environmental sources, such as the INMA project (INfancia y Medio Ambiente [childhood and environment]). In addition, biomonitoring projects have been implemented in Catalonia and the Canary Islands, together with a national biomonitoring programme in the adult working population. However, further progress is needed to develop a system that covers the general population as well as subgroups at risk, which relies on the collaboration of the involved authorities and the participation of professionals from different sectors and citizen organisations interested in the relationship between health and the environment. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of predictive capacities of biomarkers based on research synthesis.

PubMed

Hattori, Satoshi; Zhou, Xiao-Hua

2016-11-10

The objective of diagnostic studies or prognostic studies is to evaluate and compare predictive capacities of biomarkers. Suppose we are interested in evaluation and comparison of predictive capacities of continuous biomarkers for a binary outcome based on research synthesis. In analysis of each study, subjects are often classified into two groups of the high-expression and low-expression groups according to a cut-off value, and statistical analysis is based on a 2 × 2 table defined by the response and the high expression or low expression of the biomarker. Because the cut-off is study specific, it is difficult to interpret a combined summary measure such as an odds ratio based on the standard meta-analysis techniques. The summary receiver operating characteristic curve is a useful method for meta-analysis of diagnostic studies in the presence of heterogeneity of cut-off values to examine discriminative capacities of biomarkers. We develop a method to estimate positive or negative predictive curves, which are alternative to the receiver operating characteristic curve based on information reported in published papers of each study. These predictive curves provide a useful graphical presentation of pairs of positive and negative predictive values and allow us to compare predictive capacities of biomarkers of different scales in the presence of heterogeneity in cut-off values among studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.

PubMed

Laskowitz, Daniel T; Kasner, Scott E; Saver, Jeffrey; Remmel, Kerri S; Jauch, Edward C

2009-01-01

One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a

US EPA BIOMONITORING AND BIOINDICATOR CONCEPTS NEEDED TO EVALUATE THE BIOLOGICAL INTEGRITY OF AQUATIC SYSTEMS

EPA Science Inventory

This chapter presents the current uses, concepts and anticipated future directions of biomonitoring and bioindicators in the regulatory and research programs of the United States Environmental Protection Agency (USEPA). The chapter provides a historical look on how biomonitoring ...

Mercury in Children: Current State on Exposure through Human Biomonitoring Studies

PubMed Central

Ruggieri, Flavia; Majorani, Costanza; Domanico, Francesco; Alimonti, Alessandro

2017-01-01

Mercury (Hg) in children has multiple exposure sources and the toxicity of Hg compounds depends on exposure routes, dose, timing of exposure, and developmental stage (be it prenatal or postnatal). Over the last decades, Hg was widely recognized as a threat to the children’s health and there have been acknowledgements at the international level of the need of a global policy intervention—like the Minamata treaty—aimed at reducing or preventing Hg exposure and protecting the child health. National human biomonitoring (HBM) data has demonstrated that low levels of exposure of Hg are still an important health concern for children, which no one country can solve alone. Although independent HBM surveys have provided the basis for the achievements of exposure mitigation in specific contexts, a new paradigm for a coordinated global monitoring of children’s exposure, aimed at a reliable decision-making tool at global level is yet a great challenge for the next future. The objective of the present review is to describe current HBM studies on Hg exposure in children, taking into account the potential pathways of Hg exposure and the actual Hg exposure levels assessed by different biomarkers. PMID:28498344

Computational Toxicology of Chloroform: Reverse Dosimetry Using Bayesian Inference, Markov Chain Monte Carlo Simulation, and Human Biomonitoring Data

PubMed Central

Lyons, Michael A.; Yang, Raymond S.H.; Mayeno, Arthur N.; Reisfeld, Brad

2008-01-01

Background One problem of interpreting population-based biomonitoring data is the reconstruction of corresponding external exposure in cases where no such data are available. Objectives We demonstrate the use of a computational framework that integrates physiologically based pharmacokinetic (PBPK) modeling, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of environmental chloroform source concentrations consistent with human biomonitoring data. The biomonitoring data consist of chloroform blood concentrations measured as part of the Third National Health and Nutrition Examination Survey (NHANES III), and for which no corresponding exposure data were collected. Methods We used a combined PBPK and shower exposure model to consider several routes and sources of exposure: ingestion of tap water, inhalation of ambient household air, and inhalation and dermal absorption while showering. We determined posterior distributions for chloroform concentration in tap water and ambient household air using U.S. Environmental Protection Agency Total Exposure Assessment Methodology (TEAM) data as prior distributions for the Bayesian analysis. Results Posterior distributions for exposure indicate that 95% of the population represented by the NHANES III data had likely chloroform exposures ≤ 67 μg/L in tap water and ≤ 0.02 μg/L in ambient household air. Conclusions Our results demonstrate the application of computer simulation to aid in the interpretation of human biomonitoring data in the context of the exposure–health evaluation–risk assessment continuum. These results should be considered as a demonstration of the method and can be improved with the addition of more detailed data. PMID:18709138

Clinical diagnosis of sepsis and the combined use of biomarkers and culture- and non-culture-based assays.

PubMed

Bloos, Frank

2015-01-01

Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can

Wastewater-based epidemiology to assess human exposure to pyrethroid pesticides.

PubMed

Rousis, Nikolaos I; Zuccato, Ettore; Castiglioni, Sara

2017-02-01

Pesticides are active substances with potentially adverse effects on human health, and therefore great effort is addressed to study the relation between their widespread use and the effects on humans. To track human exposure to pesticides, novel approaches are needed to give additional information on exposure at population level. In this study, a novel application of Wastewater-Based Epidemiology (WBE) was developed to measure the intake of pyrethroid pesticides in a population. Three human urinary metabolites of pyrethroids were selected and validated as biomarkers of exposure by evaluating their sources and stability in wastewater. They were measured by liquid chromatography-tandem mass spectrometry in raw urban wastewater collected from the wastewater treatment plants of six Italian cities. Their concentrations were used as biomarkers to back-calculate the intake of pyrethroid pesticides in the population. WBE results were in line with the urinary biomarker levels of biomonitoring studies considering dilution in wastewater. Significant differences in the metabolites levels were observed among different cities. Seasonal variations in human intake of pyrethroids were also seen, as expected, with higher intakes during spring/summer. Intakes in the six cities were compared with the acceptable daily intake (ADI) and it was concluded that some of the populations examined might face significant health risks. Results confirm that this method can provide supplementary information to biomonitoring studies and can be a valuable tool for obtaining objective, direct information on the real levels of exposure to pyrethroids of different populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Predictive Biomarkers for Asthma Therapy.

PubMed

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.

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

PubMed

Rantalainen, Mattias; Klevebring, Daniel; Lindberg, Johan; Ivansson, Emma; Rosin, Gustaf; Kis, Lorand; Celebioglu, Fuat; Fredriksson, Irma; Czene, Kamila; Frisell, Jan; Hartman, Johan; Bergh, Jonas; Grönberg, Henrik

2016-11-30

Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data. Non-routine biomarkers, including mutations in BRCA1, BRCA2 and ERBB2(HER2), and additional clinically actionable somatic alterations were also investigated. Concordance with routine diagnostic biomarkers was high for ER status (AUC = 0.95;AUC(replication) = 0.97) and HER2 status (AUC = 0.97;AUC(replication) = 0.92). The transcriptomic grade model enabled classification of histological grade 1 and histological grade 3 tumors with high accuracy (AUC = 0.98;AUC(replication) = 0.94). Clinically actionable mutations in BRCA1, BRCA2 and ERBB2(HER2) were detected in 5.5% of patients, while 53% had genomic alterations matching ongoing or concluded breast cancer studies. Sequencing-based molecular profiling can be applied as an alternative to histopathology to determine ER and HER2 status, in addition to providing improved tumor grading and clinically actionable mutations and molecular subtypes. Our results suggest that sequencing-based breast cancer diagnostics in a near future can replace routine biomarkers.

Metabolomics-based promising candidate biomarkers and pathways in Alzheimer's disease.

PubMed

Kang, Jian; Lu, Jingli; Zhang, Xiaojian

2015-05-01

Pathologically, loss of synapses and neurons, extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) are observed in the brains of patients with Alzheimer's disease (AD). These features are associated with changes Aβ (amyloid β) 40, Aβ42, total tau and phosphorylated tau (p-tau), which are as definitely biomarkers for severe AD state. However, biomarkers for effectively diagnosing AD in the pre-clinical state for directing therapeutic strategies are lacking. Metabolic profiling as a powerful tool to identify new biomarkers is receiving increasing attention in AD. This review will focus on metabolomics-based detection of promising candidate biomarkers and pathways in AD to facilitate the discovery of new medicines and disease pathways.

Response characteristics of an aquatic biomonitor used for rapid toxicity detection.

PubMed

van der Schalie, W H; Shedd, T R; Widder, M W; Brennan, L M

2004-01-01

The response characteristics of an aquatic biomonitor that detects toxicity by monitoring changes in bluegill (Lepomis macrochirus Rafinesque) ventilatory and movement patterns were evaluated in single chemical laboratory studies at concentrations near the 96-h LC(50) concentration and at the EILATox-Oregon Workshop in sequential tests of multiple unknown samples. Baseline data collected prior to exposure allows each fish to serve as its own control. When at least 70% of exposed fish exhibit ventilatory or movement parameters significantly different from baseline observations, a group alarm is declared. In the laboratory studies, the aquatic biomonitor responded to the majority of chemicals at the 96-h lc(50) within an hour or less, although substantially higher response times were found for malathion and pentachlorophenol. Workshop tests of single chemical concentrations presented as blind samples were consistent with the laboratory test results. There were no alarms under control conditions in any test. Although data are limited, the aquatic biomonitor appears to respond more rapidly to chemicals causing membrane irritation, narcosis or polar narcosis than to acetylcholinesterase inhibitors or oxidative phosphorylation uncouplers. All four monitored parameters (ventilatory rate, cough rate, ventilatory depth and movement) contributed to identification of first alarms at acutely toxic levels. Understanding these response patterns can be useful in data interpretation for biomonitor applications such as surface water monitoring for watershed protection, wastewater treatment plant effluent monitoring or source water monitoring for drinking water protection. Copyright (c) 2004 John Wiley & Sons, Ltd.

The Use of Biomonitoring Data in Exposure and Human Health Risk Assessment: BENZENE CASE STUDY.

EPA Science Inventory

HESI Biomonitoring Technical Committee A framework of "Common Criteria" (i.e., a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment (Albertini et al., 2006). The data-rich chemical b...

Human biomonitoring data interpretation and ethics; obstacles or surmountable challenges?

PubMed Central

Sepai, Ovnair; Collier, Clare; Van Tongelen, Birgit; Casteleyn, Ludwine

2008-01-01

The use of human samples to assess environmental exposure and uptake of chemicals is more than an analytical exercise and requires consideration of the utility and interpretation of data as well as due consideration of ethical issues. These aspects are inextricably linked. In 2004 the EC expressed its commitment to the development of a harmonised approach to human biomonitoring (HBM) by including an action in the EU Environment and Health Strategy to develop a Human Biomonitoring Pilot Study. This further underlined the need for interpretation strategies as well as guidance on ethical issues. A workshop held in December 2006 brought together stakeholders from academia, policy makers as well as non-governmental organisations and chemical industry associations to a two day workshop built a mutual understanding of the issues in an open and frank discussion forum. This paper describes the discussion and recommendations from the workshop. The workshop developed key recommendations for a Pan-European HBM Study: 1. A strategy for the interpretation of human biomonitoring data should be developed. 2. The pilot study should include the development of a strategy to integrate health data and environmental monitoring with human biomonitoring data at national and international levels. 3. Communication strategies should be developed when designing the study and evolve as the study continues. 4. Early communication with stakeholders is essential to achieve maximum efficacy of policy developments and facilitate subsequent monitoring. 5. Member states will have to apply individually for project approval from their National Research Ethics Committees. 6. The study population needs to have sufficient information on the way data will be gathered, interpreted and disseminated and how samples will be stored and used in the future (if biobanking) before they can give informed consent. 7. The participants must be given the option of anonymity. This has an impact on follow-up. 8. The pilot

USING BIOMONITORING DATA TO INFORM EXPOSURE ASSESSMENT IN CHILDREN

EPA Science Inventory

Discussing the challenges associated with estimating and interpreting toxicant exposures and health risks from biomonitoring data. Extended abstract will also be translated in Spanish and published in Acta Toxicologica Argentina.

Human body burdens of chemicals used in plastic manufacture

PubMed Central

Koch, Holger M.; Calafat, Antonia M.

2009-01-01

In the last decades, the availability of sophisticated analytical chemistry techniques has facilitated measuring trace levels of multiple environmental chemicals in human biological matrices (i.e. biomonitoring) with a high degree of accuracy and precision. As biomonitoring data have become readily available, interest in their interpretation has increased. We present an overview on the use of biomonitoring in exposure and risk assessment using phthalates and bisphenol A as examples of chemicals used in the manufacture of plastic goods. We present and review the most relevant research on biomarkers of exposure for phthalates and bisphenol A, including novel and most comprehensive biomonitoring data from Germany and the United States. We discuss several factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information. PMID:19528056

Tillandsia usneoides: A successful alternative for biomonitoring changes in air quality due to a new highway in São Paulo, Brazil.

PubMed

Cardoso-Gustavson, Poliana; Fernandes, Francine Faia; Alves, Edenise Segala; Victorio, Mariana Pereira; Moura, Barbara Baesso; Domingos, Marisa; Rodrigues, Caroline Albuquerque; Ribeiro, Andreza Portella; Nievola, Catarina Carvalho; Figueiredo, Ana Maria G

2017-05-01

Tillandsia usneoides is an aerial epiphytic bromeliad that absorbs water and nutrients directly from the atmosphere by scales covering its surface. We expanded the use of this species as a broader biomonitor based on chemical and structural markers to detect changes in air quality. The usefulness of such comprehensive approach was tested during the construction and opening of a highway (SP-21) in São Paulo State, Brazil. The biomonitoring study was performed from 2009 to 2012, thus comprising the period during construction and after the highway inauguration. Metal accumulation and structural alterations were assessed, in addition to microscopy analyses to understand the metal chelation in plant tissues and to assess the causes of alterations in the number and shape of scale cells. Altogether, our analyses support the use of this species as a wide biomonitor of air quality in urbanized areas.

Tillandsia usneoides: a successful alternative for biomonitoring changes in air quality due to a new highway in São Paulo, Brazil.

PubMed

Cardoso-Gustavson, Poliana; Fernandes, Francine Faia; Alves, Edenise Segala; Victorio, Mariana Pereira; Moura, Barbara Baesso; Domingos, Marisa; Rodrigues, Caroline Albuquerque; Ribeiro, Andreza Portella; Nievola, Catarina Carvalho; Figueiredo, Ana Maria G

2016-01-01

Tillandsia usneoides is an aerial epiphytic bromeliad that absorbs water and nutrients directly from the atmosphere by scales covering its surface. We expanded the use of this species as a broader biomonitor based on chemical and structural markers to detect changes in air quality. The usefulness of such comprehensive approach was tested during the construction and opening of a highway (SP-21) in São Paulo State, Brazil. The biomonitoring study was performed from 2009 to 2012, thus comprising the period during construction and after the highway inauguration. Metal accumulation and structural alterations were assessed, in addition to microscopy analyses to understand the metal chelation in plant tissues and to assess the causes of alterations in the number and shape of scale cells. Altogether, our analyses support the use of this species as a wide biomonitor of air quality in urbanized areas.

PHARMACOKINETIC MODELS IN THE DESIGN OF BIOMONITORING PROGRAMS

EPA Science Inventory

Measurements of chemicals in tissues, blood, or urine can be related to health effects because they are an integrated measure of absorbed dose following exposure. However, the direct relationship between biomonitoring data and pathway-specific exposures is more tenuous. In chem...

Integrated multi-biomarker responses in two dreissenid species following metal and thermal cross-stress.

PubMed

Potet, Marine; Devin, Simon; Pain-Devin, Sandrine; Rousselle, Philippe; Giambérini, Laure

2016-11-01

With current global changes, the combination of several stressors such as temperature and contaminants may impact species distribution and ecosystem functioning. In this study, we evaluated the combined impact of two metals (Ni and Cr) with a thermal stress (from 12 to 17 °C) on biomarker responses in two bivalves, Dreissena rostriformis bugensis and Dreissena polymorpha. Biomarkers are informative tools to evaluate exposure and effects of stressors on organisms. The set of 14 biomarkers measured here was representative of both physiologic (filtration activity) and cellular antioxidant and detoxification mechanisms. Our aim was to study the response pattern of both species, and its meaning in terms of invasive potential. The implications for the use of these mussels in environmental monitoring are also discussed. Results evidenced that the two species do not respond to multiple stressors in the same way. Indeed, the effects of contamination on biomarker responses were more marked for D. polymorpha, especially under nickel exposure. While we cannot conclude as to the effect of temperature, invasiveness could be influenced by species sensitivity to contaminants. The physiological and cellular differences between D. polymorpha and D. r. bugensis might also be of concern for environmental risk assessment. The two species present differential bioaccumulation patterns, filtration activity and cellular biomarker responses. If D. polymorpha populations decline, their substitution by D. r. bugensis for biomonitoring or laboratory studies will not be possible without a deeper understanding of biomarker responses of the new invasive. Copyright © 2016 Elsevier Ltd. All rights reserved.

Leveraging molecular datasets for biomarker-based clinical trial design in glioblastoma.

PubMed

Tanguturi, Shyam K; Trippa, Lorenzo; Ramkissoon, Shakti H; Pelton, Kristine; Knoff, David; Sandak, David; Lindeman, Neal I; Ligon, Azra H; Beroukhim, Rameen; Parmigiani, Giovanni; Wen, Patrick Y; Ligon, Keith L; Alexander, Brian M

2017-07-01

Biomarkers can improve clinical trial efficiency, but designing and interpreting biomarker-driven trials require knowledge of relationships among biomarkers, clinical covariates, and endpoints. We investigated these relationships across genomic subgroups of glioblastoma (GBM) within our institution (DF/BWCC), validated results in The Cancer Genome Atlas (TCGA), and demonstrated potential impacts on clinical trial design and interpretation. We identified genotyped patients at DF/BWCC, and clinical associations across 4 common GBM genomic biomarker groups were compared along with overall survival (OS), progression-free survival (PFS), and survival post-progression (SPP). Significant associations were validated in TCGA. Biomarker-based clinical trials were simulated using various assumptions. Epidermal growth factor receptor (EGFR)(+) and p53(-) subgroups were more likely isocitrate dehydrogenase (IDH) wild-type. Phosphatidylinositol-3 kinase (PI3K)(+) patients were older, and patients with O6-DNA methylguanine-methyltransferase (MGMT)-promoter methylation were more often female. OS, PFS, and SPP were all longer for IDH mutant and MGMT methylated patients, but there was no independent prognostic value for other genomic subgroups. PI3K(+) patients had shorter PFS among IDH wild-type tumors, however, and no DF/BWCC long-term survivors were either EGFR(+) (0% vs 7%, P = .014) or p53(-) (0% vs 10%, P = .005). The degree of biomarker overlap impacted the efficiency of Bayesian-adaptive clinical trials, while PFS and OS distribution variation had less impact. Biomarker frequency was proportionally associated with sample size in all designs. We identified several associations between GBM genomic subgroups and clinical or molecular prognostic covariates and validated known prognostic factors in all survival periods. These results are important for biomarker-based trial design and interpretation of biomarker-only and nonrandomized trials. © The Author(s) 2017. Published by

Evaluating Ethanol-based Sample Preservation to Facilitate Use of DNA Barcoding in Routine Freshwater Biomonitoring Programs Using Benthic Macroinvertebrates

EPA Science Inventory

Molecular methods, such as DNA barcoding, have the potential in enhance biomonitoring programs worldwide. Altering routinely used sample preservation methods to protect DNA from degradation may pose a potential impediment to application of DNA barcoding and metagenomics for biom...

Blood-based protein biomarkers for diagnosis of Alzheimer disease.

PubMed

Doecke, James D; Laws, Simon M; Faux, Noel G; Wilson, William; Burnham, Samantha C; Lam, Chiou-Peng; Mondal, Alinda; Bedo, Justin; Bush, Ashley I; Brown, Belinda; De Ruyck, Karl; Ellis, Kathryn A; Fowler, Christopher; Gupta, Veer B; Head, Richard; Macaulay, S Lance; Pertile, Kelly; Rowe, Christopher C; Rembach, Alan; Rodrigues, Mark; Rumble, Rebecca; Szoeke, Cassandra; Taddei, Kevin; Taddei, Tania; Trounson, Brett; Ames, David; Masters, Colin L; Martins, Ralph N

2012-10-01

To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. General community-based, prospective, longitudinal study of aging. A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β(2) microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.

Field protection effectiveness of chemical protective suits and gloves evaluated by biomonitoring

PubMed Central

Chang, F K; Chen, M L; Cheng, S F; Shih, T S; Mao, I F

2007-01-01

Objectives To determine the effectiveness of protective suits and gloves by biomonitoring. Methods Fifteen male spray painters at a ship coating factory were studied for two weeks. Workers wore no protective clothing during the first week and wore protective suits and gloves during the second week. Sampling was conducted on four consecutive working days each week. Ethyl benzene and xylene in the air were collected by using 3M 3500 organic vapour monitors. Urine was collected before and after each work shift. Results Urinary mandelic acid (MA) and methyl hippuric acid (MHA) levels were divided by the personal exposure concentrations of ethyl benzene and xylene, respectively. Mean (SE) corrected MA and MHA concentrations in the first week were 1.07 (0.18) and 2.66 (0.68) (mg/g creatinine)/(mg/m3), and concentrations in the second week were 0.50 (0.12) and 1.76 (0.35) (mg/g creatinine)/(mg/m3) in the second week, respectively. Both MA and MHA concentrations in the second week (when spray painters wore protective suits and gloves) were lower than in the first week, respectively (p<0.001, p = 0.011). Mean decrease in MA and MHA biomarkers were 69% and 49%, respectively. Conclusion This study successfully evaluated the effectiveness of chemical protective suits and gloves by using biomarkers as urinary MA and MHA. This method is feasible for determining the performance of workers wearing personal protective equipment. Moreover, the experimental results suggest that dermal exposure may be the major contributor to total body burden of solvents in spray painters without protective suits and gloves. PMID:17522137

Metabolomics Based Dietary Biomarkers in Nutritional Epidemiology- Current Status and Future Opportunities.

PubMed

Brennan, Lorraine; Hu, Frank B

2018-04-24

The application of metabolomics in nutrition epidemiology holds great promise and there is a high expectation that it will play a leading role in deciphering the interactions between diet and health. However, while significant progress has been made in identification of putative biomarkers more work is needed to address the use of the biomarkers in dietary assessment. The aim of this review to critically evaluate progress in these areas and to identify challenges that need to be addressed going forward. The notable applications of dietary biomarkers in nutritional epidemiology include (1) Determination of food intake based on biomarkers levels and calibration equations from feeding studies (2) Classification of individuals into dietary patterns based on the urinary metabolic profile and (3) Application of metabolome-wide-association studies. Further work is needed to address some specific challenges to enable biomarkers to reach their full potential. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Biomonitoring Human Exposure to Household Air Pollution and Association with Self-reported Health Symptoms - A Stove Intervention Study in Peru.

PubMed

Li, Zheng; Commodore, Adwoa; Hartinger, Stella; Lewin, Michael; Sjödin, Andreas; Pittman, Erin; Trinidad, Debra; Hubbard, Kendra; Lanata, Claudio F; Gil, Ana I; Mäusezahl, Daniel; Naeher, Luke P

2016-12-01

Household air pollution (HAP) from indoor biomass stoves contains harmful pollutants, such as polycyclic aromatic hydrocarbons (PAHs), and is a leading risk factor for global disease burden. We used biomonitoring to assess HAP exposure and association with self-reported symptoms in 334 non-smoking Peruvian women to evaluate the efficacy of a stove intervention program. We conducted a cross-sectional study within the framework of a community randomized control trial. Using urinary PAH metabolites (OH-PAHs) as the exposure biomarkers, we investigated whether the intervention group (n=155, with new chimney-equipped stoves) were less exposed to HAP compared to the control group (n=179, with mostly open-fire stoves). We also estimated associations between the exposure biomarkers, risk factors, and self-reported health symptoms, such as recent eye conditions, respiratory conditions, and headache. We observed reduced headache and ocular symptoms in the intervention group than the control group. Urinary 2-naphthol, a suggested biomarker for inhalation PAH exposure, was significantly lower in the intervention group (GM with 95% CI: 13.4 [12.3, 14.6] μg/g creatinine) compared to control group (16.5 [15.0, 18.0] μg/g creatinine). Stove type and/or 2-naphthol was associated with a number of self-reported symptoms, such as red eye (adjusted OR with 95% CI: 3.80 [1.32, 10.9]) in the past 48h. Even with the improved stoves, the biomarker concentrations in this study far exceeded those of the general populations and were higher than a no-observed-genotoxic-effect-level, indicating high exposure and a potential for increased cancer risk in the population. Published by Elsevier Ltd.

Mass spectrometry based biomarker discovery, verification, and validation--quality assurance and control of protein biomarker assays.

PubMed

Parker, Carol E; Borchers, Christoph H

2014-06-01

In its early years, mass spectrometry (MS)-based proteomics focused on the cataloging of proteins found in different species or different tissues. By 2005, proteomics was being used for protein quantitation, typically based on "proteotypic" peptides which act as surrogates for the parent proteins. Biomarker discovery is usually done by non-targeted "shotgun" proteomics, using relative quantitation methods to determine protein expression changes that correlate with disease (output given as "up-or-down regulation" or "fold-increases"). MS-based techniques can also perform "absolute" quantitation which is required for clinical applications (output given as protein concentrations). Here we describe the differences between these methods, factors that affect the precision and accuracy of the results, and some examples of recent studies using MS-based proteomics to verify cancer-related biomarkers. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Weakly electric fish for biomonitoring water quality.

PubMed

Clausen, Juergen; van Wijk, Roeland; Albrecht, Henning

2012-06-01

Environmental pollution is a major issue that calls for suitable monitoring systems. The number of possible pollutants of municipal and industrial water grows annually as new chemicals are developed. Technical devices for pollutant detection are constructed in a way to detect a specific and known array of pollutants. Biological systems react to lethal or non-lethal environmental changes without pre-adjustment, and a wide variety have been employed as broad-range monitors for water quality. Weakly electric fish have proven particularly useful for the purpose of biomonitoring municipal and industrial waters. The frequency of their electric organ discharges directly correlates with the quality of the surrounding water and, in this way, concentrations of toxicants down to the nanomolar range have been successfully detected by these organisms. We have reviewed the literature on biomonitoring studies to date, comparing advantages and disadvantages of this test system and summarizing the lowest concentrations of various toxicants tested. Eighteen publications were identified investigating 35 different chemical substances and using six different species of weakly electric fish.

Verifying community-wide exposure to endocrine disruptors in personal care products - In quest for metabolic biomarkers of exposure via in vitro studies and wastewater-based epidemiology.

PubMed

Lopardo, Luigi; Adams, David; Cummins, Andrew; Kasprzyk-Hordern, Barbara

2018-06-14

This study aimed to identify human specific metabolites of selected known or suspected endocrine disruptors (EDCs), mainly UV filters, used in personal care and consumer products whose metabolism has hardly been explored and to select suitable candidate biomarkers for human exposure studies using wastewater based epidemiology (WBE). The analysis of metabolic biomarkers of target chemicals is crucial in order to distinguish between internal and external exposure, since many sources contribute to chemicals being discharged into wastewater. This was achieved through the employment of a new analytical framework for verification of biomarkers of exposure to chemicals combining human biomonitoring and water fingerprinting. Eight EDCs with unknown metabolic pathways (benzophenone-1 (BP-1); benzophenone-2 (BP-2); 4,4'-dihydroxybenzophenone (4,4'-DHBP); 4-benzylphenol (4-BenzPh); homosalate (HO); octocrylene (OC); 3-benzylidene camphor (3-BC), and two EDCs with known metabolism (bisphenol A (BPA) and benzophenone-3 (BP-3)) were tested. The biotransformation observed consisted mainly of phase I processes such as hydrolysis and hydroxylation together with phase II conjugation reactions such as sulphation and glucuronidation. Only two chemicals (BP-1, BP-3) were identified in urine and three chemicals (BPA, BP-1, BP-3) in wastewater. Five newly discovered metabolites (HO-Met1, OC-Met1, 4-BenzPh-Met4, 4-BenzPh-Met5 and 4-BenzPh-Met6) and one previously known metabolite (BPA-Met3) were detected in tested urine/wastewater samples from five WWTPs serving large communities ranging between 17 and 100 thousand inhabitants. The presence of metabolic biotransformation products of OC, 4-BenzPh, BPA and HO in wastewater provides evidence for internal exposure of studied populations to these chemicals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biomarkers of polycyclic aromatic hydrocarbon exposure in European coke oven workers.

PubMed

Talaska, Glenn; Thoroman, Jeff; Schuman, Brenda; Käfferlein, Heiko Udo

2014-12-01

Biomonitoring is an excellent method for capturing the results of all exposures, regardless of route. Coke oven workers include certain groups that have the potential for high exposure to polycyclic aromatic hydrocarbons (PAH) and other materials. Biomarkers of exposure to these agents include PAH metabolites as markers of internal dose and carcinogen-DNA adducts as measure of effective dose. The purpose of this study was to determine the levels of these biomarkers in persons with different job duties in a modern coke oven plant. We report that the mean levels of 1-hydroxypyrene (1HP) and carcinogen DNA adducts in the exfoliated urothelial cells of coke oven workers are increased the closer a group of workers is to the ovens and highest in the top oven workers with average 1HP level of 11.6 μg/l and 22 adducts per 10(9) unadducted nucleotides. Both 1HP and carcinogen DNA adduct levels increased in supervisors, area workers, side oven workers, top and side oven workers, and top oven workers, respectively. These data are the first to demonstrate an increase in target organ genotoxicity in coke oven workers and a relationship with other biomarkers. Future studies will determine the identity of the DNA adducts, their correlation with 1HP levels and the relationship between levels in individual workers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Resource-Based Capability on Development Knowledge Management Capabilities of Coastal Community

NASA Astrophysics Data System (ADS)

Teniwut, Roberto M. K.; Hasyim, Cawalinya L.; Teniwut, Wellem A.

2017-10-01

Building sustainable knowledge management capabilities in the coastal area might face a whole new challenge since there are many intangible factors involved from openness on new knowledge, access and ability to use the latest technology to the various local wisdom that still in place. The aimed of this study was to identify and analyze the resource-based condition of coastal community in this area to have an empirical condition of tangible and intangible infrastructure on developing knowledge management capability coastal community in Southeast Maluku, Indonesia. We used qualitative and quantitative analysis by depth interview and questionnaire for collecting the data with multiple linear regression as our analysis method. The result provided the information on current state of resource-based capability of a coastal community in this Southeast Maluku to build a sustainability model of knowledge management capabilities especially on utilization marine and fisheries resources. The implication of this study can provide an empirical information for government, NGO and research institution to dictate on how they conducted their policy and program on developing coastal community region.

Evaluating environmental modeling and sampling data with biomarker data to identify sources and routes of exposure

NASA Astrophysics Data System (ADS)

Shin, Hyeong-Moo; McKone, Thomas E.; Bennett, Deborah H.

2013-04-01

Exposure to environmental chemicals results from multiple sources, environmental media, and exposure routes. Ideally, modeled exposures should be compared to biomonitoring data. This study compares the magnitude and variation of modeled polycyclic aromatic hydrocarbons (PAHs) exposures resulting from emissions to outdoor and indoor air and estimated exposure inferred from biomarker levels. Outdoor emissions result in both inhalation and food-based exposures. We modeled PAH intake doses using U.S. EPA's 2002 National Air Toxics Assessment (NATA) county-level emissions data for outdoor inhalation, the CalTOX model for food ingestion (based on NATA emissions), and indoor air concentrations from field studies for indoor inhalation. We then compared the modeled intake with the measured urine levels of hydroxy-PAH metabolites from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) survey as quantifiable human intake of PAH parent-compounds. Lognormal probability plots of modeled intakes and estimated intakes inferred from biomarkers suggest that a primary route of exposure to naphthalene, fluorene, and phenanthrene for the U.S. population is likely inhalation from indoor sources. For benzo(a)pyrene, the predominant exposure route is likely from food ingestion resulting from multi-pathway transport and bioaccumulation due to outdoor emissions. Multiple routes of exposure are important for pyrene. We also considered the sensitivity of the predicted exposure to the proportion of the total naphthalene production volume emitted to the indoor environment. The comparison of PAH biomarkers with exposure variability estimated from models and sample data for various exposure pathways supports that both indoor and outdoor models are needed to capture the sources and routes of exposure to environmental contaminants.

Challenges in Biomarker Discovery: Combining Expert Insights with Statistical Analysis of Complex Omics Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Jason E.; Wang, Jing; Mitchell, Hugh D.

2013-01-01

The advent of high throughput technologies capable of comprehensive analysis of genes, transcripts, proteins and other significant biological molecules has provided an unprecedented opportunity for the identification of molecular markers of disease processes. However, it has simultaneously complicated the problem of extracting meaningful signatures of biological processes from these complex datasets. The process of biomarker discovery and characterization provides opportunities both for purely statistical and expert knowledge-based approaches and would benefit from improved integration of the two. Areas covered In this review we will present examples of current practices for biomarker discovery from complex omic datasets and the challenges thatmore » have been encountered. We will then present a high-level review of data-driven (statistical) and knowledge-based methods applied to biomarker discovery, highlighting some current efforts to combine the two distinct approaches. Expert opinion Effective, reproducible and objective tools for combining data-driven and knowledge-based approaches to biomarker discovery and characterization are key to future success in the biomarker field. We will describe our recommendations of possible approaches to this problem including metrics for the evaluation of biomarkers.« less

CONCLUSIONS AND RECOMMENDATIONS OF THE EXPERT PANEL: TECHNICAL WORKSHOP ON HUMAN MILK SURVEILLANCE AND BIOMONITORING FOR ENVIRONMENTAL CHEMICALS IN THE UNITED STATES

EPA Science Inventory

The Technical Workshop focused on questions related to interpretation of information gathered from human milk biomonitoring studies. Biomonitoring can measure a person’s exposure to a chemical in his/her tissue. Human milk is a unique biological matrix for biomonitoring because i...

Biomonitoring Human Exposure to Household Air Pollution and Association with Self-reported Health Symptoms – A Stove Intervention Study in Peru

PubMed Central

Li, Zheng; Commodore, Adwoa; Hartinger, Stella; Lewin, Michael; Sjödin, Andreas; Pittman, Erin; Trinidad, Debra; Hubbard, Kendra; Lanata, Claudio F.; Gil, Ana I.; Mäusezahl, Daniel; Naeher, Luke P.

2016-01-01

Background Household air pollution (HAP) from indoor biomass stoves contains harmful pollutants, such as polycyclic aromatic hydrocarbons (PAHs), and is a leading risk factor for global disease burden. We used biomonitoring to assess HAP exposure and association with self-reported symptoms in 334 non-smoking Peruvian women to evaluate the efficacy of a stove intervention program. Methods We conducted a cross-sectional study within the framework of a community randomized control trial. Using urinary PAH metabolites (OH-PAHs) as the exposure biomarkers, we investigated whether the intervention group (n = 155, with new chimney-equipped stoves) were less exposed to HAP compared to the control group (n = 179, with mostly open-fire stoves). We also estimated associations between the exposure biomarkers, risk factors, and self-reported health symptoms, such as recent eye conditions, respiratory conditions, and headache. Results We observed reduced headache and ocular symptoms in the intervention group than the control group. Urinary 2-naphthol, a suggested biomarker for inhalation PAH exposure, was significantly lower in the intervention group (GM with 95% CI: 13.4 [12.3, 14.6] μg/g creatinine) compared to control group (16.5 [15.0, 18.0] μg/g creatinine). Stove type and/or 2-naphthol was associated with a number of self-reported symptoms, such as red eye (adjusted OR with 95% CI: 3.80 [1.32, 10.9]) in the past 48 h. Conclusions Even with the improved stoves, the biomarker concentrations in this study far exceeded those of the general populations and were higher than a no-observed-genotoxic-effect-level, indicating high exposure and a potential for increased cancer risk in the population. PMID:27680405

Ultratrace level determination and quantitative analysis of kidney injury biomarkers in patient samples attained by zinc oxide nanorods

NASA Astrophysics Data System (ADS)

Singh, Manpreet; Alabanza, Anginelle; Gonzalez, Lorelis E.; Wang, Weiwei; Reeves, W. Brian; Hahm, Jong-In

2016-02-01

Determining ultratrace amounts of protein biomarkers in patient samples in a straightforward and quantitative manner is extremely important for early disease diagnosis and treatment. Here, we successfully demonstrate the novel use of zinc oxide nanorods (ZnO NRs) in the ultrasensitive and quantitative detection of two acute kidney injury (AKI)-related protein biomarkers, tumor necrosis factor (TNF)-α and interleukin (IL)-8, directly from patient samples. We first validate the ZnO NRs-based IL-8 results via comparison with those obtained from using a conventional enzyme-linked immunosorbent method in samples from 38 individuals. We further assess the full detection capability of the ZnO NRs-based technique by quantifying TNF-α, whose levels in human urine are often below the detection limits of conventional methods. Using the ZnO NR platforms, we determine the TNF-α concentrations of all 46 patient samples tested, down to the fg per mL level. Subsequently, we screen for TNF-α levels in approximately 50 additional samples collected from different patient groups in order to demonstrate a potential use of the ZnO NRs-based assay in assessing cytokine levels useful for further clinical monitoring. Our research efforts demonstrate that ZnO NRs can be straightforwardly employed in the rapid, ultrasensitive, quantitative, and simultaneous detection of multiple AKI-related biomarkers directly in patient urine samples, providing an unparalleled detection capability beyond those of conventional analysis methods. Additional key advantages of the ZnO NRs-based approach include a fast detection speed, low-volume assay condition, multiplexing ability, and easy automation/integration capability to existing fluorescence instrumentation. Therefore, we anticipate that our ZnO NRs-based detection method will be highly beneficial for overcoming the frequent challenges in early biomarker development and treatment assessment, pertaining to the facile and ultrasensitive quantification

Biomonitoring persistent organic pollutants in the atmosphere with mosses: performance and application.

PubMed

Wu, Qimei; Wang, Xin; Zhou, Qixing

2014-05-01

Persistent organic pollutants (POPs) have aroused environmentalists and public concerns due to their toxicity, bioaccumulation and persistency in the environment. However, monitoring atmospheric POPs using conventional instrumental methods is difficult and expensive, and POP levels in air samples represent an instantaneous value at a sampling time. Biomonitoring methods can overcome this limitation, because biomonitors can accumulate POPs, serve as long-term integrators of POPs and provide reliable information to assess the impact of pollutants on the biota and various ecosystems. Recently, mosses are increasingly employed to monitor atmospheric POPs. Mosses have been applied to indicate POP pollution levels in the remote continent of Antarctica, trace distribution of POPs in the vicinity of pollution sources, describe the spatial patterns at the regional scale, and monitor the changes in the pollution intensity along time. In the future, many aspects need to be improved and strengthened: (i) the relationship between the concentrations of POPs in mosses and in the atmosphere (different size particulates and vapor phases); and (ii) the application of biomonitoring with mosses in human health studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

HISTORY OF BIOMONITORING IN THE UNITED STATES - EXTENDED ABSTRACT

EPA Science Inventory

Biomonitoring of ecological systems has a long history dating back several centuries when high levels of industrial and urban pollution caused discolored rivers, noxious smells, fish kills, and other obvious indicators of ecosystem dysfunction. As a result, significant environmen...

EQCM Immunoassay for Phosphorylated Acetylcholinesterase as a Biomarker for Organophosphate Exposures Based on Selective Zirconia Adsorption and Enzyme-Catalytic Precipitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hua; Wang, Jun; Choi, Daiwon

2009-03-01

A zirconia (ZrO2) adsorption-based immunoassay by electrochemical quartz crystal microbalance (EQCM) has been initially developed, aiming at the detection of phosphorylated acetylcholinesterase (AChE) as a potential biomarker for bio-monitoring exposures to organophosphate (OP) pesticides and chemical warfare agents. Hydroxyl-derivatized monolayer was preferably chosen to modify the crystal serving as the template for directing the electro-deposition of ZrO2 film with uniform nanostructures. The resulting ZrO2 film was utilized to selectively capture phosphorylated AChE from the sample media. Horseradish peroxidase (HRP)-labeled anti-AChE antibodies were further employed to recognize the captured phosphorylated protein. Enzyme-catalytic oxidation of the benzidine substrate resulted in the accumulationmore » of insoluble product on the functionalized crystal. Ultrasensitive EQCM quantification by mass-amplified frequency responses as well as rapid qualification by visual color changes of product could be thus achieved. Moreover, 4-chloro-1-naphthol (CN) was comparably studied as an ideal chromogenic substrate for the enzyme-catalytic precipitation. Experimental results show that the developed EQCM technique can allow for the detection of phosphorylated AChE in human plasma. Such an EQCM immunosensing format opens a new door towards the development of simple, sensitive, and field-applicable biosensor for biologically monitoring low-level OP exposures.« less

HUMAN MILK BIOMONITORING DATA: INTERPRETATION AND RISK ASSESSMENT ISSUES

EPA Science Inventory

Biomonitoring data can, under certain conditions, be used to describe potential risks to human health (for example, blood lead levels used to determine children's neurodevelopmental risk). At present, there are very few chemical exposures at low levels for which sufficient data ...

Current and Prospective Protein Biomarkers of Lung Cancer

PubMed Central

Zamay, Tatiana N.; Zamay, Galina S.; Kolovskaya, Olga S.; Zukov, Ruslan A.; Petrova, Marina M.; Gargaun, Ana; Berezovski, Maxim V.

2017-01-01

Lung cancer is a malignant lung tumor with various histological variants that arise from different cell types, such as bronchial epithelium, bronchioles, alveoli, or bronchial mucous glands. The clinical course and treatment efficacy of lung cancer depends on the histological variant of the tumor. Therefore, accurate identification of the histological type of cancer and respective protein biomarkers is crucial for adequate therapy. Due to the great diversity in the molecular-biological features of lung cancer histological types, detection is impossible without knowledge of the nature and origin of malignant cells, which release certain protein biomarkers into the bloodstream. To date, different panels of biomarkers are used for screening. Unfortunately, a uniform serum biomarker composition capable of distinguishing lung cancer types is yet to be discovered. As such, histological analyses of tumor biopsies and immunohistochemistry are the most frequently used methods for establishing correct diagnoses. Here, we discuss the recent advances in conventional and prospective aptamer based strategies for biomarker discovery. Aptamers like artificial antibodies can serve as molecular recognition elements for isolation detection and search of novel tumor-associated markers. Here we will describe how these small synthetic single stranded oligonucleotides can be used for lung cancer biomarker discovery and utilized for accurate diagnosis and targeted therapy. Furthermore, we describe the most frequently used in-clinic and novel lung cancer biomarkers, which suggest to have the ability of differentiating between histological types of lung cancer and defining metastasis rate. PMID:29137182

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

PubMed

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.

Sensitive Detection of Protein and miRNA Cancer Biomarkers using Silicon-Based Photonic Crystals and A Resonance Coupling Laser Scanning Platform

PubMed Central

George, Sherine; Chaudhery, Vikram; Lu, Meng; Takagi, Miki; Amro, Nabil; Pokhriyal, Anusha; Tan, Yafang; Ferreira, Placid; Cunningham, Brian T.

2013-01-01

Enhancement of the fluorescent output of surface-based fluorescence assays by performing them upon nanostructured photonic crystal (PC) surfaces has been demonstrated to increase signal intensities by >8000×. Using the multiplicative effects of optical resonant coupling to the PC in increasing the electric field intensity experienced by fluorescent labels (“enhanced excitation”) and the spatially biased funneling of fluorophore emissions through coupling to PC resonances (“enhanced extraction”), PC enhanced fluorescence (PCEF) can be adapted to reduce the limits of detection of disease biomarker assays, and to reduce the size and cost of high sensitivity detection instrumentation. In this work, we demonstrate the first silicon-based PCEF detection platform for multiplexed biomarker assay. The sensor in this platform is a silicon-based PC structure, comprised of a SiO2 grating that is overcoated with a thin film of high refractive index TiO2 and is produced in a semiconductor foundry for low cost, uniform, and reproducible manufacturing. The compact detection instrument that completes this platform was designed to efficiently couples fluorescence excitation from a semiconductor laser to the resonant optical modes of the PC, resulting in elevated electric field strength that is highly concentrated within the region <100 nm from the PC surface. This instrument utilizes a cylindrically focused line to scan a microarray in <1 minute. To demonstrate the capabilities of this sensor-detector platform, microspot fluorescent sandwich immunoassays using secondary antibodies labeled with Cy5 for two cancer biomarkers (TNF-α and IL-3) were performed. Biomarkers were detected at concentrations as low as 0.1 pM. In a fluorescent microarray for detection of a breast cancer miRNA biomarker miR-21, the miRNA was detectable at a concentration of 0.6 pM. PMID:23963502

Omics-based biomarkers: current status and potential use in the clinic.

PubMed

Quezada, Héctor; Guzmán-Ortiz, Ana Laura; Díaz-Sánchez, Hugo; Valle-Rios, Ricardo; Aguirre-Hernández, Jesús

In recent years, the use of high-throughput omics technologies has led to the rapid discovery of many candidate biomarkers. However, few of them have made the transition to the clinic. In this review, the promise of omics technologies to contribute to the process of biomarker development is described. An overview of the current state in this area is presented with examples of genomics, proteomics, transcriptomics, metabolomics and microbiomics biomarkers in the field of oncology, along with some proposed strategies to accelerate their validation and translation to improve the care of patients with neoplasms. The inherent complexity underlying neoplasms combined with the requirement of developing well-designed biomarker discovery processes based on omics technologies present a challenge for the effective development of biomarkers that may be useful in guiding therapies, addressing disease risks, and predicting clinical outcomes. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Biomonitoring of polycyclic aromatic compounds in the urine of mining workers occupationally exposed to diesel exhaust.

PubMed

Seidel, Albrecht; Dahmann, Dirk; Krekeler, Horst; Jacob, Juergen

2002-02-01

Diesel exhaust is considered a probable human carcinogen by the IARC. Biomonitoring of workers occupationally exposed to diesel exhaust was performed to determine their internal burden of diesel associated aromatic compounds. Personal air sampling also allowed to determine the exposure of the miners at their work place towards several polycyclic aromatic hydrocarbons (PAH) and nitro-arenes, the latter of which are thought to be specific constituents of diesel exhaust. For biomonitoring the urine of 18 underground salt miners was collected during and after their shift for 24-hours. half of the 18 miners were smokers. The urinary levels of 1-hydroxypyrene and hydroxylated phenanthrene metabolites were determined as biomarkers of PAH exposure, whereas urinary levels of some aromatic amines were chosen to monitor exposure towards specific nitro-arenes from diesel exhaust like 1-nitropyrene and 3-nitrobenzanthrone and to monitor the human burden by these compounds from inhaled cigarette smoke. Non-smoking workers exposed to diesel exhaust excrete an average level of about 4 micrograms phenanthrene metabolites, whereas the urinary levels in smokers were up to 3-fold higher. In summary the results indicate that (i) diesel exposure led to an increase of PAH metabolism in the workers examined, most probably by an induction of cytochrome P450 (ii) smokers could be identified in accordance with earlier studies by their increased ratio of phenanthrene metabolites derived from 1,2- and 3,4-oxidation and their higher amounts of excreted 1-naphthylamine, and (iii) the excreted amounts of aromatic amines found as metabolites of the nitro-arenes were about 5- to 10-fold higher as one might expect from the levels determined by personal air sampling at the workplace of the individuals.

Suitability of Tillandsia usneoides and Aechmea fasciata for biomonitoring toxic elements under tropical seasonal climate.

PubMed

Giampaoli, Patricia; Wannaz, Eduardo D; Tavares, Armando R; Domingos, Marisa

2016-04-01

Aechmea fasciata was evaluated for the first time as a biomonitor of toxic elements, in comparison to the biomonitoring capacity of Tillandsia usneoides, a well-established biomonitor bromeliad species. Plants of both species were exposed to air pollutants from industrial, urban, and agricultural sources, under the tropical seasonal climate, from June/2011 to April/2013, in five sites of São Paulo State, Brazil, for 8 consecutive exposure periods of 12 weeks each. The levels of essential and non-essential elements, including trace metals, were quantified at the end of each exposure. T. usneoides and A. fasciata indicated N, Fe, Zn, Co, Cr, and V as air contaminants in the studied sites, during wet and dry seasons and both species were recommended for qualitative biomonitoring. Concentration levels of N, Ca, S, Fe, Zn, Cu, B, Co, and Ni were significantly higher in T. usneoides than in A. fasciata. However, A. fasciata showed a higher effective retention capacity of Ni, Pb, V, Cu, Fe, Cr, and Co during field exposure, as indicated by the estimate of enrichment factor relative to basal concentrations. This species is more suitable for detecting the atmospheric pollution level of those metals than the T. usneoides. Both species indicated adequately the seasonal differences in the pollution levels of several elements, but T. usneoides presented higher ability for biomonitoring the spatial variations and for indicating more properly the sources of each element in the studied region than the A. fasciata. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of Biomonitoring Data from the CDC National Exposure Report in a Risk Assessment Context: Perspectives across Chemicals

EPA Science Inventory

BACKGROUND: Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals (NER) provide information on the presence and concentrations of more than 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment...

Nanomaterial-Based Electrochemical Immunosensors for Clinically Significant Biomarkers

PubMed Central

Ronkainen, Niina J.; Okon, Stanley L.

2014-01-01

Nanotechnology has played a crucial role in the development of biosensors over the past decade. The development, testing, optimization, and validation of new biosensors has become a highly interdisciplinary effort involving experts in chemistry, biology, physics, engineering, and medicine. The sensitivity, the specificity and the reproducibility of biosensors have improved tremendously as a result of incorporating nanomaterials in their design. In general, nanomaterials-based electrochemical immunosensors amplify the sensitivity by facilitating greater loading of the larger sensing surface with biorecognition molecules as well as improving the electrochemical properties of the transducer. The most common types of nanomaterials and their properties will be described. In addition, the utilization of nanomaterials in immunosensors for biomarker detection will be discussed since these biosensors have enormous potential for a myriad of clinical uses. Electrochemical immunosensors provide a specific and simple analytical alternative as evidenced by their brief analysis times, inexpensive instrumentation, lower assay cost as well as good portability and amenability to miniaturization. The role nanomaterials play in biosensors, their ability to improve detection capabilities in low concentration analytes yielding clinically useful data and their impact on other biosensor performance properties will be discussed. Finally, the most common types of electroanalytical detection methods will be briefly touched upon. PMID:28788700

Biomarker-based risk prediction in the community.

PubMed

AbouEzzeddine, Omar F; McKie, Paul M; Scott, Christopher G; Rodeheffer, Richard J; Chen, Horng H; Michael Felker, G; Jaffe, Allan S; Burnett, John C; Redfield, Margaret M

2016-11-01

Guided by predictive characteristics of cardiovascular biomarkers, we explored the clinical implications of a simulated biomarker-guided heart failure (HF) and major adverse cardiovascular events (MACE) prevention strategy in the community. In a community cohort (n = 1824), the predictive characteristics for HF and MACE of galectin-3 (Gal-3), ST2, high-sensitivity cardiac troponin I (hscTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) were established. We performed number needed to screen (NNS) and treat (NNT) with the intervention analyses according to biomarker screening strategy and intervention efficacy in persons with at least one cardiovascular risk factor. In the entire cohort, for both HF and MACE, the predictive characteristics of NT-proBNP and hscTnI were superior to other biomarkers; alone, in a multimarker model, and adjusting for clinical risk factors. An NT-proBNP-guided preventative intervention with an intervention effect size (4-year hazard ratio for intervention in biomarker positive cohort) of ≤0.7 would reduce the global burden of HF by ≥20% and MACE by ≥15%. From this simulation, the NNS to prevent one HF event or MACE in 4 years would be ≤100 with a NNT to prevent one HF event of ≤20 and one MACE of ≤10. The predictive characteristics of NT-proBNP and hscTnI for HF or MACE in the community are superior to other biomarkers. Biomarker-guided preventative interventions with reasonable efficacy would compare favourably to established preventative interventions. This data provides a framework for biomarker selection which may inform design of biomarker-guided preventative intervention trials. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Human biomonitoring pilot study DEMOCOPHES in Germany: Contribution to a harmonized European approach.

PubMed

Schwedler, Gerda; Seiwert, Margarete; Fiddicke, Ulrike; Ißleb, Sissy; Hölzer, Jürgen; Nendza, Julia; Wilhelm, Michael; Wittsiepe, Jürgen; Koch, Holger M; Schindler, Birgit K; Göen, Thomas; Hildebrand, Jörg; Joas, Reinhard; Joas, Anke; Casteleyn, Ludwine; Angerer, Jürgen; Castano, Argelia; Esteban, Marta; Schoeters, Greet; Den Hond, Elly; Sepai, Ovnair; Exley, Karen; Bloemen, Louis; Knudsen, Lisbeth E; Kolossa-Gehring, Marike

2017-06-01

BP that exceeded health based guidance values, indicating reasons for concern. Continuous HBM is necessary to track changes of pollutant exposure over time. Therefore Germany will continue to cooperate on the harmonisation of European human biomonitoring to support the chemicals regulation with the best possible exposure data to protect Europe's people against environmental health risks. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Moving Genetic Biomonitoring from a Concept to a Tool

EPA Science Inventory

Molecular genetic techniques like DNA barcoding and environmental DNA have been proposed as tools for aquatic biomonitoring for nearly a decade, but have yet to break through into widespread acceptance. The potential benefits of these methods, such as quicker, cheaper, more detai...

Hg localisation in Tillandsia usneoides L. (Bromeliaceae), an atmospheric biomonitor

NASA Astrophysics Data System (ADS)

Amado Filho, G. M.; Andrade, L. R.; Farina, M.; Malm, O.

The Spanish moss, Tillandsia usneoides, has been applied as an atmospheric biomonitor of Hg contamination, although the mechanism of metal plant accumulation has not been understood until now. In the present work, analytical scanning electron microscopy (SEM) was used to localize Hg in T. usneoides exposed to a Hg-air-contaminated area during 15 days. After this period, Hg was determined by the flow injection mercury system, and plants were prepared for SEM observation and energy-dispersive X-ray analysis. A concentration of 2702±318 μg Hg g -1 was determined in exposed plants. The presented microanalytical results demonstrated that Hg was partly associated with atmospheric particles deposited upon the plant surface, but it was highly absorbed by the scales, stem and leaves surfaces and less absorbed by epidermal cells of T. usneoides. No Hg was detected in mesophyll parenchyma or in vascular system cells. The great surface adsorption area provided by the scales, in addition to the characteristics of T. usneoides morphology, especially of the node region, are suggested to confer the great capability of T. usneoides in Hg holding.

Clinical trial designs for testing biomarker-based personalized therapies

PubMed Central

Lai, Tze Leung; Lavori, Philip W; Shih, Mei-Chiung I; Sikic, Branimir I

2014-01-01

Background Advances in molecular therapeutics in the past decade have opened up new possibilities for treating cancer patients with personalized therapies, using biomarkers to determine which treatments are most likely to benefit them, but there are difficulties and unresolved issues in the development and validation of biomarker-based personalized therapies. We develop a new clinical trial design to address some of these issues. The goal is to capture the strengths of the frequentist and Bayesian approaches to address this problem in the recent literature and to circumvent their limitations. Methods We use generalized likelihood ratio tests of the intersection null and enriched strategy null hypotheses to derive a novel clinical trial design for the problem of advancing promising biomarker-guided strategies toward eventual validation. We also investigate the usefulness of adaptive randomization (AR) and futility stopping proposed in the recent literature. Results Simulation studies demonstrate the advantages of testing both the narrowly focused enriched strategy null hypothesis related to validating a proposed strategy and the intersection null hypothesis that can accommodate to a potentially successful strategy. AR and early termination of ineffective treatments offer increased probability of receiving the preferred treatment and better response rates for patients in the trial, at the expense of more complicated inference under small-to-moderate total sample sizes and some reduction in power. Limitations The binary response used in the development phase may not be a reliable indicator of treatment benefit on long-term clinical outcomes. In the proposed design, the biomarker-guided strategy (BGS) is not compared to ‘standard of care’, such as physician’s choice that may be informed by patient characteristics. Therefore, a positive result does not imply superiority of the BGS to ‘standard of care’. The proposed design and tests are valid asymptotically

Challenges in Biomarker Discovery: Combining Expert Insights with Statistical Analysis of Complex Omics Data

PubMed Central

McDermott, Jason E.; Wang, Jing; Mitchell, Hugh; Webb-Robertson, Bobbie-Jo; Hafen, Ryan; Ramey, John; Rodland, Karin D.

2012-01-01

Introduction The advent of high throughput technologies capable of comprehensive analysis of genes, transcripts, proteins and other significant biological molecules has provided an unprecedented opportunity for the identification of molecular markers of disease processes. However, it has simultaneously complicated the problem of extracting meaningful molecular signatures of biological processes from these complex datasets. The process of biomarker discovery and characterization provides opportunities for more sophisticated approaches to integrating purely statistical and expert knowledge-based approaches. Areas covered In this review we will present examples of current practices for biomarker discovery from complex omic datasets and the challenges that have been encountered in deriving valid and useful signatures of disease. We will then present a high-level review of data-driven (statistical) and knowledge-based methods applied to biomarker discovery, highlighting some current efforts to combine the two distinct approaches. Expert opinion Effective, reproducible and objective tools for combining data-driven and knowledge-based approaches to identify predictive signatures of disease are key to future success in the biomarker field. We will describe our recommendations for possible approaches to this problem including metrics for the evaluation of biomarkers. PMID:23335946

Chromatography/Mass Spectrometry-Based Biomarkers in the Field of Obstructive Sleep Apnea

PubMed Central

Xu, Huajun; Zheng, Xiaojiao; Jia, Wei; Yin, Shankai

2015-01-01

Abstract Biomarker assessment is based on quantifying several proteins and metabolites. Recent developments in proteomics and metabolomics have enabled detection of these small molecules in biological samples and exploration of the underlying disease mechanisms in obstructive sleep apnea (OSA). This systemic review was performed to identify biomarkers, which were only detected by chromatography and/or mass spectrometry (MS) and to discuss the role of these biomarkers in the field of OSA. We systemically reviewed relevant articles from PubMed and EMBASE referring to proteins and metabolite profiles of biological samples in patients with OSA. The analytical platforms in this review were focused on chromatography and/or MS. In total, 30 studies evaluating biomarkers in patients with OSA using chromatography and/or MS methods were included. Numerous proteins and metabolites, including lipid profiles, adrenergic/dopaminergic biomarkers and derivatives, amino acids, oxidative stress biomarkers, and other micromolecules were identified in patients with OSA. Applying chromatography and/or MS methods to detect biomarkers helps develop an understanding of OSA mechanisms. More proteomic and metabolomic studies are warranted to develop potential diagnostic and clinical monitoring methods for OSA. PMID:26448002

The biology of environmental stress: molecular biomarkers in Sydney rock oysters (Saccostrea glomerata).

PubMed

Raftos, D A; Melwani, A R; Haynes, P A; Muralidharan, S; Birch, G F; Amaral, V; Thompson, E L; Taylor, D A

2016-09-14

This review describes our recent work on environmental stress in Sydney rock oysters, focusing on the identification of molecular biomarkers for ecotoxicological analysis. We begin by describing the environmental pressures facing coastal estuaries in Australia, with particular reference to Sydney Harbour. After providing that context, we summarise our transcriptional and proteomic analyses of Sydney rock oysters responding to chemical contamination and other forms of environmental stress. This work has shown that the intracellular processes of oysters are highly responsive to environmental threats. Our data agree with the broader literature, which suggests that there is a highly conserved intracellular stress response in oysters involving a limited number of biological processes. We conclude that many effective molecular markers for environmental biomonitoring are likely to lie within these biological pathways.

Biomonitoring of intermittent rivers and ephemeral streams in Europe: Current practice and priorities to enhance ecological status assessments.

PubMed

Stubbington, Rachel; Chadd, Richard; Cid, Núria; Csabai, Zoltán; Miliša, Marko; Morais, Manuela; Munné, Antoni; Pařil, Petr; Pešić, Vladimir; Tziortzis, Iakovos; Verdonschot, Ralf C M; Datry, Thibault

2018-03-15

Intermittent rivers and ephemeral streams (IRES) are common across Europe and dominate some Mediterranean river networks. In all climate zones, IRES support high biodiversity and provide ecosystem services. As dynamic ecosystems that transition between flowing, pool, and dry states, IRES are typically poorly represented in biomonitoring programmes implemented to characterize EU Water Framework Directive ecological status. We report the results of a survey completed by representatives from 20 European countries to identify current challenges to IRES status assessment, examples of best practice, and priorities for future research. We identify five major barriers to effective ecological status classification in IRES: 1. the exclusion of IRES from Water Framework Directive biomonitoring based on their small catchment size; 2. the lack of river typologies that distinguish between contrasting IRES; 3. difficulties in defining the 'reference conditions' that represent unimpacted dynamic ecosystems; 4. classification of IRES ecological status based on lotic communities sampled using methods developed for perennial rivers; and 5. a reliance on taxonomic characterization of local communities. Despite these challenges, we recognize examples of innovative practice that can inform modification of current biomonitoring activity to promote effective IRES status classification. Priorities for future research include reconceptualization of the reference condition approach to accommodate spatiotemporal fluctuations in community composition, and modification of indices of ecosystem health to recognize both taxon-specific sensitivities to intermittence and dispersal abilities, within a landscape context. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Validation of biomarkers of food intake-critical assessment of candidate biomarkers.

PubMed

Dragsted, L O; Gao, Q; Scalbert, A; Vergères, G; Kolehmainen, M; Manach, C; Brennan, L; Afman, L A; Wishart, D S; Andres Lacueva, C; Garcia-Aloy, M; Verhagen, H; Feskens, E J M; Praticò, G

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 promise for direct and objective measurement of food intake. However, the number of comprehensively validated biomarkers of food intake is limited to just a few. Many new candidate biomarkers emerge from metabolic profiling studies and from advances in food chemistry. Furthermore, candidate food intake biomarkers may also be identified based on extensive literature reviews such as described in the guidelines for Biomarker of Food Intake Reviews (BFIRev). To systematically and critically assess the validity of candidate biomarkers of food intake, it is necessary to outline and streamline an optimal and reproducible validation process. A consensus-based procedure was used to provide and evaluate a set of the most important criteria for systematic validation of BFIs. As a result, a validation procedure was developed including eight criteria, plausibility, dose-response, time-response, robustness, reliability, stability, analytical performance, and inter-laboratory reproducibility. The validation has a dual purpose: (1) to estimate the current level of validation of candidate biomarkers of food intake based on an objective and systematic approach and (2) to pinpoint which additional studies are needed to provide full validation of each candidate biomarker of food intake. This position paper on biomarker of food intake validation outlines the second step of the BFIRev procedure but may also be used as such for validation of new candidate biomarkers identified, e.g., in food metabolomic studies.

Hair and Nails as Noninvasive Biomarkers of Human Exposure to Brominated and Organophosphate Flame Retardants.

PubMed

Liu, Liang-Ying; He, Ka; Hites, Ronald A; Salamova, Amina

2016-03-15

After the phase-out of polybrominated diphenyl ethers (PBDEs), the use of alternative flame retardants (AFRs), such as FireMaster 550, and of organophosphate esters (OPEs) has increased. However, little is known about human exposure to these chemicals. This lack of biomonitoring studies is partially due to the absence of reliable noninvasive biomarkers of exposure. Human hair and nails can provide integrated exposure measurements, and as such, these matrices can potentially be used as noninvasive biomarkers of exposure to these flame retardants. Paired human hair, fingernail, toenail, and serum samples obtained from 50 adult participants recruited at Indiana University Bloomington campus were analyzed by gas chromatographic mass spectrometry for 36 PBDEs, 9 AFRs, and 12 OPEs. BDE-47, BDE-99, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), di(2-ethylhexyl) tetrabromophthalate (TBPH), tris(1,3-dichloro-2-propyl)phosphate (TDCIPP), and triphenyl phosphate (TPHP) were the most abundant compounds detected in almost all hair, fingernail, and toenail samples. The concentrations followed the order OPEs > TBB+TBPH > Σpenta-BDE. PBDE levels in the hair and nail samples were significantly correlated with their levels in serum (P < 0.05), suggesting that human hair and nails can be used as biomarkers to assess human exposure to PBDEs.

The use of vegetables in the biomonitoring of cadmium and lead pollution in the environment.

PubMed

Szczygłowska, Marzena; Bodnar, Małgorzata; Namieśnik, Jacek; Konieczka, Piotr

2014-01-01

Lead and cadmium emitted from various anthropogenic sources have the ability to accumulate in tissues of living organisms. The phenomenon of accumulation of metals in the body is harmful and undesirable. The ability of plants to accumulate heavy metals from the individual elements of the environment has been used in biomonitoring of pollution. Leaves and roots of vegetables have particular predisposition for accumulating toxic metals such as lead and cadmium and therefore can be used for biomonitoring of the environment, mainly as a tool for assessing the extent of soil contamination. The article discusses information in the literature on entry paths of lead and cadmium into the body, toxic effects of lead and cadmium on the human organism, and the use of vegetables as a tool in the biomonitoring of heavy metals in different elements of the environment.

Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example.

PubMed

Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha

2013-01-01

The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.

Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example

PubMed Central

Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha

2013-01-01

The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases. PMID:23405244

Mass spectrometry-based biomarker discovery: toward a global proteome index of individuality.

PubMed

Hawkridge, Adam M; Muddiman, David C

2009-01-01

Biomarker discovery and proteomics have become synonymous with mass spectrometry in recent years. Although this conflation is an injustice to the many essential biomolecular techniques widely used in biomarker-discovery platforms, it underscores the power and potential of contemporary mass spectrometry. Numerous novel and powerful technologies have been developed around mass spectrometry, proteomics, and biomarker discovery over the past 20 years to globally study complex proteomes (e.g., plasma). However, very few large-scale longitudinal studies have been carried out using these platforms to establish the analytical variability relative to true biological variability. The purpose of this review is not to cover exhaustively the applications of mass spectrometry to biomarker discovery, but rather to discuss the analytical methods and strategies that have been developed for mass spectrometry-based biomarker-discovery platforms and to place them in the context of the many challenges and opportunities yet to be addressed.

The use of reverse iontophoresis based surface plasmon resonance for the development of a noninvasive real time transdermal biomarker sensor

NASA Astrophysics Data System (ADS)

Gupta, Niraj K.; Hwang, Yongsoon; Cameron, Brent D.

2016-03-01

Recent developments in the identification of biomarkers offer a potential means to facilitate early disease detection, gauge treatment in drug therapy clinical trials, and to assess the impact of fatigue and/or stress as related to human physical and cognitive performance. For practical implementation, however, real-time sensing and quantification of such physiological biomarkers is preferred. Some key aspects in this process are continuous sample collection and real time detection. Traditionally, blood is considered the gold standard for samples but frequent phlebotomy is painful and inconvenient. Other sources like saliva and passive sweat cannot be precisely controlled and are affected by other limitations. Some of these can be addressed by reverse iontophoresis which is a noninvasive technique capable of facilitating controlled transport of biomolecules up to 20kDa in size across the skin barrier by passing a low level current between two dermal electrodes. The samples collected at the electrode site can then be monitored at site or transported via a microfluidic channel towards a sensor. In the case reported here, the sensor is based on surface plasmon resonance (SPR), which is a label free, real time, and highly sensitive optical sensing technique. The real time SPR detection of targeted biomarkers is then achieved through the use of aptamer surface modification. In this experiment, extraction and detection of orexin A, a stress related biomarker, is used for demonstration purposes.

Ethoxyresorufin-O-deethylase (EROD) activity in fish as a biomarker of chemical exposure

USGS Publications Warehouse

Whyte, J.J.; Jung, R.E.; Schmitt, C.J.; Tillitt, D.E.

2000-01-01

This review compiles and evaluates existing scientific information on the use, limitations, and procedural considerations for EROD activity (a catalytic measurement of cytochrome P4501A induction) as a biomarker in fish. A multitude of chemicals induce EROD activity in a variety of fish species, the most potent inducers being structural analogs of 2,3,7,8-tetracholordibenzo-p-dioxin. Although certain chemicals may inhibit EROD induction/activity, this interference is generally not a drawback to the use of EROD induction as a biomarker. The various methods of EROD analysis currently in use yield comparable results, particularly when data are expressed as relative rates of EROD activity. EROD induction in fish is well characterized, the most important modifying factors being fish species, reproductive status and age, all of which can be controlled through proper study design. Good candidate species for biomonitoring should have a wide range between basal and induced EROD activity (e.g., common carp, channel catfish, and mummichog). EROD activity has proven value as a biomarker in a number of field investigations of bleached kraft mill and industrial effluents, contaminated sediments, and chemical spills. Research on mechanisms of CYP1A-induced toxicity suggests that EROD activity may not only indicate chemical exposure, but also may also precede effects at various levels of biological organization. A current research need is the development of chemical exposure-response relationships for EROD activity in fish. In addition, routine reporting in the literature of EROD activity in standard positive and negative control material will enhance confidence in comparing results from different studies using this biomarker.

Biomonitoring Data for 2,4-Dichlorophenoxyacetic Acid in the United States and Canada: Interpretation in a Public Health Risk Assessment Context Using Biomonitoring Equivalents

EPA Science Inventory

Several extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents ...

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smolders, R., E-mail: roel.smolders@vito.be; Den Hond, E.; Koppen, G.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother–child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality andmore » lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making. - Highlights: • External data was collected to interpret HBM data from DEMOCOPHES. • Hg in hair could be related to fish consumption across different countries. • Urinary cotinine was related to strictness of anti-smoking legislation. • Urinary Cd was borderline significantly related to air and food quality. • Lack of comparable data among countries hampered the analysis.« less

SERS-based inverse molecular sentinel (iMS) nanoprobes for multiplexed detection of microRNA cancer biomarkers in biological samples

NASA Astrophysics Data System (ADS)

Crawford, Bridget M.; Wang, Hsin-Neng; Fales, Andrew M.; Bowie, Michelle L.; Seewaldt, Victoria L.; Vo-Dinh, Tuan

2017-02-01

The development of sensitive and selective biosensing techniques is of great interest for clinical diagnostics. Here, we describe the development and application of a surface enhanced Raman scattering (SERS) sensing technology, referred to as "inverse Molecular Sentinel (iMS)" nanoprobes, for the detection of nucleic acid biomarkers in biological samples. This iMS nanoprobe involves the use of plasmonic-active nanostars as the sensing platform for a homogenous assay for multiplexed detection of nucleic acid biomarkers, including DNA, RNA and microRNA (miRNA). The "OFF-to-ON" signal switch is based on a non-enzymatic strand-displacement process and the conformational change of stem-loop (hairpin) oligonucleotide probes upon target binding. Here, we demonstrate the development of iMS nanoprobes for the detection of DNA sequences as well as a modified design of the nanoprobe for the detection of short (22-nt) microRNA sequences. The application of iMS nanoprobes to detect miRNAs in real biological samples was performed with total small RNA extracted from breast cancer cell lines. The multiplex capability of the iMS technique was demonstrated using a mixture of the two differently labeled nanoprobes to detect miR-21 and miR-34a miRNA biomarkers for breast cancer. The results of this study demonstrate the feasibility of applying the iMS technique for multiplexed detection of nucleic acid biomarkers, including short miRNAs molecules.

Selecting Species Traits for Biomonitoring Applications in light of Phylogenetic Relationships among Lotic Insects

NASA Astrophysics Data System (ADS)

Poff, N.; Vieira, N. K.; Simmons, M. P.; Olden, J. D.; Kondratieff, B. C.; Finn, D. S.

2005-05-01

The use of species traits as indicators of environmental disturbance is being considered for biomonitoring programs globally. As such, methods to select relevant and informative traits for inclusion in biometrics need to be developed. In this research, we identified 20 traits of aquatic insects within six trait groups: morphology, mobility, life-history strategy, thermal tolerance, feeding guild and ecology (e.g., habitat preference). We constructed phylogenetic trees for 1) all lotic insect species of North America and 2) all Ephemeroptera, Plecoptera and Trichoptera species based on morphology- and molecular-based analyses and classifications. We then measured variability (i.e., plasticity) of the 20 traits and six trait groups across the two phylogenetic trees. Traits with higher degrees of plasticity indicated traits that were less phylogenetically constrained, and were considered informative for biomonitoring purposes. Thermal tolerance, rheophily, body size at maturity and feeding guild showed the highest plasticity across both phylogenetic trees. Two mobility traits, occurrence in drift and adult dispersal distance, showed moderate plasticity. By contrast, adult exiting ability, degree of attachment, adult lifespan and body shape showed low variability and were thus less informative. Plastic species traits that are less phylogenetically constrained may be most useful in detecting community change along environmental gradients.

Inferring Population Exposure from Biomonitoring Data on Urinary Concentrations (SOT)

EPA Science Inventory

Biomonitoring studies such as the National Health and Nutrition Examination Survey (NHANES) are valuable to exposure assessment both as sources of data to evaluate exposure models and as training sets to develop heuristics for rapid-exposure-assessment tools. However, linking in...

Development towards compact nitrocellulose interferometric biochips for dry eye diagnosis based on MMP9, S100A6 and CST4 biomarkers using a Point-of-Care device

NASA Astrophysics Data System (ADS)

Santamaría, Beatriz; Laguna, María. Fe; López-Romero, David; López-Hernandez, A.; Sanza, F. J.; Lavín, A.; Casquel, R.; Maigler, M.; Holgado, M.

2018-02-01

A novel compact optical biochip based on a thin layer-sensing BICELL surface of nitrocellulose is used for in-situ labelfree detection of dry eye disease (DED). In this work the development of a compact biosensor that allows obtaining quantitative diagnosis with a limited volume of sample is reported. The designed sensors can be analyzed with an optical integrated Point-of-Care read-out system based on the "Increase Relative Optical Power" principle which enhances the performance and Limit of Detection. Several proteins involved with dry eye dysfunction have been validated as biomarkers. Presented biochip analyzes three of those biomarkers: MMP9, S100A6 and CST4. BICELLs based on nitrocellulose permit to immobilize antibodies for each biomarker recognition. The optical response obtained from the biosensor through the readout platform is capable to recognize specifically the desired proteins in the concentrations range for control eye (CE) and dry eye syndrome (DES). Preliminary results obtained will allow the development of a dry eye detection device useful in the area of ophthalmology and applicable to other possible diseases related to the eye dysfunction.

Recommendations and Standardization of Biomarker Quantification Using NMR-Based Metabolomics with Particular Focus on Urinary Analysis.

PubMed

Emwas, Abdul-Hamid; Roy, Raja; McKay, Ryan T; Ryan, Danielle; Brennan, Lorraine; Tenori, Leonardo; Luchinat, Claudio; Gao, Xin; Zeri, Ana Carolina; Gowda, G A Nagana; Raftery, Daniel; Steinbeck, Christoph; Salek, Reza M; Wishart, David S

2016-02-05

NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to nondestructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Precise metabolite quantification is a prerequisite to move any chemical biomarker or biomarker panel from the lab to the clinic. Among the biofluids commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, and easily obtained, needs little sample preparation, and does not require invasive medical procedures for collection. Furthermore, urine captures and concentrates many "unwanted" or "undesirable" compounds throughout the body, providing a rich source of potentially useful disease biomarkers; however, incredible variation in urine chemical concentrations makes analysis of urine and identification of useful urinary biomarkers by NMR challenging. We discuss a number of the most significant issues regarding NMR-based urinary metabolomics with specific emphasis on metabolite quantification for disease biomarker applications and propose data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, sample preparation, and biomarker assessment.

Inhibition-Based Biomarkers for Autism Spectrum Disorder.

PubMed

Levin, April R; Nelson, Charles A

2015-07-01

Autism spectrum disorder (ASD) is a behaviorally defined and heterogeneous disorder. Biomarkers for ASD offer the opportunity to improve prediction, diagnosis, stratification by severity and subtype, monitoring over time and in response to interventions, and overall understanding of the underlying biology of this disorder. A variety of potential biomarkers, from the level of genes and proteins to network-level interactions, is currently being examined. Many of these biomarkers relate to inhibition, which is of particular interest because in many cases ASD is thought to be a disorder of imbalance between excitation and inhibition. Abnormalities in inhibition at the cellular level lead to emergent properties in networks of neurons. These properties take into account a more complete genetic and cellular background than findings at the level of individual genes or cells, and are able to be measured in live humans, offering additional potential as diagnostic biomarkers and predictors of behaviors. In this review we provide examples of how altered inhibition may inform the search for ASD biomarkers at multiple levels, from genes to cells to networks.

Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

PubMed Central

Sinharay, Sanhita; Pagel, Mark D.

2016-01-01

Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting

PubMed Central

DeBord, D. Gayle; Burgoon, Lyle; Edwards, Stephen W.; Haber, Lynne T.; Kanitz, M. Helen; Kuempel, Eileen; Thomas, Russell S.; Yucesoy, Berran

2015-01-01

In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments.( 1 ) This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identi-fication of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process. The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application. The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely. PMID:26132979

Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting.

PubMed

DeBord, D Gayle; Burgoon, Lyle; Edwards, Stephen W; Haber, Lynne T; Kanitz, M Helen; Kuempel, Eileen; Thomas, Russell S; Yucesoy, Berran

2015-01-01

In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments. This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identification of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process. The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application. The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely.

Phonologically-based biomarkers for major depressive disorder

NASA Astrophysics Data System (ADS)

Trevino, Andrea Carolina; Quatieri, Thomas Francis; Malyska, Nicolas

2011-12-01

Of increasing importance in the civilian and military population is the recognition of major depressive disorder at its earliest stages and intervention before the onset of severe symptoms. Toward the goal of more effective monitoring of depression severity, we introduce vocal biomarkers that are derived automatically from phonologically-based measures of speech rate. To assess our measures, we use a 35-speaker free-response speech database of subjects treated for depression over a 6-week duration. We find that dissecting average measures of speech rate into phone-specific characteristics and, in particular, combined phone-duration measures uncovers stronger relationships between speech rate and depression severity than global measures previously reported for a speech-rate biomarker. Results of this study are supported by correlation of our measures with depression severity and classification of depression state with these vocal measures. Our approach provides a general framework for analyzing individual symptom categories through phonological units, and supports the premise that speaking rate can be an indicator of psychomotor retardation severity.

Urban health and ecology: the promise of an avian biomonitoring tool.

PubMed

Pollack, Lea; Ondrasek, Naomi R; Calisi, Rebecca

2017-04-01

Urban-dwelling birds have the potential to serve as powerful biomonitors that reveal the impact of environmental change due to urbanization. Specifically, urban bird populations can be used to survey cities for factors that may pose both public and wildlife health concerns. Here, we review evidence supporting the use of avian biomonitors to identify threats associated with urbanization, including bioaccumulation of toxicants and the dysregulation of behavior and physiology by related stressors. In addition, we consider the use of birds to examine how factors in the urban environment can impact immunity against communicable pathogens. By studying the behavior, physiology, and ecology of urban bird populations, we can elucidate not only how avian populations are responding to environmental change, but also how unintended consequences of urbanization affect the well-being of human and non-human inhabitants.

Exposure Assessment and Biomonitoring of Workers in Magnetic Resonance Environment: An Exploratory Study

PubMed Central

Sannino, Anna; Romeo, Stefania; Scarfì, Maria Rosaria; Massa, Rita; d’Angelo, Raffaele; Petrillo, Antonella; Cerciello, Vincenzo; Fusco, Roberta; Zeni, Olga

2017-01-01

Magnetic resonance imaging (MRI) has evolved rapidly over the past few decades as one of the most flexible tools in medical research and diagnostic imaging. MRI facilities are important sources of multiple exposure to electromagnetic fields for both patients and health-care staff, due to the presence of electromagnetic fields of multiple frequency ranges, different temporal variations, and field strengths. Due to the increasing use and technological advancements of MRI systems, clearer insights into exposure assessment and a better understanding of possible harmful effects due to long-term exposures are highly needed. In the present exploratory study, exposure assessment and biomonitoring of MRI workers at the Radio-diagnostics Unit of the National Cancer Institute of Naples “Pascale Foundation” (Naples, Italy) have been carried out. In particular, exposure to the MRI static magnetic field (SMF) has been evaluated by means of personal monitoring, while an application tool has been developed to provide an estimate of motion-induced, time-varying electric fields. Measurement results have highlighted a high day-to-day and worker-to-worker variability of the exposure to the SMF, which strongly depends on the characteristics of the environment and on personal behaviors, and the developed application tool can be adopted as an easy-to-use tool for rapid and qualitative evaluation of motion-induced, time-varying electric field exposure. Regarding biomonitoring, the 24 workers of the Radio-diagnostics Unit were enrolled to evaluate both spontaneous and mitomycin C-induced chromosomal fragility in human peripheral blood lymphocytes, by means of the cytokinesis-block micronucleus assay. The study subjects were 12 MRI workers, representative of different professional categories, as the exposed group, and 12 workers with no MRI exposure history, as the reference group. The results show a high worker-to-worker variability for both field exposure assessment and biomonitoring

The novel approach to the biomonitor survey using one- and two-dimensional Kohonen networks.

PubMed

Deljanin, Isidora; Antanasijević, Davor; Urošević, Mira Aničić; Tomašević, Milica; Perić-Grujić, Aleksandra; Ristić, Mirjana

2015-10-01

To compare the applicability of the leaves of horse chestnut (Aesculus hippocastanum) and linden (Tilia spp.) as biomonitors of trace element concentrations, a coupled approach of one- and two-dimensional Kohonen networks was applied for the first time. The self-organizing networks (SONs) and the self-organizing maps (SOMs) were applied on the database obtained for the element accumulation (Cr, Fe, Ni, Cu, Zn, Pb, V, As, Cd) and the SOM for the Pb isotopes in the leaves for a multiyear period (2002-2006). A. hippocastanum seems to be a more appropriate biomonitor since it showed more consistent results in the analysis of trace elements and Pb isotopes. The SOM proved to be a suitable and sensitive tool for assessing differences in trace element concentrations and for the Pb isotopic composition in leaves of different species. In addition, the SON provided more clear data on seasonal and temporal accumulation of trace elements in the leaves and could be recommended complementary to the SOM analysis of trace elements in biomonitoring studies.

Recommendations and Standardization of Biomarker Quantification Using NMR-Based Metabolomics with Particular Focus on Urinary Analysis

PubMed Central

2016-01-01

NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to nondestructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Precise metabolite quantification is a prerequisite to move any chemical biomarker or biomarker panel from the lab to the clinic. Among the biofluids commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, and easily obtained, needs little sample preparation, and does not require invasive medical procedures for collection. Furthermore, urine captures and concentrates many “unwanted” or “undesirable” compounds throughout the body, providing a rich source of potentially useful disease biomarkers; however, incredible variation in urine chemical concentrations makes analysis of urine and identification of useful urinary biomarkers by NMR challenging. We discuss a number of the most significant issues regarding NMR-based urinary metabolomics with specific emphasis on metabolite quantification for disease biomarker applications and propose data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, sample preparation, and biomarker assessment. PMID:26745651

Novel CT-based objective imaging biomarkers of long term radiation-induced lung damage.

PubMed

Veiga, Catarina; Landau, David; Devaraj, Anand; Doel, Tom; White, Jared; Ngai, Yenting; Hawkes, David J; McClelland, Jamie R

2018-06-14

and Purpose: Recent improvements in lung cancer survival have spurred an interest in understanding and minimizing long term radiation-induced lung damage (RILD). However, there is still no objective criteria to quantify RILD leading to variable reporting across centres and trials. We propose a set of objective imaging biomarkers to quantify common radiological findings observed 12-months after lung cancer radiotherapy (RT). Baseline and 12-month CT scans of 27 patients from a phase I/II clinical trial of isotoxic chemoradiation were included in this study. To detect and measure the severity of RILD, twelve quantitative imaging biomarkers were developed. These describe basic CT findings including parenchymal change, volume reduction and pleural change. The imaging biomarkers were implemented as semi-automated image analysis pipelines and assessed against visual assessment of the occurrence of each change. The majority of the biomarkers were measurable in each patient. Their continuous nature allows objective scoring of severity for each patient. For each imaging biomarker the cohort was split into two groups according to the presence or absence of the biomarker by visual assessment, testing the hypothesis that the imaging biomarkers were different in these two groups. All features were statistically significant except for rotation of the main bronchus and diaphragmatic curvature. The majority of the biomarkers were not strongly correlated with each other suggesting that each of the biomarkers is measuring a separate element of RILD pathology. We developed objective CT-based imaging biomarkers that quantify the severity of radiological lung damage after RT. These biomarkers are representative of typical radiological findings of RILD. Copyright © 2018. Published by Elsevier Inc.

Effects of organism preparation in metallothionein and metal analysis in marine invertebrates for biomonitoring marine pollution.

PubMed

Oaten, J F P; Hudson, M D; Jensen, A C; Williams, I D

2015-06-15

to future biomonitoring studies and will improve the comparability and repeatability of using MT as a biomarker. Copyright © 2015 Elsevier B.V. All rights reserved.

A proposed panel of biomarkers of healthy ageing.

PubMed

Lara, Jose; Cooper, Rachel; Nissan, Jack; Ginty, Annie T; Khaw, Kay-Tee; Deary, Ian J; Lord, Janet M; Kuh, Diana; Mathers, John C

2015-09-15

There is no criterion reference for assessing healthy ageing and this creates difficulties when conducting and comparing research on ageing across studies. A cardinal feature of ageing is loss of function which translates into wide-ranging consequences for the individual and for family, carers and society. We undertook comprehensive reviews of the literature searching for biomarkers of ageing on five ageing-related domains including physical capability and cognitive, physiological and musculoskeletal, endocrine and immune functions. Where available, we used existing systematic reviews, meta-analyses and other authoritative reports such as the recently launched NIH Toolbox for assessment of neurological and behavioural function, which includes test batteries for cognitive and motor function (the latter described here as physical capability). We invited international experts to comment on our draft recommendations. In addition, we hosted an experts workshop in Newcastle, UK, on 22-23 October 2012, aiming to help capture the state-of-the-art in this complex area and to provide an opportunity for the wider ageing research community to critique the proposed panel of biomarkers. Here we have identified important biomarkers of healthy ageing classified as subdomains of the main areas proposed. Cardiovascular and lung function, glucose metabolism and musculoskeletal function are key subdomains of physiological function. Strength, locomotion, balance and dexterity are key physical capability subdomains. Memory, processing speed and executive function emerged as key subdomains of cognitive function. Markers of the HPA-axis, sex hormones and growth hormones were important biomarkers of endocrine function. Finally, inflammatory factors were identified as important biomarkers of immune function. We present recommendations for a panel of biomarkers that address these major areas of function which decline during ageing. This biomarker panel may have utility in epidemiological

Macroinvertebrate biomonitoring in intermittent coastal plain streams impacted by animal agriculture.

PubMed

Davis, Stephanie; Golladay, Stephen W; Vellidis, George; Pringle, Catherine M

2003-01-01

Little attention has been given to the ecology of intermittent coastal plain streams in the southeastern United States, and it is not known whether available macroinvertebrate biomonitoring methods reliably detect degradation in these streams. This study compared differences in biomonitoring metrics between reference and agricultural streams, and between the flow period (January-April) and the intermittent flow period (May-December). Percentages of crustaceans, isopods, and Ephemeroptera-Plecoptera-Trichoptera (EPT) were significantly higher at the reference site than the two most impacted sites during the flow period, probably resulting from the abundance of leaf litter and lower temperatures. During this same period, the agriculturally impacted sites had a significantly higher percentage of dipterans--a group that thrives in the silty, nutrient-rich waters. Four metrics (percent Crustacea, Isopoda, Diptera, and EPT) had no overlap between values for the most impacted and the least impacted sites during the flow period, but no metrics were able to detect more discrete differences among sites. Sites were physically and biologically similar during the intermittent period when natural stresses (i.e., stagnant water, high temperatures, low dissolved oxygen) were high, with many metrics, such as percentages of dominant family, burrowers, chironomids, and dipterans becoming similar at all sites. Our findings indicate that development of a better understanding of invertebrate fauna in reference conditions and of the natural variation in intermittent streams is necessary to develop effective biomonitoring programs for these systems.

Magnetic wire trap arrays for biomarker-based molecular detection

NASA Astrophysics Data System (ADS)

Vieira, Gregory; Mahajan, Kalpesh; Ruan, Gang; Winter, Jessica; Sooryakumar, R.

2012-02-01

Submicrometer-scale magnetic devices built on chip-based platforms have recently been shown to present opportunities for new particle trapping and manipulation technologies. Meanwhile, advances in nanoparticle fabrication allow for the building of custom-made particles with precise control of their size, composition, and other properties such as magnetism, fluorescence, and surface biomarker characteristics. In particular, carefully tailored surface biomarkers facilitate precise binding to targeted molecules, self-actuated construction of hybrid structures, and fluorescence-based detection schemes. Based on these progresses, we present an on-chip detection mechanism for molecules with known surface markers. Hybrid nanostructures consisting of micelle nanoparticles, fluorescent quantum dots, and superparamagnetic iron oxide nanoparticles are used to detect proteins or DNA molecules. The target is detected by the magnetic and fluorescent functionalities of the composite nanostructure, whereas in the absence of the target these signals are not present. Underlying this approach is the simultaneous manipulation via ferromagnetic zigzag nanowire arrays and imaging via quantum dot excitation. This chip-based detection technique could provide a powerful, low cost tool for ultrasensitive molecule detection with ramifications in healthcare diagnostics and small-scale chemical synthesis.

Characterizing biomarkers in osteosarcoma metastasis based on an ego-network.

PubMed

Liu, Zhen; Song, Yan

2017-06-01

To characterize biomarkers that underlie osteosarcoma (OS) metastasis based on an ego-network. From the microarray data, we obtained 13,326 genes. By combining PPI data and microarray data, 10,520 shared genes were found and constructed into ego-networks. 17 significant ego-networks were identified with p < 0.05. In the pathway enrichment analysis, seven ego-networks were identified with the most significant pathway. These significant ego-modules were potential biomarkers that reveal the potential mechanisms in OS metastasis, which may contribute to understanding cancer prognoses and providing new perspectives in the treatment of cancer.

Urban health and ecology: the promise of an avian biomonitoring tool

PubMed Central

Pollack, Lea; Ondrasek, Naomi R.

2017-01-01

Abstract Urban-dwelling birds have the potential to serve as powerful biomonitors that reveal the impact of environmental change due to urbanization. Specifically, urban bird populations can be used to survey cities for factors that may pose both public and wildlife health concerns. Here, we review evidence supporting the use of avian biomonitors to identify threats associated with urbanization, including bioaccumulation of toxicants and the dysregulation of behavior and physiology by related stressors. In addition, we consider the use of birds to examine how factors in the urban environment can impact immunity against communicable pathogens. By studying the behavior, physiology, and ecology of urban bird populations, we can elucidate not only how avian populations are responding to environmental change, but also how unintended consequences of urbanization affect the well-being of human and non-human inhabitants. PMID:29491978

Essential Indicators Identifying Chronic Inorganic Mercury Intoxication: Pooled Analysis across Multiple Cross-Sectional Studies.

PubMed

Doering, Stefan; Bose-O'Reilly, Stephan; Berger, Ursula

2016-01-01

The continuous exposure to inorganic mercury vapour in artisanal small-scale gold mining (ASGM) areas leads to chronic health problems. It is therefore essential to have a quick, but reliable risk assessing tool to diagnose chronic inorganic mercury intoxication. This study re-evaluates the state-of-the-art toolkit to diagnose chronic inorganic mercury intoxication by analysing data from multiple pooled cross-sectional studies. The primary research question aims to reduce the currently used set of indicators without affecting essentially the capability to diagnose chronic inorganic mercury intoxication. In addition, a sensitivity analysis is performed on established biomonitoring exposure limits for mercury in blood, hair, urine and urine adjusted by creatinine, where the biomonitoring exposure limits are compared to thresholds most associated with chronic inorganic mercury intoxication in artisanal small-scale gold mining. Health data from miners and community members in Indonesia, Tanzania and Zimbabwe were obtained as part of the Global Mercury Project and pooled into one dataset together with their biomarkers mercury in urine, blood and hair. The individual prognostic impact of the indicators on the diagnosis of mercury intoxication is quantified using logistic regression models. The selection is performed by a stepwise forward/backward selection. Different models are compared based on the Bayesian information criterion (BIC) and Cohen`s kappa is used to evaluate the level of agreement between the diagnosis of mercury intoxication based on the currently used set of indicators and the result based on our reduced set of indicators. The sensitivity analysis of biomarker exposure limits of mercury is based on a sequence of chi square tests. The variable selection in logistic regression reduced the number of medical indicators from thirteen to ten in addition to the biomarkers. The estimated level of agreement using ten of thirteen medical indicators and all four

Essential Indicators Identifying Chronic Inorganic Mercury Intoxication: Pooled Analysis across Multiple Cross-Sectional Studies

PubMed Central

Doering, Stefan

2016-01-01

Background The continuous exposure to inorganic mercury vapour in artisanal small-scale gold mining (ASGM) areas leads to chronic health problems. It is therefore essential to have a quick, but reliable risk assessing tool to diagnose chronic inorganic mercury intoxication. This study re-evaluates the state-of-the-art toolkit to diagnose chronic inorganic mercury intoxication by analysing data from multiple pooled cross-sectional studies. The primary research question aims to reduce the currently used set of indicators without affecting essentially the capability to diagnose chronic inorganic mercury intoxication. In addition, a sensitivity analysis is performed on established biomonitoring exposure limits for mercury in blood, hair, urine and urine adjusted by creatinine, where the biomonitoring exposure limits are compared to thresholds most associated with chronic inorganic mercury intoxication in artisanal small-scale gold mining. Methods Health data from miners and community members in Indonesia, Tanzania and Zimbabwe were obtained as part of the Global Mercury Project and pooled into one dataset together with their biomarkers mercury in urine, blood and hair. The individual prognostic impact of the indicators on the diagnosis of mercury intoxication is quantified using logistic regression models. The selection is performed by a stepwise forward/backward selection. Different models are compared based on the Bayesian information criterion (BIC) and Cohen`s kappa is used to evaluate the level of agreement between the diagnosis of mercury intoxication based on the currently used set of indicators and the result based on our reduced set of indicators. The sensitivity analysis of biomarker exposure limits of mercury is based on a sequence of chi square tests. Results The variable selection in logistic regression reduced the number of medical indicators from thirteen to ten in addition to the biomarkers. The estimated level of agreement using ten of thirteen medical

Evaluations and Comparisons of Treatment Effects Based on Best Combinations of Biomarkers with Applications to Biomedical Studies

PubMed Central

Chen, Xiwei; Yu, Jihnhee

2014-01-01

Abstract Many clinical and biomedical studies evaluate treatment effects based on multiple biomarkers that commonly consist of pre- and post-treatment measurements. Some biomarkers can show significant positive treatment effects, while other biomarkers can reflect no effects or even negative effects of the treatments, giving rise to a necessity to develop methodologies that may correctly and efficiently evaluate the treatment effects based on multiple biomarkers as a whole. In the setting of pre- and post-treatment measurements of multiple biomarkers, we propose to apply a receiver operating characteristic (ROC) curve methodology based on the best combination of biomarkers maximizing the area under the receiver operating characteristic curve (AUC)-type criterion among all possible linear combinations. In the particular case with independent pre- and post-treatment measurements, we show that the proposed method represents the well-known Su and Liu's (1993) result. Further, proceeding from derived best combinations of biomarkers' measurements, we propose an efficient technique via likelihood ratio tests to compare treatment effects. We show an extensive Monte Carlo study that confirms the superiority of the proposed test in comparison with treatment effects based on multiple biomarkers in a paired data setting. For practical applications, the proposed method is illustrated with a randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients as well as a treatment study for children with attention deficit-hyperactivity disorder and severe mood dysregulation. PMID:25019920

Image Based Biomarker of Breast Cancer Risk: Analysis of Risk Disparity among Minority Populations

DTIC Science & Technology

2013-03-01

TITLE: Image Based Biomarker of Breast Cancer Risk: Analysis of Risk Disparity among Minority Populations PRINCIPAL INVESTIGATOR: Fengshan Liu...SUBTITLE 5a. CONTRACT NUMBER Image Based Biomarker of Breast Cancer Risk: Analysis of Risk Disparity among Minority Populations 5b. GRANT NUMBER...identifying the prevalence of women with incomplete visualization of the breast . We developed a code to estimate the breast cancer risks using the

Detecting Blood-Based Biomarkers in Metastatic Breast Cancer: A Systematic Review of Their Current Status and Clinical Utility

PubMed Central

Berghuis, A. M. Sofie; Koffijberg, Hendrik; Prakash, Jai; Terstappen, Leon W. M. M.; IJzerman, Maarten J.

2017-01-01

Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC) of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%). Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence. PMID:28208771

Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology.

PubMed

Shinde, V; Burke, K E; Chakravarty, A; Fleming, M; McDonald, A A; Berger, A; Ecsedy, J; Blakemore, S J; Tirrell, S M; Bowman, D

2014-01-01

Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H-score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist's expertise with automated image analysis to support oncology drug discovery and development programs.

A POCT platform for sepsis biomarkers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Baldini, Francesco; Adinolfi, Barbara; Berneschi, Simone; Bernini, Romeo; Giannetti, Ambra; Grimaldi, Immacolata Angelica; Persichetti, Gianluca; Testa, Genni; Tombelli, Sara; Trono, Cosimo

2017-06-01

Infectious diseases and sepsis, as a severe and potential medical condition in which the immune system overreacts and finally turns against itself, are a worldwide problem. As a matter of fact, it is considered the main cause of mortality in intensive care. For such a pathology, a timely diagnosis is essential, since it has been shown that each hour of delay in the administration of an effective pharmacological treatment increases the mortality rate of 7%. Therefore, the advent of a POCT platform for sepsis is highly requested by physicians. Biomarkers have gained importance for the diagnosis and treatment monitoring of septic patients, since biomarkers can indicate the severity of sepsis and can differentiate bacterial from viral and fungal infection, and systemic sepsis from local infection. The present paper deals with the development of fluorescence-based bioassays for the sepsis biomarkers and their integration on a multianalyte chip. Among the different biomarker candidates, the attention was focused on procalcitonin (PCT), C-reactive protein (CRP) and interleukine-6 (IL-6) as well as on soluble urokinase plasminogen activator receptor (suPAR) recently proposed as a very effective inflammatory marker, potentially capable of acting also as a prognostic biomarker. Starting point of this new setup was an already developed fluorescence-based optical platform, which makes use of multichannel polymethylmetacrylate chips for the detection of different bioanalytes, and the serial interrogation of the microfluidic channels of the chip. The novel proposed optical setup makes use of a suitable fluorescence excitation and detection scheme, capable of performing the simultaneous interrogation of all the channels. For the excitation part of the optical setup, a diffractive optical element is used which generates a pattern of parallel lines, for the simultaneous excitation of all the channels and for the optimization of the optical power distribution. For the detection part

Evaluation of a new method for the collection and measurement of 8-isoprostane in exhaled breath for future application in nanoparticle exposure biomonitoring.

PubMed

Marie-Desvergne, Caroline; Dubosson, Muriel; Mossuz, Véronique Chamel

2018-05-14

In the field of nanoparticle exposure biomonitoring, oxidative stress biomarkers measured in exhaled breath condensate appear promising to detect early respiratory effects in workers handling nanomaterials. However, condensation is known for its poor efficiency in collecting non-volatiles in exhaled breath, leading to the low sensitivity of such measurements. Moreover, to be easily used in field studies on large groups of workers, the collection device must be disposable and convenient. In this study, we have tested a totally disposable commercial device that allows for the easy dry collection of exhaled air after filtration on a patented filter. The suitability and efficiency of the SensAbues (SB) device for collecting 8-isoprostane were evaluated and compared to the RTube (RT). Seven healthy volunteers performed two 15 min collections of exhaled breath, one with the SB and one with the RT. Blank devices were used to determine the background levels induced by each device. 8-isoprostane was measured in all samples using an EIA technique. The levels of 8-isoprostane in the exhaled breath of volunteers after collection with the SB were significantly higher than those after collection with the RT. Moreover, the levels obtained in volunteers with the SB were significantly higher than background levels obtained in blank devices, which was not the case for the RT. This is the first study to report the ability of the SB device to collect and measure 8-isoprostane in exhaled breath. The proposed method offers better sensitivity than a classical collection with the RT device and should be further explored before future application in biomonitoring studies.

Systematic Review of Pancreatic Cyst Fluid Biomarkers: The Path Forward

PubMed Central

Thiruvengadam, Nikhil; Park, Walter G

2015-01-01

There is significant research interest in developing and validating novel pancreatic cyst-fluid biomarkers given the increasing recognition of the prevalence of pancreatic cysts and their associated malignant potential. Although current international consensus guidelines are helpful, they fail to diagnose with certainty the cyst type and the level of epithelial dysplasia. They also fall short in predicting the future likelihood of malignant transformation. A systematic review was performed with the objective of summarizing cyst-fluid-based biomarkers that have been published in the medical literature over the past 10 years and characterizing the current quality of evidence. Our review demonstrates that there is an increasing interest in this topic with several different and innovative approaches including DNA, RNA, proteomic, and metabolomics profiling. Further techniques to improve upon cytological yield have also been studied. Besides identifying potentially useful clinical biomarkers, these empiric approaches have provided further insight into their pathogenesis. The level of evidence for the vast majority of these studies, however, is limited to retrospective early validation studies. The path forward will be to select out the most promising biomarkers and develop multicenter consortiums capable of capturing adequate sample sizes with appropriate study designs. PMID:26065716

NMR-based metabonomics and correlation analysis reveal potential biomarkers associated with chronic atrophic gastritis.

PubMed

Cui, Jiajia; Liu, Yuetao; Hu, Yinghuan; Tong, Jiayu; Li, Aiping; Qu, Tingli; Qin, Xuemei; Du, Guanhua

2017-01-05

Chronic atrophic gastritis (CAG) is one of the most important pre-cancerous states with a high prevalence. Exploring of the underlying mechanism and potential biomarkers is of significant importance for CAG. In the present work, 1 H NMR-based metabonomics with correlative analysis was performed to analyze the metabolic features of CAG. 19 plasma metabolites and 18 urine metabolites were enrolled to construct the circulatory and excretory metabolome of CAG, which was in response to alterations of energy metabolism, inflammation, immune dysfunction, as well as oxidative stress. 7 plasma biomarkers and 7 urine biomarkers were screened to elucidate the pathogenesis of CAG based on the further correlation analysis with biochemical indexes. Finally, 3 plasma biomarkers (arginine, succinate and 3-hydroxybutyrate) and 2 urine biomarkers (α-ketoglutarate and valine) highlighted the potential to indicate risks of CAG in virtue of correlation with pepsin activity and ROC analysis. Here, our results paved a way for elucidating the underlying mechanisms in the development of CAG, and provided new avenues for the diagnosis of CAG and presented potential drug targets for treatment of CAG. Copyright © 2016 Elsevier B.V. All rights reserved.

Identifying novel biomarkers in sarcoidosis using genome-based approaches

PubMed Central

Knox, Kenneth S.; Garcia, Joe G.N.

2015-01-01

Synopsis We briefly review conventional biomarkers used clinically to 1) support a diagnosis and 2) monitor disease progression in patients with sarcoidosis. We describe potential new biomarkers identified by genome-wide screening and the approaches to discover these biomarkers. PMID:26593137

qFlow Cytometry-Based Receptoromic Screening: A High-Throughput Quantification Approach Informing Biomarker Selection and Nanosensor Development.

PubMed

Chen, Si; Weddell, Jared; Gupta, Pavan; Conard, Grace; Parkin, James; Imoukhuede, Princess I

2017-01-01

Nanosensor-based detection of biomarkers can improve medical diagnosis; however, a critical factor in nanosensor development is deciding which biomarker to target, as most diseases present several biomarkers. Biomarker-targeting decisions can be informed via an understanding of biomarker expression. Currently, immunohistochemistry (IHC) is the accepted standard for profiling biomarker expression. While IHC provides a relative mapping of biomarker expression, it does not provide cell-by-cell readouts of biomarker expression or absolute biomarker quantification. Flow cytometry overcomes both these IHC challenges by offering biomarker expression on a cell-by-cell basis, and when combined with calibration standards, providing quantitation of biomarker concentrations: this is known as qFlow cytometry. Here, we outline the key components for applying qFlow cytometry to detect biomarkers within the angiogenic vascular endothelial growth factor receptor family. The key aspects of the qFlow cytometry methodology include: antibody specificity testing, immunofluorescent cell labeling, saturation analysis, fluorescent microsphere calibration, and quantitative analysis of both ensemble and cell-by-cell data. Together, these methods enable high-throughput quantification of biomarker expression.

Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome.

PubMed

Yehya, Nadir; Wong, Hector R

2018-01-01

The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. Prospective observational cohort study. University affiliated PICU. Mechanically ventilated children with acute respiratory distress syndrome. Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics. A validated, biomarker-based

Biomonitoring of trace elements in urine samples of children from a coal-mining region.

PubMed

Santos, Marina Dos; Flores Soares, Maria Cristina; Martins Baisch, Paulo Roberto; Muccillo Baisch, Ana Luíza; Rodrigues da Silva Júnior, Flavio Manoel

2018-04-01

Biomonitoring through urine samples is important for evaluating environmental exposure, since urine is the main form of excretion for most chemical elements. Children are considered more vulnerable to adverse environmental conditions, especially children in developing countries. This study aimed to biomonitor trace elements in urine samples in children from a coal-mining region in the extreme south of Brazil. A cross-sectional study was conducted on 96 children between 6 and 11 years of age. Socioeconomic data and urine samples were collected to estimate the concentration of iron, zinc, selenium, lead, and cadmium. The prevalence of metals above the reference values was 52.0% for Se, followed by 15.6% for Zn. The data point toward a vulnerability to adverse environmental conditions in these children. Although the concentrations of the elements did not reveal intoxication cases, biomonitoring should be carried out continuously in order to assess exposure to metals and ensure the health of the population. This article provides data that help determine natural levels of metallic elements in children, specifically in South America, which have not yet been established. Copyright © 2018 Elsevier Ltd. All rights reserved.

Communication in a Human biomonitoring study: Focus group work, public engagement and lessons learnt in 17 European countries.

PubMed

Exley, Karen; Cano, Noemi; Aerts, Dominique; Biot, Pierre; Casteleyn, Ludwine; Kolossa-Gehring, Marike; Schwedler, Gerda; Castaño, Argelia; Angerer, Jürgen; Koch, Holger M; Esteban, Marta; Schoeters, Greet; Den Hond, Elly; Horvat, Milena; Bloemen, Louis; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Dewolf, Marie-Christine; Van de Mieroop, Els; Katsonouri, Andromachi; Hadjipanayis, Adamos; Cerna, Milena; Krskova, Andrea; Becker, Kerstin; Fiddicke, Ulrike; Seiwert, Margarete; Mørck, Thit A; Rudnai, Peter; Kozepesy, Szilvia; Cullen, Elizabeth; Kellegher, Anne; Gutleb, Arno C; Fischer, Marc E; Ligocka, Danuta; Kamińska, Joanna; Namorado, Sónia; Reis, M Fátima; Lupsa, Ioana-Rodica; Gurzau, Anca E; Halzlova, Katarina; Jajcaj, Michal; Mazej, Darja; Tratnik, Janja Snoj; Huetos, Olga; López, Ana; Berglund, Marika; Larsson, Kristin; Sepai, Ovnair

2015-08-01

A communication strategy was developed by The Consortium to Perform Human Biomonitoring on a European Scale (COPHES), as part of its objectives to develop a framework and protocols to enable the collection of comparable human biomonitoring data throughout Europe. The framework and protocols were tested in the pilot study DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale). The aims of the communication strategy were to raise awareness of human biomonitoring, encourage participation in the study and to communicate the study results and their public health significance. It identified the audiences and key messages, documented the procedure for dissemination of results and was updated as the project progressed. A communication plan listed the tools and materials such as press releases, flyers, recruitment letters and information leaflets required for each audience with a time frame for releasing them. Public insight research was used to evaluate the recruitment material, and the feedback was used to improve the documents. Dissemination of results was coordinated in a step by step approach by the participating countries within DEMOCOPHES, taking into account specific national messages according to the needs of each country. Participants received individual results, unless they refused to be informed, along with guidance on what the results meant. The aggregate results and policy recommendations were then communicated to the general public and stakeholders, followed by dissemination at European level. Several lessons were learnt that may assist other future human biomonitoring studies. Recruitment took longer than anticipated and so social scientists, to help with community engagement, should be part of the research team from the start. As a European study, involving multiple countries, additional considerations were needed for the numerous organisations, different languages, cultures, policies and priorities

1-D grating based SPR biosensor for the detection of lung cancer biomarkers using Vroman effect

NASA Astrophysics Data System (ADS)

Teotia, Pradeep Kumar; Kaler, R. S.

2018-01-01

Grating based surface plasmon resonance waveguide biosensor have been reported for the detection of lung cancer biomarkers using Vroman effect. The proposed grating based multilayered biosensor is designed with high detection accuracy for Epidermal growth factor receptor (EGFR) and also analysed to show high detection accuracy with acceptable sensitivity for both cancer biomarkers. The introduction of periodic grating with multilayer metals generates a good resonance that make it possible for early detection of cancerous cells. Using finite difference time domain method, it is observed wavelength of biosensor get red-shifted on variations of the refractive index due to the presence of both the cancerous bio-markers. The reported detection accuracy and sensitivity of proposed biosensor is quite acceptable for both lung cancer biomarkers i.e. Carcinoembryonic antigen (CEA) and Epidermal growth factor receptor (EGFR) which further offer us label free early detection of lung cancer using these biomarkers.

Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort.

PubMed

Fortner, Renée T; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Peeters, Petra H M; Weiderpass, Elisabete; Gram, Inger T; Gavrilyuk, Oxana; Quirós, J Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay-Tee; Allen, Naomi E; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

2017-03-15

Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination. © 2016 UICC.

Online Biomonitoring and Early Warning Systems for Protection of Water Sources

EPA Science Inventory

The ability to perform real time biomonitoring of behavioral responses and stress levels experienced by fish is important as it could be used for assessing source water toxicity as a first line of defense to protect and encourage recreational use of waterbodies. This paper propos...

High-throughput and targeted in-depth mass spectrometry-based approaches for biofluid profiling and biomarker discovery.

PubMed

Jimenez, Connie R; Piersma, Sander; Pham, Thang V

2007-12-01

Proteomics aims to create a link between genomic information, biological function and disease through global studies of protein expression, modification and protein-protein interactions. Recent advances in key proteomics tools, such as mass spectrometry (MS) and (bio)informatics, provide tremendous opportunities for biomarker-related clinical applications. In this review, we focus on two complementary MS-based approaches with high potential for the discovery of biomarker patterns and low-abundant candidate biomarkers in biofluids: high-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy-based methods for peptidome profiling and label-free liquid chromatography-based methods coupled to MS for in-depth profiling of biofluids with a focus on subproteomes, including the low-molecular-weight proteome, carrier-bound proteome and N-linked glycoproteome. The two approaches differ in their aims, throughput and sensitivity. We discuss recent progress and challenges in the analysis of plasma/serum and proximal fluids using these strategies and highlight the potential of liquid chromatography-MS-based proteomics of cancer cell and tumor secretomes for the discovery of candidate blood-based biomarkers. Strategies for candidate validation are also described.

Developing Biomarkers in Mood Disorders Research Through the Use of Rapid-Acting Antidepressants

PubMed Central

Niciu, Mark J.; Mathews, Daniel C.; Nugent, Allison C.; Ionescu, Dawn F.; Furey, Maura L.; Richards, Erica M.; Machado-Vieira, Rodrigo; Zarate, Carlos A.

2014-01-01

An impediment to progress in mood disorders research is the lack of analytically valid and qualified diagnostic and treatment biomarkers. Consistent with the National Institute of Mental Health (NIMH)’s Research Domain Criteria (RDoC) initiative, the lack of diagnostic biomarkers has precluded us from moving away from a purely subjective (symptom-based) towards a more objective diagnostic system. In addition, treatment response biomarkers in mood disorders would facilitate drug development and move beyond trial-and-error towards more personalized treatments. As such, biomarkers identified early in the pathophysiological process are proximal biomarkers (target engagement), while those occurring later in the disease process are distal (disease pathway components). One strategy to achieve this goal in biomarker development is to increase efforts at the initial phases of biomarker development (i.e., exploration and validation) at single sites with the capability of integrating multimodal approaches across a biological systems level. Subsequently, resultant putative biomarkers could then undergo characterization and surrogacy as these latter phases require multisite collaborative efforts. We have used multimodal approaches – genetics, proteomics/metabolomics, peripheral measures, multimodal neuroimaging, neuropsychopharmacological challenge paradigms and clinical predictors – to explore potential predictor and mediator/moderator biomarkers of the rapid-acting antidepressants ketamine and scopolamine. These exploratory biomarkers may then be used for a priori stratification in larger multisite controlled studies during the validation and characterization phases with the ultimate goal of surrogacy. In sum, the combination of target engagement and well-qualified disease-related measures are crucial to improve our pathophysiological understanding, personalize treatment selection and expand our armamentarium of novel therapeutics. PMID:24353110

Developing biomarkers in mood disorders research through the use of rapid-acting antidepressants.

PubMed

Niciu, Mark J; Mathews, Daniel C; Nugent, Allison C; Ionescu, Dawn F; Furey, Maura L; Richards, Erica M; Machado-Vieira, Rodrigo; Zarate, Carlos A

2014-04-01

An impediment to progress in mood disorders research is the lack of analytically valid and qualified diagnostic and treatment biomarkers. Consistent with the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC) initiative, the lack of diagnostic biomarkers has precluded us from moving away from a purely subjective (symptom-based) toward a more objective diagnostic system. In addition, treatment response biomarkers in mood disorders would facilitate drug development and move beyond trial-and-error toward more personalized treatments. As such, biomarkers identified early in the pathophysiological process are proximal biomarkers (target engagement), while those occurring later in the disease process are distal (disease pathway components). One strategy to achieve this goal in biomarker development is to increase efforts at the initial phases of biomarker development (i.e. exploration and validation) at single sites with the capability of integrating multimodal approaches across a biological systems level. Subsequently, resultant putative biomarkers could then undergo characterization and surrogacy as these latter phases require multisite collaborative efforts. We have used multimodal approaches - genetics, proteomics/metabolomics, peripheral measures, multimodal neuroimaging, neuropsychopharmacological challenge paradigms and clinical predictors - to explore potential predictor and mediator/moderator biomarkers of the rapid-acting antidepressants ketamine and scopolamine. These exploratory biomarkers may then be used for a priori stratification in larger multisite controlled studies during the validation and characterization phases with the ultimate goal of surrogacy. In sum, the combination of target engagement and well-qualified disease-related measures are crucial to improve our pathophysiological understanding, personalize treatment selection, and expand our armamentarium of novel therapeutics. © 2013 Wiley Periodicals, Inc.

Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.

PubMed

Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos

2017-05-01

Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Assessing indoor air quality of school environments: transplanted lichen Pseudovernia furfuracea as a new tool for biomonitoring and bioaccumulation.

PubMed

Protano, Carmela; Owczarek, Malgorzata; Antonucci, Arianna; Guidotti, Maurizio; Vitali, Matteo

2017-07-01

The aim of this research is to evaluate the ability of transplanted lichen Pseudovernia (P). furfuracea to biomonitor and bioaccumulate in urban indoor environments. The elements As, Cd, Cr, Cu, Hg, Ni and Pb and 12 selected polycyclic aromatic hydrocarbons (PAHs) were used to assess P. furfuracea as a biomonitoring tool for the indoor air quality of school environments. To achieve this purpose, lichen samples were exposed for 2 months in the outdoor and indoor environments of five school settings located in urban and rural areas. The results demonstrated that transplanted lichen P. furfuracea is a suitable biomonitoring tool for metals and PAHs in indoor settings and can discriminate between different levels of air pollution related to urbanisation and indoor conditions, such as those characterised by school environments. A transplanted lichen biomonitoring strategy is cost-effective, "green", educational for attending children and less "invasive" than traditional air sampling methods. The feasibility of indoor monitoring by P. furfuracea is a relevant finding and could be a key tool to improve air quality monitoring programmes in school scenarios and thus focus on health prevention interventions for children, who are one of the most susceptible groups in the population.

Tissue microarrays and quantitative tissue-based image analysis as a tool for oncology biomarker and diagnostic development.

PubMed

Dolled-Filhart, Marisa P; Gustavson, Mark D

2012-11-01

Translational oncology has been improved by using tissue microarrays (TMAs), which facilitate biomarker analysis of large cohorts on a single slide. This has allowed for rapid analysis and validation of potential biomarkers for prognostic and predictive value, as well as for evaluation of biomarker prevalence. Coupled with quantitative analysis of immunohistochemical (IHC) staining, objective and standardized biomarker data from tumor samples can further advance companion diagnostic approaches for the identification of drug-responsive or resistant patient subpopulations. This review covers the advantages, disadvantages and applications of TMAs for biomarker research. Research literature and reviews of TMAs and quantitative image analysis methodology have been surveyed for this review (with an AQUA® analysis focus). Applications such as multi-marker diagnostic development and pathway-based biomarker subpopulation analyses are described. Tissue microarrays are a useful tool for biomarker analyses including prevalence surveys, disease progression assessment and addressing potential prognostic or predictive value. By combining quantitative image analysis with TMAs, analyses will be more objective and reproducible, allowing for more robust IHC-based diagnostic test development. Quantitative multi-biomarker IHC diagnostic tests that can predict drug response will allow for greater success of clinical trials for targeted therapies and provide more personalized clinical decision making.

Towards improved biomonitoring tools for an intensified sustainable multi-use environment.

PubMed

van der Meer, Jan Roelof

2016-09-01

The increasing use of our environment for multiple contrasting activities (e.g. fisheries, tourism) will have to be accompanied by improved monitoring of environmental quality, to avoid transboundary conflicts and ensure long-term sustainable intensified usage. Biomonitoring approaches are appropriate for this, since they can integrate biological effects of environmental exposure rather than measure individual compound concentrations. Recent advances in biomonitoring concepts and tools focus on single-cell assays and purified biological components that can be miniaturized and integrated in automated systems. Despite these advances, we are still very far from being able to deploy bioassays routinely in environmental monitoring, mostly because of lack of experience in interpreting responses and insufficient robustness of the biosensors for their environmental application. Further future challenges include broadening the spectrum of detectable compounds by biosensors, accelerate response times and combining sample pretreatment strategies with bioassays. © 2016 The Author. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

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.

PubMed

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.

The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study.

PubMed

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Siegbahn, Agneta; Yusuf, Salim; Granger, Christopher B; Wallentin, Lars

2016-06-04

The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation. We developed and internally validated a new biomarker-based risk score for major bleeding in 14,537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov, numbers NCT00412984 and NCT00262600, respectively. The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers [GDF-15, cTnT-hs, and haemoglobin], and clinical history [previous bleeding]) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0·68 [95% CI 0·66-0·70] vs 0·61 [0·59-0·63] vs 0·65 [0·62-0·67], respectively; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0·71 [95% CI 0·68-0·73] vs 0·62 [0·59-0·64] for HAS-BLED vs 0·68 [0·65-0·70] for ORBIT; ABC-bleeding vs HAS-BLED p<0·0001 and ABC

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

PubMed

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.

EVALUATION OF A DAPHNIA BIOMONITOR FOR REAL-TIME DRINKING WATER SOURCE TESTING

EPA Science Inventory

The quality of drinking water sources has come under closer scrutiny in recent years. Issues ranging from ecological to public health, to national security are under consideration. With advances in electronic and computer technology, biomonitors are being developed that can asses...

Mass spectrometry for biomarker development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chaochao; Liu, Tao; Baker, Erin Shammel

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.

Comprehensive analytical strategy for biomonitoring of pesticides in urine by liquid chromatography–orbitrap high resolution masss pectrometry.

PubMed

Roca, M; Leon, N; Pastor, A; Yusà, V

2014-12-29

In this study we propose an analytical strategy that combines a target approach for the quantitative analysis of contemporary pesticide metabolites with a comprehensive post-target screening for the identification of biomarkers of exposure to environmental contaminants in urine using liquid chromatography coupled to high-resolution mass spectrometry (LC–HRMS). The quantitative method for the target analysis of 29 urinary metabolites of organophosphate (OP) insecticides, synthetic pyrethroids, herbicides and fungicides was validated after a previous statistical optimization of the main factors governing the ion source ionization and a fragmentation study using the high energy collision dissociation (HCD) cell. The full scan accurate mass data were acquired with a resolving power of 50,000 FWHM (scan speed, 2 Hz), in both ESI+ and ESI− modes, and with and without HCD-fragmentation. The method – LOQ was lower than 3.2 μg L−1 for the majority of the analytes. For post-target screening a customized theoretical database was built, for the identification of 60 metabolites including pesticides, PAHs, phenols, and other metabolites of environmental pollutants. For identification purposes, accurate exact mass with less than 5 ppm, and diagnostic ions including isotopes and/or fragments were used. The analytical strategy was applied to 20 urine sample collected from children living in Valencia Region. Eleven target metabolites were detected with concentrations ranging from 1.18 to 131 μg L−1. Likewise, several compounds were tentatively identified in the post-target analysis belonging to the families of phthalates, phenols and parabenes. The proposed strategy is suitable for the determination of target pesticide biomarkers in urine in the framework of biomonitoring studies, and appropriate for the identification of other non-target metabolites.

Negative biomarker-based male fertility evaluation: sperm phenotypes associated with molecular-level anomalies

PubMed Central

Sutovsky, Peter; Aarabi, Mahmoud; Miranda-Vizuete, Antonio; Oko, Richard

2015-01-01

Biomarker-based sperm analysis elevates the treatment of human infertility and ameliorates reproductive performance in livestock. The negative biomarker-based approach focuses on proteins and ligands unique to defective spermatozoa, regardless of their morphological phenotype, lending itself to analysis by flow cytometry (FC). A prime example is the spermatid specific thioredoxin SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of defective human spermatozoa. Infertile couples with high semen SPTRX3 are less likely to conceive by assisted reproductive therapies (ART) and more prone to recurrent miscarriage while low SPTRX3 has been associated with multiple ART births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational protein modifier is found on the surface of defective posttesticular spermatozoa and in the damaged protein aggregates, the aggresomes of spermiogenic origin. Semen ubiquitin content correlates negatively with fertility and conventional semen parameters, and with sperm binding of lectins LCA (Lens culinaris agglutinin; reveals altered sperm surface) and PNA (Arachis hypogaea/peanut agglutinin; reveals acrosomal malformation or damage). The Postacrosomal Sheath WWI Domain Binding Protein (PAWP), implicated in oocyte activation during fertilization, is ectopic or absent from defective human and animal spermatozoa. Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile couples and with fertility in bulls. Assays based on the above biomarkers have been combined into multiplex FC semen screening protocols, and the surface expression of lectins and ubiquitin has been utilized to develop nanoparticle-based bull semen purification method validated by field artificial insemination trials. These advances go hand-in-hand with the innovation of FC-technology and genomics/proteomics-based biomarker discovery. PMID:25999356

Nanoparticle exposure biomonitoring: exposure/effect indicator development approaches

NASA Astrophysics Data System (ADS)

Marie-Desvergne, C.; Dubosson, M.; Lacombe, M.; Brun, V.; Mossuz, V.

2015-05-01

The use of engineered nanoparticles (NP) is more and more widespread in various industrial sectors. The inhalation route of exposure is a matter of concern (adverse effects of air pollution by ultrafine particles and asbestos). No NP biomonitoring recommendations or standards are available so far. The LBM laboratory is currently studying several approaches to develop bioindicators for occupational health applications. As regards exposure indicators, new tools are being implemented to assess potentially inhaled NP in non-invasive respiratory sampling (nasal sampling and exhaled breath condensates (EBC)). Diverse NP analytical characterization methods are used (ICP-MS, dynamic light scattering and electron microscopy coupled to energy-dispersive X-ray analysis). As regards effect indicators, a methodology has been developed to assess a range of 29 cytokines in EBCs (potential respiratory inflammation due to NP exposure). Secondly, collaboration between the LBM laboratory and the EDyp team has allowed the EBC proteome to be characterized by means of an LC-MS/MS process. These projects are expected to facilitate the development of individual NP exposure biomonitoring tools and the analysis of early potential impacts on health. Innovative techniques such as field-flow fractionation combined with ICP-MS and single particle-ICPMS are currently being explored. These tools are directly intended to assist occupational physicians in the identification of exposure situations.

Innovative biomarkers for predicting type 2 diabetes mellitus: relevance to dietary management of frailty in older adults.

PubMed

Ikwuobe, John; Bellary, Srikanth; Griffiths, Helen R

2016-06-01

Type 2 diabetes mellitus (T2DM) increases in prevalence in the elderly. There is evidence for significant muscle loss and accelerated cognitive impairment in older adults with T2DM; these comorbidities are critical features of frailty. In the early stages of T2DM, insulin sensitivity can be improved by a "healthy" diet. Management of insulin resistance by diet in people over 65 years of age should be carefully re-evaluated because of the risk for falling due to hypoglycaemia. To date, an optimal dietary programme for older adults with insulin resistance and T2DM has not been described. The use of biomarkers to identify those at risk for T2DM will enable clinicians to offer early dietary advice that will delay onset of disease and of frailty. Here we have used an in silico literature search for putative novel biomarkers of T2DM risk and frailty. We suggest that plasma bilirubin, plasma, urinary DPP4-positive microparticles and plasma pigment epithelium-derived factor merit further investigation as predictive biomarkers for T2DM and frailty risk in older adults. Bilirubin is screened routinely in clinical practice. Measurement of specific microparticle frequency in urine is less invasive than a blood sample so is a good choice for biomonitoring. Future studies should investigate whether early dietary changes, such as increased intake of whey protein and micronutrients that improve muscle function and insulin sensitivity, affect biomarkers and can reduce the longer term complication of frailty in people at risk for T2DM.

Constraint programming based biomarker optimization.

PubMed

Zhou, Manli; Luo, Youxi; Sun, Guoquan; Mai, Guoqin; Zhou, Fengfeng

2015-01-01

Efficient and intuitive characterization of biological big data is becoming a major challenge for modern bio-OMIC based scientists. Interactive visualization and exploration of big data is proven to be one of the successful solutions. Most of the existing feature selection algorithms do not allow the interactive inputs from users in the optimizing process of feature selection. This study investigates this question as fixing a few user-input features in the finally selected feature subset and formulates these user-input features as constraints for a programming model. The proposed algorithm, fsCoP (feature selection based on constrained programming), performs well similar to or much better than the existing feature selection algorithms, even with the constraints from both literature and the existing algorithms. An fsCoP biomarker may be intriguing for further wet lab validation, since it satisfies both the classification optimization function and the biomedical knowledge. fsCoP may also be used for the interactive exploration of bio-OMIC big data by interactively adding user-defined constraints for modeling.

Glycoprofiling of cancer biomarkers: Label-free electrochemical lectin-based biosensors

PubMed Central

Pihíková, Dominika; Kasák, Peter

2016-01-01

Glycosylation of biomolecules is one of the most prevalent post- and co-translational modification in a human body, with more than half of all human proteins being glycosylated. Malignant transformation of cells influences glycosylation machinery resulting in subtle changes of the glycosylation pattern within the cell populations as a result of cancer. Thus, an altered terminal glycan motif on glycoproteins could provide a warning signal about disease development and progression and could be applied as a reliable biomarker in cancer diagnostics. Among all highly effective glycoprofiling tools, label-free electrochemical impedance spectroscopy (EIS)-based biosensors have emerged as especially suitable tool for point-of-care early-stage cancer detection. Herein, we highlight the current challenges in glycoprofiling of various cancer biomarkers by ultrasensitive impedimetric-based biosensors with low sample consumption, low cost fabrication and simple miniaturization. Additionally, this review provides a short introduction to the field of glycomics and lectinomics and gives a brief overview of glycan alterations in different types of cancer. PMID:27275016

Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study.

PubMed

Calafat, Antonia M; McKee, Richard H

2006-11-01

The probability of nonoccupational exposure to phthalates is high given their use in a vast range of consumables, including personal care products (e.g., perfumes, lotions, cosmetics), paints, industrial plastics, and certain medical devices and pharmaceuticals. Phthalates are of high interest because of their potential for human exposure and because animal toxicity studies suggest that some phthalates affect male reproductive development apparently via inhibition of androgen biosynthesis. In humans, phthalates are rapidly metabolized to their monoesters, which can be further transformed to oxidative products, conjugated, and eliminated. Phthalate metabolites have been used as biomarkers of exposure. Using urinary phthalate metabolite concentrations allows accurate assessments of human exposure because these concentrations represent an integrative measure of exposure to phthalates from multiple sources and routes. However, the health significance of this exposure is unknown. To link biomarker measurements to exposure, internal dose, or health outcome, additional information (e.g., toxicokinetics, inter- and intraindividual differences) is needed. We present a case study using diethyl phthalate and di(2-ethylhexyl) phthalate as examples to illustrate scientific approaches and their limitations, identify data gaps, and outline research needs for using biomonitoring data in the context of human health risk assessment, with an emphasis on exposure and dose. Although the vast and growing literature on phthalates research could not be covered comprehensively in this article, we made every attempt to include the most relevant publications as of the end of 2005.

Mapping Exposure to Multi-Pollutants Using Environmental Biomonitors-A Multi-Exposure Index.

PubMed

Serrano, Helena C; Köbel, Melanie; Palma-Oliveira, José; Pinho, Pedro; Branquinho, Cristina

2017-01-01

Atmosphere is a major pathway for transport and deposition of pollutants in the environment. In industrial areas, organic compounds are released or formed as by-products, such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F's). Inorganic chemical elements, including lead and arsenic, are also part of the pollutants mixture, and even in low concentrations may potentially be toxic and carcinogenic. However, assessing the spatial pattern of their deposition is difficult due to high spatial and temporal heterogeneity. Lichens have been used as biomonitors of atmospheric deposition, because these organisms encompass greater spatial detail than air monitoring stations and provide an integration of overall pollution. Based upon the ability of lichens to concentrate pollutants such as PCDD/F and chemical elements, the main objectives of this study were to develop a new semi-quantitative multi-pollutant toxicity exposure index (TEQ-like), derived from risk estimates, in an attempt to correlate several atmospheric pollutants to human exposure levels. The actual pollutant concentrations were measured in the environment, from biomonitors (organisms that integrate multi-pollutants), enabling interpolation and mapping of contaminant deposition within the region. Thus, the TEQ-like index provides a spatial representation not from absolute accumulation of the different pollutants, but from the accumulation weighted by their relative risk. The assessment of environmental human exposure to multi-pollutants through atmospheric deposition may be applied to industries to improve mitigation processes or to health stakeholders to target populations for a comprehensive risk assessment, epidemiological studies, and health recommendations.

Air Pollution Study in the Republic of Moldova Using Moss Biomonitoring Technique.

PubMed

Zinicovscaia, Inga; Hramco, Constantin; Duliu, Octavian G; Vergel, Konstantin; Culicov, Otilia A; Frontasyeva, Marina V; Duca, Gheorghe

2017-02-01

Moss biomonitoring using the species Hypnum cupressiforme (Hedw.) and Pleurocarpous sp was applied to study air pollution in the Republic of Moldova. A total of 41 elements (Na, Mg, Al, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br, Rb, Sr, Zr, Cd, Sb, Cs, Ba, La, Ce, Nd, Sm, Eu, Gd, Tb, Tm, Yb, Hf, Ta, W, Pb, Th, and U) were determined by instrumental epithermal neutron activation analysis and atomic absorption spectrometry. Principal component analysis was used to identify and characterize different pollution sources. Geographical distribution maps were prepared to point out the regions most affected by air pollution and relate this to potential sources of contamination. Median values of the elements studied were compared with data from the European moss biomonitoring program. The cities of Chisinau and Balti were determined to experience particular environmental stress.

Emerging Role of MicroRNAs as Liquid Biopsy Biomarkers in Gastrointestinal Cancers

PubMed Central

Shigeyasu, Kunitoshi; Toden, Shusuke; Zumwalt, Timothy J.; Okugawa, Yoshinaga; Goel, Ajay

2017-01-01

Cancer has emerged as a leading cause of mortality worldwide, claiming over 8 million lives annually. Gastrointestinal (GI) cancers account for ~35% of these mortalities. Recent advances in diagnostic and treatment strategies have reduced mortality among GI cancer patients, yet a significant number of patients still develop late-stage cancer, where treatment options are inadequate. Emerging interests in ‘liquid biopsies’ have encouraged investigators to identify and develop clinically-relevant noninvasive genomic and epigenomic signatures that can be exploited as biomarkers capable of detecting premalignant and early-stage cancers. In this context, microRNAs (miRNAs), which are small non-coding RNAs that are frequently dysregulated in cancers, have emerged as promising entities for such diagnostic purposes. Albeit the future looks promising, current approaches for detecting miRNAs in blood and other biofluids remain inadequate. This review summarizes existing efforts to exploit circulating miRNAs as cancer biomarkers, evaluates their potential and challenges as liquid biopsy-based biomarkers for GI cancers. PMID:28143873

Using devitalized moss for active biomonitoring of water pollution.

PubMed

Debén, S; Fernández, J A; Carballeira, A; Aboal, J R

2016-03-01

This paper presents the results of an experiment carried out for the first time in situ to select a treatment to devitalize mosses for use in active biomonitoring of water pollution. Three devitalizing treatments for the aquatic moss Fontinalis antipyretica were tested (i.e. oven-drying at 100 °C, oven-drying with a 50-80-100 °C temperature ramp, and boiling in water), and the effects of these on loss of material during exposure of the transplants and on the accumulation of different heavy metals and metalloids were determined. The suitability of using devitalized samples of the terrestrial moss Sphagnum denticulatum to biomonitor aquatic environments was also tested. The structure of mosses was altered in different ways by the devitalizing treatments. Devitalization by boiling water led to significantly less loss of material (p < 0.01) than the oven-drying treatments. However, devitalization by oven-drying with a temperature ramp yielded more stable results in relation to both loss of material and accumulation of elements. With the aim of standardizing the moss bag technique, the use of F. antipyretica devitalized by oven-drying with a temperature ramp is recommended, rather than other devitalization treatments or use of S. denticulatum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biochemical responses of Mytilus galloprovincialis as biomarkers of acute environmental pollution caused by the Don Pedro oil spill (Eivissa Island, Spain).

PubMed

Sureda, Antoni; Box, Antonio; Tejada, Silvia; Blanco, Andreu; Caixach, Josep; Deudero, Salud

2011-02-01

In the present work, the potential use of several antioxidant and detoxification biomarkers in the digestive gland of wild mussels (Mytilus galloprovincialis) for biomonitoring the marine pollution induced by the Don Pedro oil spill has been investigated. Two locations from the East to South-East of Eivissa (Ibiza) and Formentera islands were selected, one extensively affected by the oil spill and the other one not affected and considered as the control area. Mussels were sampled one, two and six months after the Don Pedro accident. Polycyclic aromatic hydrocarbon (PAH) levels were significantly increased in the soft tissues of mussels in the affected area one month after the disaster, returning to normal values after six months. Markers of oxidative damage in lipids--malondialdehyde, and in proteins--carbonyl derivates, and antioxidant enzyme--catalase, superoxide dismutase and glutathione peroxidase, activities significantly increased as result of the spill oil after one month, returning to basal values at two month sampling time. Glutathione/glutathione disulfide ratio (GSH/GSSG), as a marker of the redox status, was reduced after one and two months indicating a more oxidized situation. Markers of detoxification--glutathione-S-transferase and cytochrome P4501A activities and metallothionein gene expression--were significantly increased by the oil spill one month after the accident, returning to the basal values at two month sampling time. In conclusion, the Don Pedro accident induced a transient situation of PAHs pollution resulting in enhanced antioxidant and detoxification defense systems in the wild mussel M. galloprovincialis returning to normal levels six months from the spill. The selected biomarkers are a useful tool for biomonitoring the response to acute exposure to pollutants in marine mussels. Copyright © 2011 Elsevier B.V. All rights reserved.

Technological innovation capability in Malaysian-owned resource-based manufacturing companies: Early findings

NASA Astrophysics Data System (ADS)

Razali, Nur Fhathyhah; Mohd Suradi, Nur Riza; Ahmad Shahabuddin, Faridatul Azna; Ismail, Wan Rosmanira; Abidin, Norkisme Zainal; Ahmad, Nor Amalina; Mustafa, Zainol

2013-04-01

This study aims to identify the determinants of technological innovation capability of Malaysian-owned companies in the resources-based manufacturing, to identify the relationship between technological innovation capability (TIC) and technological innovation performance (TIP) for the resource-based manufacturing. Furthermore, this study also aims to identify innovation capability factors that need more emphasis and improvements from the respective authority. The scope of the study covers four industries which are petrochemical industries, pharmaceutical industries, palm oil-based industries and food processing industries which are located in the state of Selangor. Descriptive analysis, correlation analysis and performance capability analysis were used in this study. It was found that, technological innovation capabilities (TIC) for companies in the resource-based manufacturing are moderate. Factors such as policies capability, human resources capability and facilities capability have a positive relationship with the performance of technological innovation (TIP). These findings will help the government in making decisions and better implementation of policies to strengthen the competitiveness of the company, particularly in resource-based manufacturing.

Biomonitoring: Uses and Considerations for Assessing Non-Occupational Human Exposure to Pesticides

EPA Science Inventory

Biomonitoring is an important tool that can be used to evaluate human exposure to pesticides by measuring the levels of pesticides, pesticide metabolites, or altered biological structures or functions in biological specimens or tissues (Barr et al., 2005b; Needham et al., 2005, 2...

Development and application of LC–APCI–MS method for biomonitoring of animal and human exposure to imidacloprid.

PubMed

Kavvalakis, Matthaios P; Tzatzarakis, Manolis N; Theodoropoulou, Eleftheria P; Barbounis, Emmanouil G; Tsakalof, Andreas K; Tsatsakis, Aristidis M

2013-11-01

Imidacloprid (IMI) is a relatively new neuro-active neonicotinoid insecticide and nowadays one of the largest selling insecticides worldwide. In the present study a LC–APCI–MS based method was developed and validated for the quantification of imidacloprid and its main metabolite 6-chloronicotinic acid (6- CINA) in urine and hair specimens. The method was tested in biomonitoring of intentionally exposed animals and subsequently applied for biomonitoring of Cretan urban and rural population. The developed analytical method comprises two main steps of analytes isolation from specimen (solid– liquid extraction with methanol for hair, liquid–liquid extraction with methanol for urine) and subsequent instrumental analysis by LC–APCI–MS. The developed method was applied for the monitoring of IMI and 6-ClNA in hair and urine of laboratory animals (rabbits) intentionally fed with insecticide at low or high doses (40 and 80 mg kg(-1) weight d(-1) respectively) for 24 weeks. The analytes were detected in the regularly acquired hair and urine specimens and their found levels were proportional to the feeding dose and time of exposure with the exception of slight decline of IMI levels in high dose fed rabbits after 24 weeks of feeding. This decline can be explained by the induction of IMI metabolizing enzymes by the substrate. After testing on animal models the method was applied for pilot biomonitoring of Crete urban (n = 26) and rural (n = 32) population. Rural but not urban population is exposed to IMI with 21 positive samples (65.6%) and found median concentration 0.03 ng mg(-1). Maximum concentration detected was 27 ng mg(-1)

Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

PubMed

Ecke, Thorsten H

2015-01-01

The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC

Cancer.gov

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.

Intra-urban biomonitoring: Source apportionment using tree barks to identify air pollution sources.

PubMed

Moreira, Tiana Carla Lopes; de Oliveira, Regiani Carvalho; Amato, Luís Fernando Lourenço; Kang, Choong-Min; Saldiva, Paulo Hilário Nascimento; Saiki, Mitiko

2016-05-01

It is of great interest to evaluate if there is a relationship between possible sources and trace elements using biomonitoring techniques. In this study, tree bark samples of 171 trees were collected using a biomonitoring technique in the inner city of São Paulo. The trace elements (Al, Ba, Ca, Cl, Cu, Fe, K, Mg, Mn, Na, P, Rb, S, Sr and Zn) were determined by the energy dispersive X-ray fluorescence (EDXRF) spectrometry. The Principal Component Analysis (PCA) was applied to identify the plausible sources associated with tree bark measurements. The greatest source was vehicle-induced non-tailpipe emissions derived mainly from brakes and tires wear-out and road dust resuspension (characterized with Al, Ba, Cu, Fe, Mn and Zn), which was explained by 27.1% of the variance, followed by cement (14.8%), sea salt (11.6%) and biomass burning (10%), and fossil fuel combustion (9.8%). We also verified that the elements related to vehicular emission showed different concentrations at different sites of the same street, which might be helpful for a new street classification according to the emission source. The spatial distribution maps of element concentrations were obtained to evaluate the different levels of pollution in streets and avenues. Results indicated that biomonitoring techniques using tree bark can be applied to evaluate dispersion of air pollution and provide reliable data for the further epidemiological studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advances in the design of nanomaterial-based electrochemical affinity and enzymatic biosensors for metabolic biomarkers: A review.

PubMed

Farzin, Leila; Shamsipur, Mojtaba; Samandari, Leila; Sheibani, Shahab

2018-05-02

This review (with 340 refs) focuses on methods for specific and sensitive detection of metabolites for diagnostic purposes, with particular emphasis on electrochemical nanomaterial-based sensors. It also covers novel candidate metabolites as potential biomarkers for diseases such as neurodegenerative diseases, autism spectrum disorder and hepatitis. Following an introduction into the field of metabolic biomarkers, a first major section classifies electrochemical biosensors according to the bioreceptor type (enzymatic, immuno, apta and peptide based sensors). A next section covers applications of nanomaterials in electrochemical biosensing (with subsections on the classification of nanomaterials, electrochemical approaches for signal generation and amplification using nanomaterials, and on nanomaterials as tags). A next large sections treats candidate metabolic biomarkers for diagnosis of diseases (in the context with metabolomics), with subsections on biomarkers for neurodegenerative diseases, autism spectrum disorder and hepatitis. The Conclusion addresses current challenges and future perspectives. Graphical abstract This review focuses on the recent developments in electrochemical biosensors based on the use of nanomaterials for the detection of metabolic biomarkers. It covers the critical metabolites for some diseases such as neurodegenerative diseases, autism spectrum disorder and hepatitis.

A matrix approach to guide IHC-based tissue biomarker development in oncology drug discovery.

PubMed

Smith, Neil R; Womack, Christopher

2014-01-01

Immunohistochemistry (IHC) is a core platform for the analysis of tissue samples, and there is an increasing demand for reliable and quantitative IHC-based tissue biomarkers in oncology clinical research and development (R&D) environments. Biomarker assay and drug development proceed in parallel. Furthermore, biomarker assay requirements change with each phase of drug development. We have therefore developed a matrix tool to enable researchers to evaluate whether a particular IHC biomarker assay is fit for purpose. Experience gained from the development of 130 IHC biomarkers, supporting a large number of oncology drug projects, was used to formulate a practical approach to IHC assay development. The resultant matrix grid and accompanying work flow incorporates 16 core decision points that link antibody and assay specificity and sensitivity, and assay performance in preclinical and clinical samples, with stages of drug development. The matrix provides a means to ensure that relevant information on an IHC assay in development is recorded and communicated consistently and that minimum assay validation requirements are met. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Brain-Based Biomarkers for the Treatment of Depression: Evolution of an Idea.

PubMed

Waters, Allison C; Mayberg, Helen S

2017-10-01

An ambition of depression biomarker research is to augment psychometric and cognitive assessment of clinically relevant phenomena with neural measures. Although such applications have been slow to arrive, we observe a steady evolution of the idea and anticipate emerging technologies with some optimism. To highlight critical themes and innovations in depression biomarker research, we take as our point of reference a specific research narrative. We begin with an early model of frontal-limbic dysfunction, which represents a conceptual shift from localized pathology to understanding symptoms as an emergent property of distributed networks. Over the decades, this model accommodates perspectives from neurology, psychiatry, clinical, and cognitive neuroscience, and preserves past insight as more complex methods become available. We also track the expanding mission of brain biomarker research: from the development of diagnostic tools to treatment selection algorithms, measures of neurocognitive functioning and novel targets for neuromodulation. To conclude, we draw from this particular research narrative future directions for biomarker research. We emphasize integration of measurement modalities to describe dynamic change in domain-general networks, and we speculate that a brain-based framework for psychiatric problems may dissolve classical diagnostic and disciplinary boundaries. (JINS, 2017, 23, 870-880).

Octocorals in a changing environment: Seasonal response of stress biomarkers in natural populations of Veretillum cynomorium

NASA Astrophysics Data System (ADS)

Madeira, Carolina; Madeira, Diana; Vinagre, Catarina; Diniz, Mário

2015-09-01

Current concerns about climate change emphasize the need for an accurate monitoring of physiological conditions in wild populations. Therefore, the aims of this work were to a) assess the response of the octocoral Veretillum cynomorium to thermal variation in natural populations during low tide, by quantifying several biochemical indicators of thermal and oxidative stress and b) evaluate the effect of seasonality in the results and the adequacy of the use of biochemical indicators of stress in field monitoring studies in octocorals. Sampling took place during spring (April) and summer (June). Heat shock protein (Hsp70) and ubiquitin (Ub) content, enzyme activities - superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and lipid peroxidation (LPO) were assessed in rachis and peduncle tissues separately. The results showed significant seasonal fluctuations in the set of biomarkers tested. Differences were detected between spring and summer, with significant decreases in biomarker levels from April to June being a major observed trend. These results suggest that V. cynomorium is thermo-tolerant during summer low tide conditions. Seasonal variation seems to reflect a metabolic suppression strategy and/or may also be related to seasonal changes in food availability and reproductive status. Differences in activity between tissue types were also found significant for GST, LPO and Ub. Biomarker levels were correlated with total protein concentration, but not with wet body weight of the specimens. This study suggests that season influences the expression of biomarkers and must be taken into consideration in the preliminary stages of sampling design for climate change biomonitoring studies. In addition, the results suggest that this octocoral species is likely to survive in future challenging thermal conditions.

Clinical, functional, behavioural and epigenomic biomarkers of obesity.

PubMed

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.

Evaluation of the use of moss transplants (Pseudoscleropodium purum) for biomonitoring different forms of air pollutant nitrogen compounds.

PubMed

Varela, Z; García-Seoane, R; Arróniz-Crespo, M; Carballeira, A; Fernández, J A; Aboal, J R

2016-06-01

We investigated whether three different types of moss transplants (devitalized moss bags with and without cover and auto-irrigated moss transplants) are suitable for use as biomonitors of the deposition of oxidised and/or reduced forms of N. For this purpose, we determined whether the concentration of atmospheric NO2 was related to the % N, δ(15)N and the activity of the enzyme biomarkers phosphomonoesterase (PME) and nitrate reductase (NR) in the tissues of moss transplants. We exposed the transplants in 5 different environments of Galicia (NW Spain) and Cataluña (NE Spain): industrial environments, urban and periurban environments, the surroundings of a cattle farm and in a monitoring site included in the sampling network of the European Monitoring Programme. The results showed that the moss in the auto-irrigated transplants was able of incorporating the N in its tissues because it was metabolically active, whereas in devitalized moss bags transplants, moss simply intercepts physically the N compounds that reached it in particulate or gaseous form. In addition, this devitalization could limit the capacity of moss to capture gaseous compounds (i.e. reduced N) and to reduce the oxidised compounds that reach the specimens. These findings indicate that devitalized moss transplants cannot be used to monitor either oxidised or reduced N compounds, whereas transplants of metabolically active moss can be used for this purpose. Finally, the NR and PME biomarkers should be used with caution because of the high variability in their activities and the limits of quantification should be evaluated in each case. Copyright © 2016 Elsevier Ltd. All rights reserved.

Magnetic Electrochemical Sensing Platform for Biomonitoring of Exposure to Organophosphorus Pesticides and Nerve Agents Based on Simultaneous Measurement of Total Enzyme Amount and Enzyme Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Dan; Wang, Jun; Wang, Limin

We report a new approach for electrochemical quantification of enzymatic inhibition and phosphorylation for biomonitoring of exposure to organophosphorus (OP) pesticides and nerve agents based on a magnetic beads (MBs) immunosensing platform. The principle of this approach is based on the combination of MBs immuno-capture based enzyme activity assay and competitive immunoassay of total amount of enzyme for simultaneous detection of enzyme inhibition and phosphorylation in biological fluids. Butyrylcholinesterase (BChE) was chosen as a model enzyme. In competitive immunoassay, the target total BChE in a sample (mixture of OP-inhibited BChE and active BChE) competes with the BChE modified on themore » MBs to bind to the limited anti-BChE antibody labeled with quantum dots (QDs-anti-BChE), and followed by electrochemical stripping analysis of the bound QDs conjugate on the MBs. This assay shows a linear response over the total BChE concentration range of 0.1~20 nM. Simultaneously, real time BChE activity was measured on an electrochemical carbon nanotube-based sensor coupled with microflow injection system after immuno-capture by MBs-anti-BChE conjugate. Therefore, the formed phosphorylated adduct (OP-BChE) can be estimated by the difference values of the total amount BChE (including active and OP-inhibited) and active BChE from established calibration curves. This approach not only eliminates the difficulty in screening of low-dose OP exposure (less than 20% inhibition of BChE) because of individual variation of BChE values, but also avoids the drawback of the scarce availability of OP-BChE antibody. It is sensitive enough to detect 0.5 nM OP-BChE, which is less than 2% BChE inhibition. This method offers a new method for rapid, accurate, selective and inexpensive quantification of phosphorylated adducts and enzyme inhibition for biomonitoring of OP and nerve agent exposures.« less

Microanalyzer for Biomonitoring of Lead (Pb) in Blood and Urine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yantasee, Wassana; Timchalk, Chuck; Lin, Yuehe

2007-01-01

Biomonitoring of lead (Pb) in blood and urine enables quantitative evaluation of human occupational and environmental exposures to Pb. The state-of-the-art ICP-MS instruments analyze metals in laboratories, resulting in lengthy turn around time, and are expensive. In response to the growing need for metal analyzer for on-site, real-time monitoring of trace metals in individuals, we developed a portable microanalyzer based on flow-injection/adsorptive stripping voltammetry and used it to analyze Pb in rat blood and urine. Fouling of electrodes by proteins often prevents the effective use of electrochemical sensors in biological matrices. Minimization of such fouling was accomplished with the suitablemore » sample pretreatment and the turbulent flowing of Pb contained blood and urine onto the glassy electrode inside the microanalyzer, which resulted in no apparent electrode fouling even when the samples contained 50% urine or 10% blood by volume. There was no matrix effect on the voltammetric Pb signals even when the samples contained 10% blood or 10% urine. The microanalyzer offered linear concentration range relevant to Pb exposure levels in human (0-20 ppb in 10%-blood samples, 0-50 ppb in 50%-urine samples). The device had excellent sensitivity and reproducibility; Pb detection limits were 0.54 ppb and 0.42 ppb, and % RSDs were 4.9 and 2.4 in 50%-urine and 10%-blood samples, respectively. It offered a high throughput (3 min per sample) and had economical use of samples (60 ?L per measurement), making the collection of blood being less invasive especially to children, and had low reagent consumption (1 ?g of Hg per measurement), thus minimizing the health concerns of mercury use. Being miniaturized in size, the microanalyzer is portable and field-deployable. Thus, it has a great potential to be the next-generation analyzer for biomonitoring of toxic metals.« less

A novel paradigm for telemedicine using the personal bio-monitor.

PubMed

Bhatikar, Sanjay R; Mahajan, Roop L; DeGroff, Curt

2002-01-01

The foray of solid-state technology in the medical field has yielded an arsenal of sophisticated healthcare tools. Personal, portable computing power coupled with the information superhighway open up the possibility of sophisticated healthcare management that will impact the medical field just as much. The full synergistic potential of three interwoven technologies: (1) compact electronics, (2) World Wide Web, and (3) Artificial Intelligence is yet to be realized. The system presented in this paper integrates these technologies synergistically, providing a new paradigm for healthcare. Our idea is to deploy internet-enabled, intelligent, handheld personal computers for medical diagnosis. The salient features of the 'Personal Bio-Monitor' we envisage are: (1) Utilization of the peripheral signals of the body which may be acquired non-invasively and with ease, for diagnosis of medical conditions; (2) An Artificial Neural Network (ANN) based approach for diagnosis; (3) Configuration of the diagnostic device as a handheld for personal use; (4) Internet connectivity, following the emerging bluetooth protocol, for prompt conveyance of information to a patient's health care provider via the World Wide Web. The proposal is substantiated with an intelligent handheld device developed by the investigators for pediatric cardiac auscultation. This device performed accurate diagnoses of cardiac abnormalities in pediatrics using an artificial neural network to process heart sounds acquired by a low-frequency microphone and transmitted its diagnosis to a desktop PC via infrared. The idea of the personal biomonitor presented here has the potential to streamline healthcare by optimizing two valuable resources: physicians' time and sophisticated equipment time. We show that the elements of such a system are in place, with our prototype. Our novel contribution is the synergistic integration of compact electronics' technology, artificial neural network methodology and the wireless web

The comet assay as a tool for human biomonitoring studies: the ComNet project.

PubMed

Collins, Andrew; Koppen, Gudrun; Valdiglesias, Vanessa; Dusinska, Maria; Kruszewski, Marcin; Møller, Peter; Rojas, Emilio; Dhawan, Alok; Benzie, Iris; Coskun, Erdem; Moretti, Massimo; Speit, Günter; Bonassi, Stefano

2014-01-01

The comet assay is widely used in human biomonitoring to measure DNA damage as a marker of exposure to genotoxic agents or to investigate genoprotective effects. Studies often involve small numbers of subjects, and design may be sub-optimal in other respects. In addition, comet assay protocols in use in different laboratories vary significantly. In spite of these difficulties, it is appropriate to carry out a pooled analysis of all available comet assay biomonitoring data, in order to establish baseline parameters of DNA damage, and to investigate associations between comet assay measurements and factors such as sex, age, smoking status, nutrition, lifestyle, etc. With this as its major objective, the ComNet project has recruited almost 100 research groups willing to share datasets. Here we provide a background to this project, discussing the history of the comet assay and practical issues that can critically affect its performance. We survey its diverse applications in biomonitoring studies, including environmental and occupational exposure to genotoxic agents, genoprotection by dietary and other factors, DNA damage associated with various diseases, and intrinsic factors that affect DNA damage levels in humans. We examine in depth the quality of data from a random selection of studies, from an epidemiological and statistical point of view. Copyright © 2013 Elsevier B.V. All rights reserved.

Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers.

PubMed

Wilhelmsen, Michael; Christensen, Ib J; Rasmussen, Louise; Jørgensen, Lars N; Madsen, Mogens R; Vilandt, Jesper; Hillig, Thore; Klaerke, Michael; Nielsen, Knud T; Laurberg, Søren; Brünner, Nils; Gawel, Susan; Yang, Xiaoqing; Davis, Gerard; Heijboer, Annemieke; Martens, Frans; Nielsen, Hans J

2017-03-15

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC. © 2016 UICC.

Conceptual framework for a Danish human biomonitoring program

PubMed Central

Thomsen, Marianne; Knudsen, Lisbeth E; Vorkamp, Katrin; Frederiksen, Marie; Bach, Hanne; Bonefeld-Jorgensen, Eva Cecilie; Rastogi, Suresch; Fauser, Patrik; Krongaard, Teddy; Sorensen, Peter Borgen

2008-01-01

The aim of this paper is to present the conceptual framework for a Danish human biomonitoring (HBM) program. The EU and national science-policy interface, that is fundamental for a realization of the national and European environment and human health strategies, is discussed, including the need for a structured and integrated environmental and human health surveillance program at national level. In Denmark, the initiative to implement such activities has been taken. The proposed framework of the Danish monitoring program constitutes four scientific expert groups, i.e. i. Prioritization of the strategy for the monitoring program, ii. Collection of human samples, iii. Analysis and data management and iv. Dissemination of results produced within the program. This paper presents the overall framework for data requirements and information flow in the integrated environment and health surveillance program. The added value of an HBM program, and in this respect the objectives of national and European HBM programs supporting environmental health integrated policy-decisions and human health targeted policies, are discussed. In Denmark environmental monitoring has been prioritized by extensive surveillance systems of pollution in oceans, lakes and soil as well as ground and drinking water. Human biomonitoring has only taken place in research programs and few incidences of e.g. lead contamination. However an arctic program for HBM has been in force for decades and from the preparations of the EU-pilot project on HBM increasing political interest in a Danish program has developed. PMID:18541069

Biomarker responses to environmental contamination in estuaries: A comparative multi-taxa approach.

PubMed

Duarte, Irina A; Reis-Santos, Patrick; França, Susana; Cabral, Henrique; Fonseca, Vanessa F

2017-08-01

Estuaries are highly productive ecosystems subjected to numerous anthropogenic pressures with consequent environmental quality degradation. In this study, multiple biomarker responses [superoxide dismutase (SOD), catalase (CAT), ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities, as well as lipid peroxidation (LPO) and DNA damage (DNAd)] were determined in two fish (Dicentrarchus labrax and Pomatoschistus microps) and four macroinvertebrate species (Carcinus maenas, Crangon crangon, Hediste diversicolor and Scrobicularia plana) from the Ria de Aveiro and Tejo estuaries over distinct months. Two sites per estuarine system were selected based on anthropogenic pressures and magnitude of environmental contamination. Antioxidant enzyme activities in fish species suggested a ubiquitous response to oxidative stress, while biotransformation and effect biomarkers exhibited higher spatial and temporal variation. In invertebrate species, biotransformation enzyme activity was clearly less variable than in fish evidencing lower xenobiotic transformation capability. Overall, largest biomarker responses were found in the most contaminated sites (Tejo), yet species-specific patterns were evident. These should be factored in multi-taxa approaches, considering that the differential functional traits of species, such as habitat use, life-stage, feeding or physiology can influence exposure routes and biomarker responses. The Integrated Biomarker Response index highlighted patterns in biomarker responses which were not immediately evident when analyzing biomarkers individually. Overall, results provided insights into the complexity of species responses to contamination in naturally varying estuarine environments. Ultimately, multi-taxa and multi-biomarker approaches provide a comprehensive and complementary view of ecosystem health, encompassing diverse forms of biological integration and exposure routes, and allow the validation of results among markers

Potential Uses of Biomonitoring Data: A Case Study Using the Organophosphorus Pesticides Chlorpyrifos and Malathion

PubMed Central

Barr, Dana B.; Angerer, Jürgen

2006-01-01

Background Organophosphorus pesticides such as chlorpyrifos and malathion are widely used insecticides. They do not bioaccumulate appreciably in humans and are rapidly metabolized and excreted in the urine. In nonoccupational settings, exposures to these pesticides are typically sporadic and short-lived because the pesticides tend to degrade in the environment over time; however, dietary exposures may be more chronic. Biologic monitoring has been widely used to assess exposures, susceptibility, and effects of chlorpyrifos and malathion; thus, the information base on these compounds is data rich. For biomonitoring of exposure, chlorpyrifos and malathion have been measured in blood, but most typically their urinary metabolites have been measured. For assessing early effects and susceptibility, cholinesterase and microsomal esterase activities, respectively, have been measured. Objectives Although many biologic monitoring data have been generated and published on these chemicals, their interpretation is not straightforward. For example, exposure to environmental degradates of chlorpyrifos and malathion may potentially increase f urinary metabolite levels, thus leading to overestimation of exposure. Also, the temporal nature of the exposures makes the evaluation of both exposure and effects difficult. We present an overview of the current biomonitoring and other relevant data available on exposure to chlorpyrifos and malathion and the use of these data in various environmental public health applications. PMID:17107865

Hepatic monooxygenase (CYP1A and CYP3A) and UDPGT enzymatic activities as biomarkers for long-term carbofuran exposure in tench (Tinca tinca L).

PubMed

Hernández-Moreno, David; Soler-Rodríguez, Francisco; Míguez-Santiyán, M Prado; Pérez-López, Marcos

2008-06-01

The effect of a long-term exposure of tenchs to different concentrations (10 and 100 micro g/L) of the pesticide carbofuran has been evaluated. Microsomal hepatic cytochrome P450 subfamily 1A (CYP1A) and 3A (CYP3A) activities, as well as the phase II enzyme uridine diphospho-glucuronosyltransferase (UDPGT) activity were evaluated as adequate biomarkers of fish exposure to environmentally relevant concentrations of the pesticide carbofuran in freshwater ecosystems. A clear time-dependent inhibition of both CYP1A and UDPGT activities was observed in fish exposed to the highest dose of carbofuran with respect to controls, whereas in the case of CYP3A activity, values of exposed animals did not show a clear pattern of alteration during the experiment. The results of the present study demonstrated that hepatic CYP1A and UDPGT activities from tench could be considered as sensitive biomarkers for carbamate pesticides in polluted water, thus allowing future and ecologically relevant biomonitoring studies with this species.

Clinical proteomic biomarkers: relevant issues on study design & technical considerations in biomarker development

PubMed Central

2014-01-01

Biomarker research is continuously expanding in the field of clinical proteomics. A combination of different proteomic–based methodologies can be applied depending on the specific clinical context of use. Moreover, current advancements in proteomic analytical platforms are leading to an expansion of biomarker candidates that can be identified. Specifically, mass spectrometric techniques could provide highly valuable tools for biomarker research. Ideally, these advances could provide with biomarkers that are clinically applicable for disease diagnosis and/ or prognosis. Unfortunately, in general the biomarker candidates fail to be implemented in clinical decision making. To improve on this current situation, a well-defined study design has to be established driven by a clear clinical need, while several checkpoints between the different phases of discovery, verification and validation have to be passed in order to increase the probability of establishing valid biomarkers. In this review, we summarize the technical proteomic platforms that are available along the different stages in the biomarker discovery pipeline, exemplified by clinical applications in the field of bladder cancer biomarker research. PMID:24679154

BIOMONIITORING RESEARCH WITHIN THE U.S. EPA'S OFFICE OF RESEARCH AND DEVELOPMENT

EPA Science Inventory

Current ORD exposure research is directed toward developing the processes, tools, and information to put biomonitoring data into perspective for the risk assessment process, to define the appropriate uses of specific biomarkers, and to integrate biomarker measurements with exposu...

PAH detection in Quercus robur leaves and Pinus pinaster needles: A fast method for biomonitoring purpose.

PubMed

De Nicola, F; Concha Graña, E; Aboal, J R; Carballeira, A; Fernández, J Á; López Mahía, P; Prada Rodríguez, D; Muniategui Lorenzo, S

2016-06-01

Due to the complexity and heterogeneity of plant matrices, new procedure should be standardized for each single biomonitor. Thus, here is described a matrix solid-phase dispersion extraction method, previously used for moss samples, improved and modified for the analyses of PAHs in Quercus robur leaves and Pinus pinaster needles, species widely used in biomonitoring studies across Europe. The improvements compared to the previous procedure are the use of Florisil added with further clean-up sorbents, 10% deactivated silica for pine needles and PSA for oak leaves, being these matrices rich in interfering compounds, as shown by the gas chromatography-mass spectrometry analyses acquired in full scan mode. Good trueness, with values in the range 90-120% for the most of compounds, high precision (intermediate precision between 2% and 12%) and good sensitivity using only 250mg of samples (limits of quantification lower than 3 and 1.5ngg(-1), respectively for pine and oak) were achieved by the selected procedures. These methods proved to be reliable for PAH analyses and, having advantage of fastness, can be used in biomonitoring studies of PAH air contamination. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessing arsenic exposure from consumption of seafood from Vieques-Puerto Rico: a pilot biomonitoring study using different biomarkers.

PubMed

Mansilla-Rivera, Imar; Nazario, Cruz M; Ramírez-Marrero, Farah A; Crespo, Carlos J; Rodríguez-Sierra, Carlos J

2014-02-01

The various toxic effects associated with inorganic arsenic (iAs) warrants that exposure sources be identified. This pilot study evaluated if greater seafood consumption from Vieques-Puerto Rico is associated with increased exposure to iAs. Nail, hair, and urine samples were used as biomarkers of iAs exposure in adult women and men from Vieques classified as high (n = 31) and low (n = 21) seafood consumers, who reported eating fish and/or shellfish ≥1 time per week and once per month or less, respectively. The sum of urinary iAs (As III + As V), monomethylarsonic acid (MA[V]), and dimethylarsinic acid (DMA[V]), denoted as SumAs, fluctuated from 3.3 µg/g Cr (1.2 μg/L) to 42.7 μg/g Cr (42 μg/L) (n = 52). Levels of As in nail samples (n = 49) varied from 0.04 to 0.82 μg/g dry weight (dw), whereas in hair (n = 49) As was only detected in 49 % of the samples with a maximum value of 0.95 μg/g dw. None of the biomarkers of exposure to As exceeded exposure reference values for urine (50 μg/g Cr or 50 μg/L), nails (1 μg/g), or hair (1 μg/g). However, median (10.0 μg/g Cr; 10.6 μg/L) and 95th percentile (31.9 μg/g Cr; 40.4 μg/L) of urinary SumAs were higher in Vieques samples than in the those from the general population of other countries. Among the three biomarkers of exposure, nail samples reflected better the exposure to iAs from seafood consumption with significantly higher average As concentrations in high (0.24 μg/g) than low (0.12 μg/g) seafood consumers. Multivariate results for As in nail samples (R(2) = 0.55, p < 0.0001) showed a positive association with fish consumption, particularly for men, with levels increasing with years of residency in Vieques.

Computational Biomarker Pipeline from Discovery to Clinical Implementation: Plasma Proteomic Biomarkers for Cardiac Transplantation

PubMed Central

Cohen Freue, Gabriela V.; Meredith, Anna; Smith, Derek; Bergman, Axel; Sasaki, Mayu; Lam, Karen K. Y.; Hollander, Zsuzsanna; Opushneva, Nina; Takhar, Mandeep; Lin, David; Wilson-McManus, Janet; Balshaw, Robert; Keown, Paul A.; Borchers, Christoph H.; McManus, Bruce; Ng, Raymond T.; McMaster, W. Robert

2013-01-01

Recent technical advances in the field of quantitative proteomics have stimulated a large number of biomarker discovery studies of various diseases, providing avenues for new treatments and diagnostics. However, inherent challenges have limited the successful translation of candidate biomarkers into clinical use, thus highlighting the need for a robust analytical methodology to transition from biomarker discovery to clinical implementation. We have developed an end-to-end computational proteomic pipeline for biomarkers studies. At the discovery stage, the pipeline emphasizes different aspects of experimental design, appropriate statistical methodologies, and quality assessment of results. At the validation stage, the pipeline focuses on the migration of the results to a platform appropriate for external validation, and the development of a classifier score based on corroborated protein biomarkers. At the last stage towards clinical implementation, the main aims are to develop and validate an assay suitable for clinical deployment, and to calibrate the biomarker classifier using the developed assay. The proposed pipeline was applied to a biomarker study in cardiac transplantation aimed at developing a minimally invasive clinical test to monitor acute rejection. Starting with an untargeted screening of the human plasma proteome, five candidate biomarker proteins were identified. Rejection-regulated proteins reflect cellular and humoral immune responses, acute phase inflammatory pathways, and lipid metabolism biological processes. A multiplex multiple reaction monitoring mass-spectrometry (MRM-MS) assay was developed for the five candidate biomarkers and validated by enzyme-linked immune-sorbent (ELISA) and immunonephelometric assays (INA). A classifier score based on corroborated proteins demonstrated that the developed MRM-MS assay provides an appropriate methodology for an external validation, which is still in progress. Plasma proteomic biomarkers of acute cardiac

Characterization of biomarkers in stroke based on ego-networks and pathways.

PubMed

Li, Haixia; Guo, Qianqian

2017-12-01

To explore potential biomarkers in stroke based on ego-networks and pathways. EgoNet method was applied to search for the underlying biomarkers in stroke using transcription profiling of E-GEOD-58294 and protein-protein interaction (PPI) data. Eight ego-genes were identified from PPI network according to the degree characteristics at the criteria of top 5% ranked z-sore and degree >1. Eight candidate ego-networks with classification accuracy ≥0.9 were selected. After performed randomization test, seven significant ego-networks with adjusted p value < 0.05 were identified. Pathway enrichment analysis was then conducted with these ego-networks to search for the significant pathways. Finally, two significant pathways were identified, and six of seven ego-networks were enriched to "3'-UTR-mediated translational regulation" pathway, indicating that this pathway performs an important role in the development of stroke. Seven ego-networks were constructed using EgoNet and two significant enriched by pathways were identified. These may provide new insights into the potential biomarkers for the development of stroke.

Biomarker identification and pathway analysis of preeclampsia based on serum metabolomics.

PubMed

Chen, Tingting; He, Ping; Tan, Yong; Xu, Dongying

2017-03-25

Preeclampsia presents serious risk of both maternal and fetal morbidity and mortality. Biomarkers for the detection of preeclampsia are critical for risk assessment and targeted intervention. The goal of this study is to screen potential biomarkers for the diagnosis of preeclampsia and to illuminate the pathogenesis of preeclampsia development based on the differential expression network. Two groups of subjects, including healthy pregnant women, subjects with preeclampsia, were recruited for this study. The metabolic profiles of all of the subjects' serum were obtained by liquid chromatography quadruple time-of-flight mass spectrometry. Correlation between metabolites was analyzed by bioinformatics technique. Results showed that the PC(14:0/00), proline betaine and proline were potential sensitive and specific biomarkers for preeclampsia diagnosis and prognosis. Perturbation of corresponding biological pathways, such as iNOS signaling, nitric oxide signaling in the cardiovascular system, mitochondrial dysfunction were responsible for the pathogenesis of preeclampsia. This study indicated that the metabolic profiling had a good clinical significance in the diagnosis of preeclampsia as well as in the study of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Determinants of occupational exposure to metals by gas metal arc welding and risk management measures: a biomonitoring study.

PubMed

Persoons, Renaud; Arnoux, Damien; Monssu, Théodora; Culié, Olivier; Roche, Gaëlle; Duffaud, Béatrice; Chalaye, Denis; Maitre, Anne

2014-12-01

Welding fumes contain various toxic metals including chromium (Cr), nickel (Ni) and manganese (Mn). An assessment of the risk to health of local and systemic exposure to welding fumes requires the assessment of both external and internal doses. The aims of this study were to test the relevance in small and medium sized enterprises of a biomonitoring strategy based on urine spot-samples, to characterize the factors influencing the internal doses of metals in gas metal arc welders and to recommend effective risk management measures. 137 welders were recruited and urinary levels of metals were measured by ICP-MS on post-shift samples collected at the end of the working week. Cr, Ni and Mn mean concentrations (respectively 0.43, 1.69 and 0.27 μg/g creatinine) were well below occupational health guidance values, but still higher than background levels observed in the general population, confirming the absorption of metals generated in welding fumes. Both welding parameters (nature of base metal, welding technique) and working conditions (confinement, welding and grinding durations, mechanical ventilation and welding experience) were predictive of occupational exposure. Our results confirm the interest of biomonitoring for assessing health risks and recommending risk management measures for welders. Copyright © 2014. Published by Elsevier Ireland Ltd.

Hair biomonitoring and health status of a general population exposed to Nickel.

PubMed

Sazakli, Eleni; Leotsinidis, Michalis

2017-09-01

An epidemiological cross-sectional study was conducted in a Greek population, being orally exposed to Ni via food consumption, in order to investigate possible health effects and to evaluate hair Ni concentration as a biomarker of exposure. The study population consisted of 139 men and 155 women, aged 25-69. Socio-demographics, lifestyle, dietary habits, occupational and medical history data were recorded through a personal interview. Hematological and biochemical examinations were conducted in blood specimens. Metals - Ni, Cr, Cd, Pb, Hg, Cu and Zn - were determined in hair samples. Women were characterized by higher Ni and Cu hair concentrations, while men by higher Cr and Hg. Factors affecting hair metal concentrations were identified to be dietary habits, consumption of local crops, occupation and smoking. Hair element content in the study population was comparable to the "reference ranges" reported in Europe, except for Ni, found higher in a fraction of our population. Men in the upper quartile of hair Ni distribution are at higher risk for abnormal high cholesterol, LDL, albumin and calcium, with odds ratios (OR) varying between 3.5 and 6.2. Accordingly, high hair Ni content in women is associated with abnormal glucose (OR=3.9), triglycerides (OR=3.1) and low abnormal sodium (OR=4.3). The study provides evidence of the suitability of hair analysis in assessing environmental exposure to Ni and supports the use of hair Ni content as a valuable and relatively inexpensive tool of biomonitoring, to identify people at risk for certain biochemical alterations. Copyright © 2017 Elsevier GmbH. All rights reserved.

Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor

NASA Astrophysics Data System (ADS)

Kosaka, P. M.; Pini, V.; Ruz, J. J.; da Silva, R. A.; González, M. U.; Ramos, D.; Calleja, M.; Tamayo, J.

2014-12-01

Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for ‘weighing’ the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10-16 g ml-1 in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ˜10-4.

Computational prediction of human salivary proteins from blood circulation and application to diagnostic biomarker identification.

PubMed

Wang, Jiaxin; Liang, Yanchun; Wang, Yan; Cui, Juan; Liu, Ming; Du, Wei; Xu, Ying

2013-01-01

Proteins can move from blood circulation into salivary glands through active transportation, passive diffusion or ultrafiltration, some of which are then released into saliva and hence can potentially serve as biomarkers for diseases if accurately identified. We present a novel computational method for predicting salivary proteins that come from circulation. The basis for the prediction is a set of physiochemical and sequence features we found to be discerning between human proteins known to be movable from circulation to saliva and proteins deemed to be not in saliva. A classifier was trained based on these features using a support-vector machine to predict protein secretion into saliva. The classifier achieved 88.56% average recall and 90.76% average precision in 10-fold cross-validation on the training data, indicating that the selected features are informative. Considering the possibility that our negative training data may not be highly reliable (i.e., proteins predicted to be not in saliva), we have also trained a ranking method, aiming to rank the known salivary proteins from circulation as the highest among the proteins in the general background, based on the same features. This prediction capability can be used to predict potential biomarker proteins for specific human diseases when coupled with the information of differentially expressed proteins in diseased versus healthy control tissues and a prediction capability for blood-secretory proteins. Using such integrated information, we predicted 31 candidate biomarker proteins in saliva for breast cancer.

Computational Prediction of Human Salivary Proteins from Blood Circulation and Application to Diagnostic Biomarker Identification

PubMed Central

Wang, Jiaxin; Liang, Yanchun; Wang, Yan; Cui, Juan; Liu, Ming; Du, Wei; Xu, Ying

2013-01-01

Proteins can move from blood circulation into salivary glands through active transportation, passive diffusion or ultrafiltration, some of which are then released into saliva and hence can potentially serve as biomarkers for diseases if accurately identified. We present a novel computational method for predicting salivary proteins that come from circulation. The basis for the prediction is a set of physiochemical and sequence features we found to be discerning between human proteins known to be movable from circulation to saliva and proteins deemed to be not in saliva. A classifier was trained based on these features using a support-vector machine to predict protein secretion into saliva. The classifier achieved 88.56% average recall and 90.76% average precision in 10-fold cross-validation on the training data, indicating that the selected features are informative. Considering the possibility that our negative training data may not be highly reliable (i.e., proteins predicted to be not in saliva), we have also trained a ranking method, aiming to rank the known salivary proteins from circulation as the highest among the proteins in the general background, based on the same features. This prediction capability can be used to predict potential biomarker proteins for specific human diseases when coupled with the information of differentially expressed proteins in diseased versus healthy control tissues and a prediction capability for blood-secretory proteins. Using such integrated information, we predicted 31 candidate biomarker proteins in saliva for breast cancer. PMID:24324552

Heavy metal biomonitoring and phytoremediation potentialities of aquatic macrophytes in River Nile.

PubMed

Fawzy, Manal Ahmed; Badr, Nadia El-sayed; El-Khatib, Ahmed; Abo-El-Kassem, Amany

2012-03-01

The concentrations of Cd, Cu, Pb, and Zn in sediments, water, and different plant organs of six aquatic vascular plant species, Ceratophyllum demersum L. Echinochloa pyramidalis (Lam.) Hitchc. & Chase; Eichhornia crassipes (Mart.) Solms-Laub; Myriophyllum spicatum L.; Phragmites australis (Cav.) Trin. ex Steud; and Typha domingensis (Pers.) Poir. ex Steud, growing naturally in the Nile system (Sohag Governorate), were investigated. The aim was to define which species and which plant organs exhibit the greatest accumulation and evaluate whether these species could be usefully employed in biomonitoring and phytoremediation programs. The recorded metals in water samples were above the standard levels of both US Environmental Protection Agency and Egyptian Environmental Affairs Agency except for Pb. The concentrations of heavy metals in water, sediments, and plants possess the same trend: Zn > Cu > Pb > Cd which reflects the biomonitoring potentialities of the investigated plant species. Generally, the variation of heavy element concentrations in water and sediments in relation to site and season, as assessed by two-way repeated measured ANOVA, was significant (p < 0.05). However, insignificant variations were observed in the concentrations of Pb and Cd in sediments in relation to season and of Cu and Zn in relation to site. Results also showed that the selectivity of the heavy elements for the investigated plants varied significantly (p < 0.05) with species variation. The accumulation capability of the investigated species could be arranged according to this pattern: C. demersum > E. crassipes > M. spicatum > E. pyramidalis > T. domingensis > P. australis. On the basis of the element concentrations, roots of all the studied species contain higher concentrations of Cu and Zn than shoots while leaves usually acquire the highest concentrations of Pb. Cd concentrations among different plant organs are comparable except in M. spicatum where the highest Cd concentrations

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, Liana S.; Drake, Daniel; Alcalay, Roy N.

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 projectsmore » 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.« less

Diagnosis of IBS: symptoms, symptom-based criteria, biomarkers or 'psychomarkers'?

PubMed

Sood, Ruchit; Law, Graham R; Ford, Alexander C

2014-11-01

IBS is estimated to have a prevalence of up to 20% in Western populations and results in substantial costs to health-care services worldwide, estimated to be US$1 billion per year in the USA. IBS remains difficult to diagnose due to its multifactorial aetiology, heterogeneous nature and overlap of symptoms with organic pathologies, such as coeliac disease and IBD. As a result, IBS often continues to be a diagnosis of exclusion, resulting in unnecessary investigations. Available methods for the diagnosis of IBS-including the current gold standard, the Rome III criteria-perform only moderately well. Visceral hypersensitivity and altered pain perception do not discriminate between IBS and other functional gastrointestinal diseases or health with any great accuracy. Attention has now turned to developing novel biomarkers and using psychological markers (so-called psychomarkers) to aid the diagnosis of IBS. This Review describes how useful symptoms, symptom-based criteria, biomarkers and psychomarkers, and indeed combinations of all these approaches, are in the diagnosis of IBS. Future directions in diagnosing IBS could include combining demographic data, gastrointestinal symptoms, biomarkers and psychomarkers using statistical methods. Latent class analysis to distinguish between IBS and non-IBS symptom profiles might also represent a promising avenue for future research.

[Individual susceptibility to occupational carcinogens: the evidence from biomonitoring and molecular epidemiology studies].

PubMed

Pavanello, S; Clonfero, E

2004-01-01

This paper reviews the literature on the influence of metabolic and DNA repair polymorphisms of biological indicators of genotoxic risk commonly used in biomonitoring occupational exposure to carcinogens. Genetic polymorphisms which influence biomarkers (urinary metabolites, protein and DNA adducts), include P450 cytochromes (CYPs) and glutathione S-transferases (GSTs) in exposure to polycyclic aromatic hydrocarbons (PAHs), and acetyltransferases (NATs) in exposure to aromatic amines (AAs). As regards exposure to benzene, also relevant is the influence of epoxydohydrolase (EPHX) and NAD(P)H quinone oxidoreductase (NQO1) on the urinary excretion of t,t-muconic and phenylmercapturic acids. With respect to occupational exposure to styrene, EPHX significantly influences the levels of Chromosome Aberrations (CAs), strongly predictive genotoxic biomarkers of cancer risk. Some recent studies examine the role of polymorphisms linked to DNA repair genes in the modulation of genotoxic risk associated with PAH exposure, both for life-style (dietary and smoking behaviour) and for occupational reasons. In addition, molecular epidemiology studies (case/control studies) of lung cancer in smokers published since 2000 may also be viewed as representing models of effects due to exposure to carcinogenic mixtures, some of which are present in the working environment (e.g., BaP, benzene, AAs). Almost all studies show the clearcut influence (i.e., increased lung cancer risk with OR > or = 2) of genetic polymorphisms linked to PAH metabolism (in particular, CYPIA1, GSTM1 and P1). Among the risk factors are the different mutagen sensitivity towards, for instance, bleomycin and BaP (tested in vitro), the reduced repair capacity to DNA damage induced by BaP, and increases in some biomarkers of early biological effect (DNA adducts and stable CAs). Other risk factors, such as heredity (siblings of cancer patients have a risk factor > or = 3 with respect to the general population), ethnicity

SurvNet: a web server for identifying network-based biomarkers that most correlate with patient survival data.

PubMed

Li, Jun; Roebuck, Paul; Grünewald, Stefan; Liang, Han

2012-07-01

An important task in biomedical research is identifying biomarkers that correlate with patient clinical data, and these biomarkers then provide a critical foundation for the diagnosis and treatment of disease. Conventionally, such an analysis is based on individual genes, but the results are often noisy and difficult to interpret. Using a biological network as the searching platform, network-based biomarkers are expected to be more robust and provide deep insights into the molecular mechanisms of disease. We have developed a novel bioinformatics web server for identifying network-based biomarkers that most correlate with patient survival data, SurvNet. The web server takes three input files: one biological network file, representing a gene regulatory or protein interaction network; one molecular profiling file, containing any type of gene- or protein-centred high-throughput biological data (e.g. microarray expression data or DNA methylation data); and one patient survival data file (e.g. patients' progression-free survival data). Given user-defined parameters, SurvNet will automatically search for subnetworks that most correlate with the observed patient survival data. As the output, SurvNet will generate a list of network biomarkers and display them through a user-friendly interface. SurvNet can be accessed at http://bioinformatics.mdanderson.org/main/SurvNet.

Biomonitoring of selenoprotein P in human serum by fast affinity chromatography coupled to ICP-MS.

PubMed

Heitland, Peter; Köster, Helmut D

2018-04-01

Most of the Se in human serum is bound to selenoprotein P (SEPP1) in which Se is present in form of selenocysteine. The SEPP1 is a new possible biomarker for the Se status and for this reason we developed a fast, simple and reliable method for the quantitative determination of SEPP1 in serum by affinity chromatography coupled to ICP-MS. It is possible to separate SEPP1 from other selenoproteins in serum in only 5 min, which allows high sample throughput in clinical laboratories. Measured and certified concentrations of total Se and Se(SEPP1) are in good agreement for the reference material SRM 1950. The SEPP1 concentration was stable in serum samples of 3 persons for a minimum of 2 weeks. Further results of method validation were described including internal and external quality assurance. The analytical method was applied for a biomonitoring study of the SEPP1 and total Se concentration in human serum of 50 occupationally non-exposed persons living in northern Germany. Concentration ranges and mean concentrations for Se(SEPP1) are 31.1-59.7 and 46.2 μg/L, respectively. The corresponding values for total Se are 62-120 and 83.5 μg/L. The mean percentage of total Se in serum present as SEPP1 is 58%. Copyright © 2018 Elsevier GmbH. All rights reserved.

Inkjet-/3D-/4D-printed autonomous wearable RF modules for biomonitoring, positioning and sensing applications

NASA Astrophysics Data System (ADS)

Bito, Jo; Bahr, Ryan; Hester, Jimmy; Kimionis, John; Nauroze, Abdullah; Su, Wenjing; Tehrani, Bijan; Tentzeris, Manos M.

2017-05-01

In this paper, numerous inkjet-/3D-/4D-printed wearable flexible antennas, RF electronics, modules and sensors fabricated on paper and other polymer (e.g. LCP) substrates are introduced as a system-level solution for ultra-low-cost mass production of autonomous Biomonitoring, Positioning and Sensing applications. This paper briefly discusses the state-of-the-art area of fully-integrated wearable wireless sensor modules on paper or flexible LCP and show the first ever 4D sensor module integration on paper, as well as numerous 3D and 4D multilayer paper-based and LCP-based RF/microwave, flexible and wearable structures, that could potentially set the foundation for the truly convergent wireless sensor ad-hoc "on-body networks of the future with enhanced cognitive intelligence and "rugged" packaging. Also, some challenges concerning the power sources of "nearperpetual" wearable RF modules, including flexible miniaturized batteries as well as power-scavenging approaches involving electromagnetic and solar energy forms are discuessed. The final step of the paper will involve examples from mmW wearable (e.g. biomonitoring) antennas and RF modules, as well as the first examples of the integration of inkjet-printed nanotechnology-based (e.g.CNT) sensors on paper and organic substrates for Internet of Things (IoT) applications. It has to be noted that the paper will review and present challenges for inkjetprinted organic active and nonlinear devices as well as future directions in the area of environmentally-friendly "green") wearable RF electronics and "smart-skin conformal sensors.

Metabolomics based predictive biomarker model of ARDS: A systemic measure of clinical hypoxemia

PubMed Central

Viswan, Akhila; Singh, Chandan; Rai, Ratan Kumar; Azim, Afzal; Baronia, Arvind Kumar

2017-01-01

Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100–300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making. PMID:29095932

Metabolomics based predictive biomarker model of ARDS: A systemic measure of clinical hypoxemia.

PubMed

Viswan, Akhila; Singh, Chandan; Rai, Ratan Kumar; Azim, Afzal; Sinha, Neeraj; Baronia, Arvind Kumar

2017-01-01

Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100-300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making.

Morph-X-Select: Morphology-based tissue aptamer selection for ovarian cancer biomarker discovery

PubMed Central

Wang, Hongyu; Li, Xin; Volk, David E.; Lokesh, Ganesh L.-R.; Elizondo-Riojas, Miguel-Angel; Li, Li; Nick, Alpa M.; Sood, Anil K.; Rosenblatt, Kevin P.; Gorenstein, David G.

2016-01-01

High affinity aptamer-based biomarker discovery has the advantage of simultaneously discovering an aptamer affinity reagent and its target biomarker protein. Here, we demonstrate a morphology-based tissue aptamer selection method that enables us to use tissue sections from individual patients and identify high-affinity aptamers and their associated target proteins in a systematic and accurate way. We created a combinatorial DNA aptamer library that has been modified with thiophosphate substitutions of the phosphate ester backbone at selected 5′dA positions for enhanced nuclease resistance and targeting. Based on morphological assessment, we used image-directed laser microdissection (LMD) to dissect regions of interest bound with the thioaptamer (TA) library and further identified target proteins for the selected TAs. We have successfully identified and characterized the lead candidate TA, V5, as a vimentin-specific sequence that has shown specific binding to tumor vasculature of human ovarian tissue and human microvascular endothelial cells. This new Morph-X-Select method allows us to select high-affinity aptamers and their associated target proteins in a specific and accurate way, and could be used for personalized biomarker discovery to improve medical decision-making and to facilitate the development of targeted therapies to achieve more favorable outcomes. PMID:27839510

The skin of Commerson's dolphins (Cephalorhynchus commersonii) as a biomonitor of mercury and selenium in Subantarctic waters.

PubMed

Cáceres-Saez, Iris; Goodall, R Natalie P; Dellabianca, Natalia A; Cappozzo, H Luis; Ribeiro Guevara, Sergio

2015-11-01

The skin of bycaught Commerson's dolphins was tested for mercury (Hg) and selenium (Se) biomonitoring in Subantarctic environments. The correlation of levels detected in the skin with those found in internal tissues - lung, liver, kidney and muscle - was assessed to evaluate how skin represents internal Hg and Se distribution for monitoring purposes. Mercury in skin had a concentration range of 0.68-3.11 μg g(-1) dry weight (DW), while Se had a higher concentration range of 74.3-124.5 μg g(-1) DW. There was no significant correlation between selenium levels in any of the analyzed tissues. Thus, the skin selenium concentration did not reflect the tissular Se levels and did not provide information for biomonitoring. The lack of correlation is explained by the biological role of Se, provided that each tissue regulates Se levels according to physiological needs. However, the skin Hg level had significant positive correlation with the levels in internal tissues (ANOVA p<0.05), particularly with that of muscle (R(2)=0.79; ANOVA p=0.0008). Thus, this correlation permits the estimation of Hg content in muscle based on the multiplication of skin biopsy levels by a factor of 1.85. Mercury bioindication using skin biopsies is a non-lethal approach that allows screening of a large number of specimens with little disturbance and makes possible an adequate sampling strategy that produces statistically valid results in populations and study areas. The correlation between Hg levels in the skin and internal tissues supports the use of the epidermis of Commerson's dolphins for Hg biomonitoring in the waters of the Subantarctic, which is a poorly studied region regarding Hg levels, sources and processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Blood-borne biomarkers and bioindicators for linking exposure to health effects in environmental health science.

PubMed

Wallace, M Ariel Geer; Kormos, Tzipporah M; Pleil, Joachim D

2016-01-01

Environmental health science aims to link environmental pollution sources to adverse health outcomes to develop effective exposure intervention strategies that reduce long-term disease risks. Over the past few decades, the public health community recognized that health risk is driven by interaction between the human genome and external environment. Now that the human genetic code has been sequenced, establishing this "G × E" (gene-environment) interaction requires a similar effort to decode the human exposome, which is the accumulation of an individual's environmental exposures and metabolic responses throughout the person's lifetime. The exposome is composed of endogenous and exogenous chemicals, many of which are measurable as biomarkers in blood, breath, and urine. Exposure to pollutants is assessed by analyzing biofluids for the pollutant itself or its metabolic products. New methods are being developed to use a subset of biomarkers, termed bioindicators, to demonstrate biological changes indicative of future adverse health effects. Typically, environmental biomarkers are assessed using noninvasive (excreted) media, such as breath and urine. Blood is often avoided for biomonitoring due to practical reasons such as medical personnel, infectious waste, or clinical setting, despite the fact that blood represents the central compartment that interacts with every living cell and is the most relevant biofluid for certain applications and analyses. The aims of this study were to (1) review the current use of blood samples in environmental health research, (2) briefly contrast blood with other biological media, and (3) propose additional applications for blood analysis in human exposure research.

Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve AgentsOrganophosphate Pesticides and Nerve Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guodong; Wang, Jun; Barry, Richard C.

A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE) adducts, which is a potential exposure biomarker for organophosphate pesticides (OP) and chemical warfare nerve agent exposures. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to track the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemicalmore » stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as a model OP insecticide to prepare the phosphorylated AChE adduct to demonstrate the proof of principle for this sensor technology. The paraoxon-AChE adduct was characterized by Fourier Transform Infrared Spectrum, and the binding affinity of anti-AChE to the paraoxon-AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10 pM to 4 nM paraoxon-AChE, and the limit of detection is estimated to be 8 pM. This new nanoparticle-based electrochemical immunosensor thus provides a sensitive and quantitative tool for biomonitoring exposure to OP pesticides and nerve agents.« less

Traffic contribution to air pollution in urban street canyons: Integrated application of the OSPM, moss biomonitoring and spectral analysis

NASA Astrophysics Data System (ADS)

Lazić, Lazar; Urošević, Mira Aničić; Mijić, Zoran; Vuković, Gordana; Ilić, Luka

2016-09-01

To investigate the air pollutant distribution within the ambient of urban street canyon, Operational Street Pollution Model (OSPM) was used to predict hourly content of NOX, NO, NO2, O3, CO, BNZ and PM10. The study was performed in five street canyons in Belgrade (Serbia) during 10-week summer period. The model receptors were located on each side of street canyons at 4 m, 8 m and 16 m height. To monitor airborne trace element content, the moss bag biomonitors were simultaneously exposed with the model receptors at two heights-4 m and 16 m. The results of both methods, modelling and biomonitoring, showed significantly decreasing trend of the air pollutants with height. The results indirectly demonstrate that biomonitoring, i.e., moss bag technique could be a valuable tool to verify model performance. In addition, spectral analysis was applied to investigate weekly variation of the daily background and modelled data set. Typical periodicities and weekend effect, caused by anthropogenic influences, have been identified.

AUC-based biomarker ensemble with an application on gene scores predicting low bone mineral density.

PubMed

Zhao, X G; Dai, W; Li, Y; Tian, L

2011-11-01

The area under the receiver operating characteristic (ROC) curve (AUC), long regarded as a 'golden' measure for the predictiveness of a continuous score, has propelled the need to develop AUC-based predictors. However, the AUC-based ensemble methods are rather scant, largely due to the fact that the associated objective function is neither continuous nor concave. Indeed, there is no reliable numerical algorithm identifying optimal combination of a set of biomarkers to maximize the AUC, especially when the number of biomarkers is large. We have proposed a novel AUC-based statistical ensemble methods for combining multiple biomarkers to differentiate a binary response of interest. Specifically, we propose to replace the non-continuous and non-convex AUC objective function by a convex surrogate loss function, whose minimizer can be efficiently identified. With the established framework, the lasso and other regularization techniques enable feature selections. Extensive simulations have demonstrated the superiority of the new methods to the existing methods. The proposal has been applied to a gene expression dataset to construct gene expression scores to differentiate elderly women with low bone mineral density (BMD) and those with normal BMD. The AUCs of the resulting scores in the independent test dataset has been satisfactory. Aiming for directly maximizing AUC, the proposed AUC-based ensemble method provides an efficient means of generating a stable combination of multiple biomarkers, which is especially useful under the high-dimensional settings. lutian@stanford.edu. Supplementary data are available at Bioinformatics online.

Protozoa interaction with aquatic invertebrate: interest for watercourses biomonitoring.

PubMed

Palos Ladeiro, M; Bigot, A; Aubert, D; Hohweyer, J; Favennec, L; Villena, I; Geffard, A

2013-02-01

Toxoplasma gondii, Cryptosporidium parvum, and Giardia duodenalis are human waterborne protozoa. These worldwide parasites had been detected in various watercourses as recreational, surface, drinking, river, and seawater. As of today, water protozoa detection was based on large water filtration and on sample concentration. Another tool like aquatic invertebrate parasitism could be used for sanitary and environmental biomonitoring. In fact, organisms like filter feeders could already filtrate and concentrate protozoa directly in their tissues in proportion to ambient concentration. So molluscan shellfish can be used as a bioindicator of protozoa contamination level in a site since they were sedentary. Nevertheless, only a few researches had focused on nonspecific parasitism like protozoa infection on aquatic invertebrates. Objectives of this review are twofold: Firstly, an overview of protozoa in worldwide water was presented. Secondly, current knowledge of protozoa parasitism on aquatic invertebrates was detailed and the lack of data of their biological impact was pointed out.

Biomonitoring of boron: Development and characterization of a simple, reliable and quality controlled biomonitoring method.

PubMed

Michalke, Bernhard

2017-03-01

Boron exposure is of interest and concern from an occupational point of view. Usual daily boron intake is related to boron blood plasma concentration <1mg/L and to <3mg/L in urine, but after exposure urine concentrations are quickly elevated. Reliable boron biomonitoring, typically in urine, thus is mandatory for occupational health control institutions. This paper reports on the development of a simple, fast and reliable boron determination procedure based on inductively coupled plasma - optical emission spectrometry (ICP-OES). Major aims for this method were simplicity in sample preparation, low risk for artifacts and interferences, high precision and accuracy, possibly low costs, including lower costs for element selective detection, short total analysis time and suitability for occupational health laboratories. Precision data (serial or day-to-day) from urine and doped urine were very good: <1.5 or <2%. Accuracy was calculated from analysis of a certified reference material (ERM-CD 281), as 99% or according to recoveries of doped concentrations ranging from 102 to 109% recovery. For cross-checking ICP-OES determinations, samples were analyzed also by quadrupole ICP-qMS and by sectorfield ICP-sf-MS at low and medium resolution. Both systems confirmed ICP-OES measurements when using 11 B for quantification. Determinations based on 10 B however showed some bias, except with ICP-sf-MS at medium resolution. The observed elevated signals are discussed with respect to the known Ne ++ interference (as an impurity in Ar), which is not separated in low resolving quadrupole ICP-MS systems or ICP-sf-MS at low resolution. Copyright © 2016 Elsevier GmbH. All rights reserved.

Rapid and Sensitive Detection of Protein Biomarker Using a Portable Fluorescence Biosensor based on Quantum Dots and a Lateral Flow Test Strip

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhaohui; Wang, Ying; Wang, Jun

2010-08-15

A portable fluorescence biosensor with rapid and ultrasensitive response for trace protein has been built up with quantum dots and lateral flow test strip. The superior signal brightness and high photostability of quantum dots are combined with the promising advantages of lateral flow test strip and resulted in high sensitivity, selectivity and speedy for protein detection. Nitrated ceruloplasmin, a significant biomarker for cardiovascular disease, lung cancer and stress response to smoking, was used as model protein to demonstrate the good performances of this proposed Qdot-based lateral flow test strip. Quantitative detection of nitrated ceruloplasmin was realized by recording the fluorescencemore » intensity of quantum dots captured on the test line. Under optimal conditions, this portable fluorescence biosensor displays rapid responses for nitrated ceruloplasmin in wide dynamic range with a detection limit of 0.1ng/mL (S/N=3). Furthermore, the biosensor was successfully utilized for spiked human plasma sample detection with the concentration as low as 1ng/mL. The results demonstrate that the quantum dot-based lateral flow test strip is capable for rapid, sensitive, and quantitative detection of nitrated ceruloplasmin and hold a great promise for point-of-care and in field analysis of other protein biomarkers.« less

Development of biomarkers of exposure to xenobiotics in the honey bee Apis mellifera: application to the systemic insecticide thiamethoxam.

PubMed

Badiou-Bénéteau, Alexandra; Carvalho, Stephan M; Brunet, Jean-Luc; Carvalho, Geraldo A; Buleté, Audrey; Giroud, Barbara; Belzunces, Luc P

2012-08-01

This study describes the development of acetylcholinesterase (AChE), carboxylesterases (CaE1, CaE2, CaE3), glutathion-S-transferase (GST), alkaline phosphatase (ALP) and catalase (CAT) as enzyme biomarkers of exposure to xenobiotics such as thiamethoxam in the honey bee Apis mellifera. Extraction efficiency, stability under freezing and biological variability were studied. The extraction procedure achieved good recovery rates in one extraction step and ranged from 65 percent (AChE) to 97.3 percent (GST). Most of the enzymes were stable at -20°C, except ALP that displayed a slight but progressive decrease in its activity. Modifications of enzyme activities were considered after exposure to thiamethoxam at the lethal dose 50 percent (LD(50), 51.16 ng bee(-1)) and two sublethal doses, LD(50)/10 (5.12 ng bee(-1)) and LD(50)/20 (2.56 ng bee(-1)). The biomarker responses revealed that, even at the lowest dose used, exposure to thiamethoxam elicited sublethal effects and modified the activity of CaEs, GST, CAT and ALP. Different patterns of biomarker responses were observed: no response for AChE, an increase for GST and CAT, and differential effects for CaEs isoforms with a decrease in CaE1 and CaE3 and an increase in CaE2. ALP and CaE3 displayed contrasting variations but only at 2.56 ng bee(-1). We consider that this profile of biomarker variation could represent a useful fingerprint to characterise exposure to thiamethoxam in the honey bee A. mellifera. This battery of honey bee biomarkers might be a promising option to biomonitor the health of aerial and terrestrial ecosystems and to generate valuable information on the modes of action of pesticides. Copyright © 2012 Elsevier Inc. All rights reserved.

Population Physiologically-Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB 153 with Consideration of Worldwide Human Biomonitoring Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redding, Laurel E.; Sohn, Michael D.; McKone, Thomas E.

2008-03-01

We developed a physiologically based pharmacokinetic model of PCB 153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB 153. Data in the literature provided estimates for model development and for performance assessment. Physiological parameters were taken from a cohort in Taiwan and from reference values in the literature. We estimated partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data in Japan, we predicted acquired body burden of PCB 153 at an average childbearing age of 25 years and comparemore » predictions to measurements from studies in multiple countries. Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates. The model successfully describes the range of possible PCB 153 dispositions in maternal milk, suggesting a promising option for back estimating doses for various populations. One example of reverse dosimetry modeling was attempted using our PBPK model for possible exposure scenarios in Canadian Inuits who had the highest level of PCB 153 in their milk in the world.« less

Single-band upconversion nanoprobes for multiplexed simultaneous in situ molecular mapping of cancer biomarkers.

PubMed

Zhou, Lei; Wang, Rui; Yao, Chi; Li, Xiaomin; Wang, Chengli; Zhang, Xiaoyan; Xu, Congjian; Zeng, Aijun; Zhao, Dongyuan; Zhang, Fan

2015-04-24

The identification of potential diagnostic markers and target molecules among the plethora of tumour oncoproteins for cancer diagnosis requires facile technology that is capable of quantitatively analysing multiple biomarkers in tumour cells and tissues. Diagnostic and prognostic classifications of human tumours are currently based on the western blotting and single-colour immunohistochemical methods that are not suitable for multiplexed detection. Herein, we report a general and novel method to prepare single-band upconversion nanoparticles with different colours. The expression levels of three biomarkers in breast cancer cells were determined using single-band upconversion nanoparticles, western blotting and immunohistochemical technologies with excellent correlation. Significantly, the application of antibody-conjugated single-band upconversion nanoparticle molecular profiling technology can achieve the multiplexed simultaneous in situ biodetection of biomarkers in breast cancer cells and tissue specimens and produce more accurate results for the simultaneous quantification of proteins present at low levels compared with classical immunohistochemical technology.

Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 1: metals.

PubMed

Smolders, Roel; Koch, Holger M; Moos, Rebecca K; Cocker, John; Jones, Kate; Warren, Nick; Levy, Len; Bevan, Ruth; Hays, Sean M; Aylward, Lesa L

2014-12-01

The aim of the current HBM-study is to further the understanding of the impact of inter- and intra-individual variability in HBM surveys as it may have implications for the design and interpretation of the study outcomes. As spot samples only provide a snapshot in time of the concentrations of chemicals in an individual, it remains unclear to what extent intra-individual variability plays a role in the overall variability of population-wide HBM surveys. The current paper describes the results of an intensive biomonitoring study, in which all individual urine samples of 8 individuals were collected over a 6-day sampling period (a total of 352 unique samples). By analyzing different metals (As, Cd, Mn, Ni) in each individual sample, inter- and intra-individual variability for these four metals could be determined, and the relationships between exposure, internal dose, and sampling protocol assessed. Although the range of biomarker values for different metals was well within the normal range reported in large-scale population surveys, large intra-individual differences over a 6-day period could also be observed. Typically, measured biomarker values span at least an order of magnitude within an individual, and more if specific exposure episodes could be identified. Fish consumption for example caused a twenty- to thirty-fold increase in urinary As-levels over a period of 2-6h. Intra-class correlation coefficients (ICC) were typically low for uncorrected biomarker values (between 0.104 and 0.460 for the 4 metals), but improved when corrected for creatinine or specific gravity (SG). The results show that even though urine is a preferred matrix for HBM studies, there are certain methodological issues that need to be taken into account in the interpretation of urinary biomarker data, related to the intrinsic variability of the urination process itself, the relationship between exposure events and biomarker quantification, and the timing of sampling. When setting up HBM

Developing Foram-AMBI for biomonitoring in the Mediterranean: Species assignments to ecological categories

USGS Publications Warehouse

Jorissen, Frans; Nardelli, Maria P.; Almogi-Labin, Ahuva; Barras, Christine; Bergamin, Luisa; Bicchi, Erica; El Kateb, Akram; Ferraro, Luciana; McGann, Mary; Morigi, Caterina; Romano, Elena; Sabattini, Anna; Schweizer, Magali; Spezzaferri, Silvia

2018-01-01

Most environmental bio-monitoring methods using the species composition of marine faunas define the Ecological Quality Status of soft bottom ecosystems based on the relative proportions of species assigned to a limited number of ecological categories. In this study we analyse the distribution patterns of benthic foraminifera in the Mediterranean as a function of organic carbon gradients on the basis of 15 publications and assign the individual species to five ecological categories. Our categories (of sensitive, indifferent and 3rd, 2nd and 1st order opportunists) are very similar to the ecological categories commonly used for macrofauna, but show some minor differences. In the 15 analysed publications, we considered the numerical data of 493 taxa, of which 199 could be assigned. In all 79 taxa were classified as sensitive, 60 as indifferent, 46 as 3rd order, 12 as 2nd order and 2 as 1st order opportunists. The remaining 294 taxa are all accessory, and will only marginally contribute to biotic indices based on relative species proportions. In this paper we wanted also to explain the methodology we used for these species assignments, paying particular attention to all complications and problems encountered. We think that the species list proposed here will constitute a highly useful tool for foraminiferal bio-monitoring of soft bottoms in the Mediterranean Sea, which can be used in different ecological indices (Foram-AMBI and similar methods). With additional information becoming available in the next few years, it will be possible to expand the list, and, if necessary, to apply some minor corrections. As a next step, we intend to test this species list using several biotic indices, in a number of independent data sets, as soon as these will become available.

Biomonitoring of Organophosphorus Agent Exposure by Reactivation of Cholinesterase Enzyme Based on Carbon Nanotube-Enhanced Flow-Injection Amperometric Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Dan; Wang, Jun; Smith, Jordan N.

2009-11-15

A portable, rapid, and sensitive assessment of sub-clinical organophosphorus (OPs) agent exposure based on reactivation of cholinesterase (ChE) from OP-inhibited ChE using rat saliva (in vitro) was developed using an electrochemical sensor coupled with a microflow-injection system. The sensor was based on a carbon nanotube (CNT)-modified screen printed carbon electrode (SPE), which was integrated into a flow cell. Due to the extent of inter-individual ChE activity variability, ChE biomonitoring often requires an initial base-line determination (non-inhibited) of enzyme activity which is then directly compared with activity after OP exposure. This manuscript described an alternative strategy where reactivation of the phosphorylatedmore » enzyme was exploited to enable measurement of both inhibited and baseline ChE activity (i.e. after reactivation) in the same sample. The use of CNT makes the electrochemical detection of the products from enzymatic reactions more feasible with extremely high sensitivity and at low potentials. Paraoxon was selected as a model OP compound for in vitro inhibition studies. Some experiment parameters, (e.g. inhibition and reactivation times), have been optimized such that, 92 - 95% ChE reactivation can be achieved over a broad range of ChE inhibition (5 - 94 %) with paraoxon. The extent of enzyme inhibition using this electrochemical sensor correlates well with conventional enzyme activity measurements.« less

Leaves of Phragmites australis as potential atmospheric biomonitors of Platinum Group Elements.

PubMed

Bonanno, Giuseppe; Pavone, Pietro

2015-04-01

The increasing emissions of Platinum Group Elements (PGEs), namely Pt, Pd and Rh, may pose a significant risk to ecosystem processes and human health. A periodic assessment of PGEs distribution in the environment is thus of the utmost importance for the implementation of timely measures of mitigation. Although several studies have quantified PGEs in different life forms such as mammals, birds, fish, crustaceans, algae, mosses and even human beings, data about vascular plants need further surveys. This study aimed to test the suitability of the grass Phragmites australis (common reed) as a biomonitor of PGEs atmospheric pollution. The results showed that Pd and Pt concentrations in leaves are significantly higher in urban areas. In particular, Pd showed the highest range of values in line with current studies that consider palladium as the main element of traffic-related pollution. Overall, the leaves of Phragmites australis reflected the different gradient of PGEs emissions, and may thus be considered as potential biomonitors of atmospheric pollution. Copyright © 2015 Elsevier Inc. All rights reserved.

Biomarker-Based Approaches for Assessing Alcohol Use Disorders

PubMed Central

Niemelä, Onni

2016-01-01

Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol-induced liver dysfunction and to provide information on the risk of co-morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders. PMID:26828506

Identification of MicroRNA as Sepsis Biomarker Based on miRNAs Regulatory Network Analysis

PubMed Central

Huang, Jie; Sun, Zhandong; Yan, Wenying; Zhu, Yujie; Lin, Yuxin; Chen, Jiajai; Shen, Bairong

2014-01-01

Sepsis is regarded as arising from an unusual systemic response to infection but the physiopathology of sepsis remains elusive. At present, sepsis is still a fatal condition with delayed diagnosis and a poor outcome. Many biomarkers have been reported in clinical application for patients with sepsis, and claimed to improve the diagnosis and treatment. Because of the difficulty in the interpreting of clinical features of sepsis, some biomarkers do not show high sensitivity and specificity. MicroRNAs (miRNAs) are small noncoding RNAs which pair the sites in mRNAs to regulate gene expression in eukaryotes. They play a key role in inflammatory response, and have been validated to be potential sepsis biomarker recently. In the present work, we apply a miRNA regulatory network based method to identify novel microRNA biomarkers associated with the early diagnosis of sepsis. By analyzing the miRNA expression profiles and the miRNA regulatory network, we obtained novel miRNAs associated with sepsis. Pathways analysis, disease ontology analysis, and protein-protein interaction network (PIN) analysis, as well as ROC curve, were exploited to testify the reliability of the predicted miRNAs. We finally identified 8 novel miRNAs which have the potential to be sepsis biomarkers. PMID:24809055

Detection of Radiation-Exposure Biomarkers by Differential Mobility Prefiltered Mass Spectrometry (DMS-MS)

PubMed Central

Coy, Stephen L.; Krylov, Evgeny V.; Schneider, Bradley B.; Covey, Thomas R.; Brenner, David J.; Tyburski, John B.; Patterson, Andrew D.; Krausz, Kris W.; Fornace, Albert J.; Nazarov, Erkinjon G.

2010-01-01

Technology to enable rapid screening for radiation exposure has been identified as an important need, and, as a part of a NIH / NIAD effort in this direction, metabolomic biomarkers for radiation exposure have been identified in a recent series of papers. To reduce the time necessary to detect and measure these biomarkers, differential mobility spectrometry – mass spectrometry (DMS-MS) systems have been developed and tested. Differential mobility ion filters preselect specific ions and also suppress chemical noise created in typical atmospheric-pressure ionization sources (ESI, MALDI, and others). Differential-mobility-based ion selection is based on the field dependence of ion mobility, which, in turn, depends on ion characteristics that include conformation, charge distribution, molecular polarizability, and other properties, and on the transport gas composition which can be modified to enhance resolution. DMS-MS is able to resolve small-molecule biomarkers from nearly-isobaric interferences, and suppresses chemical noise generated in the ion source and in the mass spectrometer, improving selectivity and quantitative accuracy. Our planar DMS design is rapid, operating in a few milliseconds, and analyzes ions before fragmentation. Depending on MS inlet conditions, DMS-selected ions can be dissociated in the MS inlet expansion, before mass analysis, providing a capability similar to MS/MS with simpler instrumentation. This report presents selected DMS-MS experimental results, including resolution of complex test mixtures of isobaric compounds, separation of charge states, separation of isobaric biomarkers (citrate and isocitrate), and separation of nearly-isobaric biomarker anions in direct analysis of a bio-fluid sample from the radiation-treated group of a mouse-model study. These uses of DMS combined with moderate resolution MS instrumentation indicate the feasibility of field-deployable instrumentation for biomarker evaluation. PMID:20305793

Comparing biomarkers as principal surrogate endpoints.

PubMed

Huang, Ying; Gilbert, Peter B

2011-12-01

Recently a new definition of surrogate endpoint, the "principal surrogate," was proposed based on causal associations between treatment effects on the biomarker and on the clinical endpoint. Despite its appealing interpretation, limited research has been conducted to evaluate principal surrogates, and existing methods focus on risk models that consider a single biomarker. How to compare principal surrogate value of biomarkers or general risk models that consider multiple biomarkers remains an open research question. We propose to characterize a marker or risk model's principal surrogate value based on the distribution of risk difference between interventions. In addition, we propose a novel summary measure (the standardized total gain) that can be used to compare markers and to assess the incremental value of a new marker. We develop a semiparametric estimated-likelihood method to estimate the joint surrogate value of multiple biomarkers. This method accommodates two-phase sampling of biomarkers and is more widely applicable than existing nonparametric methods by incorporating continuous baseline covariates to predict the biomarker(s), and is more robust than existing parametric methods by leaving the error distribution of markers unspecified. The methodology is illustrated using a simulated example set and a real data set in the context of HIV vaccine trials. © 2011, The International Biometric Society.

DNA Methylation Biomarkers: Cancer and Beyond

PubMed Central

Mikeska, Thomas; Craig, Jeffrey M.

2014-01-01

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. PMID:25229548

Perspectives on Communicating Biomarker-Based Assessments of Alzheimer’s Disease to Cognitively Healthy Individuals

PubMed Central

Milne, Richard; Bunnik, Eline; Diaz, Ana; Richard, Edo; Badger, Shirlene; Gove, Dianne; Georges, Jean; Fauria, Karine; Molinuevo, Jose-Luis; Wells, Katie; Ritchie, Craig; Brayne, Carol

2018-01-01

In clinical trials which target pathophysiological mechanisms associated with Alzheimer’s disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer’s dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants’ experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer’s disease biomarkers. PMID:29480179

Risk communication and human biomonitoring: which practical lessons from the Belgian experience are of use for the EU perspective?

PubMed Central

Keune, Hans; Morrens, Bert; Loots, Ilse

2008-01-01

Background In order to investigate and monitor environmental health in Flanders (the Dutch speaking part of Belgium), the Flemish government funded the Centre of Expertise for Environment and Health, which started a human biomonitoring campaign in 2001. In addition to environmental health experts measuring environmental pollutants and health effects in human beings, social scientific experts at the Centre focus on risk communication associated with the human biomonitoring campaign. Methods In the literature about risk communication an evolution can be traced from traditional, one-way communication, restricted to the dissemination of information from experts to the public, to more modern, two-way risk communication, with a focus on participation and cooperation between scientists, policy-makers and the public. Within the Centre of Expertise for Environment and Health this discourse was first translated into some general principles and guidelines for external communication, at a 'Ten Commandments level'. These principles needed to be incorporated in the day-to-day practice of human biomonitoring research. Results The social scientific experts at the Centre developed a combined risk communication strategy. On the one hand the strategy consists of traditional risk communication for external communication purposes, for example information meetings and digital newsletters. On the other hand it consists of a step by step approach of incorporating more modern risk communication, for example a risk perception questionnaire, dialogical experiments for involving local stakeholders, and an action-plan for interpreting results for policy making. Conclusion With a parallel strategy of traditional and modern communication, of external and internal reflection, and through different social scientific projects, the Flemish Centre of Expertise of Environment and Health incorporates risk communication in the day-to-day practice of human biomonitoring research. A direct and continuous

Risk communication and human biomonitoring: which practical lessons from the Belgian experience are of use for the EU perspective?

PubMed

Keune, Hans; Morrens, Bert; Loots, Ilse

2008-06-05

In order to investigate and monitor environmental health in Flanders (the Dutch speaking part of Belgium), the Flemish government funded the Centre of Expertise for Environment and Health, which started a human biomonitoring campaign in 2001. In addition to environmental health experts measuring environmental pollutants and health effects in human beings, social scientific experts at the Centre focus on risk communication associated with the human biomonitoring campaign. In the literature about risk communication an evolution can be traced from traditional, one-way communication, restricted to the dissemination of information from experts to the public, to more modern, two-way risk communication, with a focus on participation and cooperation between scientists, policy-makers and the public.Within the Centre of Expertise for Environment and Health this discourse was first translated into some general principles and guidelines for external communication, at a 'Ten Commandments level'. These principles needed to be incorporated in the day-to-day practice of human biomonitoring research. The social scientific experts at the Centre developed a combined risk communication strategy. On the one hand the strategy consists of traditional risk communication for external communication purposes, for example information meetings and digital newsletters. On the other hand it consists of a step by step approach of incorporating more modern risk communication, for example a risk perception questionnaire, dialogical experiments for involving local stakeholders, and an action-plan for interpreting results for policy making. With a parallel strategy of traditional and modern communication, of external and internal reflection, and through different social scientific projects, the Flemish Centre of Expertise of Environment and Health incorporates risk communication in the day-to-day practice of human biomonitoring research. A direct and continuous involvement of the social scientist, an

Biological monitoring of carcinogens: current status and perspectives.

PubMed

Pavanello, Sofia; Lotti, Marcello

2012-04-01

Biomonitoring exposures to carcinogens is common practice and a variety of biomarkers have been developed to assess both exposures and biochemical/biological effects. However, their clinical and preventive relevance is still uncertain. The understanding of cancer as a genetic disease has dramatically evolved during last decades, showing that cancer cell types acquire their characteristics with different strategies, time frames and microenvironments. Therefore, the place of current biomarkers within this complex scenario of gene-environment interactions leading to cancer cannot be defined. Reasons are manifold. Most studies assessed cancer risk on a group basis through snapshots taken at unknown time-points of the postulated chain of events. Little attention has been paid to the variety and variability of exposures, and no prospective study validated the indicators of biochemical/biological effects. New opportunities and suggestions for biomonitoring exposures to carcinogens could derive from exploring the exposome that combines exposures from all sources both external and internal. The discovery of new biomarkers and the identification of relevant gene-specific pathways could be achieved through metabolomic and genome-wide studies. In conclusion, it is possible to envisage personalized biomonitoring procedures, such as those already implemented in the context of nutrition and clinical oncology.

Multiplex detection of pancreatic cancer biomarkers using a SERS-based immunoassay

NASA Astrophysics Data System (ADS)

Banaei, Nariman; Foley, Anne; Houghton, Jean Marie; Sun, Yubing; Kim, Byung

2017-11-01

Early diagnosis of pancreatic cancer (PC) is critical to reduce the mortality rate of this disease. Current biological analysis approaches cannot robustly detect several low abundance PC biomarkers in sera, limiting the clinical application of these biomarkers. Enzyme linked immunosorbent assay and radioimmunoassay are two common platforms for detection of biomarkers; however, they suffer from some limitation. This study demonstrates a novel system for multiplex detection of pancreatic biomarkers CA19-9, MMP7 and MUC4 in sera samples with high sensitivity using surface enhanced Raman spectroscopy. Measuring the levels of these biomarkers in PC patients, pancreatitis patients, and healthy individuals reveals the unique expression pattern of these markers in PC patients, suggesting the great potential of using this approach for early diagnostics of PCs.

The role of native lichens in the biomonitoring of gaseous mercury at contaminated sites.

PubMed

López Berdonces, Miguel A; Higueras, Pablo L; Fernández-Pascual, Mercedes; Borreguero, Ana M; Carmona, Manuel

2017-01-15

Contamination by atmospheric mercury has been assessed in two different areas from Spain (Las Cuevas, Ciudad Real and Flix, Tarragona) using lichens as biomonitors. The relationship established between mercury contents in the soils and the gaseous mercury (GM) was also observed. It was found that the GM is highest in the vicinity of the source and it is dispersed depending on of the distance to the source and the wind directions. The mercury concentration in the gas phase in Flix was higher than that found in Las Cuevas and also higher than the value that the US EPA recommended. The mercury bioaccumulation in the native lichens from genders Ramalina and Xanthoria were used as biomonitors for absorbing mercury in Las Cuevas and Flix, respectively. The mercury uptake by Ramalina was higher than the amount accumulated by Xanthoria, a difference that was mainly due to the lichen characteristics. The content of mercury in lichens in relation to the mercury in gas was fitted by a Freundlich type equation, indicating that the equilibrium between both phases was established. Besides, transplanted Ramalina lichen in Las Cuevas allowed to obtain the kinetic of mercury uptake. A kinetic model of first order based on the equilibrium was proposed and the mass transfer constants for each sampling station were estimated. As it was expected, these values increased with the predominant wind flow direction. Copyright © 2016 Elsevier Ltd. All rights reserved.

BluePen Biomarkers LLC: integrated biomarker solutions

PubMed Central

Blair, Ian A; Mesaros, Clementina; Lilley, Patrick; Nunez, Matthew

2016-01-01

BluePen Biomarkers provides a unique comprehensive multi-omics biomarker discovery and validation platform. We can quantify, integrate and analyze genomics, proteomics, metabolomics and lipidomics biomarkers, alongside clinical data, demographics and other phenotypic data. A unique bio-inspired signal processing analytic approach is used that has the proven ability to identify biomarkers in a wide variety of diseases. The resulting biomarkers can be used for diagnosis, prognosis, mechanistic studies and predicting treatment response, in contexts from core research through clinical trials. BluePen Biomarkers provides an additional groundbreaking research goal: identifying surrogate biomarkers from different modalities. This not only provides new biological insights, but enables least invasive, least-cost tests that meet or exceed the predictive quality of current tests. PMID:28031971

Candidate immune biomarkers for radioimmunotherapy.

PubMed

Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

2017-08-01

Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

Use of Pathogen-Specific Antibody Biomarkers to Estimate Waterborne Infections in Population-Based Settings.

PubMed

Exum, Natalie G; Pisanic, Nora; Granger, Douglas A; Schwab, Kellogg J; Detrick, Barbara; Kosek, Margaret; Egorov, Andrey I; Griffin, Shannon M; Heaney, Christopher D

2016-09-01

This review discusses the utility of pathogen-specific antibody biomarkers for improving estimates of the population burden of waterborne infections, assessing the fraction of infections that can be prevented by specific water treatments, and understanding transmission routes and the natural history and ecology of disease in different populations (including asymptomatic infection rates). We review recent literature on the application of pathogen-specific antibody response data to estimate incidence and prevalence of acute infections and their utility to assess the contributions of waterborne transmission pathways. Advantages and technical challenges associated with the use of serum versus minimally invasive salivary antibody biomarkers in cross-sectional and prospective surveys are discussed. We highlight recent advances and challenges and outline future directions for research, development, and application of antibody-based and other immunological biomarkers of waterborne infections.

The current evidence for a biomarker-based approach in cancer of unknown primary.

PubMed

El Rassy, Elie; Pavlidis, Nicholas

2018-05-02

Cancer of unknown primary (CUP) accounts for the seventh to eighth most frequently diagnosed cancer yet its prognosis remains poor with conventional chemotherapy. The spectrum of therapeutic management includes both locoregional and systemic therapy and should intend to offer optimal benefit to favorable CUP patients and palliative care to unfavorable cases. The recent molecular advances have revolutionized the armamentarium of cancer treatments though a biomarker-based approach. Unfortunately, solid data in CUP is lacking in the absence of a CUP-specific driver molecular signature. This prompted us to screen the medical literature for clinical data that evaluates the efficacy and safety of the biomarker-based approach in CUP patients. In this review, we will summarize the available evidence for the applicability of targeted therapies in CUP. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantitative imaging biomarker ontology (QIBO) for knowledge representation of biomedical imaging biomarkers.

PubMed

Buckler, Andrew J; Liu, Tiffany Ting; Savig, Erica; Suzek, Baris E; Ouellette, M; Danagoulian, J; Wernsing, G; Rubin, Daniel L; Paik, David

2013-08-01

A widening array of novel imaging biomarkers is being developed using ever more powerful clinical and preclinical imaging modalities. These biomarkers have demonstrated effectiveness in quantifying biological processes as they occur in vivo and in the early prediction of therapeutic outcomes. However, quantitative imaging biomarker data and knowledge are not standardized, representing a critical barrier to accumulating medical knowledge based on quantitative imaging data. We use an ontology to represent, integrate, and harmonize heterogeneous knowledge across the domain of imaging biomarkers. This advances the goal of developing applications to (1) improve precision and recall of storage and retrieval of quantitative imaging-related data using standardized terminology; (2) streamline the discovery and development of novel imaging biomarkers by normalizing knowledge across heterogeneous resources; (3) effectively annotate imaging experiments thus aiding comprehension, re-use, and reproducibility; and (4) provide validation frameworks through rigorous specification as a basis for testable hypotheses and compliance tests. We have developed the Quantitative Imaging Biomarker Ontology (QIBO), which currently consists of 488 terms spanning the following upper classes: experimental subject, biological intervention, imaging agent, imaging instrument, image post-processing algorithm, biological target, indicated biology, and biomarker application. We have demonstrated that QIBO can be used to annotate imaging experiments with standardized terms in the ontology and to generate hypotheses for novel imaging biomarker-disease associations. Our results established the utility of QIBO in enabling integrated analysis of quantitative imaging data.

Defense Industrial Base Capabilities Study: Battlespace Awareness

DTIC Science & Technology

2004-01-01

not production capacity or workforce issues. It considers the best capabilities in both the domestic and foreign components of the industrial base...www.maliburesearch.com Ground Penetrating Radar MARIMATECH 1989 Aarhus, Denmark n.a. n.a. www.marimatech.com Sonar Maser Technology (NZ) Ltd. 1983 Auckland , New

A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score

PubMed Central

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Yusuf, Salim; Granger, Christopher B; Siegbahn, Agneta; Wallentin, Lars

2018-01-01

Abstract Aims In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers. Methods and results The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score. Conclusion A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF. ClinicalTrials.gov identifier NCT00412984 and NCT00262600 PMID:29069359

Population-based study of blood biomarkers in prediction of sub-acute recurrent stroke

PubMed Central

Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Silver, Louise E; Rothwell, Peter M

2017-01-01

Background and purpose Risk of recurrent stroke is high in the first few weeks after TIA or stroke and clinic risk prediction tools have only limited accuracy, particularly after the hyper-acute phase. Previous studies of the predictive value of biomarkers have been small, been done in selected populations and have not concentrated on the acute phase or on intensively treated populations. We aimed to determine the predictive value of a panel of blood biomarkers in intensively treated patients early after TIA and stroke. Methods We studied 14 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in early TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were related to 90-day risk of recurrent stroke as Hazard Ratio (95%CI) per decile increase, adjusted for age and sex. Results Among 1292 eligible patients there were 53 recurrent ischaemic strokes within 90 days. There were moderate correlations (r>0.40; p<0001) between the inflammatory biomarkers and between the cell damage and thrombotic subsets. However, associations with risk of early recurrent stroke were weak, with significant associations limited to Interleukin-6 (HR=1.12, 1.01-1.24; p=0.035) and C-reactive protein (1.16, 1.02-1.30; p=0.019). When stratified by type of presenting event, P-selectin predicted stroke after TIA (1.31, 1.03-1.66; p=0.028) and C-reactive protein predicted stroke after stroke (1.16, 1.01-1.34; p=0.042). These associations remained after fully adjusting for other vascular risk factors. Conclusion In the largest study to date, we found very limited predictive utility for early recurrent stroke for a panel of inflammatory, thrombotic and cell damage biomarkers. PMID:25158774

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

PubMed

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.

Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

PubMed

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).

Identification of Surface Protein Biomarkers of Listeria monocytogenes via Bioinformatics and Antibody-Based Protein Detection Tools

PubMed Central

Zhang, Cathy X. Y.; Brooks, Brian W.; Huang, Hongsheng; Pagotto, Franco

2016-01-01

ABSTRACT The Gram-positive bacterium Listeria monocytogenes causes a significant percentage of the fatalities among foodborne illnesses in humans. Surface proteins specifically expressed in a wide range of L. monocytogenes serotypes under selective enrichment culture conditions could serve as potential biomarkers for detection and isolation of this pathogen via antibody-based methods. Our study aimed to identify such biomarkers. Interrogation of the L. monocytogenes serotype 4b strain F2365 genome identified 130 putative or known surface proteins. The homologues of four surface proteins, LMOf2365_0578, LMOf2365_0581, LMOf2365_0639, and LMOf2365_2117, were assessed as biomarkers due to the presence of conserved regions among strains of L. monocytogenes which are variable among other Listeria species. Rabbit polyclonal antibodies against the four recombinant proteins revealed the expression of only LMOf2365_0639 on the surface of serotype 4b strain LI0521 cells despite PCR detection of mRNA transcripts for all four proteins in the organism. Three of 35 monoclonal antibodies (MAbs) to LMOf2365_0639, MAbs M3643, M3644, and M3651, specifically recognized 42 (91.3%) of 46 L. monocytogenes lineage I and II isolates grown in nonselective brain heart infusion medium. While M3644 and M3651 reacted with 14 to 15 (82.4 to 88.2%) of 17 L. monocytogenes lineage I and II isolates, M3643 reacted with 22 (91.7%) of 24 lineage I, II, and III isolates grown in selective enrichment media (UVM1, modified Fraser, Palcam, and UVM2 media). The three MAbs exhibited only weak reactivities (the optical densities at 414 nm were close to the cutoff value) to some other Listeria species grown in selective enrichment media. Collectively, the data indicate the potential of LMOf2365_0639 as a surface biomarker of L. monocytogenes, with the aid of specific MAbs, for pathogen detection, identification, and isolation in clinical, environmental, and food samples. IMPORTANCE L. monocytogenes is

PSA and beyond: alternative prostate cancer biomarkers

PubMed Central

2016-01-01

Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

An innovative approach to capability-based emergency operations planning

PubMed Central

Keim, Mark E

2013-01-01

This paper describes the innovative use information technology for assisting disaster planners with an easily-accessible method for writing and improving evidence-based emergency operations plans. This process is used to identify all key objectives of the emergency response according to capabilities of the institution, community or society. The approach then uses a standardized, objective-based format, along with a consensus-based method for drafting capability-based operational-level plans. This information is then integrated within a relational database to allow for ease of access and enhanced functionality to search, sort and filter and emergency operations plan according to user need and technological capacity. This integrated approach is offered as an effective option for integrating best practices of planning with the efficiency, scalability and flexibility of modern information and communication technology. PMID:28228987

An innovative approach to capability-based emergency operations planning.

PubMed

Keim, Mark E

2013-01-01

This paper describes the innovative use information technology for assisting disaster planners with an easily-accessible method for writing and improving evidence-based emergency operations plans. This process is used to identify all key objectives of the emergency response according to capabilities of the institution, community or society. The approach then uses a standardized, objective-based format, along with a consensus-based method for drafting capability-based operational-level plans. This information is then integrated within a relational database to allow for ease of access and enhanced functionality to search, sort and filter and emergency operations plan according to user need and technological capacity. This integrated approach is offered as an effective option for integrating best practices of planning with the efficiency, scalability and flexibility of modern information and communication technology.

Biomonitoring at the UK Health and Safety Laboratory.

PubMed

Cocker, J; Jones, K; Morton, J; Mason, H J

2007-05-01

The UK Health and Safety Laboratory (HSL) provides research and analytical support to the Health and Safety Executive, other Government Departments and employers. In the area of biomonitoring HSL conducts research studies and provides an analytical service for regular surveillance of worker exposure to hazardous substances. This paper gives brief examples of how data from such studies can be used to develop biological monitoring guidance values for isocyanates, polycyclic aromatic hydrocarbons and hexavalent chromium. In addition, a study of occupational exposure to copper chrome arsenic wood preservatives is briefly described to show how biological monitoring can be used for post-approval surveillance of a biocide.

Collaborative environments for capability-based planning

NASA Astrophysics Data System (ADS)

McQuay, William K.

2005-05-01

Distributed collaboration is an emerging technology for the 21st century that will significantly change how business is conducted in the defense and commercial sectors. Collaboration involves two or more geographically dispersed entities working together to create a "product" by sharing and exchanging data, information, and knowledge. A product is defined broadly to include, for example, writing a report, creating software, designing hardware, or implementing robust systems engineering and capability planning processes in an organization. Collaborative environments provide the framework and integrate models, simulations, domain specific tools, and virtual test beds to facilitate collaboration between the multiple disciplines needed in the enterprise. The Air Force Research Laboratory (AFRL) is conducting a leading edge program in developing distributed collaborative technologies targeted to the Air Force's implementation of systems engineering for a simulation-aided acquisition and capability-based planning. The research is focusing on the open systems agent-based framework, product and process modeling, structural architecture, and the integration technologies - the glue to integrate the software components. In past four years, two live assessment events have been conducted to demonstrate the technology in support of research for the Air Force Agile Acquisition initiatives. The AFRL Collaborative Environment concept will foster a major cultural change in how the acquisition, training, and operational communities conduct business.

Use of Pathogen-Specific Antibody Biomarkers to Estimate Waterborne Infections in Population-Based Settings

PubMed Central

Exum, Natalie G.; Pisanic, Nora; Granger, Douglas A.; Schwab, Kellogg J.; Detrick, Barbara; Kosek, Margaret; Egorov, Andrey I.; Griffin, Shannon M.; Heaney, Christopher D.

2016-01-01

Purpose of review This review discusses the utility of pathogen-specific antibody biomarkers for improving estimates of the population burden of waterborne infections, assessing the fraction of infections that can be prevented by specific water treatments, and understanding transmission routes and the natural history and ecology of disease in different populations (including asymptomatic infection rates). Recent findings We review recent literature on the application of pathogen-specific antibody response data to estimate incidence and prevalence of acute infections and their utility to assess the contributions of waterborne transmission pathways. Advantages and technical challenges associated with the use of serum versus minimally invasive salivary antibody biomarkers in cross-sectional and prospective surveys are discussed. Summary We highlight recent advances and challenges and outline future directions for research, development, and application of antibody-based and other immunological biomarkers of waterborne infections. PMID:27352014

Documenting the kinetic time course of lambda-cyhalothrin metabolites in orally exposed volunteers for the interpretation of biomonitoring data.

PubMed

Khemiri, Rania; Côté, Jonathan; Fetoui, Hamadi; Bouchard, Michèle

2017-07-05

Lambda-cyhalothrin is a pyrethroid pesticide largely used in agriculture. Exposure assessment can be performed by measuring key urinary metabolites. For a proper use of biomonitoring data, it is however important to gain information on the toxicokinetics of these key biomarkers of exposure. A human volunteer study was performed to document the plasma and urinary time courses of major lambda-cyhalothrin metabolites. Seven volunteers ingested 0.025mgkg -1 body weight of lambda-cyhalothrin. Blood samples were withdrawn prior to dosing and at fixed time periods over the 72 h-period following ingestion and complete urine voids were collected pre-exposure and at pre-established intervals over 84h post-dosing. The cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were quantified in these samples. Plasma concentrations of CFMP and 3-PBA increased rapidly after ingestion, with average peak values at 3.1 and 4.0h post-dosing, respectively; subsequent elimination phase showed a rapid decay with a mean half-life (t ½ ) of ≈5.3 and 6.4h for CFMP and 3-PBA, respectively. Urinary rate time courses displayed a profile similar to the plasma concentration-time curves with corresponding mean t ½ of ≈4.2 and 5.9h. In the 84-h period post-treatment, on average 21% of lambda-cyhalothrin dose were excreted in urine as CFMP as compared to 30% as 3-PBA. Overall, CFMP and 3-PBA metabolites were confirmed to be major metabolites of lambda-cyhalothrin and exhibited similar kinetics with short half-lives; they thus both appear as useful biomarkers of exposure to lambda-cyhalothrin in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomarker detection of global infectious diseases based on magnetic particles.

PubMed

Carinelli, Soledad; Martí, Mercè; Alegret, Salvador; Pividori, María Isabel

2015-09-25

Infectious diseases affect the daily lives of millions of people all around the world, and are responsible for hundreds of thousands of deaths, mostly in the developing world. Although most of these major infectious diseases are treatable, the early identification of individuals requiring treatment remains a major issue. The incidence of these diseases would be reduced if rapid diagnostic tests were widely available at the community and primary care level in low-resource settings. Strong research efforts are thus being focused on replacing standard clinical diagnostic methods, such as the invasive detection techniques (biopsy or endoscopy) or expensive diagnostic and monitoring methods, by affordable and sensitive tests based on novel biomarkers. The development of new methods that are needed includes solid-phase separation techniques. In this context, the integration of magnetic particles within bioassays and biosensing devices is very promising since they greatly improve the performance of a biological reaction. The diagnosis of clinical samples with magnetic particles can be easily achieved without pre-enrichment, purification or pretreatment steps often required for standard methods, simplifying the analytical procedures. The biomarkers can be specifically isolated and preconcentrated from complex biological matrixes by magnetic actuation, increasing specificity and the sensitivity of the assay. This review addresses these promising features of the magnetic particles for the detection of biomarkers in emerging technologies related with infectious diseases affecting global health, such as malaria, influenza, dengue, tuberculosis or HIV. Copyright © 2015 Elsevier B.V. All rights reserved.

Large-Scale Biomonitoring of Remote and Threatened Ecosystems via High-Throughput Sequencing

PubMed Central

Gibson, Joel F.; Shokralla, Shadi; Curry, Colin; Baird, Donald J.; Monk, Wendy A.; King, Ian; Hajibabaei, Mehrdad

2015-01-01

Biodiversity metrics are critical for assessment and monitoring of ecosystems threatened by anthropogenic stressors. Existing sorting and identification methods are too expensive and labour-intensive to be scaled up to meet management needs. Alternately, a high-throughput DNA sequencing approach could be used to determine biodiversity metrics from bulk environmental samples collected as part of a large-scale biomonitoring program. Here we show that both morphological and DNA sequence-based analyses are suitable for recovery of individual taxonomic richness, estimation of proportional abundance, and calculation of biodiversity metrics using a set of 24 benthic samples collected in the Peace-Athabasca Delta region of Canada. The high-throughput sequencing approach was able to recover all metrics with a higher degree of taxonomic resolution than morphological analysis. The reduced cost and increased capacity of DNA sequence-based approaches will finally allow environmental monitoring programs to operate at the geographical and temporal scale required by industrial and regulatory end-users. PMID:26488407

Glucoweb: a case study of secure, remote biomonitoring and communication.

PubMed

Nigrin, D J; Kohane, I S

2000-01-01

As the Internet begins to play a greater role in many healthcare processes, it is inevitable that remote monitoring of patients' physiological parameters over the Internet will become increasingly commonplace. Internet-based communication between patients and their healthcare providers has already become prevalent, and has gained significant attention in terms of confidentiality issues. However, transmission of data directly from patients' physiological biomonitoring devices over the Web has garnered significantly less focus, especially in the area of authentication and security. In this paper, we describe a prototype system called Glucoweb, which allows patients with diabetes mellitus to transmit their self-monitored blood glucose data directly from their personal glucometer device to their diabetes care provider over the Internet. No customized software is necessary on the patient's computer, only a Web browser and active Internet connection. We use this example to highlight key authentication and security measures that should be considered for devices that transmit healthcare data to remote locations.

Distributed collaborative environments for virtual capability-based planning

NASA Astrophysics Data System (ADS)

McQuay, William K.

2003-09-01

Distributed collaboration is an emerging technology that will significantly change how decisions are made in the 21st century. Collaboration involves two or more geographically dispersed individuals working together to share and exchange data, information, knowledge, and actions. The marriage of information, collaboration, and simulation technologies provides the decision maker with a collaborative virtual environment for planning and decision support. This paper reviews research that is focusing on the applying open standards agent-based framework with integrated modeling and simulation to a new Air Force initiative in capability-based planning and the ability to implement it in a distributed virtual environment. Virtual Capability Planning effort will provide decision-quality knowledge for Air Force resource allocation and investment planning including examining proposed capabilities and cost of alternative approaches, the impact of technologies, identification of primary risk drivers, and creation of executable acquisition strategies. The transformed Air Force business processes are enabled by iterative use of constructive and virtual modeling, simulation, and analysis together with information technology. These tools are applied collaboratively via a technical framework by all the affected stakeholders - warfighter, laboratory, product center, logistics center, test center, and primary contractor.

The current status of clinical proteomics and the use of MRM and MRM(3) for biomarker validation.

PubMed

Lemoine, Jérôme; Fortin, Tanguy; Salvador, Arnaud; Jaffuel, Aurore; Charrier, Jean-Philippe; Choquet-Kastylevsky, Geneviève

2012-05-01

The transfer of biomarkers from the discovery field to clinical use is still, despite progress, on a road filled with pitfalls. Since the emergence of proteomics, thousands of putative biomarkers have been published, often with overlapping diagnostic capacities. The strengthening of the robustness of discovery technologies, particularly in mass spectrometry, has been followed by intense discussions on establishing well-defined evaluation procedures for the identified targets to ultimately allow the clinical validation and then the clinical use of some of these biomarkers. Some of the obstacles to the evaluation process have been the lack of the availability of quick and easy-to-develop, easy-to-use, robust, specific and sensitive alternative quantitative methods when immunoaffinity-based tests are unavailable. Multiple reaction monitoring (MRM; also called selected reaction monitoring) is currently proving its capabilities as a complementary or alternative technique to ELISA for large biomarker panel evaluation. Here, we present how MRM(3) can overcome the lack of specificity and sensitivity often encountered by MRM when tracking minor proteins diluted by complex biological matrices.

Using Cardiac Biomarkers in Veterinary Practice.

PubMed

Oyama, Mark A

2015-09-01

Blood-based assays for various cardiac biomarkers can assist in the diagnosis of heart disease in dogs and cats. The two most common markers are cardiac troponin-I and N-terminal pro-B-type natriuretic peptide. Biomarker assays can assist in differentiating cardiac from noncardiac causes of respiratory signs and detection of preclinical cardiomyopathy. Increasingly, studies indicate that cardiac biomarker testing can help assess the risk of morbidity and mortality in animals with heart disease. Usage of cardiac biomarker testing in clinical practice relies on proper patient selection, correct interpretation of test results, and incorporation of biomarker testing into existing diagnostic methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Using cardiac biomarkers in veterinary practice.

PubMed

Oyama, Mark A

2013-11-01

Blood-based assays for various cardiac biomarkers can assist in the diagnosis of heart disease in dogs and cats. The two most common markers are cardiac troponin-I and N-terminal pro-B-type natriuretic peptide. Biomarker assays can assist in differentiating cardiac from noncardiac causes of respiratory signs and detection of preclinical cardiomyopathy. Increasingly, studies indicate that cardiac biomarker testing can help assess the risk of morbidity and mortality in animals with heart disease. Usage of cardiac biomarker testing in clinical practice relies on proper patient selection, correct interpretation of test results, and incorporation of biomarker testing into existing diagnostic methods. Copyright © 2013 Elsevier Inc. All rights reserved.

Nematodes Relevance in Soil Quality Management and their Significance as Biomarkers in Aquatic Substrates: Review.

PubMed

Akpheokhai, Leonard I; Oribhabor, Blessing J

2016-01-01

The interaction of man with the ecosystem is a major factor causing environmental pollution and its attendant consequences such as climate change in our world today. Patents relating to nematodes' relevance in soil quality management and their significance as biomarkers in aquatic substrates were reviewed. Nematodes are useful in rapid, easy and inexpensive method for testing the toxicity of substance (e.g. aquatic substrates). This review paper sets out to examine and discuss the issue of soil pollution, functions of nematodes in soil and aquatic substrates as well as bio-indicators in soil health management in terrestrial ecology. The information used were on the basis of secondary sources from previous research. It is abundantly clear that the population dynamics of plant parasitic or free-living nematodes have useful potentials as biomonitor for soil health and other forms of environmental contamination through agricultural activities, industrial pollution and oil spillage, and the analysis of nematode community structure could be used as complementary information obtained from conventional soil testing approaches.

Biomarker discovery and development in pediatric critical care medicine

PubMed Central

Kaplan, Jennifer M.; Wong, Hector R.

2010-01-01

Objective To frame the general process of biomarker discovery and development, and to describe a proposal for the development of a multi-biomarker based risk model for pediatric septic shock. Data Source Narrative literature review and author generated data. Main Results Biomarkers can be grouped into four broad classes, based on the intended function: diagnostic, monitoring, surrogate, and stratification. Biomarker discovery and development requires a rigorous process, which is frequently not well followed in the critical care medicine literature. Very few biomarkers have successfully transitioned from the candidate stage to the true biomarker stage. There is great interest in developing diagnostic and stratification biomarkers for sepsis. Procalcitonin is currently the most promising diagnostic biomarker for sepsis. Recent evidence suggests that interleukin-8 can be used to stratify children with septic shock having a high likelihood of survival with standard care. Currently, there is a multi-institutional effort to develop a multi-biomarker based sepsis risk model intended to predict outcome and illness severity for individual children with septic shock. Conclusions Biomarker discovery and development is an important portion of the pediatric critical care medicine translational research agenda. This effort will require collaboration across multiple institutions and investigators. Rigorous conduct of biomarker-focused research holds the promise of transforming our ability to care for individual patients and our ability to conduct clinical trials in a more effective manner. PMID:20473243

Combining large number of weak biomarkers based on AUC

PubMed Central

Yan, Li; Tian, Lili; Liu, Song

2018-01-01

Combining multiple biomarkers to improve diagnosis and/or prognosis accuracy is a common practice in clinical medicine. Both parametric and non-parametric methods have been developed for finding the optimal linear combination of biomarkers to maximize the area under the receiver operating characteristic curve (AUC), primarily focusing on the setting with a small number of well-defined biomarkers. This problem becomes more challenging when the number of observations is not order of magnitude greater than the number of variables, especially when the involved biomarkers are relatively weak. Such settings are not uncommon in certain applied fields. The first aim of this paper is to empirically evaluate the performance of existing linear combination methods under such settings. The second aim is to propose a new combination method, namely, the pairwise approach, to maximize AUC. Our simulation studies demonstrated that the performance of several existing methods can become unsatisfactory as the number of markers becomes large, while the newly proposed pairwise method performs reasonably well. Furthermore, we apply all the combination methods to real datasets used for the development and validation of MammaPrint. The implication of our study for the design of optimal linear combination methods is discussed. PMID:26227901

Lung cancer signature biomarkers: tissue specific semantic similarity based clustering of digital differential display (DDD) data.

PubMed

Srivastava, Mousami; Khurana, Pankaj; Sugadev, Ragumani

2012-11-02

The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs) in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD) rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used 'Gene Ontology semantic similarity score' to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal) and disease (cancer) sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95) identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1-4). Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1), chemotherapy/drug resistance biomarkers (panel 2), hypoxia regulated biomarkers (panel 3) and lung extra cellular matrix biomarkers (panel 4). Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3), HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1/SAG, AIB1 and AZIN1) are significantly down regulated

Biological Networks for Cancer Candidate Biomarkers Discovery

PubMed Central

Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

2016-01-01

Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field. PMID:27625573

Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy.

PubMed

Li, Mengjiao; Li, Haoran; Liu, Fei; Bi, Rui; Tu, Xiaoyu; Chen, Lihua; Ye, Shuang; Cheng, Xi

2017-02-10

It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC). Seven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored. The expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar

Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder.

PubMed

Uddin, L Q; Dajani, D R; Voorhies, W; Bednarz, H; Kana, R K

2017-08-22

Children with neurodevelopmental disorders benefit most from early interventions and treatments. The development and validation of brain-based biomarkers to aid in objective diagnosis can facilitate this important clinical aim. The objective of this review is to provide an overview of current progress in the use of neuroimaging to identify brain-based biomarkers for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), two prevalent neurodevelopmental disorders. We summarize empirical work that has laid the foundation for using neuroimaging to objectively quantify brain structure and function in ways that are beginning to be used in biomarker development, noting limitations of the data currently available. The most successful machine learning methods that have been developed and applied to date are discussed. Overall, there is increasing evidence that specific features (for example, functional connectivity, gray matter volume) of brain regions comprising the salience and default mode networks can be used to discriminate ASD from typical development. Brain regions contributing to successful discrimination of ADHD from typical development appear to be more widespread, however there is initial evidence that features derived from frontal and cerebellar regions are most informative for classification. The identification of brain-based biomarkers for ASD and ADHD could potentially assist in objective diagnosis, monitoring of treatment response and prediction of outcomes for children with these neurodevelopmental disorders. At present, however, the field has yet to identify reliable and reproducible biomarkers for these disorders, and must address issues related to clinical heterogeneity, methodological standardization and cross-site validation before further progress can be achieved.

Using tobacco plants as biomonitors of contaminated norm areas.

PubMed

Máté, B; Horváth, M; Somlai, J; Kovács, T

2013-03-01

One of the largest biomonitoring tasks is the assessing and environment monitoring of radiological wastes produced by mining. Po-210 and Pb-210 are easy to mobilise even in a weak acidic medium and as we know the biological behaviour and accumulation capacity of tobacco, this could be a suitable option for biomonitoring. During our work the Pb-210 and Po-210 concentration values of tobacco parts and soil samples originating from a Hungarian remediated uranium mine site were determined. The source preparation was spontaneous deposition following combined acidic leaching with a Po-209 tracer; the detection was carried out with a semiconductor ('PIPS') detector alpha-spectrometer. According to the results for the tobacco plant parts and soil samples, secular equilibrium could be found between the Pb-210 and Po-210 isotopes, and the isotope content of the lower leaves of the tobacco plants was in correlation with the isotope concentration of the soil; therefore, the measurement of the activity concentration is suitable for tracing smaller levels of washing out. The Po-210 activity concentration values of tobacco (average: 15.5 ± 3.6 Bq kg(-1)) and soil (average: 60.1 ± 15.2 Bq kg(-1)) samples originating from the area investigated compared with samples from another part of Hungary, Balatonalmádi (tobacco: 12.5 ± 1.0 Bq kg(-1), soil: 57.0 ± 4.7 Bq kg(-1)), do not show significant radionuclide migration.

Satellite-based Tropical Cyclone Monitoring Capabilities

NASA Astrophysics Data System (ADS)

Hawkins, J.; Richardson, K.; Surratt, M.; Yang, S.; Lee, T. F.; Sampson, C. R.; Solbrig, J.; Kuciauskas, A. P.; Miller, S. D.; Kent, J.

2012-12-01

Satellite remote sensing capabilities to monitor tropical cyclone (TC) location, structure, and intensity have evolved by utilizing a combination of operational and research and development (R&D) sensors. The microwave imagers from the operational Defense Meteorological Satellite Program [Special Sensor Microwave/Imager (SSM/I) and the Special Sensor Microwave Imager Sounder (SSMIS)] form the "base" for structure observations due to their ability to view through upper-level clouds, modest size swaths and ability to capture most storm structure features. The NASA TRMM microwave imager and precipitation radar continue their 15+ yearlong missions in serving the TC warning and research communities. The cessation of NASA's QuikSCAT satellite after more than a decade of service is sorely missed, but India's OceanSat-2 scatterometer is now providing crucial ocean surface wind vectors in addition to the Navy's WindSat ocean surface wind vector retrievals. Another Advanced Scatterometer (ASCAT) onboard EUMETSAT's MetOp-2 satellite is slated for launch soon. Passive microwave imagery has received a much needed boost with the launch of the French/Indian Megha Tropiques imager in September 2011, basically greatly supplementing the very successful NASA TRMM pathfinder with a larger swath and more frequent temporal sampling. While initial data issues have delayed data utilization, current news indicates this data will be available in 2013. Future NASA Global Precipitation Mission (GPM) sensors starting in 2014 will provide enhanced capabilities. Also, the inclusion of the new microwave sounder data from the NPP ATMS (Oct 2011) will assist in mapping TC convective structures. The National Polar orbiting Partnership (NPP) program's VIIRS sensor includes a day night band (DNB) with the capability to view TC cloud structure at night when sufficient lunar illumination exits. Examples highlighting this new capability will be discussed in concert with additional data fusion efforts.

Volumetric CT in lung cancer: an example for the qualification of imaging as a biomarker.

PubMed

Buckler, Andrew J; Mozley, P David; Schwartz, Lawrence; Petrick, Nicholas; McNitt-Gray, Michael; Fenimore, Charles; O'Donnell, Kevin; Hayes, Wendy; Kim, Hyun J; Clarke, Laurence; Sullivan, Daniel

2010-01-01

New ways to understand biology as well as increasing interest in personalized treatments requires new capabilities for the assessment of therapy response. The lack of consensus methods and qualification evidence needed for large-scale multicenter trials, and in turn the standardization that allows them, are widely acknowledged to be the limiting factor in the deployment of qualified imaging biomarkers. The Quantitative Imaging Biomarker Alliance is organized to establish a methodology whereby multiple stakeholders collaborate. It has charged the Volumetric Computed Tomography (CT) Technical Subcommittee with investigating the technical feasibility and clinical value of quantifying changes over time in either volume or other parameters as biomarkers. The group selected solid tumors of the chest in subjects with lung cancer as its first case in point. Success is defined as sufficiently rigorous improvements in CT-based outcome measures to allow individual patients in clinical settings to switch treatments sooner if they are no longer responding to their current regimens, and reduce the costs of evaluating investigational new drugs to treat lung cancer. The team has completed a systems engineering analysis, has begun a roadmap of experimental groundwork, documented profile claims and protocols, and documented a process for imaging biomarker qualification as a general paradigm for qualifying other imaging biomarkers as well. This report addresses a procedural template for the qualification of quantitative imaging biomarkers. This mechanism is cost-effective for stakeholders while simultaneously advancing the public health by promoting the use of measures that prove effective.

Development of a Multiplexed Liquid Chromatography Multiple-Reaction-Monitoring Mass Spectrometry (LC-MRM/MS) Method for Evaluation of Salivary Proteins as Oral Cancer Biomarkers.

PubMed

Chen, Yi-Ting; Chen, Hsiao-Wei; Wu, Chun-Feng; Chu, Lichieh Julie; Chiang, Wei-Fang; Wu, Chih-Ching; Yu, Jau-Song; Tsai, Cheng-Han; Liang, Kung-Hao; Chang, Yu-Sun; Wu, Maureen; Ou Yang, Wei-Ting

2017-05-01

Multiple (selected) reaction monitoring (MRM/SRM) of peptides is a growing technology for target protein quantification because it is more robust, precise, accurate, high-throughput, and multiplex-capable than antibody-based techniques. The technique has been applied clinically to the large-scale quantification of multiple target proteins in different types of fluids. However, previous MRM-based studies have placed less focus on sample-preparation workflow and analytical performance in the precise quantification of proteins in saliva, a noninvasively sampled body fluid. In this study, we evaluated the analytical performance of a simple and robust multiple reaction monitoring (MRM)-based targeted proteomics approach incorporating liquid chromatography with mass spectrometry detection (LC-MRM/MS). This platform was used to quantitatively assess the biomarker potential of a group of 56 salivary proteins that have previously been associated with human cancers. To further enhance the development of this technology for assay of salivary samples, we optimized the workflow for salivary protein digestion and evaluated quantification performance, robustness and technical limitations in analyzing clinical samples. Using a clinically well-characterized cohort of two independent clinical sample sets (total n = 119), we quantitatively characterized these protein biomarker candidates in saliva specimens from controls and oral squamous cell carcinoma (OSCC) patients. The results clearly showed a significant elevation of most targeted proteins in saliva samples from OSCC patients compared with controls. Overall, this platform was capable of assaying the most highly multiplexed panel of salivary protein biomarkers, highlighting the clinical utility of MRM in oral cancer biomarker research. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Development of a Multiplexed Liquid Chromatography Multiple-Reaction-Monitoring Mass Spectrometry (LC-MRM/MS) Method for Evaluation of Salivary Proteins as Oral Cancer Biomarkers*

PubMed Central

Chen, Hsiao-Wei; Wu, Chun-Feng; Chu, Lichieh Julie; Chiang, Wei-Fang; Wu, Chih-Ching; Yu, Jau-Song; Tsai, Cheng-Han; Liang, Kung-Hao; Chang, Yu-Sun; Wu, Maureen; Ou Yang, Wei-Ting

2017-01-01

Multiple (selected) reaction monitoring (MRM/SRM) of peptides is a growing technology for target protein quantification because it is more robust, precise, accurate, high-throughput, and multiplex-capable than antibody-based techniques. The technique has been applied clinically to the large-scale quantification of multiple target proteins in different types of fluids. However, previous MRM-based studies have placed less focus on sample-preparation workflow and analytical performance in the precise quantification of proteins in saliva, a noninvasively sampled body fluid. In this study, we evaluated the analytical performance of a simple and robust multiple reaction monitoring (MRM)-based targeted proteomics approach incorporating liquid chromatography with mass spectrometry detection (LC-MRM/MS). This platform was used to quantitatively assess the biomarker potential of a group of 56 salivary proteins that have previously been associated with human cancers. To further enhance the development of this technology for assay of salivary samples, we optimized the workflow for salivary protein digestion and evaluated quantification performance, robustness and technical limitations in analyzing clinical samples. Using a clinically well-characterized cohort of two independent clinical sample sets (total n = 119), we quantitatively characterized these protein biomarker candidates in saliva specimens from controls and oral squamous cell carcinoma (OSCC) patients. The results clearly showed a significant elevation of most targeted proteins in saliva samples from OSCC patients compared with controls. Overall, this platform was capable of assaying the most highly multiplexed panel of salivary protein biomarkers, highlighting the clinical utility of MRM in oral cancer biomarker research. PMID:28235782

Urban soil biomonitoring by beetle and earthworm populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janossy, L.; Bitto, A.

1995-12-31

Two macro invertebrate groups were chosen for biomonitoring environmental changes. The beetle population was pitfall trapped (five month in 1994) at five downtown sites (parks) of Budapest and in a hilly original woodland as a control site 33km NW of Budapest. Earthworms were collected by using formol solution. Five heavy metals were measured (Pb, Co, Hg, Zn, Cu) in the upper soil layer at the same sampling sites. Pb, Hg, Zn and Cu was over the tolerable limit in a park near the railway, extreme high Pb (530 mg/kg dry soil) and Zn content was measured in one park. Roadsmore » are also salted in wintertime. The number of beetle species in the downtown parks varied 10 to 22 (226--462 specimen). Near to the edge of the city up to 45 beetle species were found in a park with 1,027 specimen. In the woodland area 52 beetle species with 1,061 specimen were found. Less dominance and higher specific diversity showed the direction from downtown to woodland. Only 2 or 3 cosmopolitan earthworm species existed in downtown parks with 30--35 specimen/m{sup 2}, in the control woodland area 7 mostly endemic earthworm species were found with 74 specimens/m{sup 2}. But earthworm biomass was higher in three well fertilized parks (43--157 g/m{sup 2}), than in the original woodland (25-g/m{sup 2}). The beetle populations seem to be good tools for biomonitoring. Earthworms are susceptible to environmental changes but they also strongly depend on the leaf litter and the organic matter of the soil. The change in the animal populations is the result of summarized environmental impacts in such a big city like Budapest.« less

Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease.

PubMed

Lindholm, Daniel; Lindbäck, Johan; Armstrong, Paul W; Budaj, Andrzej; Cannon, Christopher P; Granger, Christopher B; Hagström, Emil; Held, Claes; Koenig, Wolfgang; Östlund, Ollie; Stewart, Ralph A H; Soffer, Joseph; White, Harvey D; de Winter, Robbert J; Steg, Philippe Gabriel; Siegbahn, Agneta; Kleber, Marcus E; Dressel, Alexander; Grammer, Tanja B; März, Winfried; Wallentin, Lars

2017-08-15

Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD). This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD. In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study. During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This "ABC-CHD" model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts. This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

Predictive Biomarkers for Linking Disease Pathology and Drug Effect.

PubMed

Mayer, Bernd; Heinzel, Andreas; Lukas, Arno; Perco, Paul

2017-01-01

Productivity in drug R&D continues seeing significant attrition in clinical stage testing. Approval of new molecular entities proceeds with slow pace specifically when it comes to chronic, age-related diseases, calling for new conceptual approaches, methodological implementation and organizational adoption in drug development. Detailed phenotyping of disease presentation together with comprehensive representation of drug mechanism of action is considered as a path forward, and a big data spectrum has become available covering behavioral, clinical and molecular characteristics, the latter combining reductionist and explorative strategies. On this basis integrative analytics in the realm of Systems Biology has emerged, essentially aiming at traversing associations into causal relationships for bridging molecular disease specifics and clinical phenotype surrogates and finally explaining drug response and outcome. From a conceptual perspective bottom-up modeling approaches are available, with dynamical hierarchies as formalism capable of describing clinical findings as emergent properties of an underlying molecular process network comprehensively resembling disease pathology. In such representation biomarker candidates serve as proxy of a molecular process set, at the interface of a corresponding representation of drug mechanism of action allowing patient stratification and prediction of drug response. In practical implementation network analytics on a protein coding gene level has provided a number of example cases for matching disease presentation and drug molecular effect, and workflows combining computational hypothesis generation and experimental evaluation have become available for systematically optimizing biomarker candidate selection. With biomarker-based enrichment strategies in adaptive clinical trials, implementation routes for tackling development attrition are provided. Predictive biomarkers add precision in drug development and as companion diagnostics

Combining select neuropsychological assessment with blood-based biomarkers to detect mild Alzheimer's disease: a molecular neuropsychology approach.

PubMed

Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O'Bryant, Sid

2014-01-01

Current work has sought to establish a rapid and cost effective means of screening for Alzheimer's disease (AD) with the most recent findings showing utility of integrating blood-based biomarkers with cognitive measures. The current project sought to create a combined biomarker-cognitive profile to detect mild AD. Data was analyzed from 266 participants (129 AD cases [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas Alzheimer's Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochemiluminescence. Logistic Regression was utilized to detect early AD using two serum biomarkers (TNFα and IL7), demographic information (age), and one neuropsychological measure (Clock 4-point) as predictor variable. Disease severity was determined via Clinical Dementia Rating (CDR) scale global scores. In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5-1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall accuracy of 0.91. The combination of demographics, two biomarkers, and one cognitive test created a biomarker-cognitive profile that was highly accurate in detecting the presence of AD, even in the very early stages.

Active moss biomonitoring of trace elements with Sphagnum girgensohnii moss bags in relation to atmospheric bulk deposition in Belgrade, Serbia.

PubMed

Anicić, M; Tasić, M; Frontasyeva, M V; Tomasević, M; Rajsić, S; Mijić, Z; Popović, A

2009-02-01

Active biomonitoring with wet and dry moss bags was used to examine trace element atmospheric deposition in the urban area of Belgrade. The element accumulation capability of Sphagnum girgensohnii Russow was tested in relation to atmospheric bulk deposition. Moss bags were mounted for five 3-month periods (July 2005-October 2006) at three representative urban sites. For the same period monthly bulk atmospheric deposition samples were collected. The concentrations of Al, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, and Pb were determined by instrumental neutron activation analyses and atomic absorption spectrometry. Significant accumulation of most elements occurred in the exposed moss bags compared with the initial moss content. High correlations between the elements in moss and bulk deposits were found for V, Cu, As, and Ni. The enrichment factors of the elements for both types of monitor followed the same pattern at the corresponding sites.

Can nail, hair and urine be used for biomonitoring of human exposure to perfluorooctane sulfonate and perfluorooctanoic acid?

PubMed

Li, Jingguang; Guo, Feifei; Wang, Yuxin; Zhang, Jialing; Zhong, Yuxin; Zhao, Yunfeng; Wu, Yongning

2013-03-01

Because of the disadvantages of invasive sampling, it is desirable to explore non-invasive matrices for human biomonitoring of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). The aim of this study was to evaluate the application of nail, hair and urine for human biomonitoring of PFOS and PFOA. The concentrations of PFOS and PFOA in matched nail, hair, urine and serum samples collected from 64 donors were measured. The chemicals of interest were detected with high detection frequency in these matrices (90%-100%) except for PFOA in urine samples (56%). Generally, the gender influences on the levels of PFOS and PFOA in these non-invasive matrices were in agreement with that in serum. For PFOS, the coefficients of Spearman correlation between serum samples and nail, hair and urine samples were 0.786 (p<0.001), 0.545 (p<0.001) and 0.302 (p<0.05), respectively. For PFOA, the correlation was only observed between nail samples and serum samples with a correlation coefficient of 0.299 (p<0.05). The results suggested that nail has more potential than hair and urine to be applied in human biomonitoring for PFOS and PFOA in general populations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Combining large number of weak biomarkers based on AUC.

PubMed

Yan, Li; Tian, Lili; Liu, Song

2015-12-20

Combining multiple biomarkers to improve diagnosis and/or prognosis accuracy is a common practice in clinical medicine. Both parametric and non-parametric methods have been developed for finding the optimal linear combination of biomarkers to maximize the area under the receiver operating characteristic curve (AUC), primarily focusing on the setting with a small number of well-defined biomarkers. This problem becomes more challenging when the number of observations is not order of magnitude greater than the number of variables, especially when the involved biomarkers are relatively weak. Such settings are not uncommon in certain applied fields. The first aim of this paper is to empirically evaluate the performance of existing linear combination methods under such settings. The second aim is to propose a new combination method, namely, the pairwise approach, to maximize AUC. Our simulation studies demonstrated that the performance of several existing methods can become unsatisfactory as the number of markers becomes large, while the newly proposed pairwise method performs reasonably well. Furthermore, we apply all the combination methods to real datasets used for the development and validation of MammaPrint. The implication of our study for the design of optimal linear combination methods is discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Genetic Variants Influencing Biomarkers of Nutrition Are Not Associated with Cognitive Capability in Middle-Aged and Older Adults123

PubMed Central

Alfred, Tamuno; Ben-Shlomo, Yoav; Cooper, Rachel; Hardy, Rebecca; Deary, Ian J.; Elliott, Jane; Harris, Sarah E.; Hyppönen, Elina; Kivimaki, Mika; Kumari, Meena; Maddock, Jane; Power, Chris; Starr, John M.; Kuh, Diana; Day, Ian N.M.

2013-01-01

Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on Z-score for carriers vs. noncarriers: −0.05 (95% CI: −0.09, −0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D–raising allele of rs2282679 [pooled β per T allele: −0.03 (95% CI: −0.05, −0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality. PMID:23468552

Theranostic Biomarkers for Schizophrenia

PubMed Central

Nikolac Perkovic, Matea; Nedic Erjavec, Gordana; Svob Strac, Dubravka; Uzun, Suzana; Kozumplik, Oliver; Pivac, Nela

2017-01-01

Schizophrenia is a highly heritable, chronic, severe, disabling neurodevelopmental brain disorder with a heterogeneous genetic and neurobiological background, which is still poorly understood. To allow better diagnostic procedures and therapeutic strategies in schizophrenia patients, use of easy accessible biomarkers is suggested. The most frequently used biomarkers in schizophrenia are those associated with the neuroimmune and neuroendocrine system, metabolism, different neurotransmitter systems and neurotrophic factors. However, there are still no validated and reliable biomarkers in clinical use for schizophrenia. This review will address potential biomarkers in schizophrenia. It will discuss biomarkers in schizophrenia and propose the use of specific blood-based panels that will include a set of markers associated with immune processes, metabolic disorders, and neuroendocrine/neurotrophin/neurotransmitter alterations. The combination of different markers, or complex multi-marker panels, might help in the discrimination of patients with different underlying pathologies and in the better classification of the more homogenous groups. Therefore, the development of the diagnostic, prognostic and theranostic biomarkers is an urgent and an unmet need in psychiatry, with the aim of improving diagnosis, therapy monitoring, prediction of treatment outcome and focus on the personal medicine approach in order to improve the quality of life in patients with schizophrenia and decrease health costs worldwide. PMID:28358316

Biomarkers in cancer screening: a public health perspective.

PubMed

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

Comparison of Physician-, Biomarker-, and Symptom-Based Strategies for Adjustment of Inhaled Corticosteroid Therapy in Adults With Asthma

PubMed Central

Calhoun, William J.; Ameredes, Bill T.; King, Tonya S.; Icitovic, Nikolina; Bleecker, Eugene R.; Castro, Mario; Cherniack, Reuben M.; Chinchilli, Vernon M.; Craig, Timothy; Denlinger, Loren; DiMango, Emily A.; Engle, Linda L.; Fahy, John V.; Grant, J. Andrew; Israel, Elliot; Jarjour, Nizar; Kazani, Shamsah D.; Kraft, Monica; Kunselman, Susan J.; Lazarus, Stephen C.; Lemanske, Robert F.; Lugogo, Njira; Martin, Richard J.; Meyers, Deborah A.; Moore, Wendy C.; Pascual, Rodolfo; Peters, Stephen P.; Ramsdell, Joe; Sorkness, Christine A.; Sutherland, E. Rand; Szefler, Stanley J.; Wasserman, Stephen I.; Walter, Michael J.; Wechsler, Michael E.; Boushey, Homer A.

2013-01-01

Context No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms. Objective To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessment–based adjustment in preventing treatment failure in adults with mild to moderate asthma. Design, Setting, and Participants A randomized, parallel, 3-group, placebo-controlled, multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy (n=114 assigned to physician assessment–based adjustment [101 completed], n=115 to biomarker-based [exhaled nitric oxide] adjustment [92 completed], and n=113 to symptom-based adjustment [97 completed]), the Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010. Interventions For physician assessment–based adjustment and biomarker-based (exhaled nitric oxide) adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for symptom-based adjustment, inhaled corticosteroids were taken with each albuterol rescue use. Main Outcome Measure The primary outcome was time to treatment failure. Results There were no significant differences in time to treatment failure. The 9-month Kaplan-Meier failure rates were 22% (97.5% CI, 14%-33%; 24 events) for physician assessment–based adjustment, 20% (97.5% CI, 13%-30%; 21 events) for biomarker-based adjustment, and 15% (97.5% CI, 9%-25%; 16 events) for symptom-based adjustment. The hazard ratio for physician assessment–based adjustment vs biomarker-based

BIOMONITORING: INTERPRETATION AND USES

EPA Science Inventory

With advanced technologies, it is now possible to measure very low levels of many chemicals in biological fluids. However, the appropriate use and interpretation of biomarkers will depend upon many factors associated with the exposure, adsorption, deposition, metabolism, and eli...

Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery.

PubMed

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R; Nestle, Frank O

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases.

Integration of Lyoplate Based Flow Cytometry and Computational Analysis for Standardized Immunological Biomarker Discovery

PubMed Central

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A. Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R.; Nestle, Frank O.

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases. PMID:23843942

Targeted gene enrichment and high-throughput sequencing for environmental biomonitoring: a case study using freshwater macroinvertebrates.

PubMed

Dowle, Eddy J; Pochon, Xavier; C Banks, Jonathan; Shearer, Karen; Wood, Susanna A

2016-09-01

Recent studies have advocated biomonitoring using DNA techniques. In this study, two high-throughput sequencing (HTS)-based methods were evaluated: amplicon metabarcoding of the cytochrome C oxidase subunit I (COI) mitochondrial gene and gene enrichment using MYbaits (targeting nine different genes including COI). The gene-enrichment method does not require PCR amplification and thus avoids biases associated with universal primers. Macroinvertebrate samples were collected from 12 New Zealand rivers. Macroinvertebrates were morphologically identified and enumerated, and their biomass determined. DNA was extracted from all macroinvertebrate samples and HTS undertaken using the illumina miseq platform. Macroinvertebrate communities were characterized from sequence data using either six genes (three of the original nine were not used) or just the COI gene in isolation. The gene-enrichment method (all genes) detected the highest number of taxa and obtained the strongest Spearman rank correlations between the number of sequence reads, abundance and biomass in 67% of the samples. Median detection rates across rare (<1% of the total abundance or biomass), moderately abundant (1-5%) and highly abundant (>5%) taxa were highest using the gene-enrichment method (all genes). Our data indicated primer biases occurred during amplicon metabarcoding with greater than 80% of sequence reads originating from one taxon in several samples. The accuracy and sensitivity of both HTS methods would be improved with more comprehensive reference sequence databases. The data from this study illustrate the challenges of using PCR amplification-based methods for biomonitoring and highlight the potential benefits of using approaches, such as gene enrichment, which circumvent the need for an initial PCR step. © 2015 John Wiley & Sons Ltd.

Evaluating a 5-year metal contamination remediation and the biomonitoring potential of a freshwater gastropod along the Xiangjiang River, China.

PubMed

Li, Deliang; Pi, Jie; Zhang, Ting; Tan, Xiang; Fraser, Dylan J

2018-05-16

Effective remediation of heavy metal pollution in aquatic systems is desired in many regions, but it requires integrative assessments of sediments, water, and biota that can serve as robust biomonitors. We assessed the effects of a 5-year metal contamination remediation along the Xiangjiang River, China, by comparing concentrations of trace metals in water and surface sediments between 2010-2011 and 2016. We also explored the trace metal biomonitoring potential of a freshwater gastropod (Bellamya aeruginosa). Metal concentrations in water (means and ranges) dropped over time to within permissible limits of drinking water guidelines set by China, USEPA, and WHO in 2016. Although sediment means and ranges of Cd, Pb, Zn, and Mn also diminished with remediation, those for Cr and Cu slightly increased, and all six metals retained concentrations higher than standards set by China. All metals in sediments could also be associated with anthropogenic inputs using a hierarchical clustering analysis, and they generate high potential ecological risks based on several indices, especially for Cd and As. The bio-sediment accumulation factors of all measured trace metals in gastropod soft tissues and shells were lower than 1.0, except for Ca. Trace metal contents in gastropods were positively correlated with those in water and surface sediments for As (soft tissues) and Cr (shells). Collectively, our results do not yet highlight strong beneficial effects of 5-year remediation and clearly illustrate the heavy metal pollution remaining in Xiangjiang River sediment. Additional physical, chemical, and biological measurements should be implemented to improve sediment quality. We further conclude that gastropod soft tissues and shells can be suitable biomonitors of spatial differences in some heavy metals found within river sediments (e.g., As, Cr).

Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial.

PubMed

Rouzé, Anahita; Loridant, Séverine; Poissy, Julien; Dervaux, Benoit; Sendid, Boualem; Cornu, Marjorie; Nseir, Saad

2017-11-01

The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment. Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β-D-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14 days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7. A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.001, OR (95% CI) 62.6 (8.1-486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4-13) vs 13 (12-14) days, p < 0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups. The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy. This trial was registered at Clinical

Low cadmium exposure in males and lactating females–estimation of biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stajnko, Anja

Background: Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot samples, are well established biomarkers of occupational exposure. Their use and associations at low environmental level are common, but have recently been questioned, particularly in terms of physiological variability and normalisation bias in the case of urine spot samples. Aim: To determine the appropriateness of spot urine and/or blood Cd exposure biomarkers and their relationships with renal function biomarkers at low levels of exposure. To this end, we used data from Slovenian human biomonitoring program involving 1081 Slovenians (548 males, mean age 31 years; 533 lactating females,more » mean age 29 years; 2007–2015) who have not been exposed to Cd occupationally. Results: Geometric means (GMs) of Cd in blood and spot urine samples were 0.27 ng/mL (0.28 for males and 0.33 for females) and 0.19 ng/mL (0.21 for males and 0.17 for females), respectively. Differing results were obtained when contrasting normalisation by urine creatinine with specific gravity. GMs of urine albumin (Alb), alpha-1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG), and immunoglobulin G (IgG) were far below their upper reference limits. Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses with unnormalised data were taken as more valid. Relatively weak positive associations were observed between urine Cd (ng/mL) and blood Cd (β=0.11, p=0.002 for males and β=0.33, p<0.001 for females) and for females between urine NAG and blood Cd (β=0.14, p=0.04). No associations were found between other renal function biomarkers and blood Cd. Associations between Cd and renal function biomarkers in urine were stronger (p<0.05, β=0.11–0.63). Mostly, all of the associations stayed significant but weakened after normalisation for diuresis. In the case of A1M, its associations with Cd were influenced

Development of a Vision-Based Situational Awareness Capability for Unmanned Surface Vessels

DTIC Science & Technology

2017-09-01

used to provide an SA capability for USVs. This thesis addresses the following research questions: (1) Can a computer vision– based technique be...BLANK 51 VI. CONCLUSION AND RECOMMENDATIONS A. CONCLUSION This research demonstrated the feasibility of using a computer vision– based ...VISION- BASED SITUATIONAL AWARENESS CAPABILITY FOR UNMANNED SURFACE VESSELS by Ying Jie Benjemin Toh September 2017 Thesis Advisor: Oleg

Quantifying the tracking capability of space-based AIS systems

NASA Astrophysics Data System (ADS)

Skauen, Andreas Nordmo

2016-01-01

The Norwegian Defence Research Establishment (FFI) has operated three Automatic Identification System (AIS) receivers in space. Two are on dedicated nano-satellites, AISSat-1 and AISSat-2. The third, the NORAIS Receiver, was installed on the International Space Station. A general method for calculating the upper bound on the tracking capability of a space-based AIS system has been developed and the results from the algorithm applied to AISSat-1 and the NORAIS Receiver individually. In addition, a constellation of AISSat-1 and AISSat-2 is presented. The tracking capability is defined as the probability of re-detecting ships as they move around the globe and is explained to represent and upper bound on a space-based AIS system performance. AISSat-1 and AISSat-2 operates on the nominal AIS1 and AIS2 channels, while the NORAIS Receiver data used are from operations on the dedicated space AIS channels, AIS3 and AIS4. The improved tracking capability of operations on the space AIS channels is presented.

Development of Transcriptomics-based Biomarkers for Selected Endocrine Disrupting Chemicals in Zebrafish (Danio rerio)

EPA Science Inventory

Genome-wide transcriptional profiling by microarrays provides a powerful platform for gene expression-based biomarker discovery. After their wide acceptance in human disease diagnosis, prognosis, and drug discovery, these gene signatures are increasingly being adopted for environ...

Development of transcriptomics-based biomarkers for selected endocrine disrupting chemicals in zebrafish (Danio rerio)

EPA Science Inventory

Genome-wide transcriptional profiling by microarrays provides a powerful platform for gene expression-based biomarker discovery. After their wide acceptance in human disease diagnosis, prognosis, and drug discovery, these gene signatures are increasingly being adopted for environ...

Continuous Metabolic Monitoring Based on Multi-Analyte Biomarkers to Predict Exhaustion

PubMed Central

Kastellorizios, Michail; Burgess, Diane J.

2015-01-01

This work introduces the concept of multi-analyte biomarkers for continuous metabolic monitoring. The importance of using more than one marker lies in the ability to obtain a holistic understanding of the metabolism. This is showcased for the detection and prediction of exhaustion during intense physical exercise. The findings presented here indicate that when glucose and lactate changes over time are combined into multi-analyte biomarkers, their monitoring trends are more sensitive in the subcutaneous tissue, an implantation-friendly peripheral tissue, compared to the blood. This unexpected observation was confirmed in normal as well as type 1 diabetic rats. This study was designed to be of direct value to continuous monitoring biosensor research, where single analytes are typically monitored. These findings can be implemented in new multi-analyte continuous monitoring technologies for more accurate insulin dosing, as well as for exhaustion prediction studies based on objective data rather than the subject’s perception. PMID:26028477

Continuous metabolic monitoring based on multi-analyte biomarkers to predict exhaustion.

PubMed

Kastellorizios, Michail; Burgess, Diane J

2015-06-01

This work introduces the concept of multi-analyte biomarkers for continuous metabolic monitoring. The importance of using more than one marker lies in the ability to obtain a holistic understanding of the metabolism. This is showcased for the detection and prediction of exhaustion during intense physical exercise. The findings presented here indicate that when glucose and lactate changes over time are combined into multi-analyte biomarkers, their monitoring trends are more sensitive in the subcutaneous tissue, an implantation-friendly peripheral tissue, compared to the blood. This unexpected observation was confirmed in normal as well as type 1 diabetic rats. This study was designed to be of direct value to continuous monitoring biosensor research, where single analytes are typically monitored. These findings can be implemented in new multi-analyte continuous monitoring technologies for more accurate insulin dosing, as well as for exhaustion prediction studies based on objective data rather than the subject's perception.

A Proposal for Assessing Study Quality: Biomonitoring, Environmental Epidemiology, and Short-Lived Chemicals (BEES-C) Instrument

EPA Science Inventory

The quality of exposure assessment is a major determinant of the overall quality of any environmental epidemiology study. The use of biomonitoring as a tool for assessing exposure to ubiquitous chemicals with short physiologic half-lives began relatively recently. These chemicals...

Post-Remediation Biomonitoring of Pesticides in Marine Waters Near the United Heckathorn Site, Richmond, California

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antrim, Liam D.; Kohn, Nancy P.

Marine sediment remediation at the United Heckathorn Superfund Site was completed in April 1997. Water and mussel tissues were sampled in January 1998 from four stations near Lauritzen Canal in Richmond, California, for the first post-remediation monitoring of marine areas near the United Heckathorn Site. Dieldrin and DDT were analyzed in water samples, tissue samples from resident mussels, and tissue samples from transplanted mussels deployed for 4 months. Concentrations of dieldrin and total DDT in water and total DDT in tissue were compared to pre-remediation data available from the California State Mussel Watch program (tissues) and the Ecological Risk Assessmentmore » for the United Heckathorn Superfund Site (tissues and water). Biomonitoring results indicated that pesticides were still bioavailable in the water column, and have not been reduced from pre-remediation levels. Annual biomonitoring will continue to assess the effectiveness of remedial actions at the United Heckathorn Site.« less

Explanation Capabilities for Behavior-Based Robot Control

NASA Technical Reports Server (NTRS)

Huntsberger, Terrance L.

2012-01-01

A recent study that evaluated issues associated with remote interaction with an autonomous vehicle within the framework of grounding found that missing contextual information led to uncertainty in the interpretation of collected data, and so introduced errors into the command logic of the vehicle. As the vehicles became more autonomous through the activation of additional capabilities, more errors were made. This is an inefficient use of the platform, since the behavior of remotely located autonomous vehicles didn't coincide with the "mental models" of human operators. One of the conclusions of the study was that there should be a way for the autonomous vehicles to describe what action they choose and why. Robotic agents with enough self-awareness to dynamically adjust the information conveyed back to the Operations Center based on a detail level component analysis of requests could provide this description capability. One way to accomplish this is to map the behavior base of the robot into a formal mathematical framework called a cost-calculus. A cost-calculus uses composition operators to build up sequences of behaviors that can then be compared to what is observed using well-known inference mechanisms.

Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation.

PubMed

Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna; Iliuk, Anton; Tao, W Andy

2016-11-30

Glycoproteins have vast structural diversity that plays an important role in many biological processes and have great potential as disease biomarkers. Here, we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase glycoprotein array (polyGPA), to capture and profile glycoproteomes specifically, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture preoxidized glycans on glycoproteins from complex protein samples such as biofluids. The captured glycoproteins were subsequently detected using the same validated antibodies as in RPPA. We demonstrated the outstanding specificity, sensitivity, and quantitative capabilities of polyGPA by capturing and detecting purified as well as endogenous α-1-acid glycoprotein (AGP) in human plasma. We further applied quantitative N-glycoproteomics and the strategy to validate a panel of glycoproteins identified as potential biomarkers for bladder cancer by analyzing urine glycoproteins from bladder cancer patients or matched healthy individuals.

Recent advances in simultaneous analysis of bisphenol A and its conjugates in human matrices: Exposure biomarker perspectives.

PubMed

Andra, Syam S; Austin, Christine; Yang, Juan; Patel, Dhavalkumar; Arora, Manish

2016-12-01

Human exposures to bisphenol A (BPA) has attained considerable global health attention and represents one of the leading environmental contaminants with potential adverse health effects including endocrine disruption. Current practice of measuring of exposure to BPA includes the measurement of unconjugated BPA (aglycone) and total (both conjugated and unconjugated) BPA; the difference between the two measurements leads to estimation of conjugated forms. However, the measurement of BPA as the end analyte leads to inaccurate estimates from potential interferences from background sources during sample collection and analysis. BPA glucuronides (BPAG) and sulfates (BPAS) represent better candidates for biomarkers of BPA exposure, since they require in vivo metabolism and are not prone to external contamination. In this work, the primary focus was to review the current state of the art in analytical methods available to quantitate BPA conjugates. The entire analytical procedure for the simultaneous extraction and detection of aglycone BPA and conjugates is covered, from sample pre-treatment, extraction, separation, ionization, and detection. Solid phase extraction coupled with liquid chromatograph and tandem mass spectrometer analysis provides the most sensitive detection and quantification of BPA conjugates. Discussed herein are the applications of BPA conjugates analysis in human exposure assessment studies. Measuring these potential biomarkers of BPA exposure has only recently become analytically feasible and there are limitations and challenges to overcome in biomonitoring studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Review of 2,4-dichlorophenoxyacetic acid (2,4-D) biomonitoring and epidemiology.

PubMed

Burns, Carol J; Swaen, Gerard M H

2012-10-01

A qualitative review of the epidemiological literature on the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and health after 2001 is presented. In order to compare the exposure of the general population, bystanders and occupational groups, their urinary levels were also reviewed. In the general population, 2,4-D exposure is at or near the level of detection (LOD). Among individuals with indirect exposure, i.e. bystanders, the urinary 2,4-D levels were also very low except in individuals with opportunity for direct contact with the herbicide. Occupational exposure, where exposure was highest, was positively correlated with behaviors related to the mixing, loading and applying process and use of personal protection. Information from biomonitoring studies increases our understanding of the validity of the exposure estimates used in epidemiology studies. The 2,4-D epidemiology literature after 2001 is broad and includes studies of cancer, reproductive toxicity, genotoxicity, and neurotoxicity. In general, a few publications have reported statistically significant associations. However, most lack precision and the results are not replicated in other independent studies. In the context of biomonitoring, the epidemiology data give no convincing or consistent evidence for any chronic adverse effect of 2,4-D in humans.

Review of 2,4-dichlorophenoxyacetic acid (2,4-D) biomonitoring and epidemiology

PubMed Central

Burns, Carol J.; Swaen, Gerard M. H.

2012-01-01

A qualitative review of the epidemiological literature on the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and health after 2001 is presented. In order to compare the exposure of the general population, bystanders and occupational groups, their urinary levels were also reviewed. In the general population, 2,4-D exposure is at or near the level of detection (LOD). Among individuals with indirect exposure, i.e. bystanders, the urinary 2,4-D levels were also very low except in individuals with opportunity for direct contact with the herbicide. Occupational exposure, where exposure was highest, was positively correlated with behaviors related to the mixing, loading and applying process and use of personal protection. Information from biomonitoring studies increases our understanding of the validity of the exposure estimates used in epidemiology studies. The 2,4-D epidemiology literature after 2001 is broad and includes studies of cancer, reproductive toxicity, genotoxicity, and neurotoxicity. In general, a few publications have reported statistically significant associations. However, most lack precision and the results are not replicated in other independent studies. In the context of biomonitoring, the epidemiology data give no convincing or consistent evidence for any chronic adverse effect of 2,4-D in humans. PMID:22876750

Using Time-of-Flight Secondary Ion Mass Spectrometry to Study Biomarkers

NASA Astrophysics Data System (ADS)

Thiel, Volker; Sjövall, Peter

2011-05-01

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a technique designed to analyze the composition and spatial distribution of molecules and chemical structures on surfaces. These capabilities have generated much interest in its use in geobiology, in particular for the characterization of organic biomarkers (molecular biosignatures) at the microscopic level. We here discuss the strengths, weaknesses, and potential of ToF-SIMS for biomarker analyses with a focus on applications in geobiology, including biogeochemistry, organic geochemistry, geomicrobiology, and paleobiology. After describing the analytical principles of ToF-SIMS, we discuss issues of biomarker spectral formation and interpretation. Then, key applications of ToF-SIMS to soft (microbial matter, cells), hard (microbial mineral precipitates), and liquid (petroleum) samples relevant in geobiology are reviewed. Finally, we examine the potential of ToF-SIMS in biomarker research and the current limitations and obstacles for which further development would be beneficial to the field.

Metal concentrations in homing pigeon lung tissue as a biomonitor of atmospheric pollution.

PubMed

Cui, Jia; Halbrook, Richard S; Zang, Shuying; Han, Shuang; Li, Xinyu

2018-03-01

Atmospheric pollution in urban areas is a major worldwide concern with potential adverse impacts on wildlife and humans. Biomonitoring can provide direct evidence of the bioavailability and bioaccumulation of toxic metals in the environment that is not available with mechanical air monitoring. The current study continues our evaluation of the usefulness of homing pigeon lung tissue as a biomonitor of atmospheric pollution. Homing pigeons (1-2, 5-6, and 9-10+ year old (yo)) collected from Guangzhou during 2015 were necropsied and concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were measured in lung tissue. Lung Cd and Pb concentrations were significantly greater in 9-10+-year-old pigeons compared with those in other age groups, indicating their bioavailability and bioaccumulation. Lung Pb and Cd concentrations measured in 5-yo pigeons collected from Guangzhou during 2015 were significantly lower than concentrations reported in 5-yo homing pigeons collected from Guangzhou during 2011 and correlated with concentrations measured using mechanical air monitoring. In addition to temporal differences, spatial differences in concentrations of Cd, Pb, and Hg reported in ambient air samples and in pigeon lung tissues collected from Beijing and Guangzhou are discussed.

Feasibility study of feces for noninvasive biomonitoring of brominated flame retardants in toddlers.

PubMed

Sahlström, Leena M O; Sellström, Ulla; de Wit, Cynthia A; Lignell, Sanna; Darnerud, Per Ola

2015-01-06

This study investigated the feasibility of using feces as a noninvasive matrix to estimate serum concentrations of brominated flame retardants (BFRs) in toddlers for biomonitoring purposes. Tri- to decabrominated diphenyl ethers (tri-decaBDEs), isomer-specific hexabromocyclododecanes, and 16 emerging BFRs were determined in feces from 22 toddlers (11-15 months of age), and results were compared to previously analyzed matched serum samples. BDE-47, -153, -196, -197, -203, -206, -207, -208, and -209 were detected in the feces creating a matched data set (feces-serum, n = 21). Tetra-octaBDE concentrations were significantly higher (Student's paired comparisons t test, α = 0.05) in serum versus feces with BDE-153 having the highest mean difference between the sample matrices. BDE-209 was found in significantly higher concentrations in feces compared to serum. Significant correlations (Pearson's, α = 0.05) between congener-specific concentrations in feces and serum were found for all BDEs except BDE-197 and -203. The feces-serum associations found can be used to estimate serum concentrations of tetra-decaBDEs from feces concentrations and enable a noninvasive sampling method for biomonitoring BDEs in toddlers.

Long term plant biomonitoring in the vicinity of waste incinerators in The Netherlands.

PubMed

van Dijk, Chris; van Doorn, Wim; van Alfen, Bert

2015-03-01

Since the mid-nineties new waste incineration plants have come into operation in the Netherlands. Burning of waste can result in the emission of potentially toxic compounds. Although the incineration plants must comply with strict conditions concerning emission control, public concern on the possible impact on human health and the environment still exists. Multiple year (2004-2013) biomonitoring programs were set up around three waste incinerators for early detection of possible effects of stack emissions on the quality of crops and agricultural products. The results showed that the emissions did not affect the quality of crops and cow milk. Concentrations of heavy metals, PAHs and dioxins/PCBs were generally similar to background levels and did not exceed standards for maximum allowable concentrations in foodstuffs (e.g. vegetables and cow milk). Some exceedances of the fluoride standard for cattle feed were found almost every year in the maximum deposition areas of two incinerators. Biomonitoring with leafy vegetables can be used to monitor the real impact of these emissions on agricultural crops and to communicate with all stakeholders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bayesian modeling and inference for diagnostic accuracy and probability of disease based on multiple diagnostic biomarkers with and without a perfect reference standard.

PubMed

Jafarzadeh, S Reza; Johnson, Wesley O; Gardner, Ian A

2016-03-15

The area under the receiver operating characteristic (ROC) curve (AUC) is used as a performance metric for quantitative tests. Although multiple biomarkers may be available for diagnostic or screening purposes, diagnostic accuracy is often assessed individually rather than in combination. In this paper, we consider the interesting problem of combining multiple biomarkers for use in a single diagnostic criterion with the goal of improving the diagnostic accuracy above that of an individual biomarker. The diagnostic criterion created from multiple biomarkers is based on the predictive probability of disease, conditional on given multiple biomarker outcomes. If the computed predictive probability exceeds a specified cutoff, the corresponding subject is allocated as 'diseased'. This defines a standard diagnostic criterion that has its own ROC curve, namely, the combined ROC (cROC). The AUC metric for cROC, namely, the combined AUC (cAUC), is used to compare the predictive criterion based on multiple biomarkers to one based on fewer biomarkers. A multivariate random-effects model is proposed for modeling multiple normally distributed dependent scores. Bayesian methods for estimating ROC curves and corresponding (marginal) AUCs are developed when a perfect reference standard is not available. In addition, cAUCs are computed to compare the accuracy of different combinations of biomarkers for diagnosis. The methods are evaluated using simulations and are applied to data for Johne's disease (paratuberculosis) in cattle. Copyright © 2015 John Wiley & Sons, Ltd.

Biomonitoring Hexamethylene diisocyanate (HDI) exposure based on serum levels of HDI-specific IgG.

PubMed

Wisnewski, Adam V; Stowe, Meredith H; Nerlinger, Abby; Opare-Addo, Paul; Decamp, David; Kleinsmith, Christopher R; Redlich, Carrie A

2012-10-01

Isocyanate chemicals essential for polyurethane production are widely used industrially, and are increasingly found in consumer products. Asthma and other adverse health effects of isocyanates are well-documented and exposure surveillance is crucial to disease prevention. Hexamethylene diisocyanate (HDI)-specific serum immunoglobulin G (IgG) was evaluated as an exposure biomarker among workers at a US Air Force Air Logistics Center, which includes a large aircraft maintenance facility. HDI-specific IgG (HDI-IgG) titers in serum samples (n = 74) were measured using an enzyme-linked immunosorbent assay based upon the biuret form of HDI conjugated to human albumin. Information on personal protective equipment (PPE), work location/tasks, smoking, asthma history, basic demographics, and HDI skin exposure was obtained through questionnaire. HDI-specific serum IgG levels were elevated in n = 17 (23%) of the workers studied. The prevalence and/or end-titer of the HDI-IgG was significantly (P < 0.05) associated with specific job titles, self-reported skin exposure, night-shift work, and respirator use, but not atopy, asthma, or other demographic information. The highest titers were localized to specific worksites (C-130 painting), while other worksites (generator painting) had no or few workers with detectable HDI-IgG. HDI-specific immune responses (IgG) provide a practical biomarker to aid in exposure surveillance and ongoing industrial hygiene efforts. The strategy may supplement current air sampling approaches, which do not assess exposures via skin, or variability in PPE use or effectiveness. The approach may also be applicable to evaluating isocyanate exposures in other settings, and may extend to other chemical allergens.

Biomonitoring Hexamethylene Diisocyanate (HDI) Exposure Based on Serum Levels of HDI-Specific IgG

PubMed Central

Wisnewski, Adam V.; Stowe, Meredith H.; Nerlinger, Abby; Opare-addo, Paul; Decamp, David; Kleinsmith, Christopher R.; Redlich, Carrie A.

2012-01-01

Objectives: Isocyanate chemicals essential for polyurethane production are widely used industrially, and are increasingly found in consumer products. Asthma and other adverse health effects of isocyanates are well-documented and exposure surveillance is crucial to disease prevention. Hexamethylene diisocyanate (HDI)-specific serum immunoglobulin G (IgG) was evaluated as an exposure biomarker among workers at a US Air Force Air Logistics Center, which includes a large aircraft maintenance facility. Methods: HDI-specific IgG (HDI-IgG) titers in serum samples (n = 74) were measured using an enzyme-linked immunosorbent assay based upon the biuret form of HDI conjugated to human albumin. Information on personal protective equipment (PPE), work location/tasks, smoking, asthma history, basic demographics, and HDI skin exposure was obtained through questionnaire. Results: HDI-specific serum IgG levels were elevated in n = 17 (23%) of the workers studied. The prevalence and/or end-titer of the HDI-IgG was significantly (P < 0.05) associated with specific job titles, self-reported skin exposure, night-shift work, and respirator use, but not atopy, asthma, or other demographic information. The highest titers were localized to specific worksites (C-130 painting), while other worksites (generator painting) had no or few workers with detectable HDI-IgG. Conclusions: HDI-specific immune responses (IgG) provide a practical biomarker to aid in exposure surveillance and ongoing industrial hygiene efforts. The strategy may supplement current air sampling approaches, which do not assess exposures via skin, or variability in PPE use or effectiveness. The approach may also be applicable to evaluating isocyanate exposures in other settings, and may extend to other chemical allergens. PMID:22449630

Biomonitoring: Guide for the Use of Biological Endpoints in Monitoring Species, Habitats, and Projects

DTIC Science & Technology

2007-11-01

et al ., 1991; Welsh and Ollivier 1998), behavior (Daly et al ., 1995; Maltby et al ., 2002 ...include changes in species diversity and community structure (Karr 1981; Bramblett and Fausch 1991; Barbour et al ., 1999; Zweig and Rabeni 2001; Martin et ...programs in aquatic habitats; these programs typically employ benthic invertebrates such as molluscs (Maltby et al ., 2002 ; Applied Biomonitoring

Molecular Barcoding of Aquatic Oligochaetes: Implications for Biomonitoring

PubMed Central

Vivien, Régis; Wyler, Sofia; Lafont, Michel; Pawlowski, Jan

2015-01-01

Aquatic oligochaetes are well recognized bioindicators of quality of sediments and water in watercourses and lakes. However, the difficult taxonomic determination based on morphological features compromises their more common use in eco-diagnostic analyses. To overcome this limitation, we investigated molecular barcodes as identification tool for broad range of taxa of aquatic oligochaetes. We report 185 COI and 52 ITS2 rDNA sequences for specimens collected in Switzerland and belonging to the families Naididae, Lumbriculidae, Enchytraeidae and Lumbricidae. Phylogenetic analyses allowed distinguishing 41 lineages separated by more than 10 % divergence in COI sequences. The lineage distinction was confirmed by Automatic Barcode Gap Discovery (ABGD) method and by ITS2 data. Our results showed that morphological identification underestimates the oligochaete diversity. Only 26 of the lineages could be assigned to morphospecies, of which seven were sequenced for the first time. Several cryptic species were detected within common morphospecies. Many juvenile specimens that could not be assigned morphologically have found their home after genetic analysis. Our study showed that COI barcodes performed very well as species identifiers in aquatic oligochaetes. Their easy amplification and good taxonomic resolution might help promoting aquatic oligochaetes as bioindicators for next generation environmental DNA biomonitoring of aquatic ecosystems. PMID:25856230

Work Stress and Altered Biomarkers: A Synthesis of Findings Based on the Effort-Reward Imbalance Model.

PubMed

Siegrist, Johannes; Li, Jian

2017-11-10

While epidemiological studies provide statistical evidence on associations of exposures such as stressful work with elevated risks of stress-related disorders (e.g., coronary heart disease or depression), additional information on biological pathways and biomarkers underlying these associations is required. In this contribution, we summarize the current state of the art on research findings linking stressful work, in terms of an established theoretical model-effort-reward imbalance-with a broad range of biomarkers. Based on structured electronic literature search and recent available systematic reviews, our synthesis of findings indicates that associations of work stress with heart rate variability, altered blood lipids, and risk of metabolic syndrome are rather consistent and robust. Significant relationships with blood pressure, heart rate, altered immune function and inflammation, cortisol release, and haemostatic biomarkers were also observed, but due to conflicting findings additional data will be needed to reach a firm conclusion. This narrative review of empirical evidence supports the argument that the biomarkers under study can act as mediators of epidemiologically established associations of work stress, as measured by effort-reward imbalance, with incident stress-related disorders.

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study

PubMed Central

Cullen, Elizabeth; Evans, David; Griffin, Chris; Burke, Padraig; Mannion, Rory; Burns, Damien; Flanagan, Andrew; Kellegher, Ann; Schoeters, Greet; Govarts, Eva; Biot, Pierre; Casteleyn, Ludwine; Castaño, Argelia; Kolossa-Gehring, Marike; Esteban, Marta; Schwedler, Gerda; Angerer, Jürgen; Knudsen, Lisbeth E.; Joas, Reinhard; Joas, Anke; Dumez, Birgit; Sepai, Ovnair; Exley, Karen; Aerts, Dominique

2017-01-01

Background: Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the ‘Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale’ (DEMOCOPHES) pilot biomonitoring study. Methods: the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results: Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions: The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood. PMID:29186834

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study.

PubMed

Cullen, Elizabeth; Evans, David; Griffin, Chris; Burke, Padraig; Mannion, Rory; Burns, Damien; Flanagan, Andrew; Kellegher, Ann; Schoeters, Greet; Govarts, Eva; Biot, Pierre; Casteleyn, Ludwine; Castaño, Argelia; Kolossa-Gehring, Marike; Esteban, Marta; Schwedler, Gerda; Koch, Holger M; Angerer, Jürgen; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Dumez, Birgit; Sepai, Ovnair; Exley, Karen; Aerts, Dominique

2017-11-25

Background : Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the 'Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale' (DEMOCOPHES) pilot biomonitoring study. Methods : the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results : Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions : The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood.

Assessing the Quantitative Relationships between Preschool Children's Exposures to Bisphenol A by Route and Urinary Biomonitoring

EPA Science Inventory

Limited published information exists on young children’s exposures to bisphenol A (BPA) in the United States using urinary biomonitoring. In a previous project, we quantified the aggregate exposures of 257 preschool children to BPA in environmental and personal media over 48-h pe...

Biomonitoring of Toxic Effects of Pesticides in Occupationally Exposed Individuals.

PubMed

Arshad, Muhammad; Siddiqa, Maryam; Rashid, Saddaf; Hashmi, Imran; Awan, Muhammad Ali; Ali, Muhammad Arif

2016-06-01

Workers in pesticide manufacturing industries are constantly exposed to pesticides. Genetic biomonitoring provides an early identification of potential cancer and genetic diseases in exposed populations. The objectives of this biomonitoring study were to assess DNA damage through comet assay in blood samples collected from industry workers and compare these results with those of classical analytical techniques used for complete blood count analysis. Samples from controls (n = 20) and exposed workers (n = 38) from an industrial area in Multan, Pakistan, were subjected to various tests. Malathion residues in blood samples were measured by gas chromatography. The exposed workers who were employed in the pesticide manufacturing industry for a longer period (i.e., 13-25 years) had significantly higher DNA tail length (7.04 μm) than the controls (0.94 μm). Workers in the exposed group also had higher white blood cell and red blood cell counts, and lower levels of mean corpuscular hemoglobin (MCH), MCH concentration, and mean corpuscular volume in comparison with normal levels for these parameters. Malathion was not detected in the control group. However, in the exposed group, 72% of whole blood samples had malathion with a mean value of 0.14 mg/L (range 0.01-0.31 mg/L). We found a strong correlation (R (2) = 0.91) between DNA damage in terms of tail length and malathion concentration in blood. Intensive efforts and trainings are thus required to build awareness about safety practices and to change industrial workers' attitude to prevent harmful environmental and anthropogenic effects.

Affinity-based strategies to fast track development of colon cancer biomarkers — EDRN Public Portal

Cancer.gov

Our goal is to discover plasma and tissue-based tumor biomarkers that work well enough together to identity colon cancer at early stages, lead to accurate diagnosis and could ultimately allow for individualized treatment.

Biomarker selection for medical diagnosis using the partial area under the ROC curve

PubMed Central

2014-01-01

Background A biomarker is usually used as a diagnostic or assessment tool in medical research. Finding an ideal biomarker is not easy and combining multiple biomarkers provides a promising alternative. Moreover, some biomarkers based on the optimal linear combination do not have enough discriminatory power. As a result, the aim of this study was to find the significant biomarkers based on the optimal linear combination maximizing the pAUC for assessment of the biomarkers. Methods Under the binormality assumption we obtain the optimal linear combination of biomarkers maximizing the partial area under the receiver operating characteristic curve (pAUC). Related statistical tests are developed for assessment of a biomarker set and of an individual biomarker. Stepwise biomarker selections are introduced to identify those biomarkers of statistical significance. Results The results of simulation study and three real examples, Duchenne Muscular Dystrophy disease, heart disease, and breast tissue example are used to show that our methods are most suitable biomarker selection for the data sets of a moderate number of biomarkers. Conclusions Our proposed biomarker selection approaches can be used to find the significant biomarkers based on hypothesis testing. PMID:24410929

Environmental sentinel biomonitors: integrated response systems for monitoring toxic chemicals

NASA Astrophysics Data System (ADS)

van der Schalie, William H.; Reuter, Roy; Shedd, Tommy R.; Knechtges, Paul L.

2002-02-01

Operational environments for military forces are becoming potentially more dangerous due to the increased number, use, and misuse of toxic chemicals across the entire range of military missions. Defense personnel may be exposed to harmful chemicals as a result of industrial accidents or intentional or unintentional action of enemy, friendly forces, or indigenous populations. While there has been a significant military effort to enable forces to operate safely and survive and sustain operations in nuclear, biological, chemical warfare agent environments, until recently there has not been a concomitant effort associated with potential adverse health effects from exposures of deployed personnel to toxic industrial chemicals. To provide continuous real-time toxicity assessments across a broad spectrum of individual chemicals or chemical mixtures, an Environmental Sentinel Biomonitor (ESB) system concept is proposed. An ESB system will integrate data from one or more platforms of biologically-based systems and chemical detectors placed in the environment to sense developing toxic conditions and transmit time-relevant data for use in risk assessment, mitigation, and/or management. Issues, challenges, and next steps for the ESB system concept are described, based in part on discussions at a September 2001 workshop sponsored by the U.S. Army Center for Environmental Health Research.

Biomarkers of Nutrition for Development-Folate Review.

PubMed

Bailey, Lynn B; Stover, Patrick J; McNulty, Helene; Fenech, Michael F; Gregory, Jesse F; Mills, James L; Pfeiffer, Christine M; Fazili, Zia; Zhang, Mindy; Ueland, Per M; Molloy, Anne M; Caudill, Marie A; Shane, Barry; Berry, Robert J; Bailey, Regan L; Hausman, Dorothy B; Raghavan, Ramkripa; Raiten, Daniel J

2015-07-01

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development. © 2015 American Society for Nutrition.

Ultrasensitive Visual Detection of HIV DNA Biomarkers via a Multi-amplification Nanoplatform.

PubMed

Long, Yuyin; Zhou, Cuisong; Wang, Congmin; Cai, Honglian; Yin, Cuiyun; Yang, Qiufang; Xiao, Dan

2016-04-01

Methodologies to detect disease biomarkers at ultralow concentrations can potentially improve the standard of living. A facile and label-free multi-amplification strategy is proposed for the ultrasensitive visual detection of HIV DNA biomarkers in real physiological media. This multi-amplification strategy not only exhibits a signficantly low detection limit down to 4.8 pM but also provides a label-free, cost-effective and facile technique for visualizing a few molecules of nucleic acid analyte with the naked eye. Importantly, the biosensor is capable of discriminating single-based mismatch lower than 5.0 nM in human serum samples. Moreover, the visual sensing platform exhibits excellent specificity, acceptable reusability and a long-term stability. All these advantages could be attributed to the nanofibrous sensing platform that 1) has a high surface-area-to-volume provided by electrospun nanofibrous membrane, and 2) combines glucose oxidase (GOx) biocatalysis, DNAzyme-catalyzed colorimetric reaction and catalytic hairpin assembly (CHA) recycling amplification together. This multi-amplification nanoplatform promises label-free and visual single-based mismatch DNA monitoring with high sensitivity and specificity, suggesting wide applications that range from virus detection to genetic disease diagnosis.

Population-Based Biomonitoring of Exposure to Organophosphate and Pyrethroid Pesticides in New York City

PubMed Central

Jacobson, J. Bryan; Kass, Daniel; Barr, Dana Boyd; Davis, Mark; Calafat, Antonia M.; Aldous, Kenneth M.

2013-01-01

pyrethroids and dimethyl organophosphates were higher in NYC than in the United States overall, underscoring the importance of considering pest and pesticide burdens in cities when formulating pesticide use regulations. Citation: McKelvey W, Jacobson JB, Kass D, Barr DB, Davis M, Calafat AM, Aldous KM. 2013. Population-based biomonitoring of exposure to organophosphate and pyrethroid pesticides in New York City. Environ Health Perspect 121:1349–1356; http://dx.doi.org/10.1289/ehp.1206015 PMID:24076605

Biomarkers in DILI: One More Step Forward

PubMed Central

Robles-Díaz, Mercedes; Medina-Caliz, Inmaculada; Stephens, Camilla; Andrade, Raúl J.; Lucena, M. Isabel

2016-01-01

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 (e.g., 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. PMID:27597831

Predicting mortality with biomarkers: a population-based prospective cohort study for elderly Costa Ricans

PubMed Central

2012-01-01

Background Little is known about adult health and mortality relationships outside high-income nations, partly because few datasets have contained biomarker data in representative populations. Our objective is to determine the prognostic value of biomarkers with respect to total and cardiovascular mortality in an elderly population of a middle-income country, as well as the extent to which they mediate the effects of age and sex on mortality. Methods This is a prospective population-based study in a nationally representative sample of elderly Costa Ricans. Baseline interviews occurred mostly in 2005 and mortality follow-up went through December 2010. Sample size after excluding observations with missing values: 2,313 individuals and 564 deaths. Main outcome: prospective death rate ratios for 22 baseline biomarkers, which were estimated with hazard regression models. Results Biomarkers significantly predict future death above and beyond demographic and self-reported health conditions. The studied biomarkers account for almost half of the effect of age on mortality. However, the sex gap in mortality became several times wider after controlling for biomarkers. The most powerful predictors were simple physical tests: handgrip strength, pulmonary peak flow, and walking speed. Three blood tests also predicted prospective mortality: C-reactive protein (CRP), glycated hemoglobin (HbA1c), and dehydroepiandrosterone sulfate (DHEAS). Strikingly, high blood pressure (BP) and high total cholesterol showed little or no predictive power. Anthropometric measures also failed to show significant mortality effects. Conclusions This study adds to the growing evidence that blood markers for CRP, HbA1c, and DHEAS, along with organ-specific functional reserve indicators (handgrip, walking speed, and pulmonary peak flow), are valuable tools for identifying vulnerable elderly. The results also highlight the need to better understand an anomaly noted previously in other settings: despite the

Fluorescence-based Western blotting for quantitation of protein biomarkers in clinical samples.

PubMed

Zellner, Maria; Babeluk, Rita; Diestinger, Michael; Pirchegger, Petra; Skeledzic, Senada; Oehler, Rudolf

2008-09-01

Since most high throughput techniques used in biomarker discovery are very time and cost intensive, highly specific and quantitative analytical alternative application methods are needed for the routine analysis. Conventional Western blotting allows detection of specific proteins to the level of single isotypes while its quantitative accuracy is rather limited. We report a novel and improved quantitative Western blotting method. The use of fluorescently labelled secondary antibodies strongly extends the dynamic range of the quantitation and improves the correlation with the protein amount (r=0.997). By an additional fluorescent staining of all proteins immediately after their transfer to the blot membrane, it is possible to visualise simultaneously the antibody binding and the total protein profile. This allows for an accurate correction for protein load. Applying this normalisation it could be demonstrated that fluorescence-based Western blotting is able to reproduce a quantitative analysis of two specific proteins in blood platelet samples from 44 subjects with different diseases as initially conducted by 2D-DIGE. These results show that the proposed fluorescence-based Western blotting is an adequate application technique for biomarker quantitation and suggest possibilities of employment that go far beyond.

Computational biology for cardiovascular biomarker discovery.

PubMed

Azuaje, Francisco; Devaux, Yvan; Wagner, Daniel

2009-07-01

Computational biology is essential in the process of translating biological knowledge into clinical practice, as well as in the understanding of biological phenomena based on the resources and technologies originating from the clinical environment. One such key contribution of computational biology is the discovery of biomarkers for predicting clinical outcomes using 'omic' information. This process involves the predictive modelling and integration of different types of data and knowledge for screening, diagnostic or prognostic purposes. Moreover, this requires the design and combination of different methodologies based on statistical analysis and machine learning. This article introduces key computational approaches and applications to biomarker discovery based on different types of 'omic' data. Although we emphasize applications in cardiovascular research, the computational requirements and advances discussed here are also relevant to other domains. We will start by introducing some of the contributions of computational biology to translational research, followed by an overview of methods and technologies used for the identification of biomarkers with predictive or classification value. The main types of 'omic' approaches to biomarker discovery will be presented with specific examples from cardiovascular research. This will include a review of computational methodologies for single-source and integrative data applications. Major computational methods for model evaluation will be described together with recommendations for reporting models and results. We will present recent advances in cardiovascular biomarker discovery based on the combination of gene expression and functional network analyses. The review will conclude with a discussion of key challenges for computational biology, including perspectives from the biosciences and clinical areas.

Genomic Biomarkers for Breast Cancer Risk

PubMed Central

Walsh, Michael F.; Nathanson, Katherine L.; Couch, Fergus J.

2016-01-01

Clinical risk assessment for cancer predisposition includes a three-generation pedigree and physical examination to identify inherited syndromes. Additionally genetic and genomic biomarkers may identify individuals with a constitutional basis for their disease that may not be evident clinically. Genomic biomarker testing may detect molecular variations in single genes, panels of genes, or entire genomes. The strength of evidence for the association of a genomic biomarker with disease risk may be weak or strong. The factors contributing to clinical validity and utility of genomic biomarkers include functional laboratory analyses and genetic epidemiologic evidence. Genomic biomarkers may be further classified as low, moderate or highly penetrant based on the likelihood of disease. Genomic biomarkers for breast cancer are comprised of rare highly penetrant mutations of genes such as BRCA1 or BRCA2, moderately penetrant mutations of genes such as CHEK2, as well as more common genomic variants, including single nucleotide polymorphisms, associated with modest effect sizes. When applied in the context of appropriate counseling and interpretation, identification of genomic biomarkers of inherited risk for breast cancer may decrease morbidity and mortality, allow for definitive prevention through assisted reproduction, and serve as a guide to targeted therapy. PMID:26987529

Ochratoxin A and its metabolites in urines of German adults-An assessment of variables in biomarker analysis.

PubMed

Ali, Nurshad; Muñoz, Katherine; Degen, Gisela H

2017-06-05

Ochratoxin A (OTA), a mycotoxin known for its nephrotoxic and carcinogenic properties, is a worldwide occurring contaminant in a variety of food commodities. Biomonitoring (i.e. analysis in biological fluids) can serve to assess human internal exposure from all consumed foods and beverages. We now determined the concentration of OTA and its metabolite ochratoxin alpha (OTα) in plasma and in urine of two male volunteers with different food habits, in order to assess intra-individual temporal fluctuations and inter-individual differences in their biomarker levels. Moreover, the urinary levels of both OTA and OTα were analyzed in a cohort of German adults (23 males, 27 females) on their regular diet. All samples were subjected to an enzymatic hydrolysis of biomarker conjugates prior to clean-up by liquid-liquid extraction and HPLC-FD analysis. The profile in the first individual showed small fluctuations over time: mean levels in plasma were 0.42 and 0.45ng/mL for OTA and OTα, respectively, and in urine means of 0.06ng/mL for both analytes. The other individual had mean levels of 1.64 and 0.20ng/mL for OTA and OTα in plasma, and 0.24 and 2.22ng/mL for these analytes in urine. It is concluded that inter-individual differences in biomarker levels reflect dissimilar dietary exposure and/or disposition of ingested mycotoxin, with an apparently more efficient detoxification of OTA to OTα in the second individual. In the German cohort (n=50), analytes were detected in 100% (OTA: range 0.02-1.82ng/mL mean level 0.21±0.31ng/mL) and 78% (OTα: range 0.01-14.25ng/mL, mean level 1.33±2.63ng/mL) of all urines. Parameters such as gender, age and body mass index did not show a significant association with urine biomarker levels. This study indicates frequent exposure to OTA among German adults. The new results are discussed in the context of biomarker data from other countries and some methodological issues. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple biomarker responses in Prochilodus lineatus subjected to short-term in situ exposure to streams from agricultural areas in Southern Brazil.

PubMed

Vieira, Carlos Eduardo Delfino; Costa, Patrícia Gomes; Lunardelli, Bruna; de Oliveira, Luciana Fernandes; Cabrera, Liziara da Costa; Risso, Wagner Ezequiel; Primel, Ednei Gilberto; Meletti, Paulo César; Fillmann, Gilberto; Martinez, Claudia Bueno dos Reis

2016-01-15

In order to assess the quality of streams susceptible to contamination by pesticides we apply biochemical and genotoxic biomarkers in the Neotropical fish Prochilodus lineatus submitted to in situ tests. Fish were caged, for 96 h, in two streams located in areas with intensive use of pesticides, the Apertados (AP) and the Jacutinga (JC), and in a small stream (Godoy stream — GD) found inside a forest fragment adjacent to a State Park. Biochemical parameters, such as biotransformation enzymes 7-ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST), non-protein thiols (NPSH), lipoperoxidation (LPO), protein carbonylation (PCO) and acetylcholinesterase (AChE) were evaluated in various fish organs, as well as genotoxic biomarkers (damage to DNA and occurrence of micronuclei and erythrocyte nuclear abnormalities). Samples of water and sediment were collected for analysis of metals (Cu, Cr, Pb, Ni, Mn, Cd and Zn), organochloride pesticides, and triazine and glyphosate herbicides. We observed an increase in liver GST activity in fish at AP and gill GST activity in fish at JC. An increase in liver LPO was also observed in fish exposed to AP and JC. The same animals also exhibited increased DNA damage and erythrocyte nuclear abnormalities (ENAs) compared to the fish kept in GD. A number of compounds showed concentrations higher than the permitted levels, in particular, dichlorodiphenyltrichloroethane (DDT), its metabolites dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD), hexachlorocyclohexanes (HCH), heptachloride, diclofluanid and aldrins. These pesticides were detected at higher concentrations in water and sediment samples from AP, followed by JC and GD. The Integrated Biomarker Response Index (IBR) indicated that AP and JC (AP: 21.7 > JC: 18.5 > GD: 12.6) have the worst environmental quality. Integrated biomarker analysis revealed that the alterations observed related well with the levels of environmental contaminants

A multilevel-ROI-features-based machine learning method for detection of morphometric biomarkers in Parkinson's disease.

PubMed

Peng, Bo; Wang, Suhong; Zhou, Zhiyong; Liu, Yan; Tong, Baotong; Zhang, Tao; Dai, Yakang

2017-06-09

Machine learning methods have been widely used in recent years for detection of neuroimaging biomarkers in regions of interest (ROIs) and assisting diagnosis of neurodegenerative diseases. The innovation of this study is to use multilevel-ROI-features-based machine learning method to detect sensitive morphometric biomarkers in Parkinson's disease (PD). Specifically, the low-level ROI features (gray matter volume, cortical thickness, etc.) and high-level correlative features (connectivity between ROIs) are integrated to construct the multilevel ROI features. Filter- and wrapper- based feature selection method and multi-kernel support vector machine (SVM) are used in the classification algorithm. T1-weighted brain magnetic resonance (MR) images of 69 PD patients and 103 normal controls from the Parkinson's Progression Markers Initiative (PPMI) dataset are included in the study. The machine learning method performs well in classification between PD patients and normal controls with an accuracy of 85.78%, a specificity of 87.79%, and a sensitivity of 87.64%. The most sensitive biomarkers between PD patients and normal controls are mainly distributed in frontal lobe, parental lobe, limbic lobe, temporal lobe, and central region. The classification performance of our method with multilevel ROI features is significantly improved comparing with other classification methods using single-level features. The proposed method shows promising identification ability for detecting morphometric biomarkers in PD, thus confirming the potentiality of our method in assisting diagnosis of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Faecal biomarker patterns in patients with symptoms of irritable bowel syndrome

PubMed Central

Emmanuel, Anton; Landis, Darryl; Peucker, Mark; Hungin, A Pali S

2016-01-01

Objective To determine rates of faecal biomarker results capable of suggesting potentially treatable causes of irritable bowel syndrome (IBS) symptomatology in a population of patients with symptoms of IBS who meet Rome III criteria for that condition. Design Descriptive, retrospective study in which faecal biomarker results (dichotomised into ‘normal’ and ‘abnormal’ values) were related to data from patient-completed questionnaire data identifying demographics, Rome III criteria for IBS and IBS phenotype (IBS-D, IBS-C, IBS-M and IBS-U). Setting Commercial reference laboratory. Patients Individuals whose physicians ordered faecal biomarker testing for evaluation of chronic abdominal symptoms consistent with IBS. Interventions None. Main outcome measures Rates of occurrence of abnormal results on any of seven faecal biomarkers suggesting a treatable cause for IBS symptoms. Results Abdominal symptoms meeting Rome III criteria for IBS were present in 3553 records (the population), which were subjected to further analysis. Abnormal biomarker results (the outcomes) occurred in 94% of cases; 73% and 65% of records indicated growth of a bacterial potential pathogen and low growth of beneficial organisms, respectively. Abnormal results for all other faecal biomarkers occurred with frequencies from 5% to 13%. Frequency of abnormal results for elastase, calprotectin, eosinophil protein X, and beneficial organisms rose significantly with age, and differed significantly across IBS phenotypes. Conclusions A large proportion of patients manifesting symptoms meeting Rome III IBS diagnostic criteria have faecal biomarker results indicating potential underlying, treatable causes of their symptoms. Faecal biomarker testing is an appropriate means of identifying potentially treatable causes of IBS symptoms. PMID:27761231

[Pollutants from a plant which burns toxic waste in the Province of Arezzo (Tuscany Region, Central Italy): human biomonitoring pilot study to evaluate the possible type of environmental exposure].

PubMed

Chellini, Elisabetta; Fondelli, Maria Cristina; Maurello, Maria Teresa; Sciarra, Gianfranco; Aprea, Maria Cristina; Carreras, Giulia

2015-01-01

to identify the biomarkers to use in order to evaluate the level and trend of exposure to environmental pollutants from a plant which retrieves and refines precious metals and burns toxic waste. human biomonitoring cross sectional study on a small sample of population resident in the study area. blood and urinary samples, and questionnaires from volunteers resident at least for 10 years in Civitella in Val di Chiana area (Arezzo Province, Tuscany Region, Central Italy), where the plant is located, and in a control area; they had to be 5-year non-smokers or ex-smokers, in good health status and non occupationally exposed to heavy metals and/or combustion products. geometric mean and 95th percentile (P95) of mercury (Hg) and cadmium (Cd) blood concentrations, and of the urinary concentrations of antimony (Sb), silver (Ag), arsenic (As), Cd, cobalt (Co), chromium (Cr), Hg, nickel (Ni), platinum (Pt), 1-hydroxypyrene, and trans, trans-muconic acid in the two populations; quantity and pattern of porphyrins in the 24-hour urines of Civitella volunteers. Student's "t" test calculated on the means of data with logarithmic transformation was used to compare the two groups. In case of significant differences linear regression analyses have been performed using questionnaire information. The distribution of observed data was compared with specific reference values. Sb, Cd, and Ni concentrations were significantly higher in Civitella population (39 subjects), while Cr concentration was higher in the control group (18 subjects). No correlations with the individual characteristics have been observed. The 30.3%of subjects who gave their 24- hour urine had a distorted pattern of porphyrins. the results confirmed the need to perform human biomonitoring in the Civitella area, increasing the number of samples, using urine as biological matrix, and monitoring at least Sb, Cd, Ni, Pt, Ag, and porphyrins.

Leveraging sequence-based faecal microbial community survey data to identify a composite biomarker for colorectal cancer.

PubMed

Shah, Manasi S; DeSantis, Todd Z; Weinmaier, Thomas; McMurdie, Paul J; Cope, Julia L; Altrichter, Adam; Yamal, Jose-Miguel; Hollister, Emily B

2018-05-01

Colorectal cancer (CRC) is the second leading cause of cancer-associated mortality in the USA. The faecal microbiome may provide non-invasive biomarkers of CRC and indicate transition in the adenoma-carcinoma sequence. Re-analysing raw sequence and metadata from several studies uniformly, we sought to identify a composite and generalisable microbial marker for CRC. Raw 16S rRNA gene sequence data sets from nine studies were processed with two pipelines, (1) QIIME closed reference (QIIME-CR) or (2) a strain-specific method herein termed SS-UP (Strain Select, UPARSE bioinformatics pipeline). A total of 509 samples (79 colorectal adenoma, 195 CRC and 235 controls) were analysed. Differential abundance, meta-analysis random effects regression and machine learning analyses were carried out to determine the consistency and diagnostic capabilities of potential microbial biomarkers. Definitive taxa, including Parvimonas micra ATCC 33270, Streptococcus anginosus and yet-to-be-cultured members of Proteobacteria, were frequently and significantly increased in stools from patients with CRC compared with controls across studies and had high discriminatory capacity in diagnostic classification. Microbiome-based CRC versus control classification produced an area under receiver operator characteristic (AUROC) curve of 76.6% in QIIME-CR and 80.3% in SS-UP. Combining clinical and microbiome markers gave a diagnostic AUROC of 83.3% for QIIME-CR and 91.3% for SS-UP. Despite technological differences across studies and methods, key microbial markers emerged as important in classifying CRC cases and such could be used in a universal diagnostic for the disease. The choice of bioinformatics pipeline influenced accuracy of classification. Strain-resolved microbial markers might prove crucial in providing a microbial diagnostic for CRC. 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/.

A survey on lifestyle and level of biomarkers of environmental exposure in residents in Civitavecchia (Italy).

PubMed

Ancona, Carla; Bauleo, Lisa; Biscotti, Giovanni; Bocca, Beatrice; Caimi, Stefano; Cruciani, Fabio; Di Lorenzo, Sabrina; Petrolati, Morena; Pino, Anna; Piras, Giovanna; Pizzabiocca, Augusto; Rabbiosi, Silvia; Ruggieri, Flavia; Salatino, Chelo; Alimonti, Alessandro; Forastiere, Francesco