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Sample records for routine toxicity screening

  1. Routine fetal genitourinary tract screening.

    PubMed

    Arger, P H; Coleman, B G; Mintz, M C; Snyder, H P; Camardese, T; Arenson, R L; Gabbe, S G; Aquino, L

    1985-08-01

    To evaluate routine fetal genitourinary tract obstetrical ultrasound screening, and to determine what size renal pelvis is indicative of significant renal disease, we reviewed 4,832 examinations, which had been performed over 2 years, of 3,530 consecutive obstetrical patients. Any fetus that had a renal pelvis greater than 5 mm or a definable cystic area was identified for follow-up. The fetuses of 39 patients (1.1%) who underwent 112 examinations fulfilled these criteria and constitute the basis of this report. A variety of examination criteria were recorded and analyzed in relationship to the follow-up, which ranged from 2-3 days to 21 months. The fetuses of the 39 patients were grouped into three categories: those with renal pelves between 5 and 9 mm in size; those with renal pelves larger than 10 mm; and those with cystic abnormalities. Those with renal pelves larger than 10 mm had either an obstructing lesion or exceptional extrarenal pelves. The clinical and pathologic aspects of these three groups are detailed, discussed, and analyzed. Criteria for significant fetal renal hydronephrosis and aspects of a loculated appearance are given. PMID:3892578

  2. Recommendations on routine screening pelvic examination

    PubMed Central

    Tonelli, Marcello; Gorber, Sarah Connor; Moore, Ainsley; Thombs, Brett D.

    2016-01-01

    Abstract Objective To review the 2014 American College of Physicians (ACP) guideline on the use of pelvic examinations to screen for cancer (other than cervical), pelvic inflammatory disease, or other benign gynecologic conditions to determine whether the ACP guideline on routine pelvic examinations was consistent with Canadian Task Force on Preventive Health Care (CTFPHC) standards and could be adapted or adopted. Methods The SNAP-IT (Smooth National Adaptation and Presentation of Guidelines to Improve Thrombosis Treatment) method was used to determine whether the ACP guideline was consistent with CTFPHC standards and could be adapted or adopted. Recommendations The CTFPHC recommends not performing a screening pelvic examination to screen for noncervical cancer, pelvic inflammatory disease, or other gynecological conditions in asymptomatic women. This is a strong recommendation with moderate-quality evidence. Conclusion The CTFPHC adopts the recommendation on screening pelvic examination as published by the ACP in 2014. PMID:26975912

  3. [Routine hematologic parameters for thalassemia screening].

    PubMed

    Schubert, S; Christofi, Y; Papadatou, A

    1990-01-01

    There is an evaluation of routine examination of the blood film for the recognition of Thalassaemia (Th.). The results of 100 blood films from each group--Th. major, Th. minor, healthy persons (centre for Thalassaemia "Bishop Makarios"/Nikosia--Cypros)-were analyzed. MCV and MCH were most useful for the recognition of Th. minor. The constellation of increased red blood cells and normal hemoglobin seems to be typical for Th. minor. Haemoglobin and haematocrit are not suited because they were widely normal. Target cells also are not sufficient for screening--they were present only in 10% of Th. minor. To the contrary most values were clearly decreased in Th. major, and target cells were present here in almost 90%. PMID:1713894

  4. TOXICITY SCREENING WITH ZEBRAFISH ASSAY

    EPA Science Inventory

    The proposed toxicity screening will help EPA to prioritize chemicals for further testing, and it may also alert chemical manufacturers that some of their commercial products may be toxic. The proposed toxicity pathway studies will improve the research community’s abi...

  5. Routine or targeted HIV screening of Indonesian prisoners.

    PubMed

    Nelwan, Erni Juwita; Isa, Ahmad; Alisjahbana, Bachti; Triani, Nurlita; Djamaris, Iqbal; Djaja, Ilham; Pohan, Herdiman T; Zwanikken, Prisca; Crevel, Reinout van; van der Ven, Andre; Meheus, Andre

    2016-03-14

    Purpose - Routine HIV screening of prisoners is generally recommended, but rarely implemented in low-resource settings. Targeted screening can be used as an alternative. Both strategies may provide an opportunity to start HIV treatment but no formal comparisons have been done of these two strategies. The paper aims to discuss these issues. Design/methodology/approach - The authors compared yield and costs of routine and targeted screening in a narcotic prison in Indonesia. Routine HIV screening was done for all incoming prisoners from August 2007-February 2009, after it was switched for budgetary reasons to targeted ("opt-out") HIV screening of inmates classified as people who inject drugs (PWIDs), and "opt-in" HIV testing for all non-PWIDs. Findings - During routine screening 662 inmates were included. All 115 PWIDs and 93.2 percent of non-PWIDs agreed to be tested, 37.4 percent and 0.4 percent respectively were HIV-positive. During targeted screening (March 2009-October 2010), of 888 inmates who entered prison, 107 reported injecting drug use and were offered HIV testing, of whom 31 (29 percent) chose not to be tested and 25.0 percent of those tested were HIV-positive. Of 781 non-PWIDs, 187 (24 percent) came for testing (opt-in), and 2.1 percent were infected. During targeted screening fewer people admitted drug use (12.0 vs 17.4 percent). Routine screening yielded twice as many HIV-infected subjects (45 vs 23). The estimated cost per detected HIV infection was 338 USD for routine and 263 USD for targeted screening. Originality/value - In a resource limited setting like Indonesia, routine HIV screening in prison is feasible and more effective than targeted screening, which may be stigmatizing. HIV infections that remain unrecognized can fuel ongoing transmission in prison and lead to unnecessary disease progression and deaths. PMID:26933989

  6. Task Force: Routine Genital Herpes Screening Not Recommended

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_160205.html Task Force: Routine Genital Herpes Screening Not Recommended Unless someone ... 2, 2016 (HealthDay News) -- A U.S. federal task force is prepared to recommend that teens, adults and ...

  7. Factors Associated With Return for Routine Annual Screening in an Ovarian Cancer Screening Program

    PubMed Central

    Andrykowski, Michael A.; Zhang, Mei; Pavlik, Edward J.; Kryscio, Richard J.

    2007-01-01

    Objective To identify clinical, demographic, dispositional and attitudinal variables associated with return for routine, annual transvaginal sonography (TVS) screening for ovarian cancer. Methods Asymptomatic, average to high risk, women (n=585) participating in a free university-based ovarian cancer screening program completed a baseline interview prior to undergoing an initial TVS screening test. During the baseline interview, demographic (age, education, partner status, race), clinical (family history of ovarian cancer), dispositional (optimism, health values), and attitudinal (perceptions of personal risk for ovarian cancer and effectiveness of screening, intentions to return for repeat routine screening, discomfort during screening, satisfaction with the screening process, ovarian cancer specific distress) information was obtained. Return for repeat screening was documented from screening program records. Results Results from both multivariate proportional hazards and logistic regression analyses indicated that stated intentions to return for a repeat screening test within the next year was the strongest predictor of return for repeat screening. Possessing ≥ 12 years of education was also associated with a greater likelihood of repeat screening in both the proportional hazards and logistic regression analyses. Conclusions Results provide further support for low education as a risk factor for suboptimal participation in cancer screening. Results also highlight the critical link between intentions to perform a health-protective behavior and subsequent performance of that behavior and suggest repeat screening could be enhanced by eliciting both an intention to return for annual ovarian cancer screening as well as a specific plan for implementing this intention. PMID:17145075

  8. POLICYMAKING UNDER UNCERTAINTY: ROUTINE SCREENING FOR INTIMATE PARTNER VIOLENCE

    PubMed Central

    Dagher, Rada K.; Garza, Mary A.; Kozhimannil, Katy Backes

    2013-01-01

    Intimate partner violence (IPV) is a significant public health issue affecting around 3 million U.S. women during their lifetimes; this paper provides guidance to policymakers on addressing IPV. In 2011, an Institute of Medicine panel recommended routine IPV screening for women and adolescents as part of comprehensive preventive care services, which is in conflict with the 2004 U.S. Preventive Services Task Force recommendations. The current evidence base for policymaking suffers weaknesses related to study design which should be addressed in future research. Meanwhile, policymakers should consider available evidence in their settings, assess local needs, and make recommendations where appropriate. PMID:25011677

  9. Routine voluntary antenatal anti-HIV screening in Bangkok, Thailand.

    PubMed

    Phuapradit, W; Chaturachinda, K; Saropala, N; Chittacharoen, A; Sirinavin, S; Kunakorn, M

    1995-05-01

    The following recommendations are made as a result of this study. 1. Routine voluntary screening for HIV infection in all pregnant women is feasible and worthwhile. 2. Every seropositive result should be repeated for confirmation before coming to a definitive conclusion to avoid a misdiagnosis. 3. Routine screening of seronegative pregnant women should be repeated during the third trimester to detect seroconversion since this offers a chance for AZT administration to the seroconverted pregnant women for reduction of perinatal transmission. 4. There should be available the appropriate back up services for seropositive pregnant women such as: (i) C--Choice. Having been appropriately counselled the pregnant women should be able to terminate or continue with the pregnancy. (ii) H--High-risk pregnancy concept. The pregnant women should be treated as high-risk cases. Throughout their pregnancy and delivery only experienced personnel should manage them. (iii) I--Integrated services. From our experience it would be reasonable to integrate the care of seropositive pregnant women with any other high-risk cases. Special or anonymous clinics may create an atmosphere of uneasy feelings among the women who could be made to feel alienated and discriminated against. (iv) P--Provision of care. Comprehensive services must be available. These include an experienced counselling team, adequate laboratory services, services for safe first and second trimester therapeutic abortions, appropriate facility in the delivery suite (including Caesarean section) for infected cases, and dedicated paediatricians. PMID:7677680

  10. Developmental toxicity screening in zebrafish.

    PubMed

    McCollum, Catherine W; Ducharme, Nicole A; Bondesson, Maria; Gustafsson, Jan-Ake

    2011-06-01

    Given the ever-increasing toxic exposure ubiquitously present in our environment as well as emerging evidence that these exposures are hazardous to human health, the current rodent-based regulations are proving inadequate. In the process of overhauling risk assessment methodology, a nonrodent test organism, the zebrafish, is emerging as tractable for medium- and high-throughput assessments, which may help to accelerate the restructuring of standards. Zebrafish have high developmental similarity to mammals in most aspects of embryo development, including early embryonic processes, and on cardiovascular, somite, muscular, skeletal, and neuronal systems. Here, we briefly describe the development of these systems and then chronicle the toxic impacts assessed following chemical exposure. We also compare the available data in zebrafish toxicity assays with two databases containing mammalian toxicity data. Finally, we identify gaps in our collective knowledge that are ripe for future studies. PMID:21671351

  11. Rapid toxicity screening of gasification ashes.

    PubMed

    Zhen, Xu; Rong, Le; Ng, Wei Cheng; Ong, Cynthia; Baeg, Gyeong Hun; Zhang, Wenlin; Lee, Si Ni; Li, Sam Fong Yau; Dai, Yanjun; Tong, Yen Wah; Neoh, Koon Gee; Wang, Chi-Hwa

    2016-04-01

    The solid residues including bottom ashes and fly ashes produced by waste gasification technology could be reused as secondary raw materials. However, the applications and utilizations of these ashes are very often restricted by their toxicity. Therefore, toxicity screening of ash is the primary condition for reusing the ash. In this manuscript, we establish a standard for rapid screening of gasification ashes on the basis of in vitro and in vivo testing, and henceforth guide the proper disposal of the ashes. We used three different test models comprising human cell lines (liver and lung cells), Drosophila melanogaster and Daphnia magna to examine the toxicity of six different types of ashes. For each ash, different leachate concentrations were used to examine the toxicity, with C0 being the original extracted leachate concentration, while C/C0 being subsequent diluted concentrations. The IC50 for each leachate was also quantified for use as an index to classify toxicity levels. The results demonstrated that the toxicity evaluation of different types of ashes using different models is consistent with each other. As the different models show consistent qualitative results, we chose one or two of the models (liver cells or lung cells models) as the standard for rapid toxicity screening of gasification ashes. We may classify the gasification ashes into three categories according to the IC50, 24h value on liver cells or lung cells models, namely "toxic level I" (IC50, 24h>C/C0=0.5), "toxic level II" (C/C0=0.05toxic level III" (IC50, 24htoxic effects of various types of ashes generated in gasification plants every day. Subsequently, appropriate disposal methods can be recommended for each toxicity category. PMID:26923299

  12. Nanomaterial Toxicity Screening in Developing Zebrafish Embryos

    EPA Science Inventory

    To assess nanomaterial vertebrate toxicity, a high-content screening assay was created using developing zebrafish, Danio rerio. This included a diverse group of nanomaterials (n=42 total) ranging from metallic (Ag, Au) and metal oxide (CeO2, CuO, TiO2, ZnO) nanoparticles, to non...

  13. Antepartum Screening for Maternal Infection and Immune Status: Is it Time to Broaden Our Routine?

    PubMed

    Poliquin, Vanessa; Yudin, Mark H; Murphy, Kellie E; Okun, Nan

    2015-12-01

    Maternal infections with PVB19, HCV, CMV, and HIV during the antepartum period are important health problems for which the technological capacities for screening and diagnosis during the antepartum period are available. Each of these viruses requires individual consideration for inclusion in screening and for the method of screening during the antepartum period. The availability of efficacious treatments for HCV and CMV, with demonstrable benefits to the mother or fetus, is required before antepartum screening for these infections can be justified. Screening for parvovirus B19 presents a greater concern because it meets most of the features of a screening test (Wilson’s criteria) endorsed by the WHO. There is insufficient evidence to argue strongly for implementation of antepartum PVB19 screening, but the available evidence indicates a need for large studies of potential effectiveness and costs of routine PVB19 screening, either for all pregnant woman or for those at high risk of exposure to PVB19. While the technology to screen for HCV, PVB19, and CMV certainly exists, there must be careful consideration of the downstream implications of routine screening at the level of the individual patient, the general population, and other health care resources, including laboratory infrastructure, before recommending that these infections be screened for routinely in the antepartum period. A strategy for national adoption of an opt-out screening strategy for HIV should be considered. PMID:26637086

  14. Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness

    PubMed Central

    Yazdanpanah, Yazdan; Perelman, Julian; DiLorenzo, Madeline A.; Alves, Joana; Barros, Henrique; Mateus, Céu; Pereira, João; Mansinho, Kamal; Robine, Marion; Park, Ji-Eun; Ross, Eric L.; Losina, Elena; Walensky, Rochelle P.; Noubary, Farzad; Freedberg, Kenneth A.; Paltiel, A. David

    2013-01-01

    Objective To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening. Design We used Portuguese national clinical and economic data to conduct a model-based assessment. Methods We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness. Results One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively. Conclusions One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal’s challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings. PMID:24367639

  15. Screening for substance use disorders in neurodevelopmental disorders: a clinical routine?

    PubMed

    Palmqvist, Margita; Edman, Gunnar; Bölte, Sven

    2014-05-01

    Evidence suggests that substance use disorders (SUD) tend to be underdiagnosed in psychiatry. The objective of this study was to investigate whether drug and alcohol screening is a clinical routine in the assessment of two prominent neurodevelopmental disorders, namely ADHD and autism spectrum disorder (ASD). We surveyed drug and alcohol screening routines in 34 general child and adolescent (only practice for adolescents, not children, was assessed) and 29 adult psychiatric outpatient departments in Stockholm County, Sweden. Structured telephone interviews mapping SUD screening procedures were conducted with department representatives in charge. Only a minority of child and adolescent departments regularly used SUD screening questionnaires (6 %) in ADHD and ASD assessment, while this was more common in adult psychiatry (55 %). Urine/blood-based toxicology tests were always used in 28 % and sometimes or in case of clinical suspicion in 38 % of the adult units. Such tests were used sometimes or in case of clinical suspicion in 15 % of the child psychiatric departments, but never routinely. Findings reveal that screening for SUD in ADHD and ASD is not an integral part of routine clinical assessments in psychiatry, although increasingly an integral part of many clinical guidelines. Thus, SUD might be underdiagnosed in neurodevelopmental disorders, which could be particularly true for child and adolescent psychiatry settings. PMID:23949101

  16. Cardiac preparticipation screening for the young athlete: why the routine use of ECG is not necessary.

    PubMed

    Roberts, William O; Asplund, Chad A; O'Connor, Francis G; Stovitz, Steven D

    2015-01-01

    The addition of an electrocardiogram (ECG) to the current United States athlete preparticipation physical evaluation (PPE) as a screening tool has dominated the PPE discussion over the past decade despite the lack of demonstrable outcomes data supporting the routine use of the diagnostic study for reduction of sudden cardiac death (SCD). A good screening test should influence a disease or health outcome that has a significant impact on public health and the population screened must have a high prevalence of the disease to justify the screening intervention. While SCD is publicly remarkable and like any death, tragic, the prevalence of SCD in young athletes is very low and the potential for false positive results is high. While ECG screening appears to have made an impact on SCD in Italian athletes, the strategy has made no impact on Israeli athletes, and the overall impact of ECG screening on American athletes is unclear. Until outcomes studies show substantial SCD reduction benefit, the addition of routine ECG PPE screening in young athletes should not be instituted. PMID:25669141

  17. The Howard University Hospital Experience with Routineized HIV Screening: A Progress Report*

    PubMed Central

    Scott, Victor F.; Sitapati, Amy; Martin, Sayyida; Summers, Pamela; Washington, Michael; Daniels, Fernando; Mouton, Charles; Bonney, George; Apprey, Victor; Webster, Virginia; Smith, Avemaria; Mountvarner, Geoffrey; Daftary, Monica; Maxwell, Celia J.

    2009-01-01

    Background: Howard University Hospital (HUH) is the first hospital in the nation to have instituted a hospital-wide routine rapid HIV screening campaign as recommended by the CDC for healthcare settings. Methods: HUH developed a protocol and implemented a hospital-wide routine HIV screening in October 2006. Rapid oral fluid-based HIV testing was conducted throughout the hospital using the OraSure OraQuick Advance Rapid HIV-1/2 Antibody Test. Patients with a preliminarily reactive test result were either referred for confirmatory testing or offered a Western Blot confirmatory test on-site and referred for follow-up care. This is a report on the progress of this program for the first eight months. Results: Of the 9,817 patients offered HIV testing, 5,642 consented. The mean age of the screened population was 40.7 years. Ninety percent of the patients screened were black and 55% were female. A preliminarily reactive test result was identified in 139 patients for a seroprevalence rate of 2.46%. Of these patients, 136, or 98% were black; 63% were male and 37% were female. HIV prevalence in the overall sample, among blacks, and among both black males and females peaked in the 40–54 year old age group. Challenges were experienced initially in securing confirmatory tests. Conclusions: Hospital-wide routine HIV screening is both possible and productive. The routine HIV screening campaign instituted at Howard University Hospital has identified a significant number of previously unidentified HIV positive persons. Success in assuring confirmatory testing and transition to care improved as time progressed. PMID:19768195

  18. Screening wastewater for toxicity to activated sludge

    SciTech Connect

    Schneider, C.G.

    1987-01-01

    Several toxicity tests were compared to define their utility for prediction of toxicity to activated sludge. The tests included: (1) oxygen uptake rates in batch tests with activated sludge, (2) adenosine triphosphate (ATP) measurements in the same batch tests, (3) Warburg respirometer studies with activated sludge, and (4) a luminescent bacteria test (Microtox/sup TM/). An evaluation of the toxicity tests was made with several toxicants; nickel (II), mercury (II), 2,4-dichlorophenol (DCP) and 4,6-dinitro-o-cresol (DNOC). Because of differences in toxic mechanism, some of the toxicants produced greater toxic effects in some tests than in other tests. The ATP levels decreased significant when uncouplers of oxidative phosphorylation were studied (DCP and DNOC). Several procedures for measuring ATP were investigated and were found to be unsatisfactory when applied to activated sludge. A new method for extraction of ATP, which incorporated a sonic bath and trichloroacetic acid, was developed. The improved ATP method was used in the toxicity tests and for the additional studies. Current practice in environmental engineering relies on volatile suspended solids (VSS) as a measure of active biomass in activated sludge. After an improved ATP procedure was developed, ATP was investigated for estimation of active biomass. The fate of DCP in the toxicity tests was studied and an adsorptive mechanism was proposed that was based on membrane solubility. This mechanism explained the fate of DCP in the toxicity tests and is useful for understanding the fate of DCP in activated sludge.

  19. SCREENING PROTOCOL FOR ASSESSING TOXICITY OF ORGANIC CHEMICALS TOANAEROBIC PROCESSES

    EPA Science Inventory

    A screening protocol has been developed to provide a rapid andrepeatable assessment of the effect of toxic organic chemicals onanaerobic treatment processes. his protocol also providesinformation on the rate limiting biological reactions and theconcentrations at which changes in ...

  20. Evaluation of Daphnia ambigua for Routine Aquatic Toxicity Testing at the Savannah River Site

    SciTech Connect

    Specht, W.L.; Harmon, S.M.

    1997-09-01

    Short-term whole effluent toxicity testing, which is currently a requirement of the U.S. EPA`s National Pollution Discharge Elimination System (NPDES), commonly uses the cladoceran species Ceriodaphnia dubia. Despite the advantages to using a common test species to model the toxic effects of effluents, it could be argued that toxicity test results would be more meaningful if a wider variety of test organisms were commonly used. One particular argument against C. dubia is that tests conducted with this species do not always reflect local, site-specific conditions. The careful selection and use of an indigenous test species would produce a more realistic model of local instream effects and would account for regional differences in water quality. Permitted effluent discharges from Savannah River Site (SRS), a government weapons facility operated by the U.S. Department of Energy, require toxicity testing with C. dubia. However, water quality in these receiving streams is markedly different (lower pH and hardness) from standard laboratory water used for the culturing and testing of C. dubia, and it has been shown that this receiving water presents varying degrees of toxicity to C. dubia. Based on these results, it is possible that toxic effects observed during an effluent study could be the result of test organism stress from the dilution water and not the effects of SRS effluents. Therefore, this study addressed the substitution of C. dubia with an indigenous cladoceran species, Daphnia ambigua for routine regulatory testing at SRS. Given the indigenous nature of this species, combined with the fact that it has been successfully cultured by other investigators, D. ambigua was ideal for consideration as a replacement for C. dubia, but further study of the overall success and sensitivity of laboratory-reared D. ambigua was required. This investigation determined that D. ambigua could be laboratory cultured with only minimal changes to established regulatory protocol and

  1. An inexpensive apparatus for toxicity screening

    SciTech Connect

    Lo Pinto, R.W.; Santelli, J.

    1995-12-31

    An inexpensive apparatus was fabricated to monitor and record changes in the motility patterns of small aquatic invertebrates, such as Artemia salina and Daphnia magna, during acute toxicity tests. Within hours of exposure to a range toxicant concentrations the motility patterns change in a way that predicts the EC50. The work to date suggests there is a correlation between the EC50 following a 60 hour exposure, and motility data collected within the first 40 minutes of the test. The apparatus may be useful to speed range finding tests and for shortening the duration of acute toxicity tests of an effluent or receiving water. The apparatus may also be used to quantify erratic swimming in surviving organisms when a test is terminated.

  2. Implementing Routine Cognitive Screening of Older Adults in Primary Care: Process and Impact on Physician Behavior

    PubMed Central

    Scanlan, James; Hummel, Jeffrey; Gibbs, Kathy; Lessig, Mary; Zuhr, Elizabeth

    2007-01-01

    Background Early detection of cognitive impairment is a goal of high-quality geriatric medical care, but new approaches are needed to reduce rates of missed cases. Objective To evaluate whether adding routine cognitive screening to primary care visits for older adults increases rates of dementia diagnosis, specialist referral, or prescribing of antidementia medications. Setting Four primary care clinics in a university-affiliated primary care network. Design A quality improvement screening project and quasiexperimental comparison of 2 intervention clinics and 2 control clinics. The Mini-Cog was administered by medical assistants to intervention clinic patients aged 65+ years. Rates of dementia diagnoses, referrals, and medication prescribing were tracked over time using computerized administrative data. Results Twenty-six medical assistants successfully screened 70% (n = 524) of all eligible patients who made at least 1 clinic visit during the intervention period; 18% screened positive. There were no complaints about workflow interruption. Relative to baseline rates and control clinics, Mini-Cog screening was associated with increased dementia diagnoses, specialist referrals, and prescribing of cognitive enhancing medications. Patients without previous dementia indicators who had a positive Mini-Cog were more likely than all other patients to receive a new dementia diagnosis, specialty referral, or cognitive enhancing medication. However, relevant physician action occurred in only 17% of screen-positive patients. Responses were most related to the lowest Mini-Cog score level (0/5) and advanced age. Conclusion Mini-Cog screening by office staff is feasible in primary care practice and has measurable effects on physician behavior. However, new physician action relevant to dementia was likely to occur only when impairment was severe, and additional efforts are needed to help primary care physicians follow up appropriately on information suggesting cognitive

  3. Look what else we found - clinically significant abnormalities detected during routine ROP screening

    PubMed Central

    Jayadev, Chaitra; Vinekar, Anand; Bauer, Noel; Mangalesh, Shwetha; Mahendradas, Padmamalini; Kemmanu, Vasudha; Mallipatna, Ashwin; Shetty, Bhujang

    2015-01-01

    Purpose: The purpose of this study was to report the spectrum of anterior and posterior segment diagnoses in Asian Indian premature infants detected serendipitously during routine retinopathy of prematurity (ROP) screening during a 1 year period. Methods: A retrospective review of all Retcam (Clarity MSI, USA) imaging sessions during the year 2011 performed on infants born either <2001 g at birth and/or <34.1 weeks of gestation recruited for ROP screening was performed. All infants had a minimum of seven images at each session, which included the dilated anterior segment, disc, and macula center and the four quadrants using the 130° lens. Results: Of the 8954 imaging sessions of 1450 new infants recruited in 2011, there were 111 (7.66%) with a diagnosis other than ROP. Anterior segment diagnoses seen in 31 (27.9%) cases included clinically significant cataract, lid abnormalities, anophthalmos, microphthalmos, and corneal diseases. Posterior segment diagnoses in 80 (72.1%) cases included retinal hemorrhages, cherry red spots, and neonatal uveitis of infective etiologies. Of the 111 cases, 15 (13.5%) underwent surgical procedures and 24 (21.6%) underwent medical procedures; importantly, two eyes with retinoblastoma were detected which were managed timely. Conclusions: This study emphasizes the importance of ocular digital imaging in premature infants. Visually significant, potentially life-threatening, and even treatable conditions were detected serendipitously during routine ROP screening that may be missed or detected late otherwise. This pilot data may be used to advocate for a possible universal infant eye screening program using digital imaging. PMID:26139795

  4. Using enzyme bioassays as a rapid screen for metal toxicity

    USGS Publications Warehouse

    Choate, LaDonna M.; Ross, P.E.; Blumenstein, E. P.; Ranville, James F.

    2005-01-01

    Mine tailings piles and abandoned mine soils are often contaminated by a suite of toxic metals, which were released in the mining process. Traditionally, toxicity of such areas has been determined by numerous chemical methods including the Toxicity Characteristic Leachate Procedure (TCLP) and traditional toxicity tests using organisms such as the cladoceran Ceriodaphnia dubia. Such tests can be expensive and time-consuming. Enzymatic bioassays may provide an easier, less costly, and more time-effective toxicity screening procedure for mine tailings and abandoned mine soil leachates. This study evaluated the commercially available MetPLATE™ enzymatic toxicity assay test kit. The MetPLATE™ assay uses a modified strain of Escherichia coli bacteria as the test organism. Toxicity is defined by the activity of β-galactosidase enzyme which is monitored colorometrically with a 96-well spectrophotometer. The study used water samples collected from North Fork Clear Creek, a mining influenced water (MIW) located in Colorado. A great benefit to using the MetPLATE™ assay over the TCLP is that it shows actual toxicity of a sample by taking into account the bioavailability of the toxicants rather than simply measuring the metal concentration present. Benefits of the MetPLATE™ assay over the use of C. dubia include greatly reduced time for the testing process (∼2 hours), a more continuous variable due to a greater number of organisms present in each sample (100,000+), and the elimination of need to maintain a culture of organisms at all times.

  5. FIELD SCREENING METHODS FOR HAZARDOUS WASTES AND TOXIC CHEMICALS

    EPA Science Inventory

    The purpose of this document is to present the technical papers that were presented at the Second International Symposium on Field Screening Methods for Hazardous Wastes and Toxic Chemicals. ixty platform presentations were made and included in one of ten sessions: hemical sensor...

  6. Routine prenatal screening for HIV in a low-prevalence setting

    PubMed Central

    Patrick, D M; Money, D M; Forbes, J; Dobson, S R; Rekart, M L; Cook, D A; Middleton, P J; Burdge, D R

    1998-01-01

    BACKGROUND: The objectives of this study were to assess the effect of British Columbia's June 1994 guidelines for prenatal HIV screening on the rate of maternal-fetal HIV transmission and to estimate the cost-effectiveness of such screening. METHODS: The authors conducted a retrospective review of pregnancy and delivery statistics, HIV screening practices, laboratory testing volume, prenatal and labour management decisions of HIV-positive women, maternal-fetal transmission rates and associated costs. RESULTS: Over 1995 and 1996, 135,681 women were pregnant and 92,645 carried to term. The rate of HIV testing increased from 55% to 76% of pregnancies on chart review at one hospital between November 1995 and November 1996. On the basis of seroprevalence studies, an estimated 50.2 pregnancies and 34.3 (95% confidence interval 17.6 to 51.0) live births to HIV-positive women were expected. Of 42 identified mother-infant pairs with an estimated date of delivery during 1995 or 1996, 25 were known only through screening. Of these 25 cases, there were 10 terminations, 1 spontaneous abortion and 14 cases in which the woman elected to carry the pregnancy to term with antiretroviral therapy. There was one stillbirth. One instance of maternal-fetal HIV transmission occurred among the 13 live births. The net savings attributable to prevented infections among babies carried to term were $165,586, with a saving per prevented case of $75,266. INTERPRETATION: A routine offer of pregnancy screening for HIV in a low-prevalence setting reduces the rate of maternal-fetal HIV transmission and may rival other widely accepted health care expenditures in terms of cost-effectiveness. PMID:9834719

  7. Evaluation of Elecsys Syphilis Assay for Routine and Blood Screening and Detection of Early Infection.

    PubMed

    Kremastinou, J; Polymerou, V; Lavranos, D; Aranda Arrufat, A; Harwood, J; Martínez Lorenzo, M J; Ng, K P; Queiros, L; Vereb, I; Cusini, M

    2016-09-01

    Treponema pallidum infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against T. pallidum The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected T. pallidum antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results. PMID:27358468

  8. Evaluation of fetal echocardiography as a routine antenatal screening tool for detection of congenital heart disease

    PubMed Central

    Nayak, Krishnananda; Shetty, Ranjan; Narayan, Pratap Kumar

    2016-01-01

    Background Fetal echocardiography plays a pivotal role in identifying the congenital heart defects (CHDs) in utero. Though foetal echocardiography is mostly reserved for high risk pregnant women, its role as a routine prenatal screening tool still needs to be defined. Performing foetal echocardiography based on only these indications can lead to a significant numbers of CHD cases going undetected who will be deprived of further management leading to increased early neonatal mortalities. The aim of this study is to assess the incidence of CHDs by fetal echocardiography in an unselected population of pregnant women in comparison with pregnant women with conventional high risk factors for CHD. Methods This study enrolled consecutive pregnant women who attended antenatal clinic between 2008 and 2012 in a tertiary care hospital. These pregnant women were categorized into two groups: high risk group included pregnant women with traditional risk factors for CHD as laid down by Pediatric Council of the American Society of Echocardiography and low risk group. Detailed fetal 2 D echocardiography was done. Results A total of 1,280 pregnant women were included in study. The 118 women were categorized as the high risk group while remaining 1,162 were included in the low risk group. Twenty six cases of CHDs were detected based on abnormal foetal echocardiography (20.3 per 1,000). Two of the 26 cases of CHD occurred in high risk group whereas the remaining 24 occurred in low risk pregnancy. The difference in the incidence of CHDs between the two groups was not significant statistically (P=0.76). Conclusions Our study shows no difference in incidence of CHDs between pregnancies associated with high risk factors compared to low risk pregnancies. So we advocate foetal echocardiography should be included as a part of routine antenatal screening and all pregnant women irrespective of risk factors for CHDs. PMID:26885491

  9. Evaluation of Elecsys Syphilis Assay for Routine and Blood Screening and Detection of Early Infection

    PubMed Central

    Kremastinou, J.; Polymerou, V.; Lavranos, D.; Aranda Arrufat, A.; Harwood, J.; Martínez Lorenzo, M. J.; Ng, K. P.; Queiros, L.; Vereb, I.

    2016-01-01

    Treponema pallidum infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against T. pallidum. The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected T. pallidum antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results. PMID:27358468

  10. Mental Health Screening Among Newly-Arrived Refugees Seeking Routine Obstetric and Gynecologic Care

    PubMed Central

    Johnson-Agbakwu, Crista E.; Allen, Jennifer; Nizigiyimana, Jeanne F.; Ramirez, Glenda; Hollifield, Michael

    2014-01-01

    Posttraumatic stress disorder (PTSD), anxiety, and depression are the most common mental health disorders in the refugee population. High rates of violence, trauma, and PTSD among refugee women remain unaddressed. The process of implementing a mental health screening tool among multi-ethnic, newly-arrived refugee women receiving routine obstetric and gynecologic care in a dedicated refugee women’s health clinic is described. The Refugee Health Screener-15 (RHS-15) is a culturally-responsive, efficient, validated screening instrument that detects symptoms of emotional distress across diverse refugee populations and languages. An interdisciplinary community partnership was established with a local behavioral health services agency to facilitate the referral of women scoring positive on the RHS-15. Staff and provider training sessions, as well as the incorporation of bi-cultural, multi-lingual Cultural Health Navigators, greatly facilitated linguistically-appropriate care coordination for refugee women in a culturally sensitive manner. Twenty-six (23.2%) of the 112 women who completed the RHS-15 scored positive; of which 14 (53.8%) were Iraqi, one (3.8%) was Burmese, and three (11.5%) were Somali. Among these 26 women, eight (30.8%) are actively receiving mental health services, and five (19.2%) have appointments scheduled. However 13 (50%) are not enrolled in mental health care due to either declining services (46.2%), or a lack of insurance (53.8%). Screening for mental disorders among refugee women will promote greater awareness and identify those individuals who would benefit from further mental health evaluation and treatment. Sustainable interdisciplinary models of care are necessary to promote health education, dispel myths and reduce the stigma of mental health. PMID:25383999

  11. Mental health screening among newly arrived refugees seeking routine obstetric and gynecologic care.

    PubMed

    Johnson-Agbakwu, Crista E; Allen, Jennifer; Nizigiyimana, Jeanne F; Ramirez, Glenda; Hollifield, Michael

    2014-11-01

    Posttraumatic stress disorder (PTSD), anxiety, and depression are common mental health disorders in the refugee population. High rates of violence, trauma, and PTSD among refugee women remain unaddressed. The process of implementing a mental health screening tool among multiethnic, newly arrived refugee women receiving routine obstetric and gynecologic care in a dedicated refugee women's health clinic is described. The Refugee Health Screener-15 (RHS-15) is a culturally responsive, efficient, validated screening instrument that detects symptoms of emotional distress across diverse refugee populations and languages. An interdisciplinary community partnership was established with a local behavioral health services agency to facilitate the referral of women scoring positive on the RHS-15. Staff and provider training sessions, as well as the incorporation of bicultural, multilingual cultural health navigators, greatly facilitated linguistically appropriate care coordination for refugee women in a culturally sensitive manner. Twenty-six (23.2%) of the 112 women who completed the RHS-15 scored positive, of which 14 (53.8%) were Iraqi, 1 (3.8%) was Burmese, and 3 (11.5%) were Somali. Among these 26 women, 8 (30.8%) are actively receiving mental health services and 5 (19.2%) have appointments scheduled. However, 13 (50%) are not enrolled in mental health care because of either declining services (46.2%) or a lack of insurance (53.8%). Screening for mental disorders among refugee women will promote greater awareness and identify those individuals who would benefit from further mental health evaluation and treatment. Sustainable interdisciplinary models of care are necessary to promote health education, dispel myths, and reduce the stigma of mental health. PMID:25383999

  12. Understanding Barriers to Routine HIV Screening: Knowledge, Attitudes, and Practices of Healthcare Providers in King County, Washington

    PubMed Central

    Shirreffs, Alexandra; Lee, David P.; Henry, Jsani; Golden, Matthew R.; Stekler, Joanne D.

    2012-01-01

    Objective In 2006, the Centers for Disease Control and Prevention (CDC) recommended routine HIV screening in healthcare settings for persons between 13 and 64 years old. In 2010, the Washington Administrative Code (WAC) was changed to align testing rules with these recommendations. We designed this survey to ascertain the current state of HIV testing and barriers to routine screening in King County, Washington. Methods Between March 23 and April 16, 2010, a convenience sample of healthcare providers completed an online survey. Providers answered true-false and multiple choice questions about national recommendations and the WAC, policies in their primary clinical settings, and their personal HIV testing practices. Providers were asked to agree or disagree whether commonly reported barriers limited their implementation of routine HIV screening. Results Although 76% of the 221 respondents knew that the CDC recommended routine HIV screening for persons regardless of their risk, 99 (45%) providers reported that their primary clinical setting had a policy to target testing based on patient risk factors. Forty-four (20%) providers reported that their primary clinical setting had a policy of routine HIV screening, 54 (25%) reported no official policy, and 15 (7%) did not know whether a policy existed. Only 11 (5%) providers offer HIV testing to all patients at initial visits. When asked about barriers to routine screening, 57% of providers agreed that perception that their patient population is low risk limits the number of HIV tests they perform. Only 26 (13%) providers agreed that concern about reimbursement posed a barrier to testing. Conclusions Most providers participating in this survey continue to target HIV testing, despite knowledge of national recommendations. Efforts are still needed to educate providers and policymakers, clarify the recent WAC revisions, and implement structural changes in order to increase HIV testing in Washington State. PMID:22970215

  13. Developmental toxicity assay using high content screening of zebrafish embryos

    PubMed Central

    Lantz-McPeak, Susan; Guo, Xiaoqing; Cuevas, Elvis; Dumas, Melanie; Newport, Glenn D.; Ali, Syed F.; Paule, Merle G.; Kanungo, Jyotshna

    2016-01-01

    Typically, time-consuming standard toxicological assays using the zebrafish (Danio rerio) embryo model evaluate mortality and teratogenicity after exposure during the first 2 days post-fertilization. Here we describe an automated image-based high content screening (HCS) assay to identify the teratogenic/embryotoxic potential of compounds in zebrafish embryos in vivo. Automated image acquisition was performed using a high content microscope system. Further automated analysis of embryo length, as a statistically quantifiable endpoint of toxicity, was performed on images post-acquisition. The biological effects of ethanol, nicotine, ketamine, caffeine, dimethyl sulfoxide and temperature on zebrafish embryos were assessed. This automated developmental toxicity assay, based on a growth-retardation endpoint should be suitable for evaluating the effects of potential teratogens and developmental toxicants in a high throughput manner. This approach can significantly expedite the screening of potential teratogens and developmental toxicants, thereby improving the current risk assessment process by decreasing analysis time and required resources. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. PMID:24871937

  14. A comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; Schalie, W.H. van der; Leather, G.R.

    1995-05-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus calyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photobacterium phosphoreum--Microtox{reg_sign} test, and a mixture of bacterial species--the Polytox{reg_sign} test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriodaphnia dubia), green algae (Selenastrum capricornutum), fathead minnows (Pimephales promelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC50/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  15. Comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; VanDerSchal, W.H.; Leather, G.R.

    1995-10-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  16. Recombinant antigen-based enzyme immunoassay for screening of Treponema pallidum antibodies in blood bank routine.

    PubMed Central

    Zrein, M; Maure, I; Boursier, F; Soufflet, L

    1995-01-01

    This work reports a comparison of an enzyme immunoassay (EIA) using two major Treponema pallidum recombinant antigens with a T. pallidum hemagglutination (TPHA) assay and a nontreponemal Venereal Disease Reference Laboratory (VDRL) test. A total of 1,822 normal donor serum samples was tested for cardiolipin and T. pallidum antibodies, respectively, by the VDRL assay and EIA. Among these samples, 440 were further tested by TPHA technology. Four samples were found positive by EIA, while all were reported to be negative by both TPHA and VDRL routine assays. Subsequent testing of EIA-positive samples confirmed 100% (four of four samples) and 25% (one of four samples) positive results, respectively, by immunofluorescence assay and a Western blot (immunoblot) syphilis kit. The sensitivity of the recombinant EIA was estimated at virtually 100% with a reference panel of 50 syphilitic samples. According to this study, the newly developed EIA kit shows 100% sensitivity combined to a specificity greater than 99.8% for detecting treponemal immunoglobulin G antibodies in blood bank syphilis screening. PMID:7751351

  17. DetecTiff: a novel image analysis routine for high-content screening microscopy.

    PubMed

    Gilbert, Daniel F; Meinhof, Till; Pepperkok, Rainer; Runz, Heiko

    2009-09-01

    In this article, the authors describe the image analysis software DetecTiff, which allows fully automated object recognition and quantification from digital images. The core module of the LabView-based routine is an algorithm for structure recognition that employs intensity thresholding and size-dependent particle filtering from microscopic images in an iterative manner. Detected structures are converted into templates, which are used for quantitative image analysis. DetecTiff enables processing of multiple detection channels and provides functions for template organization and fast interpretation of acquired data. The authors demonstrate the applicability of DetecTiff for automated analysis of cellular uptake of fluorescence-labeled low-density lipoproteins as well as diverse other image data sets from a variety of biomedical applications. Moreover, the performance of DetecTiff is compared with preexisting image analysis tools. The results show that DetecTiff can be applied with high consistency for automated quantitative analysis of image data (e.g., from large-scale functional RNAi screening projects). PMID:19641223

  18. Personality disorders in heart failure patients requiring psychiatric management: comorbidity detections from a routine depression and anxiety screening protocol.

    PubMed

    Tully, Phillip J; Selkow, Terina

    2014-12-30

    Several international guidelines recommend routine depression screening in cardiac disease populations. No previous study has determined the prevalence and comorbidities of personality disorders in patients presenting for psychiatric treatment after these screening initiatives. In the first stage 404 heart failure (HF) patients were routinely screened and 73 underwent structured interview when either of the following criteria were met: (a) Patient Health Questionnaire ≥10; (b) Generalized Anxiety Disorder Questionnaire ≥7); (c) Response to one item panic-screener. Or (d) Suicidality. Patients with personality disorders were compared to the positive-screen patients on psychiatric comorbidities. The most common personality disorders were avoidant (8.2%), borderline (6.8%) and obsessive compulsive (4.1%), other personality disorders were prevalent in less than <3% of patients. Personality disorder patients had significantly greater risk of major depression (risk ratio (RR) 1.2; 95% confidence interval (CI) 1.2-13.3), generalized anxiety disorder (RR 3.2; 95% CI 1.0-10.0), social phobia (RR 3.8; 95% CI 1.3-11.5) and alcohol abuse/dependence (RR 3.2; 95% 1.0-9.5). The findings that HF patients with personality disorders presented with complex psychiatric comorbidity suggest that pathways facilitating the integration of psychiatric services into cardiology settings are warranted when routine depression screening is in place. PMID:25238983

  19. Rapid toxicity screening of sediment pore waters using physiological and biochemical biomarkers of Daphnia magna

    SciTech Connect

    Coen, W.M. De; Janssen, C.R.; Persoone, G.

    1995-12-31

    Two new rapid toxicity tests, based on ingestion activity and digestive enzyme activity of D. magna, were developed and evaluated. The ingestion activity was measured using fluorescent latex micro-beads and an automated microplate fluorimeter allowing a sensitive quantification of the feeding activity of the organisms. The activity of the digestive enzymes, 6-galactosidase, esterase and trypsin, was determined in test organism homogenates using the following fluorogenic{sup 1} and chromogenic{sup 2} substrates: 4-methylumbelliferyl-{beta}-D galactoside{sup 1}, fluorescin diacetate{sup 1} and N-Benzoyl-L-arginine-4-nitroanilide{sup 2}. Both biomarker techniques were developed to allow rapid toxicity screening on a routine basis. The toxicity of the pore waters of eight contaminated samples was assessed with the aid of the developed biomarker assays. Comparison of the conventional 24h EC50 values with the EC50 values obtained with the 1.5h ingestion test and the threshold concentrations of the 2h digestive enzyme tests revealed a positive correlation between the different effect concentrations. A similar correlation (r{sup 2} = 0.87) between the conventional 24h EC50 values and 1.5h EC50 values was observed in toxicity tests with pure compounds. Correlation coefficients for the relationships between the 3 enzyme effect concentrations and the 24h EC50 values ranged from 0.95 to 0.98, The positive correlations between the conventional and biomarker effect criteria, observed for both environmental samples and pure compounds, demonstrate the potential use of the developed methods as rapid toxicity screening tools.

  20. 40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening test. 799.9365 Section 799.9365 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL...

  1. Free-living amoebae and their associated bacteria in Austrian cooling towers: a 1-year routine screening.

    PubMed

    Scheikl, Ute; Tsao, Han-Fei; Horn, Matthias; Indra, Alexander; Walochnik, Julia

    2016-09-01

    Free-living amoebae (FLA) are widely spread in the environment and known to cause rare but often serious infections. Besides this, FLA may serve as vehicles for bacterial pathogens. In particular, Legionella pneumophila is known to replicate within FLA thereby also gaining enhanced infectivity. Cooling towers have been the source of outbreaks of Legionnaires' disease in the past and are thus usually screened for legionellae on a routine basis, not considering, however, FLA and their vehicle function. The aim of this study was to incorporate a screening system for host amoebae into a Legionella routine screening. A new real-time PCR-based screening system for various groups of FLA was established. Three cooling towers were screened every 2 weeks over the period of 1 year for FLA and Legionella spp., by culture and molecular methods in parallel. Altogether, 83.3 % of the cooling tower samples were positive for FLA, Acanthamoeba being the dominating genus. Interestingly, 69.7 % of the cooling tower samples were not suitable for the standard Legionella screening due to their high organic burden. In the remaining samples, positivity for Legionella spp. was 25 % by culture, but overall positivity was 50 % by molecular methods. Several amoebal isolates revealed intracellular bacteria. PMID:27177720

  2. Using a configurable EMR and decision support tools to promote process integration for routine HIV screening in the emergency department.

    PubMed

    McGuire, Robert; Moore, Eric

    2016-03-01

    Given the clinical and public health benefits of routine Human Immunodeficiency Virus (HIV) testing in the emergency department (ED) and Centers for Disease Control and Prevention recommendations, Maricopa Medical Center, as part of Maricopa Integrated Health System, started Test, Educate, Support, and Treat Arizona (TESTAZ) and became the first and, to-date, only hospital in Arizona to implement routine, non-targeted, opt-out, rapid HIV screening in the ED. The authors describe the implementation of a universal, routine, opt-out HIV screening program in the adult ED of an urban safety-net hospital serving under-served populations, including the uninsured and under-insured. Through a controlled and collaborative process, the authors integrated custom documentation elements specific to HIV screening into the triage/intake process, implemented and utilized clinical decision support tools to guide clinicians in each step of the process, and used electronic data collection and reporting to drive new screening protocols that led to a significant increase in overall HIV testing rates. PMID:26338216

  3. The role of routine cervical length screening in selected high- and low-risk women for preterm birth prevention.

    PubMed

    McIntosh, Jennifer; Feltovich, Helen; Berghella, Vincenzo; Manuck, Tracy

    2016-09-01

    Preterm birth remains a major cause of neonatal death and short and long-term disability in the US and across the world. The majority of preterm births are spontaneous and cervical length screening is one tool that can be utilized to identify women at increased risk who may be candidates for preventive interventions. The purpose of this document is to review the indications and rationale for CL screening to prevent preterm birth in various clinical scenarios. The Society for Maternal-Fetal Medicine recommends (1) routine transvaginal cervical length screening for women with singleton pregnancy and history of prior spontaneous preterm birth (grade 1A); (2) routine transvaginal cervical length screening not be performed for women with cervical cerclage, multiple gestation, preterm premature rupture of membranes, or placenta previa (grade 2B); (3) practitioners who decide to implement universal cervical length screening follow strict guidelines (grade 2B); (4) sonographers and/or practitioners receive specific training in the acquisition and interpretation of cervical imaging during pregnancy (grade 2B). PMID:27133011

  4. In Vitro Screening for Population Variability in Chemical Toxicity

    PubMed Central

    O'Shea, Shannon H.; Schwarz, John; Kosyk, Oksana; Ross, Pamela K.; Ha, Min Jin; Wright, Fred A.; Rusyn, Ivan

    2011-01-01

    Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d'Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility. PMID:20952501

  5. The Activated Coagulation Time of Whole Blood as a Routine Pre-Operative Screening Test

    PubMed Central

    Hattersley, Paul G.

    1971-01-01

    Patients with disorders of hemostasis who undergo surgical procedures are in danger of hemorrhage. While the careful medical history remains the most sensitive test of a bleeding tendency, some such patients can give no suggestive history. In three patients with coagulopathy—one with mild classical hemophilia, one with Christmas disease, and one with warfarin toxicity—the abnormality was missed by routine preoperative history but promptly detected by the routine preoperative use of the activated coagulation time (act). Either this test or the activated partial thromboplastin time should be included in the routine preoperative work-up, along with appropriate additional tests of the hemostatic mechanism. PMID:5087876

  6. Zebrafish developmental toxicity assay: A fishy solution to reproductive toxicity screening, or just a red herring?

    PubMed

    Van den Bulck, Kathleen; Hill, Adrian; Mesens, Natalie; Diekman, Heike; De Schaepdrijver, Luc; Lammens, Lieve

    2011-09-01

    The zebrafish embryotoxicity/teratogenicity assay is described as a useful alternative screening model to evaluate the effect of drugs on embryofoetal development. Fertilized eggs were exposed to different concentrations of 15 compounds with teratogenic (8) and non-teratogenic (7) potential until 96h post-fertilization when 28 morphological endpoints and the level of compound uptake was assessed. The majority of drugs testing positive in mammals was also positive in zebrafish (75% sensitivity), while a relative high number of false positives were noted (43% specificity). Compound uptake determination appears useful for clarifying classifications as teratogenic or potential overdose although assay sensitivity could be improved to 71% if the exposure threshold, previously suggested as ∼50ng/larvae, is reconsidered. The zebrafish assay shows some potential, though limited in its current form, as a screening tool for developmental toxicity within Janssen drug development. Further assay refinement with respect to endpoints and body burden threshold is required. PMID:21704152

  7. Constructing a Population-Based Research Database from Routine Maternal Screening Records: A Resource for Studying Alloimmunization in Pregnant Women

    PubMed Central

    Zhang, Zhongxing; Gryfelt, Gunilla; Wikman, Agneta; Reilly, Marie

    2011-01-01

    Background Although screening for maternal red blood cell antibodies during pregnancy is a standard procedure, the prevalence and clinical consequences of non-anti-D immunization are poorly understood. The objective was to create a national database of maternal antibody screening results that can be linked with population health registers to create a research resource for investigating these issues. Study Design and Methods Each birth in the Swedish Medical Birth Register was uniquely identified and linked to the text stored in routine maternal antibody screening records in the time window from 9 months prior to 2 weeks after the delivery date. These text records were subjected to a computerized search for specific antibodies using regular expressions. To illustrate the research potential of the resulting database, selected antibody prevalence rates are presented as tables and figures, and the complete data (from more than 60 specific antibodies) presented as online moving graphical displays. Results More than one million (1,191,761) births with valid screening information from 1982–2002 constitute the study population. Computerized coverage of screening increased steadily over time and varied by region as electronic records were adopted. To ensure data quality, we restricted analysis to birth records in areas and years with a sustained coverage of at least 80%, representing 920,903 births from 572,626 mothers in 17 of the 24 counties in Sweden. During the study period, non-anti-D and anti-D antibodies occurred in 76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences between specific antibodies over time. Conclusion This work demonstrates the feasibility of creating a nationally representative research database from the routine maternal antibody screening records from an extended calendar period. By linkage with population registers of maternal and child health, such data are a valuable resource for addressing important clinical questions

  8. Toxicity Screening of the ToxCast Chemical Library Using a Zebrafish Developmental Assay

    EPA Science Inventory

    As part of the chemical screening and prioritization research program of the U.S. Environmental Protection Agency, the toxicity of the 320 ToxCast™ Phase I chemicals were assessed using a vertebrate screen of developmental toxicity. Zebrafish embryos/larvae (Danio rerio) were exp...

  9. Public attitudes towards genomic risk profiling as a component of routine population screening1

    PubMed Central

    Nicholls, S.G.; Wilson, B.J.; Craigie, S.M.; Etchegary, H.; Castle, D.; Carroll, J.C.; Potter, B.K.; Lemyre, L.; Little, J.

    2016-01-01

    Including low penetrance genomic variants in population-based screening might enable personalization of screening intensity and follow up. The application of genomics in this way requires formal evaluation. Even if clinically beneficial, uptake would still depend on the attitudes of target populations. We developed a deliberative workshop on two hypothetical applications (in colorectal cancer and newborn screening) in which we applied stepped, neutrally-framed, information sets. Data were collected using nonparticipant observation, free-text comments by individual participants, and a structured survey. Qualitative data were transcribed and analyzed using thematic content analysis. Eight workshops were conducted with 170 individuals (120 colorectal cancer screening and 50 newborn screening for type 1 diabetes). The use of information sets promoted informed deliberation. In both contexts, attitudes appeared to be heavily informed by assessments of the likely validity of the test results and its personal and health care utility. Perceived benefits included the potential for early intervention, prevention, and closer monitoring while concerns related to costs, education needs regarding the probabilistic nature of risk, the potential for worry, and control of access to personal genomic information. Differences between the colorectal cancer and newborn screening groups appeared to reflect different assessments of potential personal utility, particularly regarding prevention. PMID:24237344

  10. Implementing routine screening for distress, the sixth vital sign, for patients with head and neck and neurologic cancers.

    PubMed

    Bultz, Barry D; Waller, Amy; Cullum, Jodi; Jones, Paula; Halland, Johan; Groff, Shannon L; Leckie, Catriona; Shirt, Lisa; Blanchard, Scott; Lau, Harold; Easaw, Jacob; Fassbender, Konrad; Carlson, Linda E

    2013-10-01

    This study examined the benefits of incorporating screening for distress as a routine part of care for patients with head and neck and neurologic cancers in a tertiary cancer center. Using a comparative 2-cohort pre-post implementation sequential design, consecutive outpatients with head and neck and neurologic cancers were recruited into 2 separate cohorts. Cohort 1 included patients attending clinics during April 2010, before the implementation of the screening program. The program was then implemented and patients completed the Screening for Distress Minimum Dataset (the Edmonton Symptom Assessment System [ESAS] and the Canadian Problem Checklist [CPC]) at each clinic visit. Cohort 2 included patients attending clinics during March 2011. Consenting patients completed screening and outcome measures (ESAS, CPC, and either the Functional Assessment of Cancer Therapy-Brain or the Functional Assessment of Cancer Therapy-Head and Neck). A total of 146 patients (78 head and neck and 68 neurologic) provided data for Cohort 1, and 143 (81 head and neck and 62 neurologic) provided data for Cohort 2. Compared with Cohort 1, patients with neurologic cancers in Cohort 2 reported significantly higher scores on the Functional Assessment of Cancer Therapy: General total and emotional quality of life subscale; fewer high scores (≥ 4) on the ESAS breathlessness item; and fewer problems with fears/worries, frustration/anger, finding meaning in life, and worry about friends/family. Head and neck patients in Cohort 2 reported significantly higher emotional quality of life and fewer problems with eating and weight than those in Cohort 1. Although no definitive causal attributions can be made, patients exposed to routine screening for distress reported better well-being and fewer emotional, physical, and practical problems than historical controls. PMID:24142826

  11. Effects of scanning (routine health information exposure) on cancer screening and prevention behaviors in the general population.

    PubMed

    Hornik, Robert; Parvanta, Sarah; Mello, Susan; Freres, Derek; Kelly, Bridget; Schwartz, J Sanford

    2013-01-01

    Research on health information exposure focuses primarily on deliberate information-seeking behavior and its effects on health. By contrast, this study explores the complementary and perhaps more influential role of health information acquired through exposure to routinely used sources, called scanning. The authors hypothesized that scanning from nonmedical sources, both mediated and interpersonal, affects cancer screening and prevention decisions. The authors used a nationally representative longitudinal survey of 2,489 adults 40 to 70 years of age to analyze the effects of scanning on 3 cancer screening behaviors (mammography, prostate-specific antigen [PSA], and colonoscopy) and 3 prevention behaviors (exercising, eating fruits and vegetables, and dieting to lose weight). After adjustment for baseline behaviors and covariates, scanning at baseline predicted weekly exercise days 1 year later as well as daily fruit and vegetable servings 1 year later for those whose consumption of fruits and vegetables was already higher at baseline. Also, among those reporting timely screening mammogram behavior at baseline, scanning predicted repeat mammography. Scanning was marginally predictive of PSA uptake among those not reporting a PSA at baseline. Although there were strong cross-sectional associations, scanning did not predict dieting or colonoscopy uptake in longitudinal analyses. These analyses provide substantial support for a claim that routine exposure to health content from nonmedical sources affects specific health behaviors. PMID:24083417

  12. Post-stroke depression, obstructive sleep apnea, and cognitive impairment: Rationale for, and barriers to, routine screening.

    PubMed

    Swartz, Richard H; Bayley, Mark; Lanctôt, Krista L; Murray, Brian J; Cayley, Megan L; Lien, Karen; Sicard, Michelle N; Thorpe, Kevin E; Dowlatshahi, Dar; Mandzia, Jennifer L; Casaubon, Leanne K; Saposnik, Gustavo; Perez, Yael; Sahlas, Demetrios J; Herrmann, Nathan

    2016-07-01

    Stroke can cause neurological impairment ranging from mild to severe, but the impact of stroke extends beyond the initial brain injury to include a complex interplay of devastating comorbidities including: post-stroke depression, obstructive sleep apnea, and cognitive impairment ("DOC"). We reviewed the frequency, impact, and treatment options for each DOC condition. We then used the Ottawa Model of Research Use to examine gaps in care, understand the barriers to knowledge translation, identification, and addressing these important post-stroke comorbidities. Each of the DOC conditions is common and result in poorer recovery, greater functional impairment, increased stroke recurrence and mortality, even after accounting for traditional vascular risk factors. Despite the strong relationships between DOC comorbidities and these negative outcomes as well as recommendations for screening based on best practice recommendations from several countries, they are frequently not assessed. Barriers related to the nature of the screening tools (e.g., time consuming in high-volume clinics), practice environment (e.g., lack of human resources or space), as well as potential adopters (e.g., equipoise surrounding the benefits of treatment for these conditions) pose challenges to routine screening implementation. Simple, feasible approaches to routine screening coupled with appropriate, evidence-based treatment protocols are required to better identify and manage depression, obstructive sleep apnea, and cognitive impairment symptoms in stroke prevention clinic patients to reduce the impact of these important post-stroke comorbidities. These tools may in turn facilitate large-scale randomized controlled treatment trials of interventions for DOC conditions that may help to improve cardiovascular outcomes after stroke or TIA. PMID:27073189

  13. Oral cancer detection. The importance of routine screening for prolongation of survival.

    PubMed

    Chiodo, G T; Eigner, T; Rosenstein, D I

    1986-08-01

    The incidence of oral cancer has increased in the past ten years. Early diagnosis and treatment are essential to long-term survival; however, patients at highest risk visit the dentist infrequently. The reddish, velvety or erythroplakial lesion at the base of the tongue or floor of the mouth is highly suspicious in any patient and requires further evaluation. High-risk patients with less suspicious appearing lesions must be reevaluated on close recall. Prognosis improves vastly when the lesion is detected and treated early. One study demonstrated a 64% five-year survival rate for patients with oral cancer that was diagnosed before regional lymph node involvement versus a 15% five-year survival for patients whose lesions were diagnosed after regional lymph node involvement. By including an oral cancer examination in routine physical examination of patients, the physician and public health nurse can increase the likelihood of early detection of oral cancer. PMID:3526308

  14. Routine prenatal ultrasound anomaly screening program in a Nigerian university hospital: Redefining obstetrics practice in a developing African country

    PubMed Central

    Akinmoladun, J.A.; Ogbole, G.I.; Lawal, T.A.; Adesina, O.A.

    2015-01-01

    Background: Congenital anomalies are among the leading causes of fetal and infant morbidity and mortality worldwide. Prenatal ultrasound (US) screening has become an essential part of antenatal care in the developed world. Such practice is just evolving in the developing countries such as Nigeria. The aim of this article is to present our initial experience and demonstrate the effectiveness of a prenatal US screening program in detecting congenital malformation in a developing country. Materials and Methods: This was a prospective evaluation of the prenatal US screenings conducted at a major referral hospital in Southwestern Nigeria. All pregnant women referred to the antenatal clinic for mid-trimester screening during the period of study were assessed. Results: Two hundred and eighty-seven pregnant women (5 with twin gestations) were presented for fetal anomaly scan during the study period. Twenty-nine anomalies (9.9%) were detected among the scanned population. Sixteen of the anomalies were followed to delivery/termination with a specificity of 93.5%. The commonest malformations were demonstrated in the genitourinary tract (34.5%) followed by malformations within the central nervous system (27.6%). Six (20.6%) of the anomalies were lethal. Five of the anomalies were surgically correctable. Conclusion: Institutions and hospitals across Nigeria and other low- and middle-income countries need to develop policies and programs that would incorporate a standardized routine screening prenatal US in order to improve feto-maternal well-being and reduce the high perinatal mortality and morbidity in developing nations. PMID:26759511

  15. Big Data in Chemical Toxicity Research: The Use of High-Throughput Screening Assays To Identify Potential Toxicants

    PubMed Central

    2015-01-01

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound’s ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  16. Big data in chemical toxicity research: the use of high-throughput screening assays to identify potential toxicants.

    PubMed

    Zhu, Hao; Zhang, Jun; Kim, Marlene T; Boison, Abena; Sedykh, Alexander; Moran, Kimberlee

    2014-10-20

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound's ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  17. Integration of Dosimetry, Exposure and High-Throughput Screening Data in Chemical Toxicity Assessment

    EPA Science Inventory

    High-throughput in vitro toxicity screening can provide an efficient way to identify potential biological targets for chemicals. However, relying on nominal assay concentrations may misrepresent potential in vivo effects of these chemicals due to differences in bioavailability, c...

  18. Trilateral retinoblastoma: neuroimaging characteristics and value of routine brain screening on admission.

    PubMed

    Rodjan, Firazia; de Graaf, Pim; Brisse, Hervé J; Göricke, Sophia; Maeder, Philippe; Galluzzi, Paolo; Aerts, Isabelle; Alapetite, Claire; Desjardins, Laurence; Wieland, Regina; Popovic, Maja Beck; Diezi, Manuel; Munier, Francis L; Hadjistilianou, Theodora; Knol, Dirk L; Moll, Annette C; Castelijns, Jonas A

    2012-09-01

    Trilateral retinoblastoma (TRb) is a rare disease associating intraocular retinoblastoma with intracranial primitive neuroectodermal tumor. Treatment is difficult and prognosis is poor. This multicenter study evaluates clinical findings and MR imaging characteristics of associated intracranial tumors in Rb patients. Clinical data of 17 patients (16 TRb and 1 quadrilateral Rb patients) included time intervals between Rb and TRb diagnosis and presence of baseline brain-imaging (BBI). Two reviewers reviewed all images individually and one reviewer per center evaluated their images. Consensus was reached during a joint scoring session. Studies were reviewed for tumor location, size and imaging characteristics (signal intensity (SI) on T1- and T2-weighted images, enhancement pattern and cystic appearance). Of 18 intracranial tumors, 78 % were located in the pineal gland and 22 % suprasellar. All tumors showed well-defined borders with mostly heterogenous enhancement (72 %) and isointense SI on T1- (78 %) and T2-weighted images (72 %) compared to gray matter. The majority of pineal TRbs showed a cystic component (57 %). TRb detected synchronously with the intraocular tumors on BBI (n = 7) were significantly smaller (P = 0.02), and mainly asymptomatic than TRb detected later on (n = 10). Overall, 5-year-survival of TRb patients detected on BBI was 67 % (95 % CI 29-100 %) compared to 11 % (95 % CI 0-32 %) for the group with delayed diagnosis. TRb mainly develops in the pineal gland and frequently presents with a cystic appearance that could be misinterpreted as benign pineal cysts. Routine BBI in all newly diagnosed Rb patients can detect TRb at a subclinical stage. PMID:22802019

  19. Intracellular calcium levels as screening tool for nanoparticle toxicity

    PubMed Central

    Meindl, Claudia; Kueznik, Tatjana; Bösch, Martina; Roblegg, Eva; Fröhlich, Eleonore

    2015-01-01

    The use of engineered nano-sized materials led to revolutionary developments in many industrial applications and in the medical field. These materials, however, also may cause cytotoxicity. In addition to size, surface properties and shape were identified as relevant parameters for cell damage. Cell damage may occur as disruption of membrane integrity, induction of apoptosis and by organelle damage. Generation of oxidative stress may serve as an indicator for cytotoxicity. Effects occurring upon short contact of particles with cells, for instance in the systemic blood circulation, could be identified according to increases of intracellular [Ca2+] levels, which are caused by variety of toxic stimuli. Negatively charged, neutral and positively charged polystyrene particles of different sizes were used to study the role of size and surface properties on viability, membrane disruption, apoptosis, lysosome function, intracellular [Ca2+] levels and generation of oxidative stress. Silica particles served to test this hypothesis. Twenty nm polystyrene particles as well as 12 nm and 40 nm silica particles caused membrane damage and apoptosis with no preference of the surface charge. Only 20 nm plain and amine functionalized polystyrene particles cause oxidative stress and only the plain particles lysosomal damage. A potential role of surface charge was identified for 200 nm polystyrene particles, where only the amidine particles caused lysosomal damage. Increases in intracellular [Ca2+] levels and cytotoxicity after 24 h was often linked but determination of intracellular [Ca2+] levels could serve to characterize further the type of membrane damage. © 2015 The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd. Nano-sized materials may cause cytotoxicity. Negatively charged, neutral and positively charged polystyrene particles of different sizes and silica nanoparticles were used to study the role of size and surface properties on viability, membrane

  20. Should pre-implantation genetic screening be implemented to routine clinical practice?

    PubMed

    Orvieto, Raoul; Shuly, Yulia; Brengauz, Masha; Feldman, Baruch

    2016-06-01

    The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. Since mosaicism has been reported in as high as 90% of blastocyst-stage embryos, we aimed to evaluate the accuracy of trophectoderm multiple biopsies using next-generation sequencing (NGS). Eight top quality blastocysts underwent three trophectoderm biopsies each, followed by NGS. In four blastocysts, the rest of the embryo, which included the inner cell mass, was also analyzed. Five of the 24 (20.8%) trophectoderm biopsies revealed inconclusive results, while 4 (16.6%) demonstrated embryonic mosaicism. Overall, 10 (35.7%) of the 28 (24 trophectoderms and 4 inner cell masses) biopsies revealed mosaicism or inconclusive results. Our preliminary observations contribute to the ongoing discussion on the unrestricted clinical adoption of PGS, suggesting, that until proper evaluation of its effectiveness and cost-effectiveness will be provided, PGS should be offered only under study conditions, and with appropriate informed consents. PMID:26872945

  1. Routine screening of harmful microorganisms in beach sands: implications to public health

    USGS Publications Warehouse

    Sabino, Raquel; Rodrigues, R.; Costa, I.; Carneiro, Carlos; Cunha, M.; Duarte, A.; Faria, N.; Ferriera, F.C.; Gargate, M.J.; Julio, C.; Martins, M.L.; Nevers, Meredith; Oleastro, M.; Solo-Gabriele, H.; Verissimo, C.; Viegas, C.; Whitman, Richard L.; Brandao, J.

    2014-01-01

    Beaches worldwide provide recreational opportunities to hundreds of millions of people and serve as important components of coastal economies. Beach water is often monitored for microbiological quality to detect the presence of indicators of human sewage contamination so as to prevent public health outbreaks associated with water contact. However, growing evidence suggests that beach sand can harbor microbes harmful to human health, often in concentrations greater than the beach water. Currently, there are no standards for monitoring, sampling, analyzing, or managing beach sand quality. In addition to indicator microbes, growing evidence has identified pathogenic bacteria, viruses, and fungi in a variety of beach sands worldwide. The public health threat associated with these populations through direct and indirect contact is unknown because so little research has been conducted relating to health outcomes associated with sand quality. In this manuscript, we present the consensus findings of a workshop of experts convened in Lisbon, Portugal to discuss the current state of knowledge on beach sand microbiological quality and to develop suggestions for standardizing the evaluation of sand at coastal beaches. The expert group at the “Microareias 2012” workshop recommends that 1) beach sand should be screened for a variety of pathogens harmful to human health, and sand monitoring should then be initiated alongside regular water monitoring; 2) sampling and analysis protocols should be standardized to allow proper comparisons among beach locations; and 3) further studies are needed to estimate human health risk with exposure to contaminated beach sand. Much of the manuscript is focused on research specific to Portugal, but similar results have been found elsewhere, and the findings have worldwide implications.

  2. Routine screening of harmful microorganisms in beach sands: implications to public health.

    PubMed

    Sabino, R; Rodrigues, R; Costa, I; Carneiro, C; Cunha, M; Duarte, A; Faria, N; Ferreira, F C; Gargaté, M J; Júlio, C; Martins, M L; Nevers, M B; Oleastro, M; Solo-Gabriele, H; Veríssimo, C; Viegas, C; Whitman, R L; Brandão, J

    2014-02-15

    Beaches worldwide provide recreational opportunities to hundreds of millions of people and serve as important components of coastal economies. Beach water is often monitored for microbiological quality to detect the presence of indicators of human sewage contamination so as to prevent public health outbreaks associated with water contact. However, growing evidence suggests that beach sand can harbor microbes harmful to human health, often in concentrations greater than the beach water. Currently, there are no standards for monitoring, sampling, analyzing, or managing beach sand quality. In addition to indicator microbes, growing evidence has identified pathogenic bacteria, viruses, and fungi in a variety of beach sands worldwide. The public health threat associated with these populations through direct and indirect contact is unknown because so little research has been conducted relating to health outcomes associated with sand quality. In this manuscript, we present the consensus findings of a workshop of experts convened in Lisbon, Portugal to discuss the current state of knowledge on beach sand microbiological quality and to develop suggestions for standardizing the evaluation of sand at coastal beaches. The expert group at the "Microareias 2012" workshop recommends that 1) beach sand should be screened for a variety of pathogens harmful to human health, and sand monitoring should then be initiated alongside regular water monitoring; 2) sampling and analysis protocols should be standardized to allow proper comparisons among beach locations; and 3) further studies are needed to estimate human health risk with exposure to contaminated beach sand. Much of the manuscript is focused on research specific to Portugal, but similar results have been found elsewhere, and the findings have worldwide implications. PMID:24355396

  3. Screening Bacillus thuringiensis strains for toxicity against Manduca sexta and Plutella xylostella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Screening Bacillus thuringiensis (Bt) isolates or strains for toxicity has traditionally been performed with one bacterial isolate at time versus a specific insect. By testing of Bt strains in groups, we identified 28 of 147 Bt isolates as toxic to either diamondback moth, Plutella xylostella (L.),...

  4. The U.S. EPA's ToxCast Chemical Screening Program and Predictive Modeling of Toxicity

    EPA Science Inventory

    The ToxCast program was developed by the U.S. EPA's National Center for Computational Toxicology to provide cost-effective high-throughput screening for the potential toxicity of thousands of chemicals. Phase I screened 309 compounds in over 500 assays to evaluate concentration-...

  5. A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity.

    PubMed

    Astashkina, Anna; Mann, Brenda; Grainger, David W

    2012-04-01

    Drug candidate and toxicity screening processes currently rely on results from early-stage in vitro cell-based assays expected to faithfully represent essential aspects of in vivo pharmacology and toxicology. Several in vitro designs are optimized for high throughput to benefit screening efficiencies, allowing the entire libraries of potential pharmacologically relevant or possible toxin molecules to be screened for different types of cell signals relevant to tissue damage or to therapeutic goals. Creative approaches to multiplexed cell-based assay designs that select specific cell types, signaling pathways and reporters are routine. However, substantial percentages of new chemical and biological entities (NCEs/NBEs) that fail late-stage human drug testing, or receive regulatory "black box" warnings, or that are removed from the market for safety reasons after regulatory approvals all provide strong evidence that in vitro cell-based assays and subsequent preclinical in vivo studies do not yet provide sufficient pharmacological and toxicity data or reliable predictive capacity for understanding drug candidate performance in vivo. Without a reliable translational assay tool kit for pharmacology and toxicology, the drug development process is costly and inefficient in taking initial in vitro cell-based screens to in vivo testing and subsequent clinical approvals. Commonly employed methods of in vitro testing, including dissociated, organotypic, organ/explant, and 3-D cultures, are reviewed here with specific focus on retaining cell and molecular interactions and physiological parameters that determine cell phenotypes and their corresponding responses to bioactive agents. Distinct advantages and performance challenges for these models pertinent to cell-based assay and their predictive capabilities required for accurate correlations to in vivo mechanisms of drug toxicity are compared. PMID:22252140

  6. Routine Screening for CYP2C19 Polymorphisms for Patients being Treated with Clopidogrel is not Recommended

    PubMed Central

    Hong, Robert A; Khan, Zia R; Valentin, Mona R; Badawi, Ramy A

    2015-01-01

    Recent efforts directed at potential litigation in Hawai‘i have resulted in a renewed interest for genetic screening for cytochrome P450 2C19 (CYP2C19) polymorphisms in patients treated with clopidogrel. Clopidogrel is an antiplatelet agent, frequently used in combination with aspirin, for the prevention of thrombotic complications with acute coronary syndrome and in patients undergoing percutaneous coronary interventions. Cytochrome P-450 (CYP) 2C19 is an enzyme involved in the bioactivation of clopidogrel from a pro-drug to an active inhibitor of platelet action. Patients of Asian and Pacific Island background have been reported to have an increase in CYP2C19 polymorphisms associated with loss-of-function of this enzyme when compared to other ethnicities. This has created an interest in genetic testing for CYP2C19 polymorphisms in Hawai‘i. Based upon our review of the current literature, we do not feel that there is support for the routine screening for CYP2C19 polymorphisms in patients being treated with clopidogrel; furthermore, the results of genetic testing may not be helpful in guiding therapeutic decisions. We recommend that decisions on the type of antiplatelet treatment be made based upon clinical evidence of potential differential outcomes associated with the use of these agents rather than on the basis of genetic testing. PMID:25628978

  7. Opportunistic Screening of Vitamin B12 Deficiency in IT Professionals Presenting for Routine Health Check-up

    PubMed Central

    Patel, Rishi Devilal; Ingole, Sonali Jitendra; Pandave, Harshal Tukaram

    2015-01-01

    Introduction Vitamin B12 deficiency is mainly diagnosed in symptomatic patients. However, the deficiency may also be prevalent in asymptomatic patients. Our aim was to study the prevalence of Vit B12 deficiency in IT professionals (Information Technology Professionals from Software industry) who presented for routine health screening and to correlate the deficiency to various parameters. Materials and Methods This was single centre, observational study comprising of 84 IT professionals. The data was collected in structured format. The study was designed to identify prevalence of Vit B12 deficiency and correlate to other factors such as type of diet, income level & regular use of medication (such as Antacid & Metformin). Results Total 28 individuals were found to be deficient (33.34%). Prevalence of Vit B12 deficiency amongst Vegetarian and non vegetarian diet adhering subjects was 47.5% and 20.45% respectively. B12 deficiency was also prevalent in high income age group. Further chronic intake of PPI (Proton pump inhibitor) and Metformin was associated with prevalence of 37.5% and 33.34% in the present study. Conclusion During health screening of IT Professionals, significant prevalence of Vit B12 deficiency was noted across all income groups & non vegetarian diet consuming subjects also. There is significant correlation between Vit B12 deficiency with chronic use of PPI and Metformin. PMID:26816929

  8. Statistical approaches to screening hazardous waste sites for toxicity

    SciTech Connect

    Thomas, J.M.; Athey, L.A.; Skalski, J.R.

    1987-06-01

    Bioassay results from two field studies illustrate how maps of toxicity can be prepared based on systematic sampling and show how cleanup decisions can be made using bioassay results based on few samples. Logarithmically spaced soil samples were obtained along four parallel transects at the Rocky Mountain Arsenal. A total of 72 soil samples were subjected to Daphnia, Microtox, algal, earthworm and lettuce root elongation bioassays. Bioassay results (excepting earthworms) were inconclusive for toxicity, but allowed us to ignore several classes of compounds, such as water-soluble heavy metals, herbicides, and insecticides, since our prior results using pure chemicals showed depressed algal growth in the presence of these contaminants. To depict the spatial pattern of observed seed mortality at each depth, we used kriging to produce contour maps. The results clearly showed that lettuce seed mortality was higher in the 15 to 30 cm fraction, that waste-trench soil was highly phytotoxic, and that toxicity decreased as a function of distance from the trench. In addition, we found that mortality contours produced by kriging could be useful in site cleanup decisions. A study was conducted using a series of water and sediment samples collected from a narrow stream adjacent to a wood treatment plant in Canton, Mississippi. Both creosote and pentachlorophenol were used for wood treatment. Sediment samples were collected every 20 m in the visibly contaminated zones. Based on simple linear interpolation of bioassay results, we found that different bioassays led to different conclusions regarding the toxicity of different areas, suggesting that contaminants other than creosote may have caused the observed toxicity. Moreover, chemical analysis was an inaccurate predictor of toxicity.

  9. TOXICOLOGICAL HIGHLIGHT: SCREENING FOR DEVELOPMENTAL TOXICITY OF TOBACCO SMOKE CONSTITUENTS

    EPA Science Inventory

    Abstract
    Cigarette smoking is unrivaled among developmental toxicants in terms of total adverse impact on the human population. According to the American Lung Association, smoking during pregnancy is estimated to account for 20 to 30 percent of low-weight babies, up to 14 per...

  10. A Different Approach to Validating Screening Assays for Developmental Toxicity

    EPA Science Inventory

    BACKGROUND: There continues to be many efforts around the world to develop assays that are shorter than the traditional embryofetal developmental toxicity assay, or use fewer or no mammals, or use less compound, or have all three attributes. Each assay developer needs to test th...

  11. PROTOCOLS FOR SHORT TERM TOXICITY SCREENING OF HAZARDOUS WASTE SITES

    EPA Science Inventory

    The manual contains short-term methods for measuring the toxicity of chemical contaminants in soil, sediment, surface water, and groundwater samples. The algal assay is a chronic test, while all other tests described in the manual are acute tests. The methods are one of several t...

  12. Zebrafish screen identifies novel compound with selective toxicity against leukemia

    PubMed Central

    Ridges, Suzanne; Heaton, Will L.; Joshi, Deepa; Choi, Henry; Eiring, Anna; Batchelor, Lance; Choudhry, Priya; Manos, Elizabeth J.; Sofla, Hossein; Sanati, Ali; Welborn, Seth; Agarwal, Archana; Spangrude, Gerald J.; Miles, Rodney R.; Cox, James E.; Frazer, J. Kimble; Deininger, Michael; Balan, Kaveri; Sigman, Matthew; Müschen, Markus; Perova, Tatiana; Johnson, Radia; Montpellier, Bertrand; Guidos, Cynthia J.; Jones, David A.

    2012-01-01

    To detect targeted antileukemia agents we have designed a novel, high-content in vivo screen using genetically engineered, T-cell reporting zebrafish. We exploited the developmental similarities between normal and malignant T lymphoblasts to screen a small molecule library for activity against immature T cells with a simple visual readout in zebrafish larvae. After screening 26 400 molecules, we identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types. LDK is well tolerated in vertebrates and induces long-term remission in adult zebrafish with cMYC-induced T-cell acute lymphoblastic leukemia (T-ALL). LDK causes dephosphorylation of members of the PI3 kinase/AKT/mTOR pathway and delays sensitive cells in late mitosis. Among human cancers, LDK selectively affects survival of hematopoietic malignancy lines and primary leukemias, including therapy-refractory B-ALL and chronic myelogenous leukemia samples, and inhibits growth of human T-ALL xenografts. This work demonstrates the utility of our method using zebrafish for antineoplastic candidate drug identification and suggests a new approach for targeted leukemia therapy. Although our efforts focused on leukemia therapy, this screening approach has broad implications as it can be translated to other cancer types involving malignant degeneration of developmentally arrested cells. PMID:22490804

  13. SCREENING FOR TOXIC INDUSTRIAL CHEMICALS USING SEMIPERMEABLE MEMBRANE DEVICES WITH RAPID TOXICITY ASSAYS

    EPA Science Inventory

    A time-integrated sampling device interfaced with two toxicity-based assays is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethylsulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

  14. Comparative Screening of Digestion Tract Toxic Genes in Proteus mirabilis

    PubMed Central

    Shi, Xiaolu; Lin, Yiman; Qiu, Yaqun; Li, Yinghui; Jiang, Min; Chen, Qiongcheng; Jiang, Yixiang; Yuan, Jianhui; Cao, Hong; Hu, Qinghua; Huang, Shenghe

    2016-01-01

    Proteus mirabilis is a common urinary tract pathogen, and may induce various inflammation symptoms. Its notorious ability to resist multiple antibiotics and to form urinary tract stones makes its treatment a long and painful process, which is further challenged by the frequent horizontal gene transferring events in P. mirabilis genomes. Three strains of P. mirabilis C02011/C04010/C04013 were isolated from a local outbreak of a food poisoning event in Shenzhen, China. Our hypothesis is that new genes may have been acquired horizontally to exert the digestion tract infection and toxicity. The functional characterization of these three genomes shows that each of them independently acquired dozens of virulent genes horizontally from the other microbial genomes. The representative strain C02011 induces the symptoms of both vomit and diarrhea, and has recently acquired a complete type IV secretion system and digestion tract toxic genes from the other bacteria. PMID:27010388

  15. Rapid toxicity screening tests for aquatic biota. 1. Methodology and experiments with Daphnia magna

    SciTech Connect

    Janssen, C.R.; Persoone, G. )

    1993-04-01

    A promising new and rapid toxicity screening test was developed, the concept and principles of which are presented. The method consists of visual observation of in vivo inhibition of an enzymatic process, using a fluorescent substrate. Juvenile Daphnia magna was exposed to a toxicant dilution series for 1 h, after which the substrate was added and the enzymatic inhibition was observed visually, using a long-wave UV light. The 1-h EC50 results of 11 pure compounds are presented and compared to the conventional 24- and 48-h Daphnia magna EC50s. All 1-h fluorescence EC50s were of the same order of magnitude and correlated very well with the 24- and 48-h EC50s. The sensitivity and reproducibility of this cost-effective screening test were compared to those of the Microtox[reg sign] test. The scope for application and the potential of this new rapid toxicity screening test are evaluated.

  16. Acute toxicity screening of sediments utilizing Chydorus sphaericus

    SciTech Connect

    Campbell, M.G.S.; Crisman, T.; Bitton, G.; Delfino, J.

    1997-08-01

    Out of over 165 species of organisms that have been proposed for use in toxicity bioassays only a few are invertebrates and even fewer have ever been cultured in the laboratory. Many of the invertebrates that have been applied in sediment toxicity tests are not benthic organisms and possess few characteristics of the ideal sediment bioassay organism. Some tests species have limited ecological ranges; some may not be widely available for testing and many are not easily maintained in the laboratory. In addition, some traditional sediment toxicity tests utilize organisms that spend no part or only part of their life cycle in contact with sediment constituents, and therefore lack, in some degree, ecological relevance. The study reported involved the development and evaluation of a 48-hour lethality bioassay employing the benthic cladoceran, Chydorus sphaericus. The bioassay is ecologically relevant because the test organism is ubiquitous and it lives associated with sediments in freshwater aquatic environments. The bioassay was evaluated by direct comparison with standard bioassays using sediment samples collected from hazardous waste sites in Florida.

  17. Toxicity of leachate from weathering plastics: An exploratory screening study with Nitocra spinipes.

    PubMed

    Bejgarn, Sofia; MacLeod, Matthew; Bogdal, Christian; Breitholtz, Magnus

    2015-08-01

    Between 60% and 80% of all marine litter is plastic. Leachate from plastics has previously been shown to cause acute toxicity in the freshwater species Daphnia magna. Here, we present an initial screening of the marine environmental hazard properties of leachates from weathering plastics to the marine harpacticoid copepod [Crustacea] Nitocra spinipes. Twenty-one plastic products made of different polymeric materials were leached and irradiated with artificial sunlight. Eight of the twenty-one plastics (38%) produced leachates that caused acute toxicity. Differences in toxicity were seen for different plastic products, and depending on the duration of irradiation. There was no consistent trend in how toxicity of leachate from plastics changed as a function of irradiation time. Leachate from four plastics became significantly more toxic after irradiation, two became significantly less toxic and two did not change significantly. Analysis of leachates from polyvinyl chloride (PVC) by liquid chromatography coupled to a full-scan high-resolution mass spectrometer showed that the leachates were a mixture of substances, but did not show evidence of degradation of the polymer backbone. This screening study demonstrates that leachates from different plastics differ in toxicity to N. spinipes and that the toxicity varies under simulated weathering. PMID:25828916

  18. Screening the toxicity and biodegradability of petroleum hydrocarbons by a rapid colorimetric method.

    PubMed

    Montagnolli, Renato Nallin; Lopes, Paulo Renato Matos; Bidoia, Ederio Dino

    2015-02-01

    Crude oil and petroleum products have a wide variety of hazardous components with high toxicity and low biodegradability. Certain dyes change their colors by intercepting electron transfer reactions during the transformation processes. This study applied resazurin and 2,6-dichlorophenol-indophenol indicators for a rapid screening biodegradation capability and toxicity response to various petroleum products such as motor oil, diesel, gasoline, and phenol. Colorimetry tests were performed in test tubes, and the absorbance values were measured over time. We observed different discoloration profiles after degradation tests using Bacillus subtilis inoculum. Phytotoxicity assays were also performed to compare colorimetric screening assays with a conventional toxicity testing with plants (seed germination). The results indicated that biotransformation of oils can increase its overall toxicity. Intermediate byproducts can be formed through biodegradation and thereby increase the toxicity of oils. The assessment of acute toxicity has shown that phenol is extremely toxic to petroleum-biodegrading microbial communities. Low molecular-weight gasoline was considered biodegradable, but it also exhibited a high acute toxic effect, mainly due to its high solubility and the presence of more volatile compounds that can penetrate cells and potentially damage cellular structures. PMID:25537922

  19. Toxicity assessment through multiple endpoint bioassays in soils posing environmental risk according to regulatory screening values.

    PubMed

    Rodriguez-Ruiz, A; Asensio, V; Zaldibar, B; Soto, M; Marigómez, I

    2014-01-01

    Toxicity profiles of two soils (a brownfield in Legazpi and an abandoned iron mine in Zugaztieta; Basque Country) contaminated with several metals (As, Zn, Pb and Cu in Legazpi; Zn, Pb, Cd and Cu in Zugaztieta) and petroleum hydrocarbons (in Legazpi) were determined using a multi-endpoint bioassay approach. Investigated soils exceeded screening values (SVs) of regulatory policies in force (Basque Country; Europe). Acute and chronic toxicity bioassays were conducted with a selected set of test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates, as well as with bioaccumulation studies in earthworms. The sensitivity of the test species and the toxicity endpoints varied depending on the soil. It was concluded that whilst Zugaztieta soil showed very little or no toxicity, Legazpi soil was toxic according to almost all the toxicity tests (solid phase Microtox, D. discoideum inhibition of fruiting body formation and developmental cycle solid phase assays, lettuce seed germination and root elongation test, earthworm acute toxicity and reproduction tests, D. discoideum cell viability and replication elutriate assays). Thus, albeit both soils had similar SVs, their ecotoxicological risk, and therefore the need for intervening, was different for each soil as unveiled after toxicity profiling based on multiple endpoint bioassays. Such a toxicity profiling approach is suitable to be applied for scenario-targeted soil risk assessment in those cases where applicable national/regional soil legislation based on SVs demands further toxicity assessment. PMID:24819436

  20. Screening housing to prevent lead toxicity in children.

    PubMed Central

    Lanphear, Bruce P.; Hornung, Richard; Ho, Mona

    2005-01-01

    OBJECTIVE: Screening children to identify those with blood lead levels > or = 10 microg/dl fails to protect children from lead-associated cognitive deficits and behavioral problems. To broaden our efforts at primary prevention, screening criteria are needed to identify lead-contaminated housing before children are unduly exposed. The purpose of this study was to identify and validate housing characteristics associated with children having elevated blood lead levels (> or = 10 microg/dl). METHODS: Two existing studies were used to examine housing characteristics linked with undue lead exposure: a cross-sectional study of 205 children aged 12 to 31 months, and a random sample from a longitudinal study of 276 children followed from 6 to 24 months of age. Logistic regression analysis was conducted to examine the association of children's blood lead levels > or = 10 microg/dl. RESULTS: The mean age of the 481 children was 17.8 months; 99 (20.6%) had a blood lead concentration of 10 microg/dl or higher. The following characteristics were associated with blood lead concentration > or = 10 microg/dl: floor lead loading > 15 microg/ft2 (odds ratio [OR]=2.2; 95% confidence interval [CI] 1.3, 3.8); rental housing (OR=3.2; 95% CI 1.3, 7.6); poor housing condition (OR=2.1; CI 1.2, 3.6); African American race (OR=3.3; CI 1.9, 6.1); paint chip ingestion (OR=5.8; CI 1.3, 26.5); and soil ingestion (OR=2.2; CI 1.1, 4.2). Housing characteristics including rental status, lead-contaminated floor dust, and housing condition had a range of sensitivity from 47% to 92%; specificity from 28% to 76%; a positive predictive value from 25% to 34%; and a negative predictive value of 85% to 93%. CONCLUSIONS: Housing characteristics and floor dust lead levels can be used to screen housing to identify lead hazards prior to occupancy, before purchasing a home, or after renovation to prevent children's exposure to lead hazards. PMID:16134573

  1. Method for screening inhibitors of the toxicity of Bacillus anthracis

    DOEpatents

    Cirino, Nick M.; Jackson, Paul J.; Lehnert, Bruce E.

    2001-01-01

    The protective antigen (PA) of Bacillus anthracis is integral to the mechanism of anthrax poisoning. The cloning, expression and purification of a 32 kDa B. anthracis PA fragment (PA32) is described. This fragment has also been expressed as a fusion construct to stabilized green fluorescent protein (EGFP-PA32). Both proteins were capable of binding to specific cell surface receptors as determined by fluorescent microscopy and a flow cytometric assay. To confirm binding specificity in the flow cytometric assay, non-fluorescent PA83 or PA32 was used to competitively inhibit fluorescent EGFP-PA32 binding to cell receptors. This assay can be employed as a rapid screen for compounds which disrupts binding of PA to cells. Additionally, the high intracellular expression levels and ease of purification make this recombinant protein an attractive vaccine candidate or therapeutic treatment for anthrax poisoning.

  2. Development of a test system for screening toxic substances: a comparison using organic substances

    SciTech Connect

    Thomas, C.L.

    1985-01-01

    The purpose of this research was to develop a test system for screening toxic substances by predicting their aquatic ecosystem effects. The system studied was a static, one liter microcosm with a diverse species assemblage. The microcosm was composed of biotic inoculum, chemically defined medium and sediment. The biotic inoculum contained primary producers, grazers, carnivores and decomposers. Three different types of sediment were studied: sand, clay, and clay plus sand. Four organic chemicals: phenol, triethylene glycol (TEG), quinoline and naphthoquinone were evaluated with this test system. The toxicities of TEG, quinoline and naphthoquinone were compared for each sediment type. Toxicity was evaluated in terms of the chemical's effects on primary productivity and heterotrophic activity though other effects are also noted. Naphthoquinone concentration exhibited no correlation between ecosystem property values and therefore, could not be ranked. Phenol exhibited the greatest toxicity to net production immediately after the toxicant addition. Quinoline was most toxic to net production over the longer time scale. TEG exhibited the least toxicity to net production, however, TEG exhibited higher toxicity to heterotrophic activity than either quinoline or phenol. Although the type of sediment used in the microcosms did not change the relative toxicities of the chemicals, the microcosms with clay sediment always were observed to exhibit lower net production and higher variability.

  3. Sequential assessment via daphnia and zebrafish for systematic toxicity screening of heterogeneous substances.

    PubMed

    Jang, Gun Hyuk; Park, Chang-Beom; Kang, Benedict J; Kim, Young Jun; Lee, Kwan Hyi

    2016-09-01

    Environment and organisms are persistently exposed by a mixture of various substances. However, the current evaluation method is mostly based on an individual substance's toxicity. A systematic toxicity evaluation of heterogeneous substances needs to be established. To demonstrate toxicity assessment of mixture, we chose a group of three typical ingredients in cosmetic sunscreen products that frequently enters ecosystems: benzophenone-3 (BP-3), ethylhexyl methoxycinnamate (EHMC), and titanium dioxide nanoparticle (TiO2 NP). We first determined a range of nominal toxic concentration of each ingredient or substance using Daphnia magna, and then for the subsequent organismal level phenotypic assessment, chose the wild-type zebrafish embryos. Any phenotype change, such as body deformation, led to further examinations on the specific organs of transgenic zebrafish embryos. Based on the systematic toxicity assessments of the heterogeneous substances, we offer a sequential environmental toxicity assessment protocol that starts off by utilizing Daphnia magna to determine a nominal concentration range of each substance and finishes by utilizing the zebrafish embryos to detect defects on the embryos caused by the heterogeneous substances. The protocol showed additive toxic effects of the mixtures. We propose a sequential environmental toxicity assessment protocol for the systematic toxicity screening of heterogeneous substances from Daphnia magna to zebrafish embryo in-vivo models. PMID:27288628

  4. Predictive Model of Rat Reproductive Toxicity from ToxCast High Throughput Screening

    EPA Science Inventory

    The EPA ToxCast research program uses high throughput screening for bioactivity profiling and predicting the toxicity of large numbers of chemicals. ToxCast Phase‐I tested 309 well‐characterized chemicals in over 500 assays for a wide range of molecular targets and cellular respo...

  5. Screening of Bioactivities and Toxicity of Cnidoscolus quercifolius Pohl

    PubMed Central

    Vasconcelos, Fábio Roger; Paim, Raquel Teixeira Terceiro; Marques, Márcia Maria Mendes; De Morais, Selene Maia; Lira, Sandra Machado; Braquehais, Isabel Desidério; Vieira, Ícaro Gusmão Pinto; Mendes, Francisca Noelia Pereira; Guedes, Maria Izabel Florindo

    2016-01-01

    The caatinga, an exclusively Brazilian biome, is one of the most endangered vegetation systems in the planet. To be exploited rationally, its potential needs to be scientifically demonstrated. Among these is the faveleira, used in northeastern Brazil. It stands out for its extraordinary drought resistance and medicinal properties. The objective of this study was to assess the therapeutic potential of compounds extracted from Cnidoscolus quercifolius Pohl in preventing disease and its rational use as a herbal therapeutic tool. The methodology began with the collection and herborization of the plant material, to obtain the chemical compounds, preliminary phytochemical analysis, and extraction of the constituents of the active extracts. To determine the biological activities the authors conducted investigation of antioxidant and antimicrobial activities, inhibition capacity of the acetylcholinesterase enzyme, and initial assessment of toxicity of the extracts. The results demonstrated great potential as an antimicrobial agent, an important antioxidant capacity, and acetylcholinesterase inhibition response with no significant difference compared with the reference drug. The authors expect to develop a new herbal product, resulting in lower production costs and that, consequently, could be commercialized in more accessible form to the population, highlighting the risk reduction of contraindication of this category of medications. PMID:27293464

  6. Screening of Bioactivities and Toxicity of Cnidoscolus quercifolius Pohl.

    PubMed

    Paredes, Paulo Fernando Machado; Vasconcelos, Fábio Roger; Paim, Raquel Teixeira Terceiro; Marques, Márcia Maria Mendes; De Morais, Selene Maia; Lira, Sandra Machado; Braquehais, Isabel Desidério; Vieira, Ícaro Gusmão Pinto; Mendes, Francisca Noelia Pereira; Guedes, Maria Izabel Florindo

    2016-01-01

    The caatinga, an exclusively Brazilian biome, is one of the most endangered vegetation systems in the planet. To be exploited rationally, its potential needs to be scientifically demonstrated. Among these is the faveleira, used in northeastern Brazil. It stands out for its extraordinary drought resistance and medicinal properties. The objective of this study was to assess the therapeutic potential of compounds extracted from Cnidoscolus quercifolius Pohl in preventing disease and its rational use as a herbal therapeutic tool. The methodology began with the collection and herborization of the plant material, to obtain the chemical compounds, preliminary phytochemical analysis, and extraction of the constituents of the active extracts. To determine the biological activities the authors conducted investigation of antioxidant and antimicrobial activities, inhibition capacity of the acetylcholinesterase enzyme, and initial assessment of toxicity of the extracts. The results demonstrated great potential as an antimicrobial agent, an important antioxidant capacity, and acetylcholinesterase inhibition response with no significant difference compared with the reference drug. The authors expect to develop a new herbal product, resulting in lower production costs and that, consequently, could be commercialized in more accessible form to the population, highlighting the risk reduction of contraindication of this category of medications. PMID:27293464

  7. The ToxCast Pathway Database for Identifying Toxicity Signatures and Potential Modes of Action from Chemical Screening Data

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA), through its ToxCast program, is developing predictive toxicity approaches that will use in vitro high-throughput screening (HTS), high-content screening (HCS) and toxicogenomic data to predict in vivo toxicity phenotypes. There are ...

  8. The Toxicant-Target Paradigm for Toxicity Screening – Pharmacophore Based Constraints

    EPA Science Inventory

    There is a compelling need to develop information for the screening and prioritization of the health and environmental effects of large numbers of man-made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the preliminary evaluation of ris...

  9. Multivariate toxicity screening of liposomal formulations on a human buccal cell line.

    PubMed

    Smistad, Gro; Jacobsen, Jette; Sande, Sverre A

    2007-02-01

    The influence of various formulation factors on the in vitro cellular toxicity of liposomes on human buccal cells (TR146), were studied by using the concept of statistical experimental design and multivariate evaluation. The factors investigated were the type of main phospholipid (egg-PC, DMPC, DPPC), lipid concentration, the type of charge, liposome size, and amount and nature of the charged component (diacyl-PA, diacyl-PG, diacyl-PS, stearylamine (SA), diacyl-TAP) in the liposomes. Both full factorial design and D-optimal designs were created. Several significant main factors and interactions were revealed. Positively charged liposomes were shown to be toxic. The toxicity of negatively charged liposomes was relatively low. Diacyl-TAP was less toxic than SA, and DPPC was less toxic than DMPC. Low level of positively charged component was favourable and essential when using egg-PC as the main lipid. The amount of negatively charged component, the liposome size, and the total lipid concentration did not affect the toxicity within the experimental room. DPPC appeared to be a good candidate when formulating both positively and negatively charged liposomes with low cellular toxicity. The concept of statistical experimental design and multivariate evaluation was shown to be a useful approach in cell toxicity screening studies. PMID:16997516

  10. A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

    PubMed

    Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

    2014-06-01

    Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations. PMID:24500598

  11. Toxicological assessment of heavy straight run naphtha in a repeated dose/reproductive toxicity screening test.

    PubMed

    McKee, Richard H; Steup, David; Schreiner, Ceinwen; Podhasky, Paula; Malley, Linda A; Roberts, Linda

    2014-01-01

    Gasoline blending stocks (naphthas) are comprised of normal, iso- and cycloparaffins and aromatic hydrocarbons with carbon numbers ranging from C4 to C12. Heavy straight run naphtha (HSRN, CAS number 64741-41-9) was selected for toxicity screening because substances of this type contain relatively high levels (28%) of cycloparaffins by comparison to other naphtha streams and the data complement toxicity information on other gasoline blending streams. Rats were exposed by inhalation to wholly vaporized material at levels of approximately 100, 500, or 3000 parts per million (ppm) daily to screen the potential for systemic toxicity, neurotoxicity, reproductive toxicity, and developmental effects to postnatal day 4. All animals survived the treatment period. Principal effects of repeated exposure included increased liver weights in males and females, increased kidney weights in males, and histological changes in the thyroid, secondary to liver enzyme induction. These changes were not considered to be toxicologically meaningful and are not relevant to humans. There were no treatment-related effects in functional observation tests or motor activity; no significant reductions in fertility or changes in other reproductive parameters; and no evidence of developmental toxicity in offspring. The overall no observed adverse effect concentration was 3000 ppm (approximately 13, 600 mg/m(3)). In conclusion the HSRN effects on liver and kidney are consistent with the results of other studies of volatile fractions or other naphthas or formulated gasoline, and there were no HSRN effects on neurological developmental or reproductive parameters. PMID:24179027

  12. Introducing routine HIV screening for patients on an internal medicine residency inpatient service: a quality improvement project

    PubMed Central

    Padrnos, Leslie J; Barr, Patrick J; Klassen, Christine L; Fields, Heather E; Azadeh, Natalya; Mendoza, Neil; Saadiq, Rayya A; Pauwels, Emanuel M; King, Christopher S; Chung, Andrew A; Sakata, Kenneth K; Blair, Janis E

    2016-01-01

    The US Centers for Disease Control and Prevention (CDC) recommend human immunodeficiency virus (HIV) screening for all persons aged 13 to 64 years who present to a health care provider. We sought to improve adherence to the CDC guidelines on the Internal Medicine Resident Hospital Service. We surveyed residents about the CDC guidelines, sent email reminders, provided education, and engaged them in friendly competition. Credit for guideline adherence was awarded if an offer of HIV screening was documented at admission, if a screening test was performed, or if a notation in the resident sign out sheet indicated why screening was not performed. We examined HIV screening of a postintervention group of patients admitted between August 8, 2012, and June 30, 2013, and compared them to a preintervention group admitted between August 1, 2011, and June 30, 2012. Postintervention offers of HIV screening increased significantly (7.9% [44/559] vs 55.5% [300/541]; P<.001), as did documentation of residents' contemplation of screening (8.9% [50/559] vs 67.5% [365/541]; P<.001). A significantly higher proportion of HIV screening tests was ordered postintervention (7.7% [43/559] vs 44.4% [240/541]; P<.001). Monthly HIV screening documentation ranged from 0% (0/53) to 17% (9/53) preintervention, whereas it ranged from 30.6% (11/36) to 100% (62/62) postintervention. HIV screening adherence can be improved through resident education, friendly competition, and system reminders. Barriers to achieving sustained adherence to the CDC guidelines include a heterogeneous patient population and provider discomfort with the subject. PMID:27239302

  13. Introducing routine HIV screening for patients on an internal medicine residency inpatient service: a quality improvement project.

    PubMed

    Padrnos, Leslie J; Barr, Patrick J; Klassen, Christine L; Fields, Heather E; Azadeh, Natalya; Mendoza, Neil; Saadiq, Rayya A; Pauwels, Emanuel M; King, Christopher S; Chung, Andrew A; Sakata, Kenneth K; Blair, Janis E

    2016-01-01

    The US Centers for Disease Control and Prevention (CDC) recommend human immunodeficiency virus (HIV) screening for all persons aged 13 to 64 years who present to a health care provider. We sought to improve adherence to the CDC guidelines on the Internal Medicine Resident Hospital Service. We surveyed residents about the CDC guidelines, sent email reminders, provided education, and engaged them in friendly competition. Credit for guideline adherence was awarded if an offer of HIV screening was documented at admission, if a screening test was performed, or if a notation in the resident sign out sheet indicated why screening was not performed. We examined HIV screening of a postintervention group of patients admitted between August 8, 2012, and June 30, 2013, and compared them to a preintervention group admitted between August 1, 2011, and June 30, 2012. Postintervention offers of HIV screening increased significantly (7.9% [44/559] vs 55.5% [300/541]; P<.001), as did documentation of residents' contemplation of screening (8.9% [50/559] vs 67.5% [365/541]; P<.001). A significantly higher proportion of HIV screening tests was ordered postintervention (7.7% [43/559] vs 44.4% [240/541]; P<.001). Monthly HIV screening documentation ranged from 0% (0/53) to 17% (9/53) preintervention, whereas it ranged from 30.6% (11/36) to 100% (62/62) postintervention. HIV screening adherence can be improved through resident education, friendly competition, and system reminders. Barriers to achieving sustained adherence to the CDC guidelines include a heterogeneous patient population and provider discomfort with the subject. PMID:27239302

  14. Study protocol—investigation of the Delirium Observation Screening Scale (DOSS) for the routine detection of delirium in the care home setting: a prospective cohort study

    PubMed Central

    Teale, Elizabeth; Young, John; Siddiqi, Najma; Munyombwe, Theresa; Harrison, Jennifer; Schuurmanns, Marieke

    2016-01-01

    Introduction Delirium is a common and distressing condition associated with frailty, dementia and comorbidity. These are common in long-term care settings. Residents in care homes are therefore at particular risk of delirium. Despite this, methods to detect delirium in care homes are lacking, with existing diagnostic tools taking too long, or requiring specific training to deliver. This limits their feasibility for use for the routine detection of delirium by care home staff. Routine screening for delirium in care homes would allow timely attention to exacerbating factors to attenuate the episode, and facilitate future research into delirium in the care home environment. Methods Residents from 4 large care homes will be asked to consent (or their consultees asked to provide a declaration of agreement) to participate in the study. Care home staff will administer the 25-item Delirium Observation Screening Scale (DOSS)—a delirium screening tool based on observed behaviours—and this will be tested against the research standard Confusion Assessment Method (CAM) administered by trained research assistants performed two times per week for all participating residents. Analysis Sensitivity, specificity, positive and negative predictive values, likelihood ratios and a diagnostic OR will be calculated for the detection of delirium with the 25-item DOSS. The feasibility of routine delirium screening and the scaling properties of the 25-item DOSS will also be explored. Ethics and Dissemination For residents lacking capacity to participate, a consultee will be approached for a declaration of agreement for inclusion in the study. Results will be published in peer-reviewed journals and disseminated in written format to clinical commissioning groups, general practitioners and relevant third parties. Trial registration number ISRCTN14608554. PMID:27324706

  15. Screening the toxicity of phosphorous-removal adsorbents using a bioluminescence inhibition test.

    PubMed

    Duranceau, Steven J; Biscardi, Paul G; Barnhill, Danielle K

    2016-04-01

    When found in excess, phosphorus (P) has been linked to surface water eutrophication. As a result, adsorbents are now used in P remediation efforts. However, possible secondary toxicological impacts on the use of new materials for P removal from surface water have not been reported. This study evaluated the toxicity of adsorbent materials used in the removal of P from surface water including: fly ash, bottom ash, alum sludge, a proprietary mix of adsorbents, and a proprietary engineered material. Toxicity screening was conducted by performing solid-liquid extractions (SLEs) followed by the bacterial bioluminescence inhibition test with a Microtox® M500. Of the materials tested, the samples extracted at lower pH levels demonstrated higher toxicity. The material exhibiting the most toxic response was the iron and aluminum oxide coated engineered material registering a 66-67% 15-min EC50 level for pH 4 and 5 SLEs, respectively. However, for SLEs prepared at pH 7, toxic effects were not detected for this engineered material. Fly ash and bottom ash demonstrated between 82 and 84% 15-min EC50 level, respectively, for pH 4 SLE conditions. Dried alum sludge and the proprietary mix of adsorbents were classified as having little to no toxicity. PMID:25348491

  16. Synergistic Metabolic Toxicity Screening Using Microsome/DNA Electrochemiluminescent Arrays and Nanoreactors

    PubMed Central

    Krishnan, Sadagopan; Hvastkovs, Eli G.; Bajrami, Besnik; Choudhary, Dharamainder; Schenkman, John B.; Rusling, James F.

    2012-01-01

    Platforms based on thin enzyme/DNA films were used in two-tier screening of chemicals for reactive metabolites capable of producing toxicity. Microsomes were used for the first time as sources of cytochrome (cyt) P450 enzymes in these devices. Initial rapid screening involved electrochemiluminescent (ECL) arrays featuring spots containing ruthenium poly(vinylpyridine), DNA, and rat liver microsomes or bicistronically expressed human cyt P450 2E1 (h2E1). Cyt P450 enzymes were activated via the NADPH/reductase cycle. When bioactivation of substrates in the films gives reactive metabolites, they are trapped by covalent attachment to DNA bases. The rate of increase in ECL with enzyme reaction time reflects relative DNA damage rates. “Toxic hits” uncovered by the array were studied in structural detail by using enzyme/DNA films on silica nanospheres as “nanoreactors” to provide nucleobase adducts from reactive metabolites. The utility of this synergistic approach was demonstrated by estimating relative DNA damage rates of three mutagenic N-nitroso compounds and styrene. Relative enzyme turnover rates for these compounds using ECL arrays and LC-UV-MS correlated well with TD50 values for liver tumor formation in rats. Combining ECL array and nanoreactor/LC–MS technologies has the potential for rapid, high-throughput, cost-effective screening for reactive metabolites and provides chemical structure information that is complementary to conventional toxicity bioassays. PMID:18563913

  17. Disease-toxicant screen reveals a neuroprotective interaction between Huntington’s disease and manganese exposure

    PubMed Central

    Williams, B. Blairanne; Li, Daphne; Wegrzynowicz, Michal; Vadodaria, Bhavin K.; Anderson, Joel G.; Kwakye, Gunnar F.; Aschner, Michael; Erikson, Keith M.; Bowman, Aaron B.

    2011-01-01

    Recognizing the similarities between Huntington’s disease pathophysiology and the neurotoxicology of various metals, we hypothesized that they may exhibit disease-toxicant interactions revealing cellular pathways underlying neurodegeneration. Here we utilize metals and the STHdh mouse striatal cell line model of Huntington’s disease to perform a gene-environment interaction screen. We report that striatal cells expressing mutant Huntingtin exhibit elevated sensitivity to cadmium toxicity and resistance to manganese toxicity. This neuroprotective gene-environment interaction with manganese is highly specific, as it does not occur with iron, copper, zinc, cobalt, cadmium, lead, or nickel ions. Analysis of the Akt cell-stress signaling pathway showed diminished activation with manganese exposure and elevated activation after cadmium exposure in the mutant cells. Direct examination of intracellular manganese levels found that mutant cells have a significant impairment in manganese accumulation. Furthermore, YAC128Q mice, a Huntington’s disease model, showed decreased total striatal manganese levels following manganese exposure relative to wild-type mice. Thus, this disease-toxicant interaction screen has revealed that expression of mutant Huntingtin results in heightened sensitivity to cadmium neurotoxicity and a selective impairment of manganese accumulation. PMID:19845833

  18. Factors Predisposing, Enabling and Reinforcing Routine Screening of Patients for Preventing Fetal Alcohol Syndrome: A Survey of New Jersey Physicians.

    ERIC Educational Resources Information Center

    Donovan, Carole L.

    1991-01-01

    Survey of 58 physicians revealed that they did not routinely ask their pregnant patients about alcohol consumption for several reasons: physician bias resulting from own abuse, lack of training, poor awareness of problem and effects, denial that Fetal Alcohol Syndrome occurs in private practice, time limitations, disinterest, fear of offending…

  19. Feasibility of FT-Raman spectroscopy in rapid and routine screening for deoxynivalenol in wheat and barley

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rapid and routine detection of deoxynivalenol (DON) in cereals-based food and feed has long been a strong desire of regulators and manufacturers. Traditional chemical methods and antibody based biosensors and immunoassays have been developed as viable tools to identify and measure DON. However, thes...

  20. QSAR screening of 70,983 REACH substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the ChemScreen project.

    PubMed

    Wedebye, Eva B; Dybdahl, Marianne; Nikolov, Nikolai G; Jónsdóttir, Svava Ó; Niemelä, Jay R

    2015-08-01

    The ChemScreen project aimed to develop a screening system for reproductive toxicity based on alternative methods. QSARs can, if adequate, contribute to the evaluation of chemical substances under REACH and may in some cases be applied instead of experimental testing to fill data gaps for information requirements. As no testing for reproductive effects should be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for 70,983 REACH substances was performed. Sixteen models and three decision algorithms were used to reach overall predictions of substances with potential effects with the following result: 6.5% genotoxic carcinogens, 16.3% mutagens, 11.5% developmental toxicants. These results are similar to findings in earlier QSAR and experimental studies of chemical inventories, and illustrate how QSAR predictions may be used to identify potential genotoxic carcinogens, mutagens and developmental toxicants by high-throughput virtual screening. PMID:25797653

  1. Toxin-screening and identification of bacteria isolated from highly toxic marine gastropod Nassarius semiplicatus.

    PubMed

    Wang, Xiao-Jie; Yu, Ren-Cheng; Luo, Xuan; Zhou, Ming-Jiang; Lin, Xiang-Tian

    2008-07-01

    Bacteria isolated from a highly toxic sample of gastropod Nassarius semiplicatus in Lianyungang, Jiangsu Province in July 2007, were studied to probe into the relationship between bacteria and toxicity of nassariid gastropod. The toxicity of the gastropod sample was 2 x 10(2)mouse unit (MU) per gram of tissue (wet weight). High concentration of tetrodotoxin (TTX) and its analogues (TTXs) were found in the digestive gland and muscle of the gastropod, using high performance liquid chromatography coupled with mass chromatography (LC-MS). Bacterial strains isolated from the digestive gland were cultured and screened for TTX with a competitive ELISA method. Tetrodotoxin was detected in a proportion of bacterial strains, but the toxin content was low. Partial 16S ribosomal DNA (rDNA) of the TTX-producing strains was then sequenced and compared with those published in the GenBank to tentatively identify the toxic strains. It was found that most of the toxic strains were closely affiliated with genus Vibrio, and the others were related to genus Shewanella, Marinomonas, Tenacibaculum and Aeromonas. These findings suggest that tetrodotoxin-producing bacteria might play an important role in tetrodotoxin accumulation/production in N. semiplicatus. PMID:18573274

  2. Toxicity testing and drug screening using iPSC-derived hepatocytes, cardiomyocytes, and neural cells.

    PubMed

    Csöbönyeiová, Mária; Polák, Štefan; Danišovič, L'uboš

    2016-07-01

    Unexpected toxicity in areas such as cardiotoxicity, hepatotoxicity, and neurotoxicity is a serious complication of clinical therapy and one of the key causes for failure of promising drug candidates in development. Animal studies have been widely used for toxicology research to provide preclinical security evaluation of various therapeutic agents under development. Species differences in drug penetration of the blood-brain barrier, drug metabolism, and related toxicity contribute to failure of drug trials from animal models to human. The existing system for drug discovery has relied on immortalized cell lines, animal models of human disease, and clinical trials in humans. Moreover, drug candidates that are passed as being safe in the preclinical stage often show toxic effects during the clinical stage. Only around 16% drugs are approved for human use. Research on induced pluripotent stem cells (iPSCs) promises to enhance drug discovery and development by providing simple, reproducible, and economically effective tools for drug toxicity screening under development and, on the other hand, for studying the disease mechanism and pathways. In this review, we provide an overview of basic information about iPSCs, and discuss efforts aimed at the use of iPSC-derived hepatocytes, cardiomyocytes, and neural cells in drug discovery and toxicity testing. PMID:27128322

  3. Extra-renal manifestations of autosomal dominant polycystic kidney disease (ADPKD): considerations for routine screening and management.

    PubMed

    Luciano, Randy L; Dahl, Neera K

    2014-02-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is a systemic disease, marked by progressive increase of bilateral renal cysts, resulting in chronic kidney disease (CKD) and often leading to end-stage renal disease (ESRD). Apart from renal cysts, patients often have extra-renal disease, involving the liver, heart and vasculature. Other less common but equally important extra-renal manifestations of ADPKD include diverticular disease, hernias, male infertility and pain. Extra-renal disease burden is often asymptomatic, but may result in increased morbidity and mortality. If the disease burden is significant, screening may prove beneficial. We review the rationale for current screening recommendations and propose some guidelines for screening and management of ADPKD patients. PMID:24215018

  4. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data.

    PubMed

    Sipes, Nisha S; Martin, Matthew T; Reif, David M; Kleinstreuer, Nicole C; Judson, Richard S; Singh, Amar V; Chandler, Kelly J; Dix, David J; Kavlock, Robert J; Knudsen, Thomas B

    2011-11-01

    Environmental Protection Agency's ToxCast project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database would correlate with cell-based and cell-free in vitro high-throughput screening (HTS) data to reveal meaningful mechanistic relationships and provide models identifying chemicals with the potential to cause developmental toxicity. To test this hypothesis, we built statistical associations based on HTS and in vivo developmental toxicity data from ToxRefDB. Univariate associations were used to filter HTS assays based on statistical correlation with distinct in vivo endpoint. This revealed 423 total associations with distinctly different patterns for rat (301 associations) and rabbit (122 associations) across multiple HTS assay platforms. From these associations, linear discriminant analysis with cross-validation was used to build the models. Species-specific models of predicted developmental toxicity revealed strong balanced accuracy (> 70%) and unique correlations between assay targets such as transforming growth factor beta, retinoic acid receptor, and G-protein-coupled receptor signaling in the rat and inflammatory signals, such as interleukins (IL) (IL1a and IL8) and chemokines (CCL2), in the rabbit. Species-specific toxicity endpoints were associated with one another through common Gene Ontology biological processes, such as cleft palate to urogenital defects through placenta and embryonic development. This work indicates the utility of HTS assays for developing pathway-level models predictive of developmental toxicity. PMID:21873373

  5. Predictive model of rat reproductive toxicity from ToxCast high throughput screening.

    PubMed

    Martin, Matthew T; Knudsen, Thomas B; Reif, David M; Houck, Keith A; Judson, Richard S; Kavlock, Robert J; Dix, David J

    2011-08-01

    The U.S. Environmental Protection Agency's ToxCast research program uses high throughput screening (HTS) for profiling bioactivity and predicting the toxicity of large numbers of chemicals. ToxCast Phase I tested 309 well-characterized chemicals in more than 500 assays for a wide range of molecular targets and cellular responses. Of the 309 environmental chemicals in Phase I, 256 were linked to high-quality rat multigeneration reproductive toxicity studies in the relational Toxicity Reference Database. Reproductive toxicants were defined here as having achieved a reproductive lowest-observed-adverse-effect level of less than 500 mg kg(-1) day(-1). Eight-six chemicals were identified as reproductive toxicants in the rat, and 68 of those had sufficient in vitro bioactivity to model. Each assay was assessed for univariate association with the identified reproductive toxicants. Significantly associated assays were linked to gene sets and used for the subsequent predictive modeling. Using linear discriminant analysis and fivefold cross-validation, a robust and stable predictive model was produced capable of identifying rodent reproductive toxicants with 77% ± 2% and 74% ± 5% (mean ± SEM) training and test cross-validation balanced accuracies, respectively. With a 21-chemical external validation set, the model was 76% accurate, further indicating the model's potential for prioritizing the many thousands of environmental chemicals with little to no hazard information. The biological features of the model include steroidal and nonsteroidal nuclear receptors, cytochrome P450 enzyme inhibition, G protein-coupled receptors, and cell signaling pathway readouts-mechanistic information suggesting additional targeted, integrated testing strategies and potential applications of in vitro HTS to risk assessment. PMID:21565999

  6. Molecular insight into arsenic toxicity via the genome-wide deletion mutant screening of Saccharomyces cerevisiae.

    PubMed

    Johnson, Adam J; Veljanoski, Filip; O'Doherty, Patrick J; Zaman, Mohammad S; Petersingham, Gayani; Bailey, Trevor D; Münch, Gerald; Kersaitis, Cindy; Wu, Ming J

    2016-02-01

    Arsenic is omnipresent in soil, air, food and water. Chronic exposure to arsenic is a serious problem to human health. In-depth understanding of this metalloid's toxicity is a fundamental step towards development of arsenic-free foods and measures for bioremediation. By screening the complete set of gene deletion mutants (4873) of Saccharomyces cerevisiae, this study uncovered 75 sensitive and 39 resistant mutants against arsenite [As(III)]. Functional analysis of the corresponding genes revealed the molecular details for its uptake, toxicity and detoxification. On the basis of the hypersensitivity of yap3Δ, the transcription factor, Yap3p, is for the first time linked to the cell's detoxification against As(III). Apart from confirming the previously described role of the mitogen-activated protein kinase (MAPK) Hog1 pathway in combating arsenic toxicity, the results show that the regulatory subunits (Ckb1p and Ckb2p) of protein kinase CK2 are also involved in the process, suggesting possible crosstalk between the two key protein kinases. The sensitivity to As(III) conferred by deletion of the genes involved in protein degradation and chromatin remodelling demonstrates protein damage is the key mode of toxicity for the metalloid. Furthermore, the resistant phenotype of fps1Δ, snf3Δ and pho81Δ against As(III) links arsenic uptake with the corresponding plasma membrane-bound transporters-aquaglyceroporin (Fps1p), hexose (Snf3p) and phosphate transporters. The molecular details obtained in this screen for As(III) uptake, detoxification and toxicity provide the basis for future investigations into arsenic-related problems in the environment, agriculture and human health. PMID:26688044

  7. Phytochemical screening and toxicity studies on the methanol extract of the seeds of moringa oleifera.

    PubMed

    Ajibade, Temitayo Olabisi; Arowolo, Ruben; Olayemi, Funsho Olakitike

    2013-01-01

    The seeds of Moringa oleifera were collected, air-dried, pulverized, and subjected to cold extraction with methanol. The methanol extract was screened phytochemically for its chemical components and used for acute and sub-acute toxicity studies in rats. The phytochemical screening revealed the presence of saponins, tannins, terpenes, alkaloids, flavonoids, carbohydrates, and cardiac glycosides but the absence of anthraquinones. Although signs of acute toxicity were observed at a dose of 4,000 mg kg-1 in the acute toxicity test, and mortality was recorded at 5,000 mg kg-1, no adverse effect was observed at concentrations lower than 3,000 mg kg-1. The median lethal dose of the extract in rat was 3,873 mg kg-1. Sub-acute administration of the seed extract caused significant (p<0.05) increase in the levels of alanine and aspartate transferases (ALT and AST), and significant (p<0.05) decrease in weight of experimental rats, at 1,600 mg kg-1. The study concludes that the extract of seeds of M. oleifera is safe both for medicinal and nutritional uses. PMID:23652639

  8. Glaucoma screening as part of the routine physical examination. What to look for and how to use the Schiotz tonometer.

    PubMed

    Pabalan, F J; Weingeist, T A

    1985-05-01

    Glaucoma is a leading cause of visual loss in the United States. The primary care physician can effectively screen patients at risk by performing Schiotz tonometry, checking the visual fields, and examining the fundus. Patients with elevated intraocular pressure, grossly abnormal visual fields, or abnormal optic disks should be referred to an ophthalmologist for confirmation of diagnosis and for therapy. PMID:3991383

  9. Toxicity Screening of the ToxCast Phase II Chemical Library Using a Zebrafish Developmental Assay (SOT)

    EPA Science Inventory

    As part of the chemical screening and prioritization research program of the US EPA, the ToxCast Phase II chemicals were assessed using a vertebrate screen for developmental toxicity. Zebrafish embryos (Danio rerio) were exposed in 96-well plates from late-blastula stage (6hr pos...

  10. An enzyme-linked immunosorbent assay for lipovitellin quantification in copepods: a screening tool for endocrine toxicity.

    PubMed

    Volz, David C; Chandler, G Thomas

    2004-02-01

    Vitellogenin (VTG) has been widely used as a biomarker of estrogenic exposure in fish, leading to the development of standardized assays for VTG quantification. However, standardized quantitative assays for invertebrate, particularly crustacean, lipovitellin (also known as vitellin [VTN]) are lacking. In this study, a fluorescence-based VTN enzyme-linked immunosorbent assay (ELISA) was developed to quantify microquantities of VTN in the estuarine, sediment-dwelling copepod Amphiascus tenuiremis. This ELISA utilizes a VTN-specific polyclonal antibody developed against amphipod (Leptocheirus plumulosus) embryo VTN and exhibits specificity toward female copepod proteins. In routine assays, the working range of the ELISA was 31.25 to 1,000 ng/ml (75-25% specific binding/maximum antibody binding [B/B0]) with a 50% B/B0 intra- and interassay variation of 3.9% (n = 9) and 12.5% (n = 26), respectively. This ELISA is capable of detecting VTN as low as 2 ng/ml, and can accurately detect VTN in as few as four copepods. The ELISA significantly discriminated positive (gravid female) and negative (male) samples, and was suitable for screening endocrine toxicity in copepods. Stage-I juvenile copepods were individually reared to adults in aqueous microvolumes of the phenylpyrazole insecticide, fipronil, and whole-body homogenate extracts were assayed for VTN levels. Fipronil-exposed virgin adult females, but not males, exhibited significantly higher levels of VTN relative to control males and females. This crustacean VTN ELISA is likely useful for evaluating endocrine activity of environmental toxicants in copepods and other crustacean species. PMID:14982375

  11. A systematic study of mitochondrial toxicity of environmental chemicals using quantitative high throughput screening

    PubMed Central

    Attene-Ramos, Matias S.; Huang, Ruili; Sakamuru, Srilatha; Witt, Kristine L.; Beeson, Gyda C.; Shou, Louie; Schnellmann, Rick G.; Beeson, Craig C.; Tice, Raymond R.; Austin, Christopher P.; Xia, Menghang

    2014-01-01

    A goal of the Tox21 program is to transit toxicity testing from traditional in vivo models to in vitro assays that assess how chemicals affect cellular responses and toxicity pathways. A critical contribution of the NIH Chemical Genomics center (NCGC) to the Tox21 program is the implementation of a quantitative high throughput screening (qHTS) approach, using cell- and biochemical-based assays to generate toxicological profiles for thousands of environmental compounds. Here, we evaluated the effect of chemical compounds on mitochondrial membrane potential in HepG2 cells by screening a library of 1,408 compounds provided by the National Toxicology Program (NTP) in a qHTS platform. Compounds were screened over 14 concentrations, and results showed that 91 and 88 compounds disrupted mitochondrial membrane potential after treatment for one or five h, respectively. Seventy-six compounds active at both time points were clustered by structural similarity, producing 11 clusters and 23 singletons. Thirty-eight compounds covering most of the active chemical space were more extensively evaluated. Thirty-six of the 38 compounds were confirmed to disrupt mitochondrial membrane potential using a fluorescence plate reader and 35 were confirmed using a high content imaging approach. Among the 38 compounds, 4 and 6 induced LDH release, a measure of cytotoxicity, at 1 or 5 h, respectively. Compounds were further assessed for mechanism of action (MOA) by measuring changes in oxygen consumption rate, which enabled identification of 20 compounds as uncouplers. This comprehensive approach allows for evaluation of thousands of environmental chemicals for mitochondrial toxicity and identification of possible MOAs. PMID:23895456

  12. Acute toxicity screening of Hanford Site waste grouts using aquatic invertebrates

    SciTech Connect

    Rebagay, T.V.; Dodd, D.A.; Lockrem, L.L.; Powell, W.J.; Voogd, J.A.

    1993-11-01

    Waste grouts prepared by mixing a simulated nonradioactive liquid waste with a dry solids blend consisting of cement, fly ash, and clay were screened for their acute toxicity using aquatic invertebrates (D. magna, D. pulex, and C. dubia) as test organisms and a fluorogenic substrate (4-methylumbelliferyl b-d galactoside) as the toxic stress indicator. After one hour of exposing juvenile daphnids to grout extracts of varying concentrations, followed by a 15-minute reaction with the fluorogenic substrate, the degree of in vivo enzymatic inhibition was measured by the number of resulting fluorescent daphnids. The effective concentration at which 50% of the daphnids were adversely affected (EC50) values calculated by probit analysis were 2,877 mg/L, 2,983 mg/L, and 3,174 mg/L for D. pulex, D. magna, and C. dubia, respectively. The results indicated that the grout extracts studied are nonhazardous and not dangerous to daphnids.

  13. Biological screening of selected Pacific Northwest forest plants using the brine shrimp (Artemia salina) toxicity bioassay.

    PubMed

    Karchesy, Yvette M; Kelsey, Rick G; Constantine, George; Karchesy, Joseph J

    2016-01-01

    The brine shrimp (Artemia salina) bioassay was used to screen 211 methanol extracts from 128 species of Pacific Northwest plants in search of general cytotoxic activity. Strong toxicity (LC50 < 100 µg/ml) was found for 17 extracts from 13 species, with highest activity observed for Angelica arguta roots at <10 µg/ml. Notably, four species of cedar trees and one of juniper in the family Cupressaceae dominated this group with LC50 for heartwood extracts ranging from 15 to 89 µg/ml. Moderate toxicity (LC50 100-500 µg/ml) was found in 38 extracts from 27 species, while weak toxicity (LC50 500-1000 µg/ml) was detected for 17 extracts in 16 species. There were 139 extracts from 99 species that were non-toxic (LC50 > 1000 µg/ml). Our subsequent studies of conifer heartwoods with strong activity confirm the assay's value for identifying new investigational leads for materials with insecticidal and fungicidal activity. PMID:27186474

  14. Routine HIV screening in North Carolina in the era of the Affordable Care Act: update on laws, reimbursement, and tests.

    PubMed

    White, Becky L; Carter, Yvonne L; Records, Katherine; Martin, Ian B K

    2013-11-01

    Eighteen percent of the 1.2 million human immunodeficiency virus (HIV)-infected individuals in the United States are undiagnosed, with North Carolina accounting for the eighth largest number of new HIV diagnoses in 2011. In an effort to identify more HIV-infected individuals by reducing physician barriers to HIV testing, the Centers for Disease Control and Prevention have expanded their HIV screening recommendations to adolescents and adults without HIV risk factors or behaviors, eliminated federal requirements for pretest counseling, and modified the informed consent process. In 2010, the Office of National AIDS (acquired immunodeficiency syndrome) Policy released the first-ever national HIV/AIDS strategy, with the goal of reducing new infections, increasing access to care, improving HIV outcomes, and reducing HIV racial/ethnic disparities. In 2013, the US Preventive Services Task Force released A-level recommendations recommending nonrisk-based HIV screening for adults and adolescents that are consistent with the recommendations of the Centers for Disease Control and Prevention. In concert with these federal recommendations, the majority of states have modified their consent and counseling requirements. The implementation of the Patient Protection and Affordable Care Act will add requirements and incentives for federal (Medicare), state (Medicaid), and private (insurance) payers to reimburse physicians and patients for nonrisk-based HIV screening. PMID:24192596

  15. Subtask 1.11 -- Spectroscopic field screening of hazardous waste and toxic spills. Final report

    SciTech Connect

    Grisanti, A.A.

    1997-10-01

    Techniques for the field characterization of soil contamination due to spillage of hazardous waste or toxic chemicals are time-consuming and expensive. Thus more economical, less time-intensive methods are needed to facilitate rapid field screening of contaminated sites. The overall objective of this project is to study the feasibility of using an evanescent field absorbance sensor Fourier transform infrared spectroscopic sensor coupled with cone penetrometry as a field screening method. The specific objectives of this project are as follows: design an accessory for use with FT-IR that interfaces the spectrometer to a cone penetrometer; characterize the response of the FT-IR accessory to selected hydrocarbons in a laboratory-simulated field environment; and determine the ability of the FT-IR-CPT instrument to measure hydrocarbon contamination in soil by direct comparison with a reference method (e.g., Soxhlet extraction followed by gas chromatography) to quantify hydrocarbons from the same soil.

  16. Studies with the USF/NASA toxicity screening test method - Exercise wheels and oxygen replenishment

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Continuing efforts to improve the University of San Francisco/NASA toxicity screening test method have included the addition of exercise wheels to provide a different measure of incapacitation, and oxygen replenishment to offset any effect of oxygen depletion by the test animals. The addition of exercise wheels limited the number of animals in each test and doubled the required number of tests without any significant improvement in reproducibility. Oxygen replenishment appears to have an effect on survival in the last 5 minutes of the 30-minute test, but the effect is expected to be similar for most materials.

  17. Screening for toxic phorbol esters in jerky pet treat products using LC-MS.

    PubMed

    Nishshanka, Upul; Jayasuriya, Hiranthi; Chattopadhaya, Chaitali; Kijak, Philip J; Chu, Pak-Sin; Reimschuessel, Renate; Tkachenko, Andriy; Ceric, Olgica; De Alwis, Hemakanthi G

    2016-05-01

    Since 2007, the U.S. FDA's Center for Veterinary Medicine (CVM) has been investigating reports of pets becoming ill after consuming jerky pet treats. Jerky used in pet treats contains glycerin, which can be made from vegetable oil or as a byproduct of biodiesel production. Because some biodiesel is produced using oil from Jatropha curcas, a plant that contains toxic compounds including phorbol esters, CVM developed a liquid chromatography-mass spectrometry (LC-MS) screening method to evaluate investigational jerky samples for the presence of these toxins. Results indicated that the samples analyzed with the new method did not contain Jatropha toxins at or above the lowest concentration tested. PMID:27038400

  18. Is ingestion of milk-associated bacteria by premature infants fed raw human milk controlled by routine bacteriologic screening?

    PubMed Central

    Law, B J; Urias, B A; Lertzman, J; Robson, D; Romance, L

    1989-01-01

    Expressed human milk is often used to feed premature infants. Raw milk contains bacteria which may be a source of infection. Milk banks have developed screening programs which combine periodic quantitative milk cultures with arbitrary rules specifying limits of bacterial concentration. It is unknown whether such programs succeed in preventing infants from being fed milk containing bacteria. At the Health Sciences Centre (Winnipeg, Manitoba, Canada), milk is screened once weekly. When a woman's milk is found to have excess bacteria, it is discarded only if she is an unrelated donor (as opposed to an infant's mother). To assess the effectiveness of this screening program, we determined the frequency at which infants fed raw human milk were exposed to milk-associated bacteria and compared the bacterial contents of donor and maternal milk. From February 1986 to April 1987, all human milk fed to 98 premature infants during the first 2 weeks of feeding (n = 10,128 feeds) was cultured quantitatively. Among study infants, 100% were exposed at least once to coagulase-negative staphylococci, 41% were exposed to Staphylococcus aureus, and 64% were exposed to gram-negative bacilli. The proportions of feeds containing bacteria and the quantities (log10 CFU [mean +/- standard deviation]) ingested per positive feed were: 39% and 5.9 +/- 0.5 for coagulase-negative staphylococci; 2.4% and 5.1 +/- 1.0 for S. aureus; and 5.2% and 4.8 +/- 1.1 for gram-negative bacilli. There were no adverse events attributable to ingestion of milk-associated bacteria. Milk coagulase-negative staphylococcal isolates were multiply antibiotic susceptible, whereas infant isolates were antibiotic resistant. Donor milk was significantly less likely than maternal milk to contain coagulase-negative staphylococcal species in any quantity (40 versus 93% of samples, respectively [P < 0.001]) or in concentrations exceeding 10(8) CFU/liter (3 versus 27% of samples, respectively [P < 0.0001]). There was no

  19. Routine Eye Screening by an Ophthalmologist Is Clinically Useful for HIV-1-Infected Patients with CD4 Count Less than 200 /μL

    PubMed Central

    Nishijima, Takeshi; Yashiro, Shigeko; Teruya, Katsuji; Kikuchi, Yoshimi; Katai, Naomichi; Oka, Shinichi; Gatanaga, Hiroyuki

    2015-01-01

    Objective To investigate whether routine eye screening by an ophthalmologist in patients with HIV-1 infection is clinically useful. Methods A single-center, retrospective study in Tokyo, Japan. HIV-1-infected patients aged over 17 years who visited our clinic for the first time between January 2004 and December 2013 and underwent full ophthalmologic examination were enrolled. At our clinic, ophthalmologic examination, including dilated retinal examination by indirect ophthalmoscopy was routinely conducted by ophthalmologists on the first visit. The prevalence of ophthalmologic diseases and associated factors including the existence of ocular symptoms were analyzed. Results Of the 1,515 study patients, cytomegalovirus retinitis (CMV-R) was diagnosed in 24 (2%) patients, HIV retinopathy (HIV-R) in 127 (8%), cataract in 31 (2%), ocular syphilis in 4 (0.3%), and uveitis with unknown cause in 8 (0.5%). Other ocular diseases were diagnosed in 14 patients. The CD4 count was <200 /μL in all CMV-R cases and 87% of HIV-R. The prevalence of any ocular diseases, CMV-R, and HIV-R in patients with CD4 <200 /μL were 22%, 3%, and 15%, respectively, whereas for those with CD4 ≥200 /μL were 5%, 0%, and 2%, respectively. No ocular symptoms were reported by 71% of CMV-R cases and 82% of patients with any ocular diseases. Conclusions Routine ophthalmologic screening is recommended for HIV-1-infected patients with CD4 <200 /μL in resource-rich settings based on the high prevalence of ocular diseases within this CD4 count category and because most patients with ocular diseases, including those with CMV-R, were free of ocular symptoms. PMID:26375282

  20. Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography–Mass Spectrometry

    PubMed Central

    Hvastkovs, Eli G.; Schenkman, John B.; Rusling, James F.

    2012-01-01

    New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography–mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates. PMID:22482786

  1. Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hvastkovs, Eli, G.; Schenkman, John B.; Rusling, James, F.

    2012-07-01

    New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography-mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates.

  2. Frequencies and Specificities of “Enzyme-Only” Detected Erythrocyte Alloantibodies in Patients Hospitalized in Austria: Is an Enzyme Test Required for Routine Red Blood Cell Antibody Screening?

    PubMed Central

    Habres, Claudia; Wallner, Franz; Mayr, Barbara; Halwachs-Baumann, Gabriele

    2014-01-01

    The aim of this study was to determine the frequencies and specificities of “enzyme-only” detected red blood cell (RBC) alloantibodies in the routine antibody screening and antibody identification in patients hospitalized in Austria. Routine blood samples of 2420 patients were investigated. The antibody screening was performed with a 3-cell panel in the low-ionic strength saline- (LISS-) indirect antiglobulin test (IAT) and with an enzyme-pretreated (papain) 3-cell panel fully automated on the ORTHO AutoVue Innova System. The antibody identification was carried out manually with an 11-cell panel in the LISS-IAT and with an enzyme-pretreated (papain) 11-cell panel. In total 4.05% (n = 98) of all patients (n = 2420) had a positive RBC antibody screening result. Of them 25.51% (25/98) showed “enzyme-only” detected specific or nonspecific RBC alloantibodies. Rhesus and Lewis system antibodies were found the only specificities of “enzyme-only” RBC alloantibodies: all in all 4.8% (4/98) were detected with anti-E, 3.06% (3/98) with anti-Lea, 3.06% (3/98) with anti-D after anti-D prophylaxis and 1.02% (1/98) with anti-e. In total, 14.29% (14/98) showed a nonspecific RBC alloantibody result with the enzyme test. The results of the present study demonstrate that a high number of unwanted positive reactions with the enzyme technique overshadows the detection of “enzyme-only” RBC alloantibodies. (Trial Registration: K-37-13). PMID:24790773

  3. Comparing rapid-screening and standard toxicity assays to assess known chemical contamination at a hazardous waste site

    SciTech Connect

    Martino, L.; Swigert, J.; Roberts, C.

    1995-12-31

    The thrust to streamline the Superfund site investigation/remediation program makes it critical for site investigators to utilize rapid screening methodologies to facilitate decision-making. However, screening methodologies providing information upon which decision-making is based must not only be rapid but also scientifically valid. This presentation compares and contrasts two rapid screening toxicity assessments, the Daphnia magna IQ Toxicity Test {trademark} and Microtox{trademark}, to a battery of standard aquatic toxicity tests using Lemna, Rana, Pimephales, Selenastruni and Ceriodaphnia. Chemical analysis of test water samples provided evidence of potential toxicological risk associated with the test samples. The study site was J-Field, Aberdeen Proving Ground, Maryland, a federal facility listed on the National Priority List that used to test and/or dispose of high explosives and chemical warfare agents in open pits or fields. Surface water samples from 20 sites were collected and used in the toxicity assessments. Water samples also were analyzed for explosives, chemical surety degradation compounds, Target Analyte List (inorganics), Target Compound List (organics) and selected pesticides and PCBs. The Microtox{trademark} assay did not reveal any toxicity present in the samples analyzed. Correlation analyses showed only slight correlation between the Daphnia magna IQ{trademark} assay and the standard 48-hour toxicity test. No correlation existed between the Microtox{trademark} assay and the aquatic toxicity tests. Results are discussed in light of the expected risk of the chemicals known to be present and the outcome of the toxicity tests.

  4. Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity.

    PubMed

    Lamore, Sarah D; Kamendi, Harriet W; Scott, Clay W; Dragan, Yvonne P; Peters, Matthew F

    2013-10-01

    Cardiovascular (CV) toxicity is a leading contributor to drug attrition. Implementing earlier testing has successfully reduced human Ether-à-go-go-Related Gene-related arrhythmias. How- ever, analogous assays targeting functional CV effects remain elusive. Demand to address this gap is particularly acute for kinase inhibitors (KIs) that suffer frequent CV toxicity. The drug class also presents some particularly challenging requirements for assessing functional CV toxicity. Specifically, an assay must sense a downstream response that integrates diverse kinase signaling pathways. In addition, sufficient throughput is essential for handling inherent KI nonselectivity. A new opportunity has emerged with cellular impedance technology, which detects spontaneous beating cardiomyocytes. Impedance assays sense morphology changes downstream of cardiomyocyte contraction. To evaluate cardiomyocyte impedance assays for KI screening, we investigated two distinct KI classes where CV toxicity was discovered late and target risks remain unresolved. Microtubule-associated protein/microtubule affinity regulating kinase (MARK) inhibitors decrease blood pressure in dogs, whereas checkpoint kinase (Chk) inhibitors (AZD7762, SCH900776) exhibit dose-limiting CV toxicities in clinical trials. These in vivo effects manifested in vitro as cardiomyocyte beat cessation. MARK effects were deemed mechanism associated because beat inhibition potencies correlated with kinase inhibition, and gene knockdown and microtubule-targeting agents suppressed beating. MARK inhibitor impedance and kinase potencies aligned with rat blood pressure effects. Chk inhibitor effects were judged off-target because Chk and beat inhibition potencies did not correlate and knockdowns did not alter beating. Taken together, the data demonstrate that cardiomyocyte impedance assays can address three unmet needs-detecting KI functional cardiotoxicity in vitro, determining mechanism of action, and supporting safety structure

  5. FINAL REPORT ON THE EVALUATION OF FOUR TOXIC CHEMICALS IN AN 'IN VIVO/IN VITRO' TOXICOLOGICAL SCREEN: ACRYLAMIDE, CHLORDECONE, CYCLOPHOSPHAMIDE, AND DIETHYLSTILBESTROL

    EPA Science Inventory

    An in vivo/in vitro Toxicological Screen (Tox Screen) has been developed for screening large numbers of wastes for biological activity. Emphasis is placed on identifying a wide range of potential toxic responses by employing diverse test methods with toxic endpoints in mutagenesi...

  6. Comparison of routine prenatal iron prophylaxis and screening and treatment for anaemia: pregnancy results and preliminary birth results from a pragmatic randomised controlled trial (PROFEG) in Maputo, Mozambique

    PubMed Central

    Parkkali, Saara; Abacassamo, Fatima; Nwaru, Bright Ibeabughichi; Salomé, Graca; Augusto, Orvalho; Regushevskaya, Elena; Dgedge, Martinho; Sousa, Cesar; Cliff, Julie; Chilundo, Baltazar; Hemminki, Elina

    2013-01-01

    Objective To present the pregnancy results and interim birth results of a pragmatic randomised controlled trial comparing routine iron prophylaxis with screening and treatment for anaemia during pregnancy in a setting of endemic malaria and HIV. Design A pragmatic randomised controlled trial. Setting Two health centres (1° de Maio and Machava) in Maputo, Mozambique, a setting of endemic malaria and high prevalence of HIV. Participants Pregnant women (≥18-year-olds; non-high-risk pregnancy, n=4326) attending prenatal care consultation at the two health centres were recruited to the trial. Interventions The women were randomly allocated to either Routine iron (n=2184; 60 mg ferrous sulfate plus 400 μg of folic acid daily throughout pregnancy) or Selective iron (n=2142; screening and treatment for anaemia and daily intake of 1 mg of folic acid). Outcome measures The primary outcomes were preterm delivery (delivery <37 weeks of gestation) and low birth weight (<2500 g). The secondary outcomes were symptoms suggestive of malaria and self-reported malaria during pregnancy; birth length; caesarean section; maternal and child health status after delivery. Results The number of follow-up visits was similar in the two groups. Between the first and fifth visits, the two groups were similar regarding the occurrence of fever, headache, cold/chills, nausea/vomiting and body aches. There was a suggestion of increased incidence of self-reported malaria during pregnancy (OR 1.37, 95% CI 0.98 to1.92) in the Routine iron group. Birth data were available for 1109 (51%) in the Routine iron group and for 1149 (54%) in the Selective iron group. The birth outcomes were relatively similar in the two groups. However, there was a suggestion (statistically non-significant) of poorer outcomes in the Routine iron group with regard to long hospital stay after birth (relative risk (RR) 1.43, 95% CI 0.97 to 1.26; risk difference (RD) 0.02, 95% CI −0.00 to 0.03) and unavailability

  7. Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint.

    PubMed

    Smith, Joel D; Raines, Geoffrey; Schneider, Hans G

    2016-06-01

    Monoclonal gammopathies are characterised by the production of a monoclonal immunoglobulin or free light chains by an abnormal plasma cell or B-cell clone and may indicate malignancy or a precursor (MGUS). There is currently no consensus on the initial test or combination of tests to be performed in suspected monoclonal gammopathies but serum protein electrophoresis and urine protein electrophoresis are commonly requested as initial investigations. If abnormal, immunofixation electrophoresis is then performed to confirm the presence of paraprotein and to determine its heavy and light chain type. Recently, some groups have developed simplified "screening" IFE methods for use in parallel to SPEP for the detection monoclonal gammopathies. We argue here that screening IFE may be of benefit in clinical laboratories using SPEP with poor resolution in the β-region, assisting in the detection of mainly IgA paraprotein, but may be of less benefit in laboratories utilising higher resolution gels. Further it may increase the detection of trace bands of questionable clinical significance, representing transient phenomena in infectious and auto-immune conditions or very low risk MGUS. The increased detection of these bands using screening IFE would require further patient follow up, possibly causing unnecessary patient anxiety and additional follow up healthcare costs. PMID:26677889

  8. A High-Throughput Screening Assay to Identify Kidney Toxic Compounds.

    PubMed

    Ramm, Susanne; Adler, Melanie; Vaidya, Vishal S

    2016-01-01

    Kidney toxicity due to drugs and chemicals poses a significant health burden for patients and a financial risk for pharmaceutical companies. However, currently no sensitive and high-throughput in vitro method exists for predictive nephrotoxicity assessment. Primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells, making them a desirable model to use in in vitro screening systems. Additionally, heme oxygenase 1 (HO-1) protein expression is upregulated as a protective mechanism during kidney toxicant-induced oxidative stress or inflammation in HPTECs and can therefore be used as a biomarker for nephrotoxicity. In this article, we describe two different methods to screen for HO-1 increase: A homogeneous time resolved fluorescence (HTRF) assay and an immunofluorescence assay. The latter provides lower throughput but higher sensitivity due to the combination of two readouts, HO-1 intensity and cell number. The methods described in the protocol are amendable for other cell types as well. © 2016 by John Wiley & Sons, Inc. PMID:27479365

  9. Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study

    PubMed Central

    2012-01-01

    Background Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. Methods The CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. Results A lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). Conclusion This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection. PMID:22734435

  10. In vitro screening for population variability in toxicity of pesticide-containing mixtures.

    PubMed

    Abdo, Nour; Wetmore, Barbara A; Chappell, Grace A; Shea, Damian; Wright, Fred A; Rusyn, Ivan

    2015-12-01

    Population-based human in vitro models offer exceptional opportunities for evaluating the potential hazard and mode of action of chemicals, as well as variability in responses to toxic insults among individuals. This study was designed to test the hypothesis that comparative population genomics with efficient in vitro experimental design can be used for evaluation of the potential for hazard, mode of action, and the extent of population variability in responses to chemical mixtures. We selected 146 lymphoblast cell lines from 4 ancestrally and geographically diverse human populations based on the availability of genome sequence and basal RNA-seq data. Cells were exposed to two pesticide mixtures - an environmental surface water sample comprised primarily of organochlorine pesticides and a laboratory-prepared mixture of 36 currently used pesticides - in concentration response and evaluated for cytotoxicity. On average, the two mixtures exhibited a similar range of in vitro cytotoxicity and showed considerable inter-individual variability across screened cell lines. However, when in vitro-to-in vivo extrapolation (IVIVE) coupled with reverse dosimetry was employed to convert the in vitro cytotoxic concentrations to oral equivalent doses and compared to the upper bound of predicted human exposure, we found that a nominally more cytotoxic chlorinated pesticide mixture is expected to have greater margin of safety (more than 5 orders of magnitude) as compared to the current use pesticide mixture (less than 2 orders of magnitude) due primarily to differences in exposure predictions. Multivariate genome-wide association mapping revealed an association between the toxicity of current use pesticide mixture and a polymorphism in rs1947825 in C17orf54. We conclude that a combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment and comparative population genomics analyses enables quantitative evaluation of human health hazard from

  11. A genome-wide screen in Saccharomyces cerevisiae Reveals Pathways affected By Arsenic Toxicity

    PubMed Central

    Zhou, Xue; Arita, Adriana; Ellen, Thomas P.; Liu, Xin; Bai, Jingxiang; Rooney, John P.; Kurtz, Adrienne D.; Klein, Catherine B.; Dai, Wei; Begley, Thomas J.; Costa, Max

    2009-01-01

    We have used Saccharomyces cerevisiae to identify toxicologically important proteins and pathways involved in arsenic-induced toxicity and carcinogenicity in humans. We performed a systemic screen of the complete set of 4,733 haploid S. cerevisiae single gene deletion mutants to identify those that have decreased or increased growth, relative to wild-type, after exposure to sodium arsenite (NaAsO2). IC50 values for all mutants were determined to further validate our results. Ultimately we identified 248 mutants sensitive to arsenite and 5 mutants resistant to arsenite exposure. We analyzed the proteins corresponding to arsenite-sensitive mutants and determined that they belonged to functional categories that include protein binding, phosphate metabolism, vacuolar/lysosomal transport, protein targeting, sorting, and translocation, cell growth/morphogenesis, cell polarity and filament formation. Furthermore, these data were mapped onto a protein interactome to identify arsenite toxicity-modulating networks. These networks are associated with the cytoskeleton, ubiquitination, histone acetylation and the MAPK signaling pathway. Our studies have potential implications for understanding toxicity and carcinogenesis in arsenic-induced human conditions, such as cancer and aging. PMID:19631266

  12. A new antiviral screening method that simultaneously detects viral replication, cell viability, and cell toxicity.

    PubMed

    Matza-Porges, Sigal; Eisen, Kobi; Ibrahim, Hadeel; Haberman, Adva; Fridlender, Bertold; Joseph, Gili

    2014-11-01

    Viruses cause a variety of illnesses in humans, yet only a few antiviral drugs have been developed; thus, new antiviral drugs are urgently needed. Plants could be a good source of antiviral drugs, they do not have mobility and can only defend themselves by producing compounds against pathogens such as viruses in their own fix environment. These compounds may have the potential to inhibit animal and human viruses as well. In this study, a fast and reliable method for screening plant extracts for specific antiviral activity against Herpes simplex virus type-1 (HSV-1) was developed. This method distinguishes between host cell death due to infectivity and multiplicity of the virus versus toxicity of the plant extract. Extracts from 80 plant and plant organs were screened using this approach. Six plant extracts showed potential to exert specific HSV-1 growth inhibition activity. In two cases, different organs from the same plant showed similar active results. With this method it is possible to screen a large number of extracts in a rapid and accurate way to detect antiviral substances against HSV-I and other viruses. PMID:25152527

  13. Inferred metagenomic comparison of mucosal and fecal microbiota from individuals undergoing routine screening colonoscopy reveals similar differences observed during active inflammation

    PubMed Central

    Tang, Mei San; Poles, Jordan; Leung, Jacqueline M; Wolff, Martin J; Davenport, Michael; Lee, Soo Ching; Lim, Yvonne Al; Chua, Kek Heng; Loke, P'ng; Cho, Ilseung

    2015-01-01

    The mucosal microbiota lives in close proximity with the intestinal epithelium and may interact more directly with the host immune system than the luminal/fecal bacteria. The availability of nutrients in the mucus layer of the epithelium is also very different from the gut lumen environment. Inferred metagenomic analysis for microbial function of the mucosal microbiota is possible by PICRUSt. We recently found that by using this approach, actively inflamed tissue of ulcerative colitis (UC) patients have mucosal communities enriched for genes involved in lipid and amino acid metabolism, and reduced for carbohydrate and nucleotide metabolism. Here, we find that the same bacterial taxa (e.g. Acinetobacter) and predicted microbial pathways enriched in actively inflamed colitis tissue are also enriched in the mucosa of subjects undergoing routine screening colonoscopies, when compared with paired samples of luminal/fecal bacteria. These results suggest that the mucosa of healthy individuals may be a reservoir of aerotolerant microbial communities expanded during colitis. PMID:25559083

  14. Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing.

    PubMed

    Sills, E Scott; Anderson, Robert E; McCaffrey, Mary; Li, Xiang; Arrach, Nabil; Wood, Samuel H

    2016-03-01

    Preimplantation genetic screening (PGS) is a component of IVF entailing selection of an embryo for transfer on the basis of chromosomal normalcy. If PGS were integrated with single embryo transfer (SET) in a surrogacy setting, this approach could improve pregnancy rates, minimize miscarriage risk, and limit multiple gestations. Even without PGS, pregnancy rates for IVF surrogacy cases are generally satisfactory, especially when treatment utilizes embryos derived from young oocytes and transferred to a healthy surrogate. However, there could be a more general role for PGS in surrogacy, since background aneuploidy in embryos remains a major factor driving implantation failure and miscarriage for all infertility patients. At present, the proportion of IVF cases involving GS is limited, while the number of IVF patients requesting PGS appears to be increasing. In this report, the relevance of PGS for surrogacy in the rapidly changing field of assisted fertility medicine is discussed. Birth Defects Research (Part C) 108:98-102, 2016. © 2015 Wiley Periodicals, Inc. PMID:26598285

  15. Implementation of an HIV-1 Triple-Target NAT Assay in the Routine Screening at Three German Red Cross Blood Centres

    PubMed Central

    Zolt, Silke De; Thermann, Rolf; Bangsow, Thorsten; Pichl, Lutz; Müller, Benjamin; Jork, Christine; Weber-Schehl, Marijke; Hedges, Doris; Schupp, Ingo; Unverzagt, Patrick; de Rue, Katrin; Roth, W. Kurt

    2016-01-01

    Summary Background Blood product safety was significantly improved by the introduction of NAT testing in the late 1990s, resulting in a strong decrease of transfusion-transmitted infections (TTIs). Due to the occurrence of HIV-1 NAT test failures as a consequence of mismatch mutations in the amplicon regions of mono-target NAT assays, the Paul Ehrlich Institute mandated the implementation of multi-target NAT assays for HIV-1 in 2014. Commercial suppliers mostly developed dual-target NAT assays, with only one implementing a triple-target NAT assay. Methods The HIV-1 triple-target NAT assay v3 (GFE Blut) was tested on mutated specimens and synthetic DNA bearing mutations that resulted in sample underquantification or false-negative test results. In addition, data from 2 years routine testing at three German Red Cross Blood centres were analysed. Results The HIV-1 triple-target PCR could compensate for all mutations tested and could compensate the loss of one amplicon without a significant loss of sensitivity. Data from 2 years routine testing showed a solid performance. Conclusion The HIV-1 triple-target v3 assay (GFE Blut) can compensate mutations in target sequences better than a dual-target assay and is applicable to high-throughput screening, thus increasing blood product safety. PMID:27403090

  16. Studies with the USF/NASA toxicity screening test method - Oxygen concentrations with various test conditions

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.; Solis, A. N.

    1977-01-01

    Continuing efforts to increase the versatility of the USF/NASA toxicity screening test method have included the use of different test conditions in order to simulate various fire environments. The use of air flow at flow rates of 16 to 48 ml/sec maintains oxygen concentrations above 19 percent throughout the 30 min exposure period, compared to above 16 percent without forced air flow. These levels of oxygen are well within the tolerance range of mice, and approach the oxygen levels found in many real fire situations. Proposed minimum oxygen levels based on experience with rats are unduly restrictive on the use of other species such as mice, and tend to eliminate the cost savings which may more than justify the selection of mice.

  17. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment.

    PubMed

    Wetmore, Barbara A; Wambaugh, John F; Ferguson, Stephen S; Sochaski, Mark A; Rotroff, Daniel M; Freeman, Kimberly; Clewell, Harvey J; Dix, David J; Andersen, Melvin E; Houck, Keith A; Allen, Brittany; Judson, Richard S; Singh, Reetu; Kavlock, Robert J; Richard, Ann M; Thomas, Russell S

    2012-01-01

    High-throughput in vitro toxicity screening can provide an efficient way to identify potential biological targets for chemicals. However, relying on nominal assay concentrations may misrepresent potential in vivo effects of these chemicals due to differences in bioavailability, clearance, and exposure. Hepatic metabolic clearance and plasma protein binding were experimentally measured for 239 ToxCast Phase I chemicals. The experimental data were used in a population-based in vitro-to-in vivo extrapolation model to estimate the daily human oral dose, called the oral equivalent dose, necessary to produce steady-state in vivo blood concentrations equivalent to in vitro AC(50) (concentration at 50% of maximum activity) or lowest effective concentration values across more than 500 in vitro assays. The estimated steady-state oral equivalent doses associated with the in vitro assays were compared with chronic aggregate human oral exposure estimates to assess whether in vitro bioactivity would be expected at the dose-equivalent level of human exposure. A total of 18 (9.9%) chemicals for which human oral exposure estimates were available had oral equivalent doses at levels equal to or less than the highest estimated U.S. population exposures. Ranking the chemicals by nominal assay concentrations would have resulted in different chemicals being prioritized. The in vitro assay endpoints with oral equivalent doses lower than the human exposure estimates included cell growth kinetics, cytokine and cytochrome P450 expression, and cytochrome P450 inhibition. The incorporation of dosimetry and exposure provide necessary context for interpretation of in vitro toxicity screening data and are important considerations in determining chemical testing priorities. PMID:21948869

  18. Targeted Routine Antenatal Anti-D Prophylaxis in the Prevention of RhD Immunisation - Outcome of a New Antenatal Screening and Prevention Program

    PubMed Central

    Tiblad, Eleonor; Taune Wikman, Agneta; Ajne, Gunilla; Blanck, Agneta; Jansson, Yvonne; Karlsson, Anita; Nordlander, Elisabeth; Holländer, Bibi Shassti; Westgren, Magnus

    2013-01-01

    Objective To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP). Materials and Methods We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy. Results During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500. Conclusions Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this

  19. Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems

    PubMed Central

    Chatterjee, Nivedita; Yang, Ji Su; Park, Kwangsik; Oh, Seung Min; Park, Jeonggue; Choi, Jinhee

    2015-01-01

    Objectives The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs) in alternative in vitro and in vivo toxicity testing models. Methods The GFNs used in this study are graphene nanoplatelets ([GNPs]–pristine, carboxylate [COOH] and amide [NH2]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs’ toxicity. Results In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. Conclusions The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial’s physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment. PMID:26602558

  20. Biological screening of some Turkish medicinal plant extracts for antimicrobial and toxicity activities.

    PubMed

    Turker, A U; Usta, C

    2008-01-20

    Screening of antibacterial activity and toxicity of 22 aqueous plant extracts from 17 Turkish plants was conducted. Antibacterial activity was performed with six bacteria including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus epidermidis. Extracts of Tussilago farfara leaves, Helichyrsum plicatum flowers, Solanum dulcamara aerial parts and Urtica dioica leaves gave the best inhibitory activity against S. pyogenes, S. aureus and S. epidermidis. Of the 22 plant extracts, 20 extracts displayed toxicity (LC50 was <1000 mg L(-1)) in the brine shrimp bioassay. For radish seed bioassay, two different determinations (root length and seed germination) were performed with a comparison between two concentrations (50,000 mg L(-1) and 10,000 mg L(-1)). At low concentration (10,000 mg L(-1)), S. dulcamara aerial parts and Primula vulgaris leaf extracts were observed to inhibit the root length more than the other plant extracts. Also, the most inhibitive plant extract for seed germination was obtained with S. dulcamara aerial parts. PMID:18075897

  1. Surface-patterned SU-8 cantilever arrays for preliminary screening of cardiac toxicity.

    PubMed

    Kim, Jong Yun; Choi, Young-Soo; Lee, Bong-Kee; Lee, Dong-Weon

    2016-06-15

    Arrays of a μgrooved SU-8 cantilever were utilized to analyze changes in the contraction force and beating frequency of cardiomyocytes in vitro. The longitudinally patterned μgrooves facilitates alignment of cardiomyocytes on top of the SU-8 cantilever, which increases the contraction force of cardiomyocytes by a factor of about 2.5. The bending displacement of the SU-8 cantilever was precisely measured in nanoscale using a laser-based measurement system combined with a motorized xyz stage. The cantilever displacement due to contraction of the cardiomyocytes showed the maximum on day 8 after their cultivation. Following preliminary experiments, Isoproterenol, Verapamil, and Astemizole were used to investigate the effect of drug toxicity on the physiology of cardiomyocytes. The experimental results indicated that 1 µM of Isoproterenol treatment increased contraction force and beating frequencies of cardiomyocytes by 30% and 200%, respectively, whereas 500 nM of Verapamil treatment decreased contraction force and beating frequencies of cardiomyocytes by 56% and 42%, respectively. A concentration of less than 5 nM of the hERG channel suppression drug Astemizole did not change the contraction forces in the displacement but slightly decreased the beating frequencies. However, irregular or abnormal heartbeats were observed at Astemizole concentrations of 5 nM and higher. We experimentally conformed that the proposed SU-8 cantilever arrays combined with the laser-based measurement systems has the great potential for a high-throughput drug toxicity screening system in future. PMID:26878482

  2. Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms.

    PubMed

    Kleinstreuer, Nicole C; Yang, Jian; Berg, Ellen L; Knudsen, Thomas B; Richard, Ann M; Martin, Matthew T; Reif, David M; Judson, Richard S; Polokoff, Mark; Dix, David J; Kavlock, Robert J; Houck, Keith A

    2014-06-01

    Addressing the safety aspects of drugs and environmental chemicals has historically been undertaken through animal testing. However, the quantity of chemicals in need of assessment and the challenges of species extrapolation require the development of alternative approaches. Our approach, the US Environmental Protection Agency's ToxCast program, utilizes a large suite of in vitro and model organism assays to interrogate important chemical libraries and computationally analyze bioactivity profiles. Here we evaluated one component of the ToxCast program, the use of primary human cell systems, by screening for chemicals that disrupt physiologically important pathways. Chemical-response signatures for 87 endpoints covering molecular functions relevant to toxic and therapeutic pathways were generated in eight cell systems for 641 environmental chemicals and 135 reference pharmaceuticals and failed drugs. Computational clustering of the profiling data provided insights into the polypharmacology and potential off-target effects for many chemicals that have limited or no toxicity information. The endpoints measured can be closely linked to in vivo outcomes, such as the upregulation of tissue factor in endothelial cell systems by compounds linked to the risk of thrombosis in vivo. Our results demonstrate that assaying complex biological pathways in primary human cells can identify potential chemical targets, toxicological liabilities and mechanisms useful for elucidating adverse outcome pathways. PMID:24837663

  3. Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening.

    PubMed

    Rotroff, Daniel M; Wetmore, Barbara A; Dix, David J; Ferguson, Stephen S; Clewell, Harvey J; Houck, Keith A; Lecluyse, Edward L; Andersen, Melvin E; Judson, Richard S; Smith, Cornelia M; Sochaski, Mark A; Kavlock, Robert J; Boellmann, Frank; Martin, Matthew T; Reif, David M; Wambaugh, John F; Thomas, Russell S

    2010-10-01

    Many chemicals in commerce today have undergone limited or no safety testing. To reduce the number of untested chemicals and prioritize limited testing resources, several governmental programs are using high-throughput in vitro screens for assessing chemical effects across multiple cellular pathways. In this study, metabolic clearance and plasma protein binding were experimentally measured for 35 ToxCast phase I chemicals. The experimental data were used to parameterize a population-based in vitro-to-in vivo extrapolation model for estimating the human oral equivalent dose necessary to produce a steady-state in vivo concentration equivalent to in vitro AC(50) (concentration at 50% of maximum activity) and LEC (lowest effective concentration) values from the ToxCast data. For 23 of the 35 chemicals, the range of oral equivalent doses for up to 398 ToxCast assays was compared with chronic aggregate human oral exposure estimates in order to assess whether significant in vitro bioactivity occurred within the range of maximum expected human oral exposure. Only 2 of the 35 chemicals, triclosan and pyrithiobac-sodium, had overlapping oral equivalent doses and estimated human oral exposures. Ranking by the potencies of the AC(50) and LEC values, these two chemicals would not have been at the top of a prioritization list. Integrating both dosimetry and human exposure information with the high-throughput toxicity screening efforts provides a better basis for making informed decisions on chemical testing priorities and regulatory attention. Importantly, these tools are necessary to move beyond hazard rankings to estimates of possible in vivo responses based on in vitro screens. PMID:20639261

  4. Evaluation of Routine HIV Opt-Out Screening and Continuum of Care Services Following Entry into Eight Prison Reception Centers--California, 2012.

    PubMed

    Lucas, Kimberley D; Eckert, Valorie; Behrends, Czarina N; Wheeler, Charlotte; MacGowan, Robin J; Mohle-Boetani, Janet C

    2016-02-26

    Early diagnosis of human immunodeficiency virus (HIV) infection and initiation of antiretroviral treatment (ART) improves health outcomes and prevents HIV transmission. Before 2010, HIV testing was available to inmates in the California state prison system upon request. In 2010, the California Correctional Health Care Services (CCHCS) integrated HIV opt-out screening into the health assessment for inmates entering California state prisons. Under this system, a medical care provider informs the inmate that an HIV test is routinely done, along with screening for sexually transmitted, communicable, and vaccine-preventable diseases, unless the inmate specifically declines the test. During 2012-2013, CCHCS, the California Department of Public Health, and CDC evaluated HIV screening, rates of new diagnoses, linkage to and retention in care, ART response, and post-release linkage to care among California prison inmates. All prison inmates are processed through one of eight specialized reception center facilities, where they undergo a comprehensive evaluation of their medical needs, mental health, and custody requirements for placement in one of 35 state prisons. Among 17,436 inmates who entered a reception center during April-September 2012, 77% were screened for HIV infection; 135 (1%) tested positive, including 10 (0.1%) with newly diagnosed infections. Among the 135 HIV-positive patient-inmates, 134 (99%) were linked to care within 90 days of diagnosis, including 122 (91%) who initiated ART. Among 83 who initiated ART and remained incarcerated through July 2013, 81 (98%) continued ART; 71 (88%) achieved viral suppression (<200 HIV RNA copies/mL). Thirty-nine patient-inmates were released on ART; 12 of 14 who were linked to care within 30 days of release were virally suppressed at that time. Only one of nine persons with a viral load test conducted between 91 days and 1 year post-release had viral suppression. Although high rates of viral suppression were achieved in

  5. Unique Nanoparticle Optical Properties Confound Fluorescent Based Assays Widely Employed in Their In Vitro Toxicity Screening and Ranking

    EPA Science Inventory

    Nanoparticles (NPs) are novel materials having at least one dimension less than 100 nm and display unique physicochemical properties due to their nanoscale size. An emphasis has been placed on developing high throughput screening (HTS) assays to characterize and rank the toxiciti...

  6. COMPARISON OF CHEMICAL SCREENING AND RANKING APPROACHES: THE WASTE MINIMIZATION PRIORITIZATION TOOL VERSUS TOXIC EQUIVALENCY POTENTIALS: JOURNAL ARTICLE

    EPA Science Inventory

    NRMRL-STD-0014 Pennington*, D.W., and Bare*, J.C. Comparison of Chemical Screening and Ranking Approaches: The Waste Minimization Prioritization Tool versus Toxic Equivalency Potentials. Risk Analysis (Anderson, E.L. (Ed.), Malden, MA: Blackwell Publishers) 21 (5):897-912 (2001)...

  7. Task 1.11 - Spectroscopic field screening of hazardous waste and toxic spills. Semi-annual report, July 1--December 31, 1995

    SciTech Connect

    Grisanti, A.A.

    1998-01-01

    Techniques for the field characterization of soil contamination due to spillage of hazardous waste or toxic chemicals are time consuming and expensive. Thus more economical, less time intensive methods are needed to facilitate rapid field screening of contaminated sites. In situ detection of toxic chemicals in soil offers both time and cost advantages for field screening, with additional application to real time site monitoring.

  8. Studies with the USF/NASA toxicity screening test method - Effect of air flow and effect of fabric dye

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Lopez, M. T.

    1976-01-01

    One sample each of commercial polyurethane and polychloroprene flexible foams were evaluated using the USF/NASA toxicity screening test method. Air flow rates of 0, 0.16, 16, and 48 ml/sec were used to determine the effect of air flow on relative toxicity. Time to first sign of incapacitation and time to death were substantially reduced with both polyurethane and polychloroprene flexible foams by the introduction of 16 to 48 ml/sec air flow. The relative toxicity rankings of these materials were not altered by changes in air flow. Under these test conditions, the polyurethane foam consistently appeared more toxic than the polychloroprene foam. Samples of six different colors from the same fabric were evaluated separately, using the USF/NASA toxicity screening test method, to determine the effect of fabric dye, if any. The material was an upholstery fabric, consisting of 46 percent cotton, 33 percent wool, and 21 percent nylon. There appeared to be no significant effect of fabric dye on relative toxicity, for this material under these test conditions.

  9. Routine DNA testing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Routine DNA testing. It’s done once you’ve Marker-Assisted Breeding Pipelined promising Qantitative Trait Loci within your own breeding program and thereby established the performance-predictive power of each DNA test for your germplasm under your conditions. By then you are ready to screen your par...

  10. Graph-Plotting Routine

    NASA Technical Reports Server (NTRS)

    Kantak, Anil V.

    1987-01-01

    Plotter routine for IBM PC (AKPLOT) designed for engineers and scientists who use graphs as integral parts of their documentation. Allows user to generate graph and edit its appearance on cathode-ray tube. Graph may undergo many interactive alterations before finally dumped from screen to be plotted by printer. Written in BASIC.

  11. Phytochemical screening and acute toxicity evaluation of Telfairia occidentalis aqueous extracts on rats.

    PubMed

    Anthony, Ogbonnaya Enyinnaya; Ojeifo, Uadia Patrick

    2016-05-01

    The phytochemical composition and acute toxicity of Telfairia occidentalis aqueous extracts were investigated in this study. Phytochemical screening was carried out on the pulverized leaf, root, pod and stem samples. Proximate analysis was also conducted for the root to ascertain the effect of drying procedures on its composition. Fifty-six (56) Wister albino rats, male and female were divided into two broad groups of 28 animals per group. The first group was randomly separated into seven (7) groups of four (4) animals per group. The control group received distilled water alone while the other groups received varied doses (1500mg/kg, 2250mg/kg and 3000mg/kg) of the Soluble and Insoluble Tefairia occidentalis root fraction. The second group of 28 animals was also distributed into 7 groups of 4 animals per group. Six test groups received varied doses (1500mg/kg, 2250mg/kg and 3000mg/kg) of Telfairia occidentalis fruit and stem extracts. The animals were observed for the first 12hr for any toxic symptoms and for 48 hr for mortality rate. Surviving animals were sacrificed after 48 hours. Phytochemical screening results reveal the presence of tannins, flavonoid, steroid, terpenoids, saponin, alkaloid, glycosides, proteins and carbohydrates. Flavonoid and saponin was not detected in stem sample; alkaloid is present in all samples except pod; and cyanogenic glycoside was found in both root and pod samples. Except for the fibre content, the method of preparation of the root had no significant effect on the proximate composition of the sample. The root extracts cause insignificant reduction in Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) activities, except for the significant reduction in ALT activity at highest dose. The pod extract significantly increased the ALT and AST activities, which is dose dependent, while the stem extract only caused increased activity of ALT, but not AST. None of the extracts administered had any significant effect on the

  12. In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity.

    PubMed

    Boisvert, Annie; Jones, Steven; Issop, Leeyah; Erythropel, Hanno C; Papadopoulos, Vassilios; Culty, Martine

    2016-10-01

    Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. PMID:27423704

  13. Direct analysis in real time-mass spectrometry (DART-MS) for rapid qualitative screening of toxic glycols in glycerin-containing products.

    PubMed

    Self, Randy L

    2013-06-01

    In 2007, the United States Food and Drug Administration released guidance recommending testing of glycerin used in regulated consumer products, such as cough syrup preparations, toothpaste, and other pharmaceutical and food products, for the toxic compounds ethylene glycol and diethylene glycol. Regulatory laboratories routinely test glycerin, and products containing glycerin or related compounds for these toxic glycols, using an official gas chromatographic method, to ensure the safety of these products. The current work describes a companion technique to compliment this GC-FID method utilizing Orbitrap mass spectrometry with direct analysis in real time ionization to rapidly screen these samples qualitatively, with results in as little as five seconds, with no sample preparation required. This allows the more time and resource intensive method to be reserved for those rare cases when these compounds are detected, potentially greatly improving laboratory efficiency. The technique was evaluated for qualitative sensitivity and repeatability, and compared against the GC-FID method. The method appears to perform well against these metrics. PMID:23584076

  14. A multiresidue screen for the analysis of toxicants in bovine rumen contents.

    PubMed

    Vudathala, Daljit K; Cummings, Margaret R; Murphy, Lisa A

    2014-07-15

    Analysis of rumen contents is helpful in solving poisoning cases when ingestion of a toxic substance by cattle or other ruminant animals is suspected. The most common technique employs extraction of the sample with organic solvent followed by clean-up method(s) before analysis with gas chromatography-mass spectrometry equipped with a library of mass spectra to help identify unknowns. A rapid method using magnesium sulfate, primary secondary amine, and C18 sorbents following principles of QuEChERS to clean up rumen contents samples is reported herein. The method was validated to analyze fortified bovine rumen contents to detect commonly found organophosphorus pesticides, carbamates, and several other compounds such as atropine, 4-aminopyridine, caffeine, scopolamine, 3-chloro-4-methylaniline, strychnine, metaldehyde, and metronidazole. For each compound, the ratio of 2 ions from the mass spectrum was monitored in fortified rumen contents. The ion ratio of fortified sample was compared with the ion ratio of standard sample spectrum and was found to be within 20%, with the exception of aldicarb and 4-aminopyridine with ion ratio of 26% and 29%, respectively. Usefulness of the method was demonstrated by not only analyzing bovine rumen contents but also canine and avian gastrointestinal contents submitted for organic chemical screening. PMID:25027495

  15. Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

    PubMed

    Louir, Raphael J; Tonneson, Jennifer E; Gowarty, Minda; Goodney, Philip P; Barth, Richard J; Rosenkranz, Kari M

    2015-11-01

    Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005–December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually. PMID:26467045

  16. SCREENING BIOAVAILABLE HYDROPHOBIC TOXICANTS IN SURFACE WATERS WITH SEMIPERMEABLE MEMBRANE DEVICES: ROLE OF INHERENT OLEIC ACID IN TOXICITY EVALUATIONS

    EPA Science Inventory

    Semipermeable membrane devices (SPMDs) were deployed for 4 weeks in two rivers in Lithuania, The SPMD dialysates were tested in the Microtox assay and, surprisingly, the sample from the relatively clean (U) over bar la River exhibited three times more toxicity than the sample fro...

  17. Dual NRASQ61R and BRAFV600E mutation-specific immunohistochemistry completes molecular screening in melanoma samples in a routine practice.

    PubMed

    Uguen, Arnaud; Guéguen, Paul; Legoupil, Delphine; Bouvier, Stéphanie; Costa, Sebastian; Duigou, Sandrine; Lemasson, Gilles; Ledé, Françoise; Sassolas, Bruno; Talagas, Matthieu; Férec, Claude; Le Maréchal, Cédric; De Braekeleer, Marc; Marcorelles, Pascale

    2015-11-01

    NRAS and BRAF mutational status has become mandatory to treat patients with metastatic melanomas. Mutation-specific immunohistochemistry (IHC) can help analyze challenging tumor samples. We report our experience integrating NRASQ61R (SP174) and BRAFV600E (VE1) IHC in routine practice in a cancer molecular genetic platform. All samples screened for BRAF and NRAS mutations during the year 2014 were analyzed by IHC and pyrosequencing, with an independent analysis of the 2 methods. Cases with first-line discordant results benefited from a complementary second-round IHC and next-generation sequencing (NGS) with a final interpretation taking into account the results of pyrosequencing, IHC, NGS, and quantification of the tumor cells. We analyzed 111 consecutive formalin-fixed and paraffin-embedded melanoma samples from 101 patients. Twenty-two and 11 samples were concordant for BRAFV600E and NRASQ61R mutations, respectively. Second-round analyses of 9 discordant and 1 molecularly inconclusive samples allowed conclusion in 4 further mutated samples (2 BRAFV600E and 2 NRASQ61R). A sample remained NRASQ61R IHC negative but NRASQ61R mutated with molecular methods. Overall, BRAFV600 and NRASQ61 mutation frequencies were 31.7% and 30.7%, respectively. When compared to molecular results, the sensitivity and specificity of IHC were 100% for BRAFV600E IHC and 92.3% and 98.9% for NRASQ61R IHC, respectively. IHC interpretation required a more stringent cutoff for BRAFV600E IHC than NRASQ61R to minimize false results. We conclude that NRASQ61R and BRAFV600E IHC coupled with NGS allow detection of mutations in melanoma challenging samples. PMID:26297254

  18. Evaluation of the limitations of using the University of Washington Quality of Life swallowing domain alone to screen patients in the routine clinical setting.

    PubMed

    Zuydam, A C; Ghazali, N; Lowe, D; Skelly, R; Rogers, S N

    2013-10-01

    A broad patient-completed screening tool in routine clinical practice in head and neck oncology has merit, but clinicians should be aware that its simplicity could lead to some patients and the detail of their problems being missed. The purpose of this study was to compare the University of Washington Quality of Life (UWQoL) swallowing domain with the MD Anderson Dysphagia Inventory (MDADI) in relation to the need for interventions for swallowing around one year after treatment. The group comprised 112 consecutively referred patients to speech and language therapy between January 2007 and August 2009 after primary operation for previously untreated oral and oropharyngeal squamous cell carcinoma (SCC). A total of 78 patients completed questionnaires (median time of assessment 11.7 months, IQR 6.1-12.2). There were significant (p<0.001) and moderately strong correlations (rs=0.51-0.62) between the UWQoL swallowing domain score and MDADI subscales and total scores, and also with individual MDADI questions: taking a great deal of effort (rs=0.71); being upset (rs=0.61); and not going out (rs=0.62) were the strongest in regard to swallowing. Use of a gastrostomy tube was associated with worse UWQoL and MDADI scores. In conclusion, patients who score 100 on the UWQoL do not require swallowing to be evaluated further. Those who score 70 could benefit from the detailed MDADI to help to clarify the specific problem and the impact it has before being referred to speech and language therapy. Those who score less than 70 should be brought to the attention of speech and language therapists to confirm that appropriate support and intervention are in place. PMID:22721809

  19. Yeast as a Model for Studies on Aβ Aggregation Toxicity in Alzheimer's Disease, Autophagic Responses, and Drug Screening.

    PubMed

    Porzoor, Afsaneh; Macreadie, Ian

    2016-01-01

    The Aβ peptide is widely considered a major cause of Alzheimer's disease since it causes neuronal death in an oligomerisation-dependent manner. In order to identify new inhibitors of Aβ that may be chemo preventative for Alzheimer's disease, a yeast assay that qualitatively determines the amounts and state of the human Aβ42 peptide has been developed. Yeast assays such as this can be applied to studies on aggregation toxicity, autophagic responses and drug screening in Alzheimer's disease. PMID:26235069

  20. Application of a fish DNA damage assay as a biological toxicity screening tool for metal plating wastewater

    SciTech Connect

    Choi, K.; Zong, M.; Meier, P.G.

    2000-01-01

    The utility of a fish DNA damage assay as a rapid monitoring tool was investigated. Metal plating wastewater was chosen as a sample because it contains various genotoxic metal species. Fish DNA damage assay results were compared to data generated from the conventional whole effluent toxicity (WET) test procedure. The Microtox{reg_sign} assay (Azur Environmental, Carlsbad, CA, USA) using Vibrio fischeri was also employed. Eleven samples from two metal plating companies were collected for this evaluation. For the fish DNA damage assay, 7-d-old fathead minnow larvae, Pimephales promelas, were utilized. They were exposed to a series of dilutions at 20 C for 2 h. Whole effluent toxicity tests conducted in this study included two acute toxicity tests with Daphnia magna and fathead minnows and two chronic toxicity tests with Ceriodaphnia dubia and fathead minnows. The fish DNA damage assay showed good correlations with both the acute and chronic WET test results, especially with those obtained with fathead minnows. The kappa values, an index of agreement, between the fish DNA damage assay and WET tests were shown to be acceptable. These findings imply that this novel fish DNA damage assay has use as an expedient toxicity screening procedure since it produces comparable results to those of the acute and chronic fathead minnow toxicity tests.

  1. The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals.

    PubMed

    van der Burg, Bart; Wedebye, Eva Bay; Dietrich, Daniel R; Jaworska, Joanna; Mangelsdorf, Inge; Paune, Eduard; Schwarz, Michael; Piersma, Aldert H; Kroese, E Dinant

    2015-08-01

    There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use. The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner preferably using validated existing tools and place them in an innovative alternative testing strategy. In our approach we combined knowledge on critical processes affected by reproductive toxicants with knowledge on the mechanistic basis of such effects. We used in silico methods for prescreening chemicals for relevant toxic effects aiming at reduced testing needs. For those chemicals that need testing we have set up an in vitro screening panel that includes mechanistic high throughput methods and lower throughput assays that measure more integrative endpoints. In silico pharmacokinetic modules were developed for rapid exposure predictions via diverse exposure routes. These modules to match in vitro and in vivo exposure levels greatly improved predictivity of the in vitro tests. As a further step, we have generated examples how to predict reproductive toxicity of chemicals using available data. We have executed formal validations of panel constituents and also used more innovative manners to validate the test panel using mechanistic approaches. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application, including case studies for read-across purposes. With this approach, a significant saving in animal use and associated costs seems very feasible. PMID:25656794

  2. Building a Tiered Approach to In Vitro Predictive Toxicity Screening: A Focus on Assays with In Vivo Relevance

    PubMed Central

    McKim, James M

    2010-01-01

    One of the greatest challenges facing the pharmaceutical industry today is the failure of promising new drug candidates due to unanticipated adverse effects discovered during preclinical animal safety studies and clinical trials. Late stage attrition increases the time required to bring a new drug to market, inflates development costs, and represents a major source of inefficiency in the drug discovery/development process. It is generally recognized that early evaluation of new drug candidates is necessary to improve the process. Building in vitro data sets that can accurately predict adverse effects in vivo would allow compounds with high risk profiles to be deprioritized, while those that possess the requisite drug attributes and a lower risk profile are brought forward. In vitro cytotoxicity assays have been used for decades as a tool to understand hypotheses driven questions regarding mechanisms of toxicity. However, when used in a prospective manner, they have not been highly predictive of in vivo toxicity. Therefore, the issue may not be how to collect in vitro toxicity data, but rather how to translate in vitro toxicity data into meaningful in vivo effects. This review will focus on the development of an in vitro toxicity screening strategy that is based on a tiered approach to data collection combined with data interpretation. PMID:20053163

  3. Comparison of three marine screening tests and four Oslo and Paris Commission procedures to evaluate toxicity of offshore chemicals

    SciTech Connect

    Weideborg, M.; Vik, E.A.; Oefjord, G.D.; Kjoennoe, O.

    1997-02-01

    The results from the screening toxicity tests Artemia salina, Microtox{reg_sign}, and Mitochondria RET test were compared with those obtained from OSPAR (Oslo and Paris Commissions)-authorized procedures for testing of offshore chemicals (Skeletonema costatum, Acartia tonsa, Abra alba, and Corophium volutator). In this study 82 test substances (26 non-water soluble) were included. The Microtox test was found to be the most sensitive of the three screening tests. Microtox and Mitochondria RET test results showed good correlation with results from Acartia and Skeletonema testing, and it was concluded that the Microtox test was a suitable screening test as a base for assessment of further testing, especially regarding water-soluble chemicals. Sensitivity of Artemia salina to the tested chemicals was too low for it to be an appropriate bioassay organism for screening testing. A very good correlation was found between the results obtained with the Skeletonema and Acartia tests. The results indicated no need for more than one of the Skeletonema or Acartia tests if the Skeletonema median effective concentration or Acartia median lethal concentration was greater than 200 mg/L. The sediment-reworker tests (A. Alba or C. volutator) for chemicals that are likely to end up in the sediments (non-water soluble or surfactants) should be performed, independent of results from screening tests and other OSPAR species.

  4. Validation of Screening Assays for Developmental Toxicity: An Exposure-Based Approach

    EPA Science Inventory

    There continue to be widespread efforts to develop assay methods for developmental toxicity that are shorter than the traditional Segment 2 study and use fewer or no animals. As with any alternative test method, novel developmental toxicity assays must be validated by evaluating ...

  5. VAPOR SAMPLING DEVICE FOR INTERFACE WITH MICROTOX ASSAY FOR SCREENING TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

  6. A Call for Nominations of Quantitative High-Throughput Screening Assays from Relevant Human Toxicity Pathways

    EPA Science Inventory

    The National Research Council of the United States National Academies of Science has recently released a document outlining a long-range vision and strategy for transforming toxicity testing from largely whole animal-based testing to one based on in vitro assays. “Toxicity Testin...

  7. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data

    EPA Science Inventory

    EPA's ToxCast™ project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database wou...

  8. Development of a fluorimetric multispecies 96-well micro-plate growth test for screening metal toxicity to phytoplankton

    SciTech Connect

    Peterson, H.G.; Ruecker, N.J.; Cantin, I.A.; Nyholm, N.; Dal-Jensen, S.

    1995-12-31

    The rapid and cost-effective screening of industrial waste is an ideal approach to regulations that offer true protection of aquatic habitats. For these tests to be ecologically important protection of large groups of organisms is also essential. This can best be done by testing batteries of species. Photosynthetic organisms compose 99.9% of habitats as well as providing food for higher trophic levels. A test was developed that can accommodate the testing of most phytoplanktonic species irrespective of morphology (unicellular, multicellular, colonial, filamentous). Forty eight to 72 h growth tests were carried out with green algae, diatoms, and cyanobacteria. The algae were incubated with different levels of toxicants in 96-well microplates which were read in a 96-well fluorometric plate reader. Phytoplankton emitting low levels of fluorescence can be incubated with DCMU, which can increase the fluorescent signal 2 to 4 times. The data from the plate reader is transferred to a computer spreadsheet and inhibition levels are automatically calculated. Eleven metal mining wastes from across Canada were tested against this method using the following phytoplanktonic species: Selenastrum, Nannochloris (green algae), Nitzschia (diatom), Microcystis, and Pseudoanabaena (cyanobacteria). These wastes were also screened against Microtox. All wastes were highly toxic to the tested phytoplankton, but only 4 were toxic to Microtox{trademark}.

  9. Application of Targeted Functional Assays to Assess a Putative Vascular Disruption Developmental Toxicity Pathway Informed By ToxCast High-Throughput Screening Data

    EPA Science Inventory

    Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...

  10. A Comparison of the Daphnids, Ceriodaphnia dubia and Daphnia ambigua, for their Utilization in Routine Toxicity Testing in the Southeastern United States

    SciTech Connect

    Harmon, S.M.; Chandler, G.T.; Specht, W.L.

    2003-02-18

    U.S. regulatory agencies commonly require effluent toxicity testing with Ceriodaphnia dubia- a practice which has led to the criticism that this species and test protocol often does not reflect local taxa nor site-specific conditions. Using an indigenous test species may produce a more realistic model of local effects and may minimize test endpoint variance due to regional differences in water quality. This study addressed the substitution of C. dubia with Daphnia ambigua for toxicity testing in the southeastern United States. This investigation determined that D. ambigua could be laboratory cultured with only minimal changes to established regulatory protocol, and that the life-cycle characteristics of this species were conducive to traditional acute and chronic aquatic toxicity test methods used with other daphnids. Acute toxicity tests showed that D. ambigua was less sensitive to some toxicants (sodium chloride, copper sulfate, and sodium lauryl sulfate) yet more sensitive to others (chlorpyrifos). Chronic tests with copper sulfate and sodium chloride resulted in lower EC50s for D. ambigua reproduction with both compounds. When exposed to low-alkalinity, low-pH stream waters typical of many southeastern United States watersheds, C. dubia demonstrated a significant reproductive depression in two of three streams tested, while D. ambigua experienced no chronic effect. These results suggest that D. ambigua may serve as a suitable surrogate for C. dubia as an toxicity indicator species in these types of receiving streams.

  11. Hazard screening of chemical releases and environmental equity analysis of populations proximate to toxic release inventory facilities in Oregon.

    PubMed Central

    Neumann, C M; Forman, D L; Rothlein, J E

    1998-01-01

    A comprehensive approach using hazard screening, demographic analysis, and a geographic information system (GIS) for mapping is employed to address environmental equity issues in Oregon. A media-specific chronic toxicity index [or chronic index (CI)] was used to compare environmental chemical releases reported in the EPA's Toxic Chemical Release Inventory (TRI) database. In 1992, 254 facilities reportedly released more than 40 million pounds of toxic chemicals directly into the environment on-site or transferred them to sewage treatment plants or other off-site facilities for disposal and recycling. For each reported on-site TRI chemical release, a CI based on oral toxicity factors and total mass was calculated. CIs were aggregated on a media-, facility-, and chemical-specific basis. Glycol ethers, nickel, trichloroethylene, chloroform, and manganese were ranked as the top five chemicals released statewide based on total CI. In contrast, based on total mass, methanol, nickel, ammonia, acetone, and toluene were identified as the top five TRI chemicals released in Oregon. TRI facility rankings were related to the demographics and household income of surrounding neighborhoods using bivariate GIS mapping and statistical analysis. TRI facilities were disproportionately located in racial and ethnic minority neighborhoods. They were also located in areas with lower incomes compared to those in the surrounding county. No relationship was observed between the hazard ranking of the TRI facilities overall and socioeconomic characteristics of the community in which they were located. Images Figure 1 Figure 2 PMID:9494125

  12. Hazard screening of chemical releases and environmental equity analysis of populations proximate to toxic release inventory facilities in Oregon.

    PubMed

    Neumann, C M; Forman, D L; Rothlein, J E

    1998-04-01

    A comprehensive approach using hazard screening, demographic analysis, and a geographic information system (GIS) for mapping is employed to address environmental equity issues in Oregon. A media-specific chronic toxicity index [or chronic index (CI)] was used to compare environmental chemical releases reported in the EPA's Toxic Chemical Release Inventory (TRI) database. In 1992, 254 facilities reportedly released more than 40 million pounds of toxic chemicals directly into the environment on-site or transferred them to sewage treatment plants or other off-site facilities for disposal and recycling. For each reported on-site TRI chemical release, a CI based on oral toxicity factors and total mass was calculated. CIs were aggregated on a media-, facility-, and chemical-specific basis. Glycol ethers, nickel, trichloroethylene, chloroform, and manganese were ranked as the top five chemicals released statewide based on total CI. In contrast, based on total mass, methanol, nickel, ammonia, acetone, and toluene were identified as the top five TRI chemicals released in Oregon. TRI facility rankings were related to the demographics and household income of surrounding neighborhoods using bivariate GIS mapping and statistical analysis. TRI facilities were disproportionately located in racial and ethnic minority neighborhoods. They were also located in areas with lower incomes compared to those in the surrounding county. No relationship was observed between the hazard ranking of the TRI facilities overall and socioeconomic characteristics of the community in which they were located. PMID:9494125

  13. A field test of substance use screening devices as part of routine drunk-driving spot detection operating procedures in South Africa.

    PubMed

    Matzopoulos, Richard; Lasarow, Avi; Bowman, Brett

    2013-10-01

    This pilot study aimed to test four substance use screening devices developed in Germany under local South African conditions and assess their utility for detecting driving under the influence of drugs (DUID) as part of the standard roadblock operations of local law enforcement agencies. The devices were used to screen a sample of motorists in the Gauteng and Western Cape provinces. The motorists were diverted for screening at roadblocks at the discretion of the law enforcement agencies involved, as per their standard operating procedures. Fieldworkers also administered a questionnaire that described the screening procedure, as well as information about vehicles, demographic information about the motorists and their attitudes to the screening process during testing. Motorists tested positive for breath alcohol in 28% of the 261 cases tested. Oral fluid was screened for drugs as per the standard calibrated cut-offs of all four devices. There were 14 cases where the under-influence drivers tested positive for alcohol and drugs simultaneously, but 14% of the 269 drivers drug-screened tested positive for drugs only. After alcohol, amphetamine, methamphetamine and cocaine were the most common drugs of impairment detected. The results suggest that under normal enforcement procedures only 76% of drivers impaired by alcohol and other drugs would have been detected. In more than 70% of cases the tests were administered within 5 min and this is likely to improve with more regular use. It was clear that the pilot screening process meets global testing standards. Although use of the screening devices alone would not serve as a basis for prosecution and provisions would need to be made for the confirmation of results through laboratory testing, rollout of this screening process would improve operational efficiency in at least two ways. Firstly, the accuracy of the tests will substantially decrease confirmatory test loads. Secondly, laboratory drug testing can be restricted to

  14. Sensitivity of screening-level toxicity tests using soils from a former petroleum refinery

    SciTech Connect

    Pauwels, S.; Bureau, J.; Roy, Y.; Allen, B.; Robidoux, P.Y.; Soucy, M.

    1995-12-31

    The authors tested five composite soil samples from a former refinery. The samples included a reference soil (Mineral Oil and Grease, MO and G < 40 ppm), thermally-treated soil, biotreated soil, and two untreated soils. They evaluated toxicity using the earthworm E. foetida, lettuce, cress, barley, Microtox, green algae, fathead minnow, and D. magna. The endpoints measured were lethality, seed germination, root elongation, growth, and bioluminescence. Toxicity, as measured by the number of positive responses, increased as follows: biotreated soil < untreated soil No. 1 < reference soil < thermally-treated soil and untreated soil No. 2. The biotreated soil generated only one positive response, whereas the thermally-treated soil and untreated soil No. 2 generated five positive responses. The most sensitive and discriminant terrestrial endpoint was lettuce root elongation which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was barley seed germination for which no toxicity was detected. The most sensitive and discriminant aquatic endpoint was green algae growth which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was D. magna for which no toxicity was detected. Overall, soil and aqueous extract toxicity was spotty and no consistent patterns emerged to differentiate the five soils. Biotreatment significantly reduced the effects of the contamination. Aqueous toxicity was measured in the reference soil, probably because of the presence of unknown dissolved compounds in the aqueous extract. Finally, clear differences in sensitivity existed among the test species.

  15. Fast Screening Techniques for Neurotoxigenic Substances and Other Toxicants and Pollutants Based on Thermal Lensing and Microfluidic Chips.

    PubMed

    Franko, Mladen; Liu, Mingqiang; Boškin, Aleš; Delneri, Ambra; Proskurnin, Mikhail A

    2016-01-01

    Efficient environment protection and human safety require high-throughput analysis techniques for pollutants or toxicants for large sample sets. State-of-the-art HPLC and GC coupled to various detecting strategies offer excellent sensitivity and selectivity, though they are quite time-extensive (2 - 3 samples/h or less when sample preparation is involved). Efforts are made towards screening techniques with high sample throughputs simultaneously providing detection limits below the maximum contaminant levels for the analyte. However, such approaches frequently sacrifice the selectivity or sensitivity (or just give a yes/no response). In this review, we demonstrate thermal-lens spectrometry and microscopy as highly sensitive spectrometric techniques in combination with flow-injection analysis (FIA) and microfluidic FIA along with lab-on-a-chip chemistry for fast screening (several samples/h and up to 20 samples/min) exemplified by organophosphates and carbamates as neurotoxigenic compounds. Various approaches to determining other topical toxicants, like microcystin and cyanopigments as its indicators, allergens, and carcinogenic chromate, are also discussed. PMID:26753701

  16. A Genetic Screen Using the PiggyBac Transposon in Haploid Cells Identifies Parp1 as a Mediator of Olaparib Toxicity

    PubMed Central

    Pettitt, Stephen J.; Rehman, Farah L.; Bajrami, Ilirjana; Brough, Rachel; Wallberg, Fredrik; Kozarewa, Iwanka; Fenwick, Kerry; Assiotis, Ioannis; Chen, Lina; Campbell, James; Lord, Christopher J.; Ashworth, Alan

    2013-01-01

    Genetic perturbation screens have the potential to dissect a wide range of cellular phenotypes. Such screens have historically been difficult in diploid mammalian cells. The recent derivation of haploid embryonic stem cells provides an opportunity to cause loss of function mutants with a random mutagen in a mammalian cell with a normal genetic background. We describe an approach to genetic screens that exploits the highly active piggyBac transposon in haploid mammalian cells. As an example of haploid transposon (HTP) screening, we apply this approach to identifying determinants of cancer drug toxicity and resistance. In a screen for 6-thioguanine resistance we recovered components of the DNA mismatch repair pathway, a known requirement for toxicity. In a further screen for resistance to the clinical poly(ADP-ribose) polymerase (PARP) inhibitor olaparib we recovered multiple Parp1 mutants. Our results show that olaparib toxicity to normal cells is mediated predominantly via Parp1, and suggest that the clinical side effects of olaparib may be on target. The transposon mutant libraries are stable and can be readily reused to screen other drugs. The screening protocol described has several advantages over other methods such as RNA interference: it is rapid and low cost, and mutations can be easily reverted to establish causality. PMID:23634208

  17. Contamination and screening level toxicity of sediments from remediated and unremediated wetlands near Sydney, Australia.

    PubMed

    Ying, Guang-Guo; Rawson, Christopher A; Kookana, Rai S; Peng, Ping-An; Warne, Michael S J; Tremblay, Louis A; Laginestra, Edwina; Chapman, John C; Lim, Richard P

    2009-10-01

    The present study assessed contamination and toxicity of sediments from seven remediated and remnant wetland sites within Sydney Olympic Park, Australia, and four unremediated sites adjacent to its boundary using chemical analysis and a luminescent bacterial biosensor assay (Escherichia coli). Concentrations of metals (Pb, Cr, Cu, Ni, Zn, Cd, and As) and persistent organic chemicals (DDT and its metabolites, dichlorodiphenyldichloroethane and dichlorodiphenyldichloroethylene; polycyclic aromatic hydrocarbons; polychlorinated biphenyls; and polychlorinated dibenzo-p-dioxins and dibenzofurans) in sediments and their pore-water samples were determined. Zinc concentrations were the highest of the metals in the sediments (84-618 mg/kg), and at eight sites, metal concentrations in sediments exceeded the Australian ecological trigger values for Pb, Zn, and Ni. Concentrations of organic contaminants in the sediments exceeded the trigger values at all 11 sites for DDTs, at 6 sites for polycyclic aromatic hydrocarbons, and 5 sites for polychlorinated biphenyls. Sediment samples from the four unremediated sites outside the Sydney Olympic Park had dioxin concentrations greater than 200 pg (toxic equivalency per gram). The same four sites were identified as contaminated in pore-water toxicity tests with the luminescent biosensor, generally consistent with the bioavailable fractions of the contaminants (pore-water and Tenax extraction data), as well as dioxin levels, in the sediments. Preliminary toxicity identification and evaluation tests of the pore water from the four sites outside the park demonstrated that organic contaminants were the main cause of toxicity to E. coli, with no evidence that metals contributed to the toxicity of the pore water. PMID:19589001

  18. Use of an organotypic mammalian in vitro follicle growth (IVFG) assay to facilitate female reproductive toxicity screening

    PubMed Central

    Xu, Yuanming; Duncan, Francesca E.; Xu, Min; Woodruff, Teresa K.

    2015-01-01

    Screening of pharmaceutical, chemical, and environmental compounds for their effects on reproductive health relies on in vivo studies. More robust and efficient methods to assess thes effects are needed. Here we adapted and validated an organotypic in vitro follicle growth (IVFG) assay to determine the impact of compounds on markers of ovarian function. We isolated mammalian follicles and cultured them in the presence of compounds with 1) known fertotoxicity (i.e., toxicity to the reproductive system; cyclophosphamide and cisplatin); 2) no known fertotoxicity (nalbuphine); and 3) unknown fertotoxicity (Corexit EC 9500 A; CE). In each case we assayed follicle growth, hormone production, and the ability of follicle-enclosed oocytes to resume meiosis and produce a mature egg. We found that cyclophosphamide and cisplatin caused dose-dependent disruption of follicle dynamics, whereas nalbuphine did not. The reproductive toxicity of CE, an oil dispersant used heavily during the 2010 Deepwater Horizon oil spill, has never been examined in a mammalian system. We found that CE compromised follicle morphology and functional parameters. Our findings demonstrate that this IVFG assay system can be used to distinguish fertotoxic from non-toxic compounds, providing an in vitro tool for assessing effects of chemical compounds on reproductive function and health. PMID:25689754

  19. STRUCTURE-ACTIVITY APPROACHES IN THE SCREENING OF ENVIRONMENTAL AGENTS FOR DEVELOPMENTAL TOXICITY

    EPA Science Inventory

    In drug development, SARs are an integral part of the process of finding efficacious and non-toxic analogues, and in vitro test systems which detect the biological activity of a particular chemical class have found an important role in SAR research. n contrast, SARs are not a pri...

  20. DEVELOPMENT OF TOXICITY REFERENCE VALUES FOR ECOLOGICAL SOIL SCREENING LEVELS (ECO-SSLS) FOR TERRESTRIAL WILDLIFE

    EPA Science Inventory

    Ecological Soil Screening Levels (Eco-SSLs) protective of terrestrial wildlife were developed by the USEPA Superfund. The wildlife Eco-SSL is the soil contaminant concentration where the Effect Dose (TRV) and Exposure Dose are equal (amount of contaminant in the diet that is take...

  1. COMPARISON OF CHEMICAL SCREENING AND RANKING APPROACHES: THE WASTE MINIMIZATION PRIORITIZATION TOOL VERSUS TOXIC EQUIVALENCY POTENTIALS

    EPA Science Inventory

    Chemical screening in the United States is often conducted using scoring and ranking methodologies. Linked models accounting for chemical fate, exposure, and toxicological effects are generally preferred in Europe and in product Life Cycle Assessment. For the first time, a compar...

  2. TOXICITY AND BIODEGRADABILITY SCREENING OF NONIONIC SURFACTANTS USING SEDIMENT-DERIVED METHANOGENIC CONSORTIA. (R825404)

    EPA Science Inventory

    Abstract

    The objective of this study was to screen and select biologically-compatible surfactants for subsequent use in enhancing the bioavailability and reductive dechlorination of sorbed-phase chlorinated organic contaminants. Sixteen surfactants commonly used in sur...

  3. Incorporating Human Dosimetry and Exposure into High-Throughput In Vitro Toxicity Screening

    EPA Science Inventory

    Many chemicals in commerce today have undergone limited or no safety testing. To reduce the number of untested chemicals and prioritize limited testing resources, several governmental programs are using high-throughput in vitro screens for assessing chemical effects across multip...

  4. Combined repeated dose and reproductive/developmental toxicity screening test of 4-methoxy-2-nitroaniline in rats.

    PubMed

    Tsubokura, Yasuhiro; Aso, Sunao; Koga, Takayuki; Kikuchi, Junichi; Kobayashi, Toshio; Hoshuyama, Satsuki; Oshima, Yutaka; Miyata, Katsumi; Kusune, Yuji; Muroi, Takako; Yoshida, Tomohiko; Hasegawa, Ryuichi; Ajimi, Shozo; Furukawa, Kotaro

    2015-10-01

    4-Methoxy-2-nitroaniline (4M2NA) is widely used as an intermediate for the synthesis of dyes, pigments and other chemical compounds. Since 4M2NA has amino-group and nitro-group on the benzene ring, it was expected that it induced obvious hemolytic anemia. We conducted a combined repeated dose and reproductive/developmental toxicity screening test according to Organisation for Economic Co-operation and Development (OECD) Test Guideline No. 422 (OECD TG 422) to enrich the toxic information and ensure the safety of 4M2NA. 4M2NA was administered to Crl:CD(SD) male and female rats by gavage at 0, 12.5, 75 or 450 mg/kg/day for 42 to maximum of 54 days through pre-mating, mating, pregnancy and lactation periods. An extramedullary hematopoiesis and congestion in spleen, and higher reticulocyte ratio were noted in only females at 450 mg/kg/day without decreased anemic parameters in the hematological examination. Hypertrophy of centrilobular hepatocytes in both sexes was observed with increased relative liver weight at 450 mg/kg/day. Furthermore, the diffuse follicular cell hypertrophy of the thyroid was observed in females at 450 mg/kg/day. No abnormalities were detected in the reproductive indices of copulation, delivery or fetal viability. We concluded the no-observed-adverse-effect level (NOAEL) for repeated-dose toxicity was 75 mg/kg/day based on the trace evidences of hemolytic anemia, and the NOAEL for reproductive/developmental toxicity as 450 mg/kg/day based on no toxicological concerns for reproductive endpoints. The hemolytic anemia was much milder than expected. Thus, we discussed the reason of this much less hemolytic effect from the point of view of the structural characteristics of 4M2NA. PMID:25367778

  5. Copper toxicity in a natural reference soil: ecotoxicological data for the derivation of preliminary soil screening values.

    PubMed

    Caetano, Ana Luísa; Marques, Catarina Ribeiro; Gonçalves, Fernando; da Silva, Eduardo Ferreira; Pereira, Ruth

    2016-01-01

    The risk assessment of contaminated soils is conventionally done with the support of soil screening values (SSVs). Since SSVs are still unavailable for many European countries, including Portugal, standardized toxicity tests are urgently claimed for their derivation. Hence, this work aimed the generation of toxicity values for copper (Cu) in a natural reference soil (PTRS1) targeting different terrestrial species, endpoints and soil functions, as to derive a preliminary Cu SSV. For this, the Assessment Factor approach was applied, which allowed calculating predicted no effect concentrations (PNEC) for Cu that will be the basis for SSV proposal. In order to increase the reliability of the PNEC, and hence of the SSV, a lab/field factor was applied to correct the toxicity values used for PNEC determination. Cu affected urease, cellulase and nitrogen mineralization activities. The EC50 values calculated for the invertebrates reproduction were 130.9, 165.1 and 191.6 mg Cu Kg(-1) soildw for Eisenia andrei, Enchytraeus crypticus and Folsomia candida, respectively. Cu inhibited seed germination mainly for Lactuca sativa, whilst it was toxic for the growth of different plant species (EC50s between 89 and 290.5 mg Cu Kg(-1) soildw). Based on the outcomes gathered, we proposed SSVs for Cu ranging between 26.3 and 31.8 mg Kg(-1) soildw, which is above the background values reported and below all the EC20s recorded for the species and endpoints herein analyzed. Overall, this work describes a procedure that could be easily followed by other European countries wishing to derive SSVs adjusted to their soils. PMID:26520436

  6. Screening of potential probiotic lactic acid bacteria based on gastrointestinal properties and perfluorooctanoate toxicity.

    PubMed

    Xing, Jiali; Wang, Fan; Xu, Qi; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q; Wang, Gang; Chen, Wei

    2016-08-01

    The consumption of lactic acid bacteria capable of binding or degrading food-borne carcinogens may reduce human exposure to these deleterious compounds. In this study, 25 Lactobacillus strains isolated from human, plant, or dairy environments were investigated for their potential probiotic capacity against perfluorooctanoate (PFOA) toxicity. The PFOA binding, tolerance ability, and acid and bile salt tolerance were investigated and assessed by principal component analysis. Additionally, the effect of different pH levels and binding times was assessed. These strains exhibited different degrees of PFOA binding; the strain with the highest PFOA binding capability was Lactobacillus plantarum CCFM738, which bound to 49.40 ± 1.5 % of available PFOA. This strain also exhibited relatively good cellular antioxidative properties, acid and bile salt tolerance, and adhesion to Caco-2 cells. This study suggests that L. plantarum CCFM738 could be used as a potential probiotic in food applications against PFOA toxicity. PMID:27094185

  7. High-Content Assay Multiplexing for Toxicity Screening in Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Hepatocytes

    PubMed Central

    Grimm, Fabian Alexander; Iwata, Yasuhiro; Sirenko, Oksana; Bittner, Michael

    2015-01-01

    Abstract Cell-based high-content screening (HCS) assays have become an increasingly attractive alternative to traditional in vitro and in vivo testing in pharmaceutical drug development and toxicological safety assessment. The time- and cost-effectiveness of HCS assays, combined with the organotypic nature of human induced pluripotent stem cell (iPSC)-derived cells, open new opportunities to employ physiologically relevant in vitro model systems to improve screening for potential chemical hazards. In this study, we used two human iPSC types, cardiomyocytes and hepatocytes, to test various high-content and molecular assay combinations for their applicability in a multiparametric screening format. Effects on cardiomyocyte beat frequency were characterized by calcium flux measurements for up to 90 min. Subsequent correlation with intracellular cAMP levels was used to determine if the effects on cardiac physiology were G-protein-coupled receptor dependent. In addition, we utilized high-content cell imaging to simultaneously determine cell viability, mitochondrial integrity, and reactive oxygen species (ROS) formation in both cell types. Kinetic analysis indicated that ROS formation is best detectable 30 min following initial treatment, whereas cytotoxic effects were most stable after 24 h. For hepatocytes, high-content imaging was also used to evaluate cytotoxicity and cytoskeletal integrity, as well as mitochondrial integrity and the potential for lipid accumulation. Lipid accumulation, a marker for hepatic steatosis, was most reliably detected 48 h following treatment with test compounds. Overall, our results demonstrate how a compendium of assays can be utilized for quantitative screening of chemical effects in iPSC cardiomyocytes and hepatocytes and enable rapid and cost-efficient multidimensional biological profiling of toxicity. PMID:26539751

  8. Bioluminescence inhibition assays for toxicity screening of wood extractives and biocides in paper mill process waters.

    PubMed

    Rigol, Anna; Latorre, Anna; Lacorte, Sílvia; Barceló, Damià

    2004-02-01

    The risk associated with wood extractives, biocides, and other additives in pulp and paper mill effluents was evaluated by performing a characterization of process waters and effluents in terms of toxicity and chemical analysis. The individual toxicity of 10 resin acids, two unsaturated fatty acids, and three biocides was estimated by measuring the bioluminescence inhibition with a ToxAlert 100 system. Median effective concentration values (EC50) of 4.3 to 17.9, 1.2 to 1.5, and 0.022 to 0.50 mg/L were obtained, respectively. Mixtures of these three families of compounds showed antagonistic effects. Chemical analysis of process waters was performed by liquid chromatography- and gas chromatography-mass spectrometry. Biocides such as 2-(thiocyanomethylthio)-benzotiazole (TCMTB) (EC50 = 0.022 mg/L) and 2,2-dibromo-3-nitrilpropionamide (DBNPA) (EC50 = 0.50 mg/L) were the most toxic compounds tested and were detected at concentrations of 16 and 59 microg/L, respectively, in a closed-circuit recycling paper mill. Process waters from kraft pulp mills, printing paper mills, and packing board paper mills showed the highest concentration of resin acids (up to 400 microg/L) and accounted for inhibition percentages up to 100%. Detergent degradation products such as nonylphenol (NP) and octylphenol (OP) and the plasticizer bisphenol A (BPA) were also detected in the waters at levels of 0.6 to 10.6, 0.3 to 1.4, and 0.7 to 187 microg/L, respectively. However, once these waters were biologically treated, the concentration of detected organic compounds diminished and the toxicity decreased in most cases to values of inhibition lower than 20%. PMID:14982380

  9. LuxCDABE--transformed constitutively bioluminescent Escherichia coli for toxicity screening: comparison with naturally luminous Vibrio fischeri.

    PubMed

    Kurvet, Imbi; Ivask, Angela; Bondarenko, Olesja; Sihtmäe, Mariliis; Kahru, Anne

    2011-01-01

    We show that in vitro toxicity assay based on inhibition of the bioluminescence of recombinant Escherichia coli encoding thermostable luciferase from Photorhabdus luminescens is a versatile alternative to Vibrio fischeri Microtox™ test. Performance of two luxCDABE-transformed E. coli MC1061 constructs (pDNlux) and (pSLlux) otherwise identical, but having 100-fold different background luminescence was compared with the performance of V. fischeri. The microplate luminometer and a kinetic Flash-Assay test format was used that differently from Microtox test is also applicable for high throughput analysis. Toxic effects (30-s till 30-min EC(50)) of four heavy metals (Zn, Cd, Hg, Cu) and three organic chemicals (aniline, 3,5-dichloroaniline and 3,5-dichlorophenol) were studied. Both E. coli strains had comparable sensitivity and the respective 30-min EC(50) values highly correlated (log-log R(2) = 0.99; p < 0.01) showing that the sensitivity of the recombinant bacteria towards chemicals analyzed did not depend on the bioluminescence level of the recombinant cells. The most toxic chemical for all used bacterial strains (E. coli, V. fischeri) was mercury whereas the lowest EC(50) values for Hg (0.04-0.05 mg/L) and highest EC(50) values for aniline (1,300-1,700 mg/L) were observed for E. coli strains. Despite of that, toxicity results obtained with both E. coli strains (pSLlux and pDNlux) significantly correlated with V. fischeri results (log-log R(2) = 0.70/0.75; p < 0.05/0.01). The use of amino acids (0.25%) and glucose (0.05%)-supplemented M9 medium instead of leucine-supplemented saline significantly (p < 0.05) reduced the apparent toxicity of heavy metals to both E. coli strains up to three orders of magnitude, but had little or no complexing effect on organic compounds. Thus, P. luminescens luxCDABE-transformed E. coli strains can be successfully used for the acute toxicity screening of various types of organic chemicals and heavy metals and can replace V. fischeri

  10. Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts

    PubMed Central

    Safinar Ismail, Intan; Azam, Amalina Ahmad; Abas, Faridah; Shaari, Khozirah; Sulaiman, Mohd Roslan

    2015-01-01

    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID:26819955

  11. Routine approach to qualitatively screen for 300 pesticides and quantify those frequently detected in fruits and vegetables using liquid chromatography tandem mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper describes an efficient and effective analytical scheme to first screen for 300 pesticides in fruit and vegetables samples using liquid chromatography tandem mass spectrometry (LC-MS/MS) with a commercial enhanced product ion method. Then, the presumed positive extracts were analyzed using...

  12. Isolated factor V deficiency in a patient with elevated PT and aPTT during routine pre-operative laboratory screening

    PubMed Central

    Thakar, Keyur; Parikh, Kaushal; Chen, Yamei

    2014-01-01

    Isolated factor V (FV) deficiency is a rare disorder with approximately 150 cases reported in the literature since 1943. Bleeding symptoms from FV deficiency vary widely. FV deficiency usually manifests early in the life. We present a 59-year-old case with FV deficiency discovered during pre-operative laboratory screen.

  13. Alcohol detoxification in Ysbyty Gwynedd: Two small sips or one big gulp? Two-step screening more reliable for identification of alcohol dependency syndrome at risk of delirium tremens for routine care.

    PubMed

    Salman, Muhammad; Subbe, Christian

    2015-01-01

    Compliance with pathways for hospitalised patients with alcohol dependency syndrome is often poor. A pathway for recognition and treatment of alcohol dependency was redesigned as part of a 12 month service improvement project in the acute medical unit using plan, do, study, act (PDSA) cycles. A needs assessment was undertaken: Audit data from 2013 showed over-prescription of chlordiazepoxide for detoxification treatment (DT) leading to prolonged hospital admissions with an average length of stay of 5.5 days in 2012/2013. Acceptability of screening tools was tested: Common screening tools (CEWA, AUDIT) were rejected by junior doctors due to the high number of questions as too cumbersome for routine practice. Compliance with usage in random samples over a three month period was persistently (n=10%. Testing of an abbreviated AUDIT questionnaire with only two questions and a specified threshold showed a AUROC of 1 (p<0.001 for correct identification). The screening tool was implemented in several PDSAs cycles. After the final cycle a random sample of 100 patients was reviewed for pathway compliance over a three months period. Eighty-six patients were screened with the two-question tool of these 18 were identified as possible risk. Of these 16 patients had the full AUDIT questionnaire, only eight with elevated values were started on DT. Overall compliance with the pathway increased to 84%. PMID:26734413

  14. Alcohol detoxification in Ysbyty Gwynedd: Two small sips or one big gulp? Two-step screening more reliable for identification of alcohol dependency syndrome at risk of delirium tremens for routine care

    PubMed Central

    Salman, Muhammad; Subbe, Christian

    2015-01-01

    Compliance with pathways for hospitalised patients with alcohol dependency syndrome is often poor. A pathway for recognition and treatment of alcohol dependency was redesigned as part of a 12 month service improvement project in the acute medical unit using plan, do, study, act (PDSA) cycles. A needs assessment was undertaken: Audit data from 2013 showed over-prescription of chlordiazepoxide for detoxification treatment (DT) leading to prolonged hospital admissions with an average length of stay of 5.5 days in 2012/2013. Acceptability of screening tools was tested: Common screening tools (CEWA, AUDIT) were rejected by junior doctors due to the high number of questions as too cumbersome for routine practice. Compliance with usage in random samples over a three month period was persistently (n=10%. Testing of an abbreviated AUDIT questionnaire with only two questions and a specified threshold showed a AUROC of 1 (p<0.001 for correct identification). The screening tool was implemented in several PDSAs cycles. After the final cycle a random sample of 100 patients was reviewed for pathway compliance over a three months period. Eighty-six patients were screened with the two-question tool of these 18 were identified as possible risk. Of these 16 patients had the full AUDIT questionnaire, only eight with elevated values were started on DT. Overall compliance with the pathway increased to 84%. PMID:26734413

  15. Multidisciplinary screening of toxicity induced by silica nanoparticles during sea urchin development.

    PubMed

    Gambardella, Chiara; Morgana, Silvia; Bari, Gaetano Di; Ramoino, Paola; Bramini, Mattia; Diaspro, Alberto; Falugi, Carla; Faimali, Marco

    2015-11-01

    The aim of this study was to investigate the potential toxicity of Silica nanoparticles (SiO2 NPs) in seawater by using the sea urchin Paracentrotus lividus as biological model. SiO2 NPs exposure effects were identified on the sperm of the sea urchin through a multidisciplinary approach, combining developmental biology, ecotoxicology, biochemistry, and microscopy analyses. The following responses were measured: (i) percentage of eggs fertilized by exposed sperm; (ii) percentage of anomalies and undeveloped embryos and larvae; (iii) enzyme activity alterations (acetylcholinesterase, AChE) in the early developmental stages, namely gastrula and pluteus. Sperms were exposed to seawater containing SiO2 NPs suspensions ranging from 0.0001mg/L to 50mg/L. Fertilization ability was not affected at any concentration, whereas a significant percentage of anomalies in the offspring were observed and quantified by means of EC50 at gastrula stage, including undeveloped and anomalous embryos (EC50=0.06mg/L), and at pluteus stage, including skeletal anomalies and delayed larvae (EC50=0.27mg/L). Moreover, morphological anomalies were observed in larvae at pluteus stage, by immunolocalizing molecules involved in larval development and neurotoxicity effects - such as acetylated tubulin and choline acetyltransferase (ChAT) - and measuring AChE activity. Exposure of sea urchins to SiO2 NPs caused neurotoxic damage and a decrease of AChE expression in a non-dose-dependent manner. In conclusion, through the multidisciplinary approach used in this study SiO2 NPs toxicity in sea urchin offspring could be assessed. Therefore, the measured responses are suitable for detecting embryo- and larval- toxicity induced by these NPs. PMID:26291678

  16. Usefulness of the Spanish version of the mood disorder questionnaire for screening bipolar disorder in routine clinical practice in outpatients with major depression

    PubMed Central

    2008-01-01

    Background According to some studies, almost 40% of depressive patients – half of them previously undetected – are diagnosed of bipolar II disorder when systematically assessed for hypomania. Thus, instruments for bipolar disorder screening are needed. The Mood Disorder Questionnaire (MDQ) is a self-reported questionnaire validated in Spanish in stable patients with a previously known diagnosis. The purpose of this study is to evaluate in the daily clinical practice the usefulness of the Spanish version of the MDQ in depressive patients. Methods Patients (n = 87) meeting DSM-IV-TR criteria for a major depressive episode, not previously known as bipolar were included. The affective module of the Structured Clinical Interview (SCID) was used as gold standard. Results MDQ screened 24.1% of depressive patients as bipolar, vs. 12.6% according to SCID. For a cut-off point score of 7 positive answers, sensitivity was 72.7% (95% CI = 63.3 – 82.1) and specificity 82.9% (95% CI = 74.9–90.9). Likelihood ratio of positive and negative tests were 4,252 y 0,329 respectively. Limitations The small sample size reduced the power of the study to 62%. Conclusion Sensitivity and specificity of the MDQ were high for screening bipolar disorder in patients with major depression, and similar to the figures obtained in stable patients. This study confirms that MDQ is a useful instrument in the daily clinical assessment of depressive patients. PMID:18498637

  17. Overcoming the toxicity effects of municipal wastewater sludge and biosolid extracts in the Yeast Estrogen Screen (YES) assay.

    PubMed

    Citulski, Joel; Farahbakhsh, Khosrow

    2012-04-01

    For nearly two decades, the Yeast Estrogen Screen (YES) has been used as a valuable tool for determining the total estrogenic potency of various environmental samples, including influent and effluent streams at municipal wastewater plants. However, applying the YES assay to wastewater sludges and stabilized biosolids has been problematic. This is due to co-extracted compounds from the solids either proving toxic to the yeast or masking the presence of estrogenic substances. The present research describes the development and validation of sample preparation steps that mitigate the toxicity effects of municipal wastewater sludge and biosolid samples in the YES assay, while allowing for reliable dose-dependent expression of estrogenic activity. A copper work-up for sulfur removal and chromatographic cleanup with silica and alumina were required in addition to solid-phase extraction to adequately remove interfering compounds. Sample stabilization methods such as autoclaving, lyophilization and formaldehyde treatment were found to be detrimental to the assay. Hence, heat-drying is recommended to prevent cytotoxicity and the degradation of estrogenic substances. PMID:22277884

  18. Comparative alternative materials assessment to screen toxicity hazards in the life cycle of CIGS thin film photovoltaics.

    PubMed

    Eisenberg, Daniel A; Yu, Mengjing; Lam, Carl W; Ogunseitan, Oladele A; Schoenung, Julie M

    2013-09-15

    Copper-indium-gallium-selenium-sulfide (CIGS) thin film photovoltaics are increasingly penetrating the market supply for consumer solar panels. Although CIGS is attractive for producing less greenhouse gas emissions than fossil-fuel based energy sources, CIGS manufacturing processes and solar cell devices use hazardous materials that should be carefully considered in evaluating and comparing net environmental benefits of energy products. Through this research, we present a case study on the toxicity hazards associated with alternative materials selection for CIGS manufacturing. We applied two numeric models, The Green Screen for Safer Chemicals and the Toxic Potential Indicator. To improve the sensitivity of the model outputs, we developed a novel, life cycle thinking based hazard assessment method that facilitates the projection of hazards throughout material life cycles. Our results show that the least hazardous CIGS solar cell device and manufacturing protocol consist of a titanium substrate, molybdenum metal back electrode, CuInS₂ p-type absorber deposited by spray pyrolysis, ZnS buffer deposited by spray ion layer gas reduction, ZnO:Ga transparent conducting oxide (TCO) deposited by sputtering, and the encapsulant polydimethylsiloxane. PMID:23811631

  19. Screening of the toxic effects of a high melamine dose on the biochemical hematological and histopathological investigations in male rats.

    PubMed

    El Rabey, Haddad A; Al-Sieni, Abdulbasit I; Majami, Abdullah A

    2014-11-01

    Screening of the toxic effect of a high oral melamine dose (30,000 ppm supplemented in the diet) was performed for 28 days on male rats. The morphology, anatomy, complete blood count (CBC), serum electrolytes, kidney function, serum proteins, serum bilirubin, serum liver enzymes, catalase, glutathion-S-transferase, lipid peroxide, serum melamine concentration, total body weight, food intake, food efficiency ratio (FER), body weight gain percentage (BWG%), body weight gain, water consumption, and histopathological examinations of kidney, urinary bladder, testis, liver, heart, and spleen were investigated. The melamine-supplemented rats turned yellow and showed different degrees of hypertrophy and congestion, particularly the kidney and the ureter as a result of melamine toxicity. The CBC showed minimal changes in the melamine-supplemented groups. Na and Cl were decreased, whereas K, P, and Ca were increased. Serum creatinine, uric acid, and urea were elevated. Liver function enzymes were nonsignificantly affected. Catalase and glutathion-S-transferase were decreased, whereas lipid peroxide was increased in the kidney tissue homogenate. It was also noted that serum protein was decreased and serum bilirubin was increased. Histopathologically, most examined organs were severely injured specially the kidneys, liver, and testes. PMID:24253415

  20. Toxicity studies of a polyurethane rigid foam

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Schneider, J. E.

    1977-01-01

    Relative toxicity tests were performed on a polyurethane foam containing a trimethylopropane-based polyol and an organophosphate flame retardant. The routine screening procedure involved the exposure of four Swiss albino male mice in a 4.2 liter hemispherical chamber to the products generated by pyrolyzing a 1.00 g sample at a heating rate of 40 deg C/min from 200 to 800 C in the absence of air flow. In addition to the routine screening, experiments were performed with a very rapid rise to 800 C, with nominal 16 and 48 ml/sec air flow and with varying sample rates. No unusual toxicity was observed with either gradual or rapid pyrolysis to 800 C. Convulsions and seizures similar to those previously reported were observed when the materials were essentially flash pyrolyzed at 800 C in the presence of air flow, and the toxicity appeared unusual because of low sample weights required to produce death.

  1. Hierarchical dose-response modeling for high-throughput toxicity screening of environmental chemicals.

    PubMed

    Wilson, Ander; Reif, David M; Reich, Brian J

    2014-03-01

    High-throughput screening (HTS) of environmental chemicals is used to identify chemicals with high potential for adverse human health and environmental effects from among the thousands of untested chemicals. Predicting physiologically relevant activity with HTS data requires estimating the response of a large number of chemicals across a battery of screening assays based on sparse dose-response data for each chemical-assay combination. Many standard dose-response methods are inadequate because they treat each curve separately and under-perform when there are as few as 6-10 observations per curve. We propose a semiparametric Bayesian model that borrows strength across chemicals and assays. Our method directly parametrizes the efficacy and potency of the chemicals as well as the probability of response. We use the ToxCast data from the U.S. Environmental Protection Agency (EPA) as motivation. We demonstrate that our hierarchical method provides more accurate estimates of the probability of response, efficacy, and potency than separate curve estimation in a simulation study. We use our semiparametric method to compare the efficacy of chemicals in the ToxCast data to well-characterized reference chemicals on estrogen receptor α (ERα) and peroxisome proliferator-activated receptor γ (PPARγ) assays, then estimate the probability that other chemicals are active at lower concentrations than the reference chemicals. PMID:24397816

  2. Sensitivity of ecological soil-screening levels for metals to exposure model parameterization and toxicity reference values

    PubMed Central

    Sample, Bradley E; Fairbrother, Anne; Kaiser, Ashley; Law, Sheryl; Adams, Bill

    2014-01-01

    Ecological soil-screening levels (Eco-SSLs) were developed by the United States Environmental Protection Agency (USEPA) for the purposes of setting conservative soil screening values that can be used to eliminate the need for further ecological assessment for specific analytes at a given site. Ecological soil-screening levels for wildlife represent a simplified dietary exposure model solved in terms of soil concentrations to produce exposure equal to a no-observed-adverse-effect toxicity reference value (TRV). Sensitivity analyses were performed for 6 avian and mammalian model species, and 16 metals/metalloids for which Eco-SSLs have been developed. The relative influence of model parameters was expressed as the absolute value of the range of variation observed in the resulting soil concentration when exposure is equal to the TRV. Rank analysis of variance was used to identify parameters with greatest influence on model output. For both birds and mammals, soil ingestion displayed the broadest overall range (variability), although TRVs consistently had the greatest influence on calculated soil concentrations; bioavailability in food was consistently the least influential parameter, although an important site-specific variable. Relative importance of parameters differed by trophic group. Soil ingestion ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different patterns were exhibited, depending on which parameter, trophic group, and analyte combination was considered. The approach for TRV selection was also examined in detail, with Cu as the representative analyte. The underlying assumption that generic body-weight–normalized TRVs can be used to derive protective levels for any species is not supported by the data. Whereas the use of site-, species-, and analyte-specific exposure parameters is recommended to reduce variation in exposure estimates (soil protection level), improvement of TRVs is more problematic. Environ Toxicol Chem 2014

  3. Improving toxicity screening and drug development by using genetically defined strains.

    PubMed

    Festing, Michael F W

    2010-01-01

    According to the US Food and Drugs Administration (Food and Drug Administration (2004) Challenge and opportunity on the critical path to new medical products.) "The inability to better assess and predict product safety leads to failures during clinical development and, occasionally, after marketing". This increases the cost of new drugs as clinical trials are even more expensive than pre-clinical testing.One relatively easy way of improving toxicity testing is to improve the design of animal experiments. A fundamental principle when designing an experiment is to control all variables except the one of interest: the treatment. Toxicologist and pharmacologists have widely ignored this principle by using genetically heterogeneous "outbred" rats and mice, increasing the chance of false-negative results. By using isogenic (inbred or F1 hybrid, see Note 1) rats and mice instead of outbred stocks the signal/noise ratio and the power of the experiments can be increased at little extra cost whilst using no more animals. Moreover, the power of the experiment can be further increased by using more than one strain, as this reduces the chance of selecting one which is resistant to the test chemical. This can also be done without increasing the total number of animals by using a factorial experimental design, e.g. if the ten outbred animals per treatment group in a 28-day toxicity test were replaced by two animals of each of five strains (still ten animals per treatment group) selected to be as genetically diverse as possible, this would increase the signal/noise ratio and power of the experiment. This would allow safety to be assessed using the most sensitive strain.Toxicologists should also consider making more use of the mouse instead of the rat. They are less costly to maintain, use less test substance, there are many inbred and genetically modified strains, and it is easier to identify gene loci controlling variation in response to xenobiotics in this species.We demonstrate

  4. The use of a behavioral response system in the USF/NASA toxicity screening test method

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.; Packham, S. C.

    1977-01-01

    Relative toxicity data on the pyrolysis effluents from bisphenol A polycarbonate and wool fabric were obtained, based on visual observations of the behavior of free-moving mice and on an avoidance response behavioral paradigm of restrained rats monitored by an instrumented behavioral system. The initial experiments show an essentially 1:1 correlation between the two systems with regard to first signs of incapacitation, collapse, and death from pyrolysis effluents from polycarbonate. It is hypothesized that similarly good correlations between these two systems might exist for other materials exhibiting predominantly carbon monoxide mechanisms of intoxication. This hypothesis needs to be confirmed, however, by additional experiments. Data with wool fabric exhibited greater variability with both procedures, indicating possibly different mechanisms of intoxication for wool as compared with bisphenol A polycarbonate.

  5. Screening and Toxicity Analysis of Catechin Isomers Against FemA Protein.

    PubMed

    Singhal, Divya; Saxena, S

    2015-01-01

    Fem proteins are the essential structural proteins of various gram-positive bacteria. These are of three different types namely FemX (FmhB), FemA and FemB. Only two Fem protein crystallographic structures are available till date, one for FemA in Staphylococcus aureus and another for FemX in Weissella viridescensis. In this study, computational methods are used to evaluate interaction of FemA protein with catechin and epicatechin analogues. The interaction of FemA protein with catechin and epicatechin analogues are confirmed by binding energy and scores given by Autodock Vina and UCSF Dock docking softwares, which is followed by Lipinski filters and toxicity studies using online Lipinski server of SCFBIO and OSIRIS. Catechin gallate has been found as the best ligand for FemA protein in all aspects and it has outperformed all catechin and epicatechin isomers. PMID:26997705

  6. Cost-effectiveness of intensive multifactorial treatment compared with routine care for individuals with screen-detected Type 2 diabetes: analysis of the ADDITION-UK cluster-randomized controlled trial

    PubMed Central

    Tao, L; Wilson, E C F; Wareham, N J; Sandbæk, A; Rutten, G E H M; Lauritzen, T; Khunti, K; Davies, M J; Borch-Johnsen, K; Griffin, S J; Simmons, R K

    2015-01-01

    Aims To examine the short- and long-term cost-effectiveness of intensive multifactorial treatment compared with routine care among people with screen-detected Type 2 diabetes. Methods Cost–utility analysis in ADDITION-UK, a cluster-randomized controlled trial of early intensive treatment in people with screen-detected diabetes in 69 UK general practices. Unit treatment costs and utility decrement data were taken from published literature. Accumulated costs and quality-adjusted life years (QALYs) were calculated using ADDITION-UK data from 1 to 5 years (short-term analysis, n = 1024); trial data were extrapolated to 30 years using the UKPDS outcomes model (version 1.3) (long-term analysis; n = 999). All costs were transformed to the UK 2009/10 price level. Results Adjusted incremental costs to the NHS were £285, £935, £1190 and £1745 over a 1-, 5-, 10- and 30-year time horizon, respectively (discounted at 3.5%). Adjusted incremental QALYs were 0.0000, – 0.0040, 0.0140 and 0.0465 over the same time horizons. Point estimate incremental cost-effectiveness ratios (ICERs) suggested that the intervention was not cost-effective although the ratio improved over time: the ICER over 10 years was £82 250, falling to £37 500 over 30 years. The ICER fell below £30 000 only when the intervention cost was below £631 per patient: we estimated the cost at £981. Conclusion Given conventional thresholds of cost-effectiveness, the intensive treatment delivered in ADDITION was not cost-effective compared with routine care for individuals with screen-detected diabetes in the UK. The intervention may be cost-effective if it can be delivered at reduced cost. PMID:25661661

  7. Toxicological screening for organophosphorous-induced delayed neurotoxicity: complications in toxicity testing

    SciTech Connect

    Not Available

    1983-01-01

    Organophosphorus-induced delayed neurotoxicity (OPIDN) is discussed. The clinical signs of OPIDN are temporally distinct from the acute anti/acetylcholinesterase (AChE) effect and the syndrome of motor end plate inhibition. OPIDN occurs 6 to 21 days after oral, inhalation, or dermal exposure and its development is independent of an acute cholinergic reaction. The clinical signs include progressive weakness and ataxia beginning distally in the hind or lower limbs and may evolve into a flaccid paralysis that may also extend to the forelimbs. The role of toxicology and possible addenda to current screening procedures for detecting OPIDN are discussed. It is concluded that the range and prevalence of neurotoxic effects of organophosphorus pesticides are greater than expected, when considered from the standpoint of current regulatory and surveillance efforts. As a minimum, every organophosphorus ester that is in commercial use should be characterized as to its ability to induce OPIDN.

  8. Use of whole genome expression analysis in the toxicity screening of nanoparticles

    SciTech Connect

    Fröhlich, Eleonore; Meindl, Claudia; Wagner, Karin; Leitinger, Gerd; Roblegg, Eva

    2014-10-15

    The use of nanoparticles (NPs) offers exciting new options in technical and medical applications provided they do not cause adverse cellular effects. Cellular effects of NPs depend on particle parameters and exposure conditions. In this study, whole genome expression arrays were employed to identify the influence of particle size, cytotoxicity, protein coating, and surface functionalization of polystyrene particles as model particles and for short carbon nanotubes (CNTs) as particles with potential interest in medical treatment. Another aim of the study was to find out whether screening by microarray would identify other or additional targets than commonly used cell-based assays for NP action. Whole genome expression analysis and assays for cell viability, interleukin secretion, oxidative stress, and apoptosis were employed. Similar to conventional assays, microarray data identified inflammation, oxidative stress, and apoptosis as affected by NP treatment. Application of lower particle doses and presence of protein decreased the total number of regulated genes but did not markedly influence the top regulated genes. Cellular effects of CNTs were small; only carboxyl-functionalized single-walled CNTs caused appreciable regulation of genes. It can be concluded that regulated functions correlated well with results in cell-based assays. Presence of protein mitigated cytotoxicity but did not cause a different pattern of regulated processes. - Highlights: • Regulated functions were screened using whole genome expression assays. • Polystyrene particles regulated more genes than short carbon nanotubes. • Protein coating of polystyrene particles did not change regulation pattern. • Functions regulated by microarray were confirmed by cell-based assay.

  9. A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity.

    PubMed

    Talbert, Dominique R; Doherty, Kimberly R; Trusk, Patricia B; Moran, Diarmuid M; Shell, Scott A; Bacus, Sarah

    2015-01-01

    Ponatinib, a multi-targeted TKI and potent pan-ABL inhibitor, approved for the treatment of Ph + ALL and CML, was temporarily withdrawn from the U.S. market due to severe vascular adverse events. Cardiac-specific toxicities including myocardial infarction, severe congestive heart failure, and cardiac arrhythmias have also been shown with ponatinib. Targeted oncology agents such as ponatinib have transformed cancer treatment but often induce toxicity due to inhibition of survival pathways shared by both cancer and cardiac cells. These toxicities are often missed by the standard preclinical toxicity assessment methods, which include human Ether-à-go-go-related gene (hERG) and animal toxicity testing. In this study, we show that a multiparameter in vitro toxicity screening approach using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) accurately predicted the cardiac toxicity potential of ponatinib. This in vitro model evaluated ponatinib's effect on the overall cell health, mitochondrial stress, and function of hiPSC-CM and also provided mechanistic insight into the signaling pathways and cellular structures altered with treatment. We show here that ponatinib rapidly inhibits prosurvival signaling pathways, induces structural cardiac toxicity (as shown by actin cytoskeleton damage, mitochondrial stress, cell death, and troponin secretion), and disrupts cardiac cell beating. Most of these effects occurred at doses between 10× and 50× ponatinib's Cmax, a dose range shown to be relevant for accurate prediction of in vivo toxicity. Together these studies show that a comprehensive in vitro screening tool in a more relevant human cardiac cell model can improve the detection of cardiac toxicity with targeted oncology agents such as ponatinib. PMID:25304212

  10. Priority screening of toxic chemicals and industry sectors in the U.S. toxics release inventory: a comparison of the life cycle impact-based and risk-based assessment tools developed by U.S. EPA.

    PubMed

    Lim, Seong-Rin; Lam, Carl W; Schoenung, Julie M

    2011-09-01

    Life Cycle Impact Assessment (LCIA) and Risk Assessment (RA) employ different approaches to evaluate toxic impact potential for their own general applications. LCIA is often used to evaluate toxicity potentials for corporate environmental management and RA is often used to evaluate a risk score for environmental policy in government. This study evaluates the cancer, non-cancer, and ecotoxicity potentials and risk scores of chemicals and industry sectors in the United States on the basis of the LCIA- and RA-based tools developed by U.S. EPA, and compares the priority screening of toxic chemicals and industry sectors identified with each method to examine whether the LCIA- and RA-based results lead to the same prioritization schemes. The Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI) is applied as an LCIA-based screening approach with a focus on air and water emissions, and the Risk-Screening Environmental Indicator (RSEI) is applied in equivalent fashion as an RA-based screening approach. The U.S. Toxic Release Inventory is used as the dataset for this analysis, because of its general applicability to a comprehensive list of chemical substances and industry sectors. Overall, the TRACI and RSEI results do not agree with each other in part due to the unavailability of characterization factors and toxic scores for select substances, but primarily because of their different evaluation approaches. Therefore, TRACI and RSEI should be used together both to support a more comprehensive and robust approach to screening of chemicals for environmental management and policy and to highlight substances that are found to be of concern from both perspectives. PMID:21561706

  11. High-throughput Screening of ToxCast™ Phase I Chemicals in a Mouse Embryonic Stem Cell (mESC) Assay Reveals Disruption of Potential Toxicity Pathways

    EPA Science Inventory

    Little information is available regarding the potential for many commercial chemicals to induce developmental toxicity. The mESC Adherent Cell Differentiation and Cytoxicity (ACDC) assay is a high-throughput screen used to close this data gap. Thus, ToxCast™ Phase I chemicals wer...

  12. Screening of Metagenomic and Genomic Libraries Reveals Three Classes of Bacterial Enzymes That Overcome the Toxicity of Acrylate

    PubMed Central

    Curson, Andrew R. J.; Burns, Oliver J.; Voget, Sonja; Daniel, Rolf; Todd, Jonathan D.; McInnis, Kathryn; Wexler, Margaret; Johnston, Andrew W. B.

    2014-01-01

    Acrylate is produced in significant quantities through the microbial cleavage of the highly abundant marine osmoprotectant dimethylsulfoniopropionate, an important process in the marine sulfur cycle. Acrylate can inhibit bacterial growth, likely through its conversion to the highly toxic molecule acrylyl-CoA. Previous work identified an acrylyl-CoA reductase, encoded by the gene acuI, as being important for conferring on bacteria the ability to grow in the presence of acrylate. However, some bacteria lack acuI, and, conversely, many bacteria that may not encounter acrylate in their regular environments do contain this gene. We therefore sought to identify new genes that might confer tolerance to acrylate. To do this, we used functional screening of metagenomic and genomic libraries to identify novel genes that corrected an E. coli mutant that was defective in acuI, and was therefore hyper-sensitive to acrylate. The metagenomic libraries yielded two types of genes that overcame this toxicity. The majority encoded enzymes resembling AcuI, but with significant sequence divergence among each other and previously ratified AcuI enzymes. One other metagenomic gene, arkA, had very close relatives in Bacillus and related bacteria, and is predicted to encode an enoyl-acyl carrier protein reductase, in the same family as FabK, which catalyses the final step in fatty-acid biosynthesis in some pathogenic Firmicute bacteria. A genomic library of Novosphingobium, a metabolically versatile alphaproteobacterium that lacks both acuI and arkA, yielded vutD and vutE, two genes that, together, conferred acrylate resistance. These encode sequential steps in the oxidative catabolism of valine in a pathway in which, significantly, methacrylyl-CoA is a toxic intermediate. These findings expand the range of bacteria for which the acuI gene encodes a functional acrylyl-CoA reductase, and also identify novel enzymes that can similarly function in conferring acrylate resistance, likely, again

  13. Incorporating Acute HIV Screening into Routine HIV Testing at Sexually Transmitted Infection Clinics, and HIV Testing and Counseling Centers in Lilongwe, Malawi

    PubMed Central

    Pettifor, Audrey E.; Phiri, Sam; Kamanga, Gift; Hoffman, Irving F.; Hosseinipour, Mina C.; Rosenberg, Nora E.; Nsona, Dominic; Pasquale, Dana; Tegha, Gerald; Powers, Kimberly A.; Phiri, Mcleod; Tembo, Bisweck; Chege, Wairimu; Miller, William C.

    2016-01-01

    Background and Objectives: Integrating acute HIV-infection (AHI) testing into clinical settings is critical to prevent transmission, and realize potential treatment-as-prevention benefits. We evaluated acceptability of AHI testing and compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV testing and counseling (HTC) clinics in Lilongwe, Malawi. Methods: We conducted HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI was defined as positive RNA and negative/discordant rapid antibody tests. We evaluated demographic, behavioral, and transmission-risk differences between STI and HTC patients and assessed performance of a risk-score for targeted screening. Results: Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)–a 0.9% case-identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs 0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25% (15/59) had VL ≥10,000,000 copies per milliliter. Median VL was higher at STI (1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among persons with AHI, those tested at STI clinics were more likely to report genital sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The risk score algorithm performed well in identifying persons with AHI at HTC clinics (sensitivity = 73%, specificity = 89%). Conclusions: The majority of patients consented to AHI testing. AHI prevalence was substantially higher in STI clinics than HTC clinics. Remarkably high VLs and concomitant genital scores demonstrate the potential for transmission. Universal AHI screening at STI clinics, and targeted screening at HTC centers, should be considered. PMID:26428231

  14. Characterization of Diversity in Toxicity Mechanism Using In Vitro Cytotoxicity Assays in Quantitative High Throughput Screening

    PubMed Central

    Huang, Ruili; Southall, Noel; Cho, Ming-Hsuang; Xia, Menghang; Inglese, James; Austin, Christopher P.

    2009-01-01

    Assessing the potential health risks of environmental chemical compounds is an expensive undertaking which has motivated the development of new alternatives to traditional in vivo toxicological testing. One approach is to stage the evaluation, beginning with less expensive and higher throughput in vitro testing before progressing to more definitive trials. In vitro testing can be used to generate a hypothesis about a compound's mechanism of action, which can then be used to design an appropriate in vivo experiment. Here we begin to address the question of how to design such a battery of in vitro cell-based assays by combining data from two different types of assays, cell viability and caspase activation, with the aim of elucidating mechanism of action. Because caspase activation is a transient event during apoptosis, it is not possible to design a single end-point assay protocol that would identify all instances of compound-induced caspase activation. Nevertheless, useful information about compound mechanism of action can be obtained from these assays in combination with cell viability data. Unsupervised clustering in combination with Dunn's cluster validity index is a robust method for identifying mechanisms of action without requiring any a priori knowledge about mechanisms of toxicity. The performance of this clustering method is evaluated by comparing the clustering results against literature annotations of compound mechanisms. PMID:18281954

  15. Sediment toxicity screening with cost-effective microbiotests and conventional assays: A comparative study

    SciTech Connect

    Vanciheluwe, M.L.; Janssen, C.R.; Persoone, G.

    1995-12-31

    A large monitoring study of freshwater sediments, using the TRIAD approach, was conducted in Flanders (Belgium). This paper reports on the results of the toxicity assessment of 80 sediment samples evaluated with a battery of microbiotests and conventional assays. Sediment pore waters, extracted by squeezing, were tested with the Microtox{reg_sign} (Vibrio fischerii) and Thamnotoxkit{trademark} F (Thamnocephalus platyurus) microbiotests and the conventional (acute) assays with algae (Selenastrum capricornutum) and daphnids (Daphnia magna). A newly developed 5 day ELS test with the catfish Clarias gariepinus was also applied to the pore waters. Solid-phase testing was performed with the Microtox Sp{reg_sign} assay and the 10 day tests with Chironomus riparius and Hyalella azteca. Uni- and multivariate statistical techniques were applied to the data matrix to select a minimal test battery from the water phase and solid phase assays and from all tests combined. The influence of sediment associated confounding factors on the validity of the test results obtained with the various assays will be discussed. Finally a comparison of the predictive power of the selected battery of signal tests and that of the complete battery will be made and the potential use of the minimal battery for the initial hazard assessment of contaminated sediments will be reviewed.

  16. Use of whole genome expression analysis in the toxicity screening of nanoparticles

    PubMed Central

    Fröhlich, Eleonore; Meindl, Claudia; Wagner, Karin; Leitinger, Gerd; Roblegg, Eva

    2014-01-01

    The use of nanoparticles (NPs) offers exciting new options in technical and medical applications provided they do not cause adverse cellular effects. Cellular effects of NPs depend on particle parameters and exposure conditions. In this study, whole genome expression arrays were employed to identify the influence of particle size, cytotoxicity, protein coating, and surface functionalization of polystyrene particles as model particles and for short carbon nanotubes (CNTs) as particles with potential interest in medical treatment. Another aim of the study was to find out whether screening by microarray would identify other or additional targets than commonly used cell-based assays for NP action. Whole genome expression analysis and assays for cell viability, interleukin secretion, oxidative stress, and apoptosis were employed. Similar to conventional assays, microarray data identified inflammation, oxidative stress, and apoptosis as affected by NP treatment. Application of lower particle doses and presence of protein decreased the total number of regulated genes but did not markedly influence the top regulated genes. Cellular effects of CNTs were small; only carboxyl-functionalized single-walled CNTs caused appreciable regulation of genes. It can be concluded that regulated functions correlated well with results in cell-based assays. Presence of protein mitigated cytotoxicity but did not cause a different pattern of regulated processes. PMID:25102311

  17. Pulmonary toxicity screening studies in male rats with M5 respirable fibers and particulates.

    PubMed

    Warheit, David B; Webb, Thomas R; Reed, Kenneth L

    2007-09-01

    M5 fiber is a high-strength, high-performance organic fiber type that is a rigid rod material and composed of heterocyclic polymer fibers of type PIPD. The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled M5 respirable fibers and particulates in rats. Using a pulmonary bioassay and bridging methodology, the acute lung toxicity of intratracheally instilled M5 particulates and that of its fibers were compared with a positive control particle type, quartz, as well as a negative control particle type, carbonyl iron particles. Moreover, the results of these instillation studies were bridged with data previously generated from inhalation studies with quartz and carbonyl iron particles, using the quartz and iron particles as the inhalation/instillation bridge material. For the bioassay experimental design, in the bronchoalveolar lavage studies, the lungs of rats were intratracheally instilled with 0.5 or 0.75 mg/kg of M5 particulate or 1 or 5 mg/kg of the following control or particle types: (1) M5 long fiber preparation, (2) silica-quartz particles, and (3) carbonyl iron particles. Phosphate-buffered saline (PBS)-instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, cell proliferation methods, and histopathological evaluation of lung tissue at 24 h, 1 wk, 1 mo and 3 mo post instillation exposure. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to M5 particulate and M5 long fiber preparation produced transient inflammatory and cell injury effects at 24 h postexposure (pe) as well as at 24 h and 1 wk pe, respectively, but these effects were not sustained when compared to quartz-silica effects. Exposures to

  18. Reproductive toxicity screen of ammonium dinitramide administered in the drinking water of Sprague-Dawley rats.

    PubMed

    Kinkead, E R; Wolfe, R E; Flemming, C D; Leahy, H F; Caldwell, D J; Miller, C R; Marit, G B

    1995-01-01

    The Department of Defense is currently considering replacing ammonium perchlorate with ammonium dinitramide (ADN), a class 1.1 explosive oxidizer to be used in solid rocket propellant mixtures and explosives. This study was intended to evaluate the potential of ADN to produce alterations in paternal fertility, maternal pregnancy and lactation, and growth and development of offspring. Male and female rats received drinking water containing 0.0, 0.2, 1.0, or 2.0 g ADN/liter throughout the study. Mating occurred following 14 days of treatment. All dams, one-half the males, and representative pups were maintained for a total of 90 days of treatment. No mortality occurred in parental animals during the study. Treatment with ADN resulted in no adverse effects on mating; 92-100% of the animals mated. No treatment-related effects were seen in parental animals clinically or histopathologically. Adverse treatment-related effects were noted in maternal and paternal fertility indices, gestational indices, and live birth indices in both the mid- and high-dose groups. Litter sizes in the mid- and high-dose groups were significantly smaller than those of the low-dose and control groups. Mean pup weights showed no statistically significant differences between ADN-treated pups and controls. Gross and histopathological examination of the animals failed to identify the cause for the decrease in litter production in the mid- and high-dose dams. This study indicates that ADN is a reproductive toxicant. The no-observable-effect level (NOEL) is 29 mg/kg/day, the median dose of the low level female rats. PMID:8748424

  19. Possibility to predict early postpartum glucose abnormality following gestational diabetes mellitus based on the results of routine mid-gestational screening

    PubMed Central

    Bartáková, Vendula; Malúšková, Denisa; Mužík, Jan; Bělobrádková, Jana; Kaňková, Kateřina

    2015-01-01

    Introduction Women with previous gestational diabetes mellitus (GDM) have increased risk of developing glucose abnormality, but current diagnostic criteria are evidence-based for adverse pregnancy outcome. The aims of our study were: (i) to ascertain a frequency of early conversion of GDM into permanent glucose abnormality, (ii) to determine predictive potential of current GDM diagnostic criteria for prediction of postpartum glucose abnormality and (iii) to find optimal cut-off values of oral glucose tolerance test (oGTT) to stratify GDM population according to postpartum risk. Materials and methods Electronic medical records of an ethnically homogenous cohort of women diagnosed and treated for GDM in a single medical centre during the period 2005–2011 who completed postpartum oGTT up to 1 year after the index delivery were retrospectively analysed (N = 305). Results Postpartum glucose abnormality was detected in 16.7% subjects. Mid-trimester oGTT values, respective area under the curve and HbA1c were significantly associated with early postpartum glucose abnormality (P < 0.05, Mann-Whitney) and exhibited significant predictive potential for postpartum glucose abnormality risk assessment. Optimal cut-off values for discrimination of at-risk sub-population were identified using ROC analysis and their comparison with WHO and IADPSG criteria exhibited superiority of IADPSG for risk-stratification of GDM population. Conclusion Risk-based stratification at the time of GDM diagnosis could improve efficiency of the post-gestational screening for diabetes. IADPSG criteria seem to optimally capture both perinatal and maternal metabolic risks and are therefore medically and economically justified. PMID:26526166

  20. Diagnostic Accuracy of Lateral Flow Urine LAM Assay for TB Screening of Adults with Advanced Immunosuppression Attending Routine HIV Care in South Africa

    PubMed Central

    Hanifa, Yasmeen; Fielding, Katherine L.; Chihota, Violet N.; Adonis, Lungiswa; Charalambous, Salome; Karstaedt, Alan; McCarthy, Kerrigan; Nicol, Mark P.; Ndlovu, Nontobeko T.; Sahid, Faieza; Churchyard, Gavin J.; Grant, Alison D.

    2016-01-01

    Background We assessed the diagnostic accuracy of Determine TB-LAM (LF-LAM) to screen for tuberculosis among ambulatory adults established in HIV care in South Africa. Methods A systematic sample of adults attending for HIV care, regardless of symptomatology, were enrolled in the XPHACTOR study, which tested a novel algorithm for prioritising investigation with Xpert MTB/RIF. In this substudy, restricted to participants with enrolment CD4<200x106/l, urine was stored at enrolment for later testing with LF-LAM. Sputum was sent for immediate Xpert MTB/RIF if any of: current cough, fever ≥3 weeks, body mass index (BMI)<18.5kg/m2, CD4<100x106/l (or <200x106/l if pre-ART), weight loss ≥10% or strong clinical suspicion were present; otherwise, sputum was stored for Xpert testing at study completion. Participants were reviewed monthly, with reinvestigation if indicated, to 3 months, when sputum and blood were taken for mycobacterial culture. We defined tuberculosis as “confirmed” if Xpert, line probe assay or culture for M. tuberculosis within six months of enrolment were positive, and “clinical” if tuberculosis treatment started without microbiological confirmation. Results Amongst 424 participants, 61% were female and 57% were taking ART (median duration 22 months); median age, CD4 and BMI were 39 years, 111x106/l, and 23 kg/m2. 56/424 (13%) participants had tuberculosis (40 confirmed, 16 clinical). 24/424 (5.7%) vs. 8/424 (1.9%) were LAM-positive using grade 1 vs. grade 2 cut-off. Using grade 1 cut-off, sensitivity for confirmed TB (all clinical TB excluded) was 12.5% (95% CI 4.2%, 26.8%) and in CD4<100x106/l vs. CD4 ≥100x106/l was 16.7% (95% CI 4.7%, 37.4%) vs. 6.3% (95% CI 0.2%, 30.2%). Specificity was >95% irrespective of diagnostic reference standard, CD4 stratum, or whether grade 1 or grade 2 cut-off was used. Conclusion Sensitivity of LF-LAM is too low to recommend as part of intensified case finding in ambulatory patients established in HIV care

  1. Reproductive toxicology of water contaminants detected by routine water quality testing

    SciTech Connect

    Golub, M.S. )

    1992-03-01

    The presence of a reproductive toxicant in drinking water is one possible explanation of differences in spontaneous abortion rates between women who drink tapwater and those who do not. As part of the investigation conducted by the California Department of Health Services, several routine water quality assays were used to screen water sources available to the populations studied. I reviewed information in the literature about the potential reproductive toxicity of contaminants detected in these assays. None of these contaminants was clearly linked to increased incidence of abortion in the studies reviewed.56 references.

  2. Evaluation of Impermeant, DNA-Binding Dye Fluorescence as a Real-Time Readout of Eukaryotic Cell Toxicity in a High Throughput Screening Format

    PubMed Central

    Chiaraviglio, Lucius

    2014-01-01

    Abstract Interpretation of high throughput screening (HTS) data in cell-based assays may be confounded by cytotoxic properties of screening compounds. Therefore, assessing cell toxicity in real time during the HTS process itself would be highly advantageous. Here, we investigate the potential of putatively impermeant, fluorescent, DNA-binding dyes to give cell toxicity readout during HTS. Amongst 19 DNA-binding dyes examined, three classes were identified that were (1) permeant, (2) cytotoxic, or (3) neither permeant nor cytotoxic during 3-day incubation with a macrophage cell line. In the last class, four dyes (SYTOX Green, CellTox Green, GelGreen, and EvaGreen) gave highly robust cytotoxicity data in 384-well screening plates. As proof of principle, successful combination with a luminescence-based assay in HTS format was demonstrated. Here, both intracellular growth of Legionella pneumophila (luminescence) and host cell viability (SYTOX Green exclusion) were assayed in the same screening well. Incorporation of membrane-impermeant, DNA-binding, fluorescent dyes in HTS assays should prove useful by allowing evaluation of cytotoxicity in real time, eliminating reagent addition steps and effort associated with endpoint cell viability analysis, and reducing the need for follow-up cytotoxicity screening. PMID:24831788

  3. EPA’s ToxCast Program for Predicting Toxicity and Prioritizing Chemicals for Further Screening and Testing

    EPA Science Inventory

    Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challengin...

  4. A screen-printed microband glucose biosensor system for real-time monitoring of toxicity in cell culture.

    PubMed

    Pemberton, R M; Xu, J; Pittson, R; Drago, G A; Griffiths, J; Jackson, S K; Hart, J P

    2011-01-15

    Microband biosensors, screen-printed from a water-based carbon ink containing cobalt phthalocyanine redox mediator and glucose oxidase (GOD) enzyme, were used to monitor glucose levels continuously in buffer and culture medium. Five biosensors were operated amperometrically (E(app) of +0.4V), in a 12-well tissue culture plate system at 37°C, using a multipotentiostat. After 24 h, a linear calibration plot was obtained from steady-state current responses for glucose concentrations up to 10 mM (dynamic range 30 mM). Within the linear region, a correlation coefficient (R(2)) of 0.981 was obtained between biosensor and spectrophotometric assays. Over 24 h, an estimated 0.15% (89 nmol) of the starting glucose concentration (24 mM) was consumed by the microbiosensor. The sensitivity of the biosensor response in full culture medium was stable between pHs 7.3 and 8.4. Amperometric responses for HepG2 monolayer cultures decreased with time in inverse proportionality to cell number (for 0 to 10(6) cell/ml), as glucose was being metabolised. HepG2 3D cultures (spheroids) were also shown to metabolise glucose, at a rate which was independent of spheroid age (between 6 and 15 days). Spheroids were used to assay the effect of a typical hepatotoxin, paracetamol. At 1 mM paracetamol, glucose uptake was inhibited by 95% after 6 h in culture; at 500 μM, around 15% inhibition was observed after 16 h. This microband biosensor culture system could form the basis for an in vitro toxicity testing system. PMID:21081270

  5. Automation of antimicrobial activity screening.

    PubMed

    Forry, Samuel P; Madonna, Megan C; López-Pérez, Daneli; Lin, Nancy J; Pasco, Madeleine D

    2016-03-01

    Manual and automated methods were compared for routine screening of compounds for antimicrobial activity. Automation generally accelerated assays and required less user intervention while producing comparable results. Automated protocols were validated for planktonic, biofilm, and agar cultures of the oral microbe Streptococcus mutans that is commonly associated with tooth decay. Toxicity assays for the known antimicrobial compound cetylpyridinium chloride (CPC) were validated against planktonic, biofilm forming, and 24 h biofilm culture conditions, and several commonly reported toxicity/antimicrobial activity measures were evaluated: the 50 % inhibitory concentration (IC50), the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC). Using automated methods, three halide salts of cetylpyridinium (CPC, CPB, CPI) were rapidly screened with no detectable effect of the counter ion on antimicrobial activity. PMID:26970766

  6. Perceptions of environmental health risks among residents in the “Toxic Doughnut”: Opportunities for risk screening and community mobilization

    EPA Science Inventory

    Surrounded by landfills, and toxic and hazardous facilities, Altgeld Gardens is located in a “toxic doughnut.” With high rates of environmentally-related conditions, residents have called for a community-based environmental health assessment to improve overall health in their com...

  7. Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

    PubMed

    Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

    2015-09-01

    Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures. PMID:25940475

  8. Application of human haploid cell genetic screening model in identifying the genes required for resistance to environmental toxicants: Chlorpyrifos as a case study

    PubMed Central

    Zhu, Jinqiu; Dubois, Amber; Ge, Yichen; Olson, James A.; Ren, Xuefeng

    2016-01-01

    Introduction High-throughput loss-of-function genetic screening tools in yeast or other model systems except in mammalian cells have been implemented to study human susceptibility to chemical toxicity. Here, we employed a newly developed human haploid cell (KBM7)-based mutagenic screening model (KBM7-mu cells) and examined its applicability in identifying genes whose absence allows cells to survive and proliferate in the presence of chemicals. Methods KBM7-mucells were exposed to 200 µM Chlorpyrifos (CPF), a widely used organophosphate pesticide, a dose causing approximately 50% death of cells after 48 h of treatment. After a 2–3 week period of continuous CPF exposure, survived single cell colonies were recovered and used for further analysis. DNA isolated from these cells was amplified using Splinkerette PCR with specific designed primers, and sequenced to determine the genomic locations with virus insertion and identify genes affected by the insertion. Quantitative realtime reverse transcription PCR (qRT-PCR) was used to confirm the knockdown of transcription of identified target genes. Results We identified total 9 human genes in which the cells carrying these genes conferred the resistance to CPF, including AGPAT6, AIG1, ATP8B2, BIK, DCAF12, FNBP4, LAT2, MZF1-AS1 and PPTC7. MZF1-AS1 is an antisense RNA and not included in the further analysis. qRT-PCR results showed that the expression of 6 genes was either significantly reduced or completely lost. There were no changes in the expression of DCAF12 and AGPAT6 genes between the KBM7-mu and the control KBM7 cells. Discussion The KBM7-mu genetic screening system can be modified and applied to identify novel susceptibility genes in response to environmental toxicants, which could provide valuable insights into potential mechanisms of toxicity. PMID:26299976

  9. A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis

    NASA Astrophysics Data System (ADS)

    Timm, David M.; Chen, Jianbo; Sing, David; Gage, Jacob A.; Haisler, William L.; Neeley, Shane K.; Raphael, Robert M.; Dehghani, Mehdi; Rosenblatt, Kevin P.; Killian, T. C.; Tseng, Hubert; Souza, Glauco R.

    2013-10-01

    There is a growing demand for in vitro assays for toxicity screening in three-dimensional (3D) environments. In this study, 3D cell culture using magnetic levitation was used to create an assay in which cells were patterned into 3D rings that close over time. The rate of closure was determined from time-lapse images taken with a mobile device and related to drug concentration. Rings of human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs) were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure correlated with the viability and migration of cells in two dimensions (2D). Images taken using a mobile device were similar in analysis to images taken with a microscope. Ring closure may serve as a promising label-free and quantitative assay for high-throughput in vivo toxicity in 3D cultures.

  10. A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis

    PubMed Central

    Timm, David M.; Chen, Jianbo; Sing, David; Gage, Jacob A.; Haisler, William L.; Neeley, Shane K.; Raphael, Robert M.; Dehghani, Mehdi; Rosenblatt, Kevin P.; Killian, T. C.; Tseng, Hubert; Souza, Glauco R.

    2013-01-01

    There is a growing demand for in vitro assays for toxicity screening in three-dimensional (3D) environments. In this study, 3D cell culture using magnetic levitation was used to create an assay in which cells were patterned into 3D rings that close over time. The rate of closure was determined from time-lapse images taken with a mobile device and related to drug concentration. Rings of human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs) were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure correlated with the viability and migration of cells in two dimensions (2D). Images taken using a mobile device were similar in analysis to images taken with a microscope. Ring closure may serve as a promising label-free and quantitative assay for high-throughput in vivo toxicity in 3D cultures. PMID:24141454

  11. Toxicology screen

    MedlinePlus

    Barbiturates - screen; Benzodiazepines - screen; Amphetamines - screen; Analgesics - screen; Antidepressants - screen; Narcotics - screen; Phenothiazines - screen; Drug abuse screen; Blood alcohol test

  12. Integration of High-Throughput Screening Data with Dosimetry and Human Exposure in the Toxicity Assessment of Environmental Chemicals

    EPA Science Inventory

    High-throughput in vitro screening and computational tools provide government an efficient way to identify those chemicals that warrant further testing while conserving limited testing resources. Incorporation of kinetic and exposure information should provide a more meaningful i...

  13. TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations.

    PubMed

    Ekstrand-Hammarström, Barbro; Hong, Jaan; Davoodpour, Padideh; Sandholm, Kerstin; Ekdahl, Kristina N; Bucht, Anders; Nilsson, Bo

    2015-05-01

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. PMID:25770998

  14. Investigation of a hepatotoxicity screening system in primary cell cultures --"what biomarkers would need to be addressed to estimate toxicity in conventional and new approaches?".

    PubMed

    Kikkawa, Rie; Yamamoto, Toshinori; Fukushima, Tamio; Yamada, Hiroshi; Horii, Ikuo

    2005-02-01

    High throughput toxicological estimation is required for safety evaluation in the early stage of drug discovery. In this context, establishment of an in vitro screening system reflecting in vivo toxicity is demanded for earlier safety assessment. We investigated LDH release and mitochondrial respiration (WST-1 reduction assay; WST-1) to detect cytotoxicity, morphological evaluation, and proteomics for estimating the reliable and sensitive biomarkers by using rat primary hepatocytes exposed to the compounds (acetaminophen, amiodarone, tetracycline and carbon tetrachloride) that are known to induce hepatotoxicity. In LDH release, no significant difference was detected between the control and compound exposed cells after exposure for 3 or 6 hr, but a dose-dependent increase was observed after exposure for 24 hr. Regarding the WST-1 assay, a dose-dependent reduction was detected after exposure for 6 and 24 hr to all of the compounds evaluated. In the proteomics analysis, 31 candidate proteins were identified from among the 103 demonstrating altered expression spots after exposure to acetaminophen. It was concluded that the cytotoxicity was detected earlier by measuring WST-1 than by measuring LDH release because the reduction of mitochondrial respiration is an expressions of earlier toxicity for cellular function, while the measured increase in the LDH release occurs after the failure of the cell membrane. Mitochondrial respiration ability was a useful parameter for cytotoxicity in in vitro hepato-toxicity screening, as cytotoxicity can be detected during the early stage of exposure. In addition to the conventional biomarkers, several protein biomarkers which relate to oxidative stress and metabolism-regulation were detected. Further comprehensive analysis of defined proteins would be necessary to estimate the more sensitive toxicology biomarker. PMID:15800402

  15. Task 1.11 - Spectroscopic field screening of hazardous waste and toxic spills. Semi-annual report, January 1--June 30, 1995

    SciTech Connect

    Gristanti, A.A.

    1995-12-31

    Techniques for the field characterization of soil contamination due to spillage of hazardous waste or toxic chemicals are time-consuming and expensive. Thus, more economical, less time-intensive methods are needed to facilitate rapid field screening of contaminated sites. In situ detection of toxic chemicals in soil offers both time and cost advantages for field screening with additional application to real-time site monitoring. Fourier-transform infrared (FT-IR) spectroscopy coupled with evanescent mode fiber-optic sensors has been demonstrated as a means to remotely detect and classify petroleum products in water using mid-infrared (MIR) optical fibers. This work demonstrated that a fiber-optic evanescent field absorbance sensor (EFAS) could be used to classify petroleum contamination into categories such as crude oil, kerosene, No. 2 fuel and residual distillates using the MIR spectral range. The overall objective of this project is to study the feasibility of using an EFAS FT-IR spectroscopic sensor coupled with cone penetrometry as a field screening method. The Fourier transform infrared cone penetrometry method (FT-IR-CPT) will be developed by building on the work cited above. The specific objectives of this project are: design an accessory for use with FT-IR that interfaces the spectrometer to a cone penetrometer; characterize the response of the FT-IR accessory to selected hydrocarbons in a laboratory-simulated field environment; and determine the ability of the FT-IR-CPT instrument to measure hydrocarbon contamination in soil by direct comparison with a reference method to quantify hydrocarbons from the same soil.

  16. shRNA-Based Screen Identifies Endocytic Recycling Pathway Components That Act as Genetic Modifiers of Alpha-Synuclein Aggregation, Secretion and Toxicity

    PubMed Central

    Macedo, Diana; Raquel, Helena; Simões, Pedro D.; Giorgini, Flaviano; Ramalho, José S.; Barral, Duarte C.; Ferreira Moita, Luís; Outeiro, Tiago Fleming

    2016-01-01

    Alpha-Synuclein (aSyn) misfolding and aggregation is common in several neurodegenerative diseases, including Parkinson’s disease and dementia with Lewy bodies, which are known as synucleinopathies. Accumulating evidence suggests that secretion and cell-to-cell trafficking of pathological forms of aSyn may explain the typical patterns of disease progression. However, the molecular mechanisms controlling aSyn aggregation and spreading of pathology are still elusive. In order to obtain unbiased information about the molecular regulators of aSyn oligomerization, we performed a microscopy-based large-scale RNAi screen in living cells. Interestingly, we identified nine Rab GTPase and kinase genes that modulated aSyn aggregation, toxicity and levels. From those, Rab8b, Rab11a, Rab13 and Slp5 were able to promote the clearance of aSyn inclusions and rescue aSyn induced toxicity. Furthermore, we found that endocytic recycling and secretion of aSyn was enhanced upon Rab11a and Rab13 expression in cells accumulating aSyn inclusions. Overall, our study resulted in the identification of new molecular players involved in the aggregation, toxicity, and secretion of aSyn, opening novel avenues for our understanding of the molecular basis of synucleinopathies. PMID:27123591

  17. Data format translation routines

    SciTech Connect

    Burris, R.D.

    1981-02-01

    To enable the effective connection of several dissimilar computers into a network, modification of the data being passed from one computer to another may become necessary. This document describes a package of routines which permit the translation of data in PDP-8 formats to PDP-11 or DECsystem-10 formats or from PDP-11 format to DECsystem-10 format. Additional routines are described which permit the effective use of the translation routines in the environment of the Fusion Energy Division (FED) network and the Elmo Bumpy Torus (EBT) data base.

  18. PROLIFERATION AS A KEY EVENT IN DEVELOPMENTAL TOXICITY: "CHEMICAL SCREENING IN HUMAN NEURAL STEM CELLS USING HIGH CONTENT IMAGING

    EPA Science Inventory

    New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

  19. Multilaboratory evaluation of 15 bioassays for (eco)toxicity screening and hazard ranking of engineered nanomaterials: FP7 project NANOVALID.

    PubMed

    Bondarenko, Olesja M; Heinlaan, Margit; Sihtmäe, Mariliis; Ivask, Angela; Kurvet, Imbi; Joonas, Elise; Jemec, Anita; Mannerström, Marika; Heinonen, Tuula; Rekulapelly, Rohit; Singh, Shashi; Zou, Jing; Pyykkö, Ilmari; Drobne, Damjana; Kahru, Anne

    2016-11-01

    Within EU FP7 project NANOVALID, the (eco)toxicity of 7 well-characterized engineered nanomaterials (NMs) was evaluated by 15 bioassays in 4 laboratories. The highest tested nominal concentration of NMs was 100 mg/l. The panel of the bioassays yielded the following toxicity order: Ag > ZnO > CuO > TiO2 > MWCNTs > SiO2 > Au. Ag, ZnO and CuO proved very toxic in the majority of assays, assumingly due to dissolution. The latter was supported by the parallel analysis of the toxicity of respective soluble metal salts. The most sensitive tests/species were Daphnia magna (towards Ag NMs, 24-h EC50 = 0.003 mg Ag/l), algae Raphidocelis subcapitata (ZnO and CuO, 72-h EC50 = 0.14 mg Zn/l and 0.7 mg Cu/l, respectively) and murine fibroblasts BALB/3T3 (CuO, 48-h EC50 = 0.7 mg Cu/l). MWCNTs showed toxicity only towards rat alveolar macrophages (EC50 = 15.3 mg/l) assumingly due to high aspect ratio and TiO2 towards R. subcapitata (EC50 = 6.8 mg Ti/l) due to agglomeration of TiO2 and entrapment of algal cells. Finally, we constructed a decision tree to select the bioassays for hazard ranking of NMs. For NM testing, we recommend a multitrophic suite of 4 in vitro (eco)toxicity assays: 48-h D. magna immobilization (OECD202), 72-h R. subcapitata growth inhibition (OECD201), 30-min Vibrio fischeri bioluminescence inhibition (ISO2010) and 48-h murine fibroblast BALB/3T3 neutral red uptake in vitro (OECD129) representing crustaceans, algae, bacteria and mammalian cells, respectively. Notably, our results showed that these assays, standardized for toxicity evaluation of "regular" chemicals, proved efficient also for shortlisting of hazardous NMs. Additional assays are recommended for immunotoxicity evaluation of high aspect ratio NMs (such as MWCNTs). PMID:27259032

  20. A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver

    PubMed Central

    Suzawa, Miyuki; Miranda, Diego A; Ramos, Karmela A; Ang, Kenny K-H; Faivre, Emily J; Wilson, Christopher G; Caboni, Laura; Arkin, Michelle R; Kim, Yeong-Sang; Fletterick, Robert J; Diaz, Aaron; Schneekloth, John S; Ingraham, Holly A

    2015-01-01

    SUMO-modification of nuclear proteins has profound effects on gene expression. However, non-toxic chemical tools that modulate sumoylation in cells are lacking. Here, to identify small molecule sumoylation inhibitors we developed a cell-based screen that focused on the well-sumoylated substrate, human Liver Receptor Homolog-1 (hLRH-1, NR5A2). Our primary gene-expression screen assayed two SUMO-sensitive transcripts, APOC3 and MUC1, that are upregulated by SUMO-less hLRH-1 or by siUBC9 knockdown, respectively. A polyphenol, tannic acid (TA) emerged as a potent sumoylation inhibitor in vitro (IC50 = 12.8 µM) and in cells. TA also increased hLRH-1 occupancy on SUMO-sensitive transcripts. Most significantly, when tested in humanized mouse primary hepatocytes, TA inhibits hLRH-1 sumoylation and induces SUMO-sensitive genes, thereby recapitulating the effects of expressing SUMO-less hLRH-1 in mouse liver. Our findings underscore the benefits of phenotypic screening for targeting post-translational modifications, and illustrate the potential utility of TA for probing the cellular consequences of sumoylation. DOI: http://dx.doi.org/10.7554/eLife.09003.001 PMID:26653140

  1. Environmental labeling of car tires--toxicity to Daphnia magna can be used as a screening method.

    PubMed

    Wik, Anna; Dave, Göran

    2005-02-01

    Car tires contain several water-soluble compounds that can leach into water and have toxic effects on aquatic organisms. Due to tire wear, 10,000 tonnes of rubber particles end up along the Swedish roads every year. This leads to a diffuse input of emissions of several compounds. Emissions of polyaromatic hydrocarbons (PAHs) are of particular concern. PAHs are ingredients of the high aromatic oil (HA oil) that is used in the rubber as a softener and as a filler. The exclusion of HA oils from car tires has started, and an environmental labeling of tires could make HA oils obsolete. The toxicity to Daphnia magna from 12 randomly selected car tires was tested in this study. Rubber from the tread of the tires was grated into small pieces, to simulate material from tire wear, and the rubber was equilibrated with dilution water for 72 h before addition of test organisms. The 24-h EC50s of the rubber pieces ranged from 0.29 to 32 gl-1, and the 48-h EC50s ranged from 0.0625 to 2.41 gl-1. Summer tires were more toxic than winter tires. After the 48-h exposure, the daphnids were exposed to UV-light for 2 h, to determine if the tires contained compounds that were phototoxic. After UV-activation the EC50s ranged from 0.0625 to 0.38 gl-1. Four of the 12 tires had a very distinct photoactivation, with a toxicity increase of >10 times. This study has shown that the used method for toxicity testing with Daphnia magna according to ISO 6341 could be used as a basis for environmental labeling of car tires. PMID:15620758

  2. Daily exercise routines

    NASA Technical Reports Server (NTRS)

    Anderson, Patrick L.; Amoroso, Michael T.

    1990-01-01

    Viewgraphs on daily exercise routines are presented. Topics covered include: daily exercise and periodic stress testings; exercise equipment; physiological monitors; exercise protocols; physiological levels; equipment control; control systems; and fuzzy logic control.

  3. Routine sputum culture

    MedlinePlus

    Sputum culture ... There, it is placed in a special dish (culture). It is then watched to see if bacteria ... Chernecky CC, Berger BJ. Culture, routine. In: Chernecky CC, Berger BJ, ... . 6th ed. Philadelphia, PA: Elsevier Saunders; 2013:409- ...

  4. Importance of Family Routines

    MedlinePlus

    ... Listen Español Text Size Email Print Share The Importance of Family Routines Page Content ​Every family needs ... child to sleep. These rituals can include storytelling, reading aloud, conversation, and songs. Try to avoid exciting ...

  5. Application of a toxicity test battery integrated index for a first screening of the ecotoxicological threat posed by ports and harbors in the southern Adriatic Sea (Italy).

    PubMed

    Manzo, Sonia; Schiavo, Simona; Aleksi, Pellumb; Tabaku, Afrim

    2014-11-01

    Ports and harbors may represent a threat for coastal ecosystems due to pollutant inputs, especially those derived from maritime activities. In this study, we report a first assessment of the ecotoxicological threat posed by six ports and harbors of opposite coastal regions, Apulia and Albania, in the southern Adriatic Sea (Italy). A bioassay battery consisting of four different species representing different trophic levels, algae Dunaliella tertiolecta, bacteria Vibrio fischeri, crustacean Artemia salina, and echinoids Paracentrotus lividus, has been used to assess sediment elutriates, pore waters, and sediment suspensions. Two different approaches of toxicity data integration, worst case and integrated index, have been used to determine the most appropriate procedure for the investigated sites. All sites with the worst case approach showed high toxicity levels. The chronic test with algae was the most sensitive identifying the highest effects in the battery. This effect can be attributable to contaminants derived from antifouling paints. The sediments, evaluated with V. fischeri test, often showed toxicity not found in the aqueous matrices of the same sites and that can be mainly linked to organic compounds. The test battery used in this study allowed us to perform a preliminary screening of the ecotoxicological risk of the studied area. In fact, the species utilized for toxicity tests responded differently to the investigated samples, showing different sensitivity. The test battery integrated index did not allow highlighting the differences among the sites and showed a general high ecotoxicological risk. A larger number of tests with higher sensitivity together with a tailored attribution of weights to endpoints and matrices will improve the final site evaluation. PMID:25012145

  6. Toxic chemical release inventory risk screening guide (Version 1. 0). Volume 1. The process. Volume 2. Appendices. Final report

    SciTech Connect

    Klauder, D.; Saunders, L.

    1989-07-01

    The guide describes some of the challenges raised by the Toxic Release Inventory (TRI) data and to suggest ways of approaching them. The guide suggests steps that can be taken to answer two key issues of concern: setting risk-based priorities for followup investigation of the TRI facilities and chemicals within geographic area of interest, and identifying data needs and approaches for collecting information necessary to respond to health and ecological questions from the public. The guide is directed at those individuals who are involved in interpreting and explaining environmental pollution, exposures, and health risks to the general public, especially at the local or sub-State level. Many users of the guide will already be well versed in evaluating risk and/or in helping members of the public understand and deal with toxic chemicals, but Title 111 - particularly, the Section 313 release data - presents new challenges for everyone.

  7. Comparison of two screening bioassays, based on the frog sciatic nerve and yeast cells, for the assessment of herbicide toxicity.

    PubMed

    Papaefthimiou, Chrisovalantis; Cabral, Maria de Guadalupe; Mixailidou, Christina; Viegas, Cristina A; Sá-Correia, Isabel; Theophilidis, George

    2004-05-01

    Two different test systems, one based on the isolated sciatic nerve of an amphibian and the other on a microbial eukaryote, were used for the assessment of herbicide toxicity. More specifically, we determined the deleterious effects of increasing concentrations of herbicides of different chemical classes (phenoxyacetic acids, triazines, and acetamides), and of 2,4-dichlorophenol (2,4-DCP), a degradation product of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), on electrophysiological parameters and the vitality of the axons of the isolated sciatic nerve of the frog (Rana ridibunda) and on the growth curve of the yeast Saccharomyces cerevisiae based on microtiter plate susceptibility assays. The no-observed-effect-concentration (NOEC), defined as the maximum concentration of the tested compound that has no effect on these biological parameters, was estimated. In spite of the different methodological approaches and biological systems compared, the NOEC values were identical and correlated with the lipophilicity of the tested compounds. The relative toxicity established here, 2,4-DCP > alachlor, metolachlor > metribuzin > 2,4-D, 2-methyl-4-chlorophenoxyacetic acid (MCPA), correlates with the toxicity indexes reported in the literature for freshwater organisms. Based on these results, we suggest that the relatively simple, rapid, and low-cost test systems examined here may be of interest as alternative or complementary tests for toxicological assessment of herbicides. PMID:15180372

  8. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

    PubMed

    Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

    2015-01-01

    Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically. PMID:26132533

  9. High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity.

    PubMed

    Qosa, Hisham; Mohamed, Loqman A; Al Rihani, Sweilem B; Batarseh, Yazan S; Duong, Quoc-Viet; Keller, Jeffrey N; Kaddoumi, Amal

    2016-07-01

    The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 μM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD. PMID:27392852

  10. Sensors for Highly Toxic Gases: Methylamine and Hydrogen Chloride Detection at Low Concentrations in an Ionic Liquid on Pt Screen Printed Electrodes

    PubMed Central

    Murugappan, Krishnan; Silvester, Debbie S.

    2015-01-01

    Commercially available Pt screen printed electrodes (SPEs) have been employed as possible electrode materials for methylamine (MA) and hydrogen chloride (HCl) gas detection. The room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][NTf2]) was used as a solvent and the electrochemical behaviour of both gases was first examined using cyclic voltammetry. The reaction mechanism appears to be the same on Pt SPEs as on Pt microelectrodes. Furthermore, the analytical utility was studied to understand the behaviour of these highly toxic gases at low concentrations on SPEs, with calibration graphs obtained from 10 to 80 ppm. Three different electrochemical techniques were employed: linear sweep voltammetry (LSV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV), with no significant differences in the limits of detection (LODs) between the techniques (LODs were between 1.4 to 3.6 ppm for all three techniques for both gases). The LODs achieved on Pt SPEs were lower than the current Occupational Safety and Health Administration Permissible Exposure Limit (OSHA PEL) limits of the two gases (5 ppm for HCl and 10 ppm for MA), suggesting that Pt SPEs can successfully be combined with RTILs to be used as cheap alternatives for amperometric gas sensing in applications where these toxic gases may be released. PMID:26506358