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Sample records for routine toxicity screening

  1. Cyst-based toxicity tests. VI: Toxkits and Fluotox tests as cost-effective tools for routine toxicity screening.

    PubMed

    Persoone, G

    1992-01-01

    During the last two decades microbiotests have been developed which are independent of recruitment, maintenance and/or culturing of live stocks of test organisms. "Culture and maintenance free" microbiotests have been worked out in the Laboratory for Biological Research in Aquatic Pollution at the University of Ghent, with selected aquatic invertebrates. The new approach is based on the use of "resting stages" (cysts) as inert biological material from which live test organisms can be hatched "on demand". The "cyst-based" bioassays have recently been miniaturized in Toxkits. Four cyst-based screening tests have reached the stage of commercialization: two freshwater 24h-LC50 tests (Rotoxkit F and Streptoxkit F) and two estuarine/marine 24h-LC50 bioassays (Rotoxkit M and Artoxkit M), based on cysts of rotifer and crustacean species, respectively. Recently, the same laboratory has also been focusing on the development of a "rapid" (one hour) sublethal bioassays with aquatic invertebrates. The so called "Fluotox" screening test is based on the visual observation of in vivo inhibition of an enzymatic process, using a fluorescent substrate. Besides the advantages of rapidity and cost-effectiveness, the Fluotox assay also appears to have a remarkable predictive potential for mortality, as displayed by the remarkable correlation between the Fluotox 1h-EC50's and conventional 24h-LC50's with the same species.

  2. Routine screening for postpartum depression.

    PubMed

    Georgiopoulos, A M; Bryan, T L; Wollan, P; Yawn, B P

    2001-02-01

    Postpartum depression (PPD) is a common and often overlooked condition. Validated screening tools for PPD exist but are not commonly used. We present the 1-year outcome of a project to implement universal PPD screening at the 6-week postpartum visit. Universal screening with the Edinburgh Postnatal Depression Scale (EPDS) was implemented in all community postnatal care sites. One-year outcome assessments (diagnosis and treatment of PPD) were completed for a sample of the women screened using medical record review of all care they received during the first year postpartum. Sixty-eight (20%) of the 342 women whose medical records were reviewed had been given a documented diagnosis of postpartum depression, resulting in an estimated population rate of 10.7%. Depression was diagnosed in 35% of the women with elevated EPDS scores (> or =10) compared with 5% of the women with low EPDS scores (<10) in the first year postpartum. Treatment was provided for all women diagnosed with depression, including drug therapy for 49% and counseling for 78%. Four women were hospitalized for depression. Some degree of suicidal ideation was noted on the EPDS by 48 women but acknowledged in the chart of only 10 women, including 1 with an immediate hospitalization. The rate of diagnosis of postpartum depression in this community increased from 3.7% before the routine use of EPDS screening to 10.7% following screening. A high EPDS score was predictive of a diagnosis of postpartum depression, and the implementation of routine EPDS screening at 6 weeks postpartum was associated with an increase in the rate of diagnosed postpartum depression in this community.

  3. Routine CMV screening during pregnancy.

    PubMed

    Collinet, P; Subtil, D; Houfflin-Debarge, V; Kacet, N; Dewilde, A; Puech, F

    2004-05-10

    Cytomegalovirus (CMV) screening during pregnancy has been widely discussed for several years, but still no consensus has been agreed. With a number of live births of 750,000 per year in France, we would expect 7500 infected infants at birth per year (rate of congenital infection of 1%). Among infected infants at birth, the number of severely infected foetuses would be approximately 75, the number of infants with severe sequelae would be 480, 675 approximately would present with hearing loss and the number of asymptomatic infants would be 6270. Five different preventive methods for congenital CMV infection are possible: (1) Routine CMV screening at the beginning of pregnancy for primary prevention. (2) Secondary prevention by antenatal diagnosis of congenital CMV infection complications. (3) Tertiary prevention by serological testing during pregnancy. (4) Tertiary prevention by serological screening at birth. (5) Tertiary prevention: Hearing loss screening at birth. The aims of this review are to define the advantages and disadvantages of these different methods of CMV screening during pregnancy and to determine if the current available information would make systematic testing acceptable.

  4. Iron toxicity screening.

    PubMed

    Cheng, C S; Sullivan, T D; Li, P K

    1979-06-01

    Fischer's method for rapid detection of acute iron toxicity is modified to suit pediatric cases. TPTZ (2,4,6-tripyridyl-s-triazine) is the chromogen of choice since in a small volume of serum slight to moderate hemolysis can cause a false positive result bathophenanthroline. Ordinary labware is amenable to this simplified procedure.

  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; van Crevel, Reinout; van der Ven, Andre; Meheus, Andre

    2016-01-01

    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. 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. 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. 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.

  6. Implementing routine HIV screening in an urban pediatric emergency department.

    PubMed

    Hack, Clare M; Scarfi, Catherine A; Sivitz, Adam B; Rosen, Michael D

    2013-03-01

    In 2006, the Centers for Disease Control and Prevention recommended that all outpatient health care settings offer routine, opt-out HIV screening for patients aged 13 to 64 years, except where the prevalence of undiagnosed HIV infection is known to be less than 0.1%. Most emergency departments (EDs) lack routine HIV screening. The objective of this investigation was to describe the results of the implementation of routine, nontargeted opt-in HIV screening for patients aged 13 to 20 years in an urban pediatric ED (PED) in a city in which 1 of 30 residents has HIV/AIDS. This was a retrospective chart review from an urban, academic PED. The implementation of routine HIV screening in the ED was funded by the New Jersey Department of Health and Senior Services and planned independently of the study investigator. Patients aged 13 to 64 years were offered HIV screening by nursing staff, physicians, and/or HIV counselors. Patients who accepted were screened with rapid HIV fingerstick testing performed via Clearview HIV 1/2 STAT-PAK by HIV counselors as per the New Jersey Department of Health and Senior Services protocol. Data collected by the study investigator were done by chart review from October through December 2009, the first 3 months after implementation of routine HIV screening. Data were collected from patients aged 13 to 20 years presenting to the PED. Primary outcomes measured included the proportion of patients offered and accepted screening, newly diagnosed HIV cases, and the rate of linking newly diagnosed HIV patients to treatment. Demographic data collected included patient age, sex, and ethnicity. Results from the first 3 months of routine, nontargeted screening were compared with the HIV screening results of October through December 2008, during which time rapid HIV screening was provided to patients in the ED based on clinical indication. Patients who were not offered testing or who refused testing were measured by forms that were placed in every chart

  7. [Prenatal ultrasound diagnosis of complex heart abnormality in routine screening].

    PubMed

    Kronich, W; Salzer-Muhar, U; Strigl, E; Gerstner, G J

    1990-02-01

    Case report on a severe cardial malformation associated with trisomia 21, diagnosed by ultrasound-screening in the 34th week of gestation. Further diagnostic evaluation of the case and therapeutic management are described. The problems of modern malformation diagnostics by routine ultrasound scanning in pregnancy are discussed.

  8. Routine screening of Halloween candy: helpful or hazardous?

    PubMed

    Cappelle, C A; Eberly, S; Paul, R I

    1993-10-01

    To determine the frequency of radiopaque items found in radiologic screening of Halloween candy and to determine the possibility of missing a small item. Prospective observational study on Halloween night, 1992. Data were collected from area medical centers that were screening Halloween candy. The ability to detect small sharp items was tested at five centers. Five hospitals and three immediate care centers. Four hundred fifty-four bags of candy were screened. No unknown radiopaque items were discovered. One of five centers tested for accuracy failed to detect a small radiopaque item. Only one hospital required parents to sign a waiver of liability. The immediate care centers recorded patients' names; the other hospitals kept no record of the names of children whose bags were screened. No physicians viewed the radiographs or fluoroscopy. The routine radiologic screening of Halloween candy has an extremely low yield in detecting radiopaque items.

  9. Implementing Routine HIV Screening in Three Chicago Hospitals: Lessons Learned

    PubMed Central

    Rucker, Monique Glover; Allgood, Kristi L.; Sinclair, Donna; Lawal, Rukiyat; Tobin, Audra; Pitrak, David; Glick, Nancy R.

    2016-01-01

    Objective This study describes routine HIV screening implementation and outcomes in three hospitals in Chicago, Illinois. Methods Retrospective data from three hospitals were examined, and routine testing procedures, testing volume, reactive test results, and linkage-to-care outcomes were documented. Results From January 2012 through March 2014, 40,788 HIV tests were administered at the three hospitals: 18,603 (46%) in the emergency department (ED), 7,546 (19%) in the inpatient departments, and 14,639 (36%) in outpatient clinics. The screened patients varied from 1% to 22% of the total eligible patient population across hospitals. A total of 297 patients tested positive for HIV for a seropositivity rate of 0.7%; 129 (43%) were newly diagnosed and 168 (57%) were previously diagnosed, with 64% of those previously diagnosed out of care at the time of screening. The inpatient areas had the highest seropositivity rate (0.6%). The percentage of newly diagnosed patients overall who were linked to care was 77%. Of newly diagnosed patients, 51% had ≥1 missed opportunity for testing (with a mean of 3.8 visits since 2006), and 30% of patients with missed opportunities were late testers (baseline CD4+ counts <200 cells per cubic millimeter). Conclusion Routine screening is an essential tool for identifying new infections and patients with known infection who are out of care. Hospitals need to provide HIV screening in inpatient and outpatient settings—not just EDs—to decrease missed opportunities. Routine screening success will be driven by how notification and testing are incorporated into the normal medical flow, the level of leadership buy-in, the ability to conduct quality assurance, and local testing laws. PMID:26862237

  10. Single newborn screen or routine second screening for primary congenital hypothyroidism.

    PubMed

    Shapira, Stuart K; Hinton, Cynthia F; Held, Patrice K; Jones, Elizabeth; Harry Hannon, W; Ojodu, Jelili

    2015-11-01

    Routine second screening of most newborns at 8-14 days of life for a panel of newborn conditions occurs in 12 U.S. states, while newborns in the other states typically undergo only a single routine newborn screen. The study objective was to evaluate screening consequences for primary congenital hypothyroidism (CH) in one- and two-screen states according to laboratory practices and medical or biochemical characteristics of screen-positive cases. Individual-level medical and biochemical data were retrospectively collected and analyzed for 2251 primary CH cases in one-screen (CA, WI) and two-screen (AL, DE, MD, OR, TX) states. Aggregate data were collected and analyzed for medical and biochemical characteristics of all screened newborns in the states. Among the states evaluated in this study, the detection rate of primary CH was higher in the one-screen states. In the two-screen states, 11.5% of cases were detected on the second screen. In multivariate analyses, only race/ethnicity was a significant predictor of cases identified on the first versus second screen, which likely reflects a physiologic difference in primary CH presentation. Newborn screening programs must heed the potential for newborns with CH not being detected by a single screen, particularly newborns of certain races/ethnicities. If the two-screen states converted to a single screen using their current algorithms, newborns currently identified on the routine second screen would presumably not be detected, resulting in probable delayed diagnosis and treatment. However, based on the one-screen state experiences, with appropriate modifications in screening method and algorithm, the two-screen states might convert to single screen operation for CH without loss in performance. Published by Elsevier Inc.

  11. Single newborn screen or routine second screening for primary congenital hypothyroidism

    PubMed Central

    Shapira, Stuart K.; Hinton, Cynthia F.; Held, Patrice K.; Jones, Elizabeth; Hannon, W. Harry; Ojodu, Jelili

    2015-01-01

    Routine second screening of most newborns at 8–14 days of life for a panel of newborn conditions occurs in 12 U.S. states, while newborns in the other states typically undergo only a single routine newborn screen. The study objective was to evaluate screening consequences for primary congenital hypothyroidism (CH) in one- and two-screen states according to laboratory practices and medical or biochemical characteristics of screen-positive cases. Individual-level medical and biochemical data were retrospectively collected and analyzed for 2,251 primary CH cases in one-screen (CA, WI) and two-screen (AL, DE, MD, OR, TX) states. Aggregate data were collected and analyzed for medical and biochemical characteristics of all screened newborns in the states. Among the states evaluated in this study, the detection rate of primary CH was higher in the one-screen states. In the two-screen states, 11.5% of cases were detected on the second screen. In multivariate analyses, only race/ethnicity was a significant predictor of cases identified on the first versus second screen, which likely reflects a physiologic difference in primary CH presentation. Newborn screening programs must heed the potential for newborns with CH not being detected by a single screen, particularly newborns of certain races/ethnicities. If the two-screen states converted to a single screen using their current algorithms, newborns currently identified on the routine second screen would presumably not be detected, resulting in probable delayed diagnosis and treatment. However, based on the one-screen state experiences, with appropriate modifications in screening method and algorithm, the two-screen states might convert to single screen operation for CH without loss in performance. PMID:26293295

  12. Screening materials for toxicity of pyrolysis gases

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.

    1979-01-01

    The USF-NASA toxicity screening test method is primarily intended to indicate which materials are more toxic under specific test conditions, and not necessarily to explain why they are more toxic. Analysis of the test data obtained, however, in the light of the experience accumulated, can provide some insight into the mechanisms of toxicity and the importance of specific toxicants. The use of free-field movement offers both advantages and disadvantages relative to other behavioral paradigms, and the use of Swiss Webster mice offers both advantages and disadvantages relative to other species and strains.

  13. 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

  14. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The routine pre-employment screening chest radiograph: Should it be routine?

    PubMed Central

    Samuel, V John; Gibikote, Sridhar; Kirupakaran, Henry

    2016-01-01

    Background and Objective: A routine chest radiograph is mandatory in many institutions as a part of pre-employment screening. The usefulness of this has been studied over the years keeping in mind the added time, cost, and radiation concerns. Studies conducted outside India have shown different results, some for and some against it. To our knowledge, there is no published data from India on this issue. Materials and Methods: A retrospective review of the reports of 4113 pre-employment chest radiographs done between 2007 and 2009 was conducted. Results: Out of 4113 radiographs, 24 (0.58%) candidates required further evaluation based on findings from the screening chest radiograph. Out of these, 7 (0.17%) candidates required appropriate further treatment. Interpretation and Conclusions: The percentage of significant abnormalities detected which needed further medical intervention was small (0.17%). Although the individual radiation exposure is very small, the large numbers done nation-wide would significantly add to the community radiation, with added significant cost and time implications. We believe that pre-employment chest radiographs should be restricted to candidates in whom there is relevant history and/or clinical findings suggestive of cardiopulmonary disease. PMID:27857470

  16. 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...

  17. 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...

  18. Routine screening for suicidal intention in patients with cancer.

    PubMed

    Leung, Yvonne W; Li, Madeline; Devins, Gerald; Zimmermann, Camilla; Rydall, Anne; Lo, Chris; Rodin, Gary

    2013-11-01

    Suicide rates are elevated in individuals with cancer, although suicidal intention is not typically assessed in cancer centers. We evaluated in a large comprehensive cancer center the utility of an electronic Distress Assessment and Response Tool (DART), in which suicidal intention is assessed with a single item. Patients attending cancer clinics completed DART as part of routine care. DART includes measures of physical symptoms, depression, anxiety, social difficulties, and practical concerns. Medical variables were obtained from the Princess Margaret Cancer Registry, the data warehouse of cancer patient statistics. A Generalized Estimating Equation (GEE) model was used to assess factors associated with suicidal intention. Between September 2009 and March 2012, 4822/5461 patients (88.3%) who completed DART consented to the use of their data for research. Amongst the latter, 280 (5.9%) of the 4775 patients who answered the question reported suicidal ideation, which was related to physical and psychological distress, and social difficulties (ps < 0.0001). Amongst those with ideation who responded to the intention question, 20/186 (10.8%) reported suicidal intention. Of respondents with more severe suicidal ideation, 12/49 (24.5%) reported suicidal intention. Using a GEE model, suicidal intention in those with ideation was significantly associated with male sex, difficulty making treatment decisions, and with everyday living concerns. Suicidal ideation is reported on an electronic distress screening tool (DART) by almost 6% of cancer patients, of whom almost 11% report suicidal intention and 33% decline to indicate intention. DART demonstrated utility in identifying patients who may be at highest risk of completed suicide and who require urgent clinical assessment. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Routine primary care screening for intimate partner violence and other adverse psychosocial exposures: what's the evidence?

    PubMed

    McLennan, John D; MacMillan, Harriet L

    2016-08-03

    Family physicians and other primary care practitioners are encouraged or expected to screen for an expanding array of concerns and problems including intimate partner violence (IPV). While there is no debate about the deleterious impact of violence and other adverse psychosocial exposures on health status, the key question raised here is about the value of routine screening in primary care for such exposures. Several characteristics of IPV have led to consideration for routine IPV screening in primary care and during other healthcare encounters (e.g., emergency room visits) including: its high prevalence, concern that it may not be raised spontaneously if not prompted, and the burden of suffering associated with this exposure. Despite these factors, there are now three randomized controlled trials showing that screening does not reduce IPV or improve health outcomes. Yet, recommendations to routinely screen for IPV persist. Similarly, adverse childhood experiences (ACEs) have several characteristics (e.g., high frequency, predictive power of such experiences for subsequent health problems, and concerns that they might not be identified without screening) suggesting they too should be considered for routine primary care screening. However, demonstration of strong associations with health outcomes, and even causality, do not necessarily translate into the benefits of routine screening for such experiences. To date, there have been no controlled trials examining the impact and outcomes - either beneficial or harmful - of routine ACEs screening. Even so, there is an expansion of calls for routine screening for ACEs. While we must prioritize how best to support and intervene with patients who have experienced IPV and other adverse psychosocial exposures, we should not be lulled into a false sense of security that our routine use of "screeners" results in better health outcomes or less violence without evidence for such. Decisions about implementation of routine

  20. General Internists' Beliefs, Behaviors, and Perceived Barriers to Routine HIV Screening in Primary Care

    PubMed Central

    Korthuis, P. Todd; Berkenblit, Gail V.; Sullivan, Lynn E.; Cofrancesco, Joseph; Cook, Robert L.; Bass, Michael; Bashook, Philip G.; Edison, Marcia; Asch, Steve M.; Sosman, James M.

    2011-01-01

    The Centers for Disease Control and Prevention (CDC) recommends routine HIV screening in primary care but little is known about general internists' views of this practice. We conducted a national, cross-sectional, Internet-based survey of 446 general internists in 2009 regarding their HIV screening behaviors, beliefs, and perceived barriers to routine HIV screening in outpatient internal medicine practices. Internists' awareness of revised CDC guidelines was high (88%), but only 52% had increased HIV testing, 61% offered HIV screening regardless of risk, and a median 2% (range 0-67%) of their patients were tested in the past month. Internists practicing in perceived higher risk communities reported greater HIV screening. Consent requirements were a barrier to screening, particularly for VA providers and those practicing in states with HIV consent statutes inconsistent with CDC guidelines. Interventions that promote HIV screening regardless of risk and streamlined consent requirements will likely increase adoption of routine HIV screening in general medicine practices. PMID:21689038

  1. Screening for diabetic microalbuminuria in routine clinical care: which method?

    PubMed Central

    Shield, J P; Hunt, L P; Baum, J D; Pennock, C A

    1995-01-01

    The measurement of albumin/creatinine ratios and simple albumin concentrations in early morning urine specimens were evaluated to establish which was the best screening test for those likely to have microalbuminuria by the reference standard analysis of timed overnight urine specimens. The measurement of an albumin/creatinine ratio with a cut off of > or = 2.0 mg/mmol was found to be suitable with a specificity of 93% and sensitivity of 97%. PMID:7618940

  2. The case for routine HIV screening before IVF treatment: a survey of UK IVF centre policies.

    PubMed

    Marcus, S F; Avery, S M; Abusheikha, N; Marcus, N K; Brinsden, P R

    2000-08-01

    The case for routine human immunodeficiency virus (HIV) screening of all couples seeking assisted reproductive treatment is so strong that it should be made obligatory for all couples entering IVF programmes to be given information about HIV transmission, and offered testing. In August 1999, questionnaires regarding routine HIV screening of couples seeking IVF treatment were sent to the medical directors of the 74 licensed assisted conception units in the UK. Of the 45 (60.8%) centres who responded, 19 (42.2%) routinely screen both partners for HIV antibodies, 25 (55.5%) do not screen and one centre selectively screens high-risk patients. There was no significant difference in the proportion of centres that routinely carried out screening with regards to the unit size: six out of 13 (46.2%) small units compared with 13/32 (40.6%) large units. In all, 17 centres (37.8%) rated HIV screening as essential, nine (20%) as desirable, 11 (24.4%) as not required, while eight (17. 8%) centres did not comment. Of the 19 centres that have a routine screening policy, 18 have management protocols in the event that the test is positive. Of these 18 centres, 12 adhere rigidly to the protocol, while five centres adhere to the protocol with few exceptions and the remaining one uses its protocol for guidance only. The main reasons for not employing routine HIV screening were: the lack of cost effectiveness, low prevalence of HIV infection in their population, necessity for and cost of counselling, uncertainty about the need for screening and potential delay to start of treatment.

  3. Factors which influence the rate of receiving a routine second newborn screening test in Washington State.

    PubMed

    Doyle, D L; Sanderson, M; Bentvelzen, J; Fineman, R M

    1995-12-04

    This study was conducted to determine whether newborns from different ethnic and socioeconomic groups in Washington State are equally likely to have a routine second newborn screening (NBS) test and if there are identifiable factors associated with not having a second test. For many years, the standard of care for NBS in Washington has been that newborns should receive a routine second screening test at age 7-10 days. However, data collected by State Department of Health (DOH) staff for the past several years indicated that only about 80% of newborns receive a routine second NBS test. The data presented here suggest that identifiable factors (i.e., barriers) exist in accessing a routine second NBS test in Washington. Increased educational efforts targeting certain high-risk infants, their parent/caretakers, and primary care providers are apparently needed to ensure equal access to a routine second test.

  4. Gastrointestinal cancer screening: screening may release new research funding to improve health service also in routine clinics.

    PubMed

    Hoff, Geir

    2015-06-01

    We are far from having seen the ideal method of screening for colorectal cancer (CRC) and the downsides of screening have not been fully addressed. Funding of adequately sized screening trials with a 10-15-year perspective for endpoints CRC mortality and incidence is difficult to get. Also, with such time horizons, there will always be an ongoing study to be awaited before feeling obliged to invest in the next. New, promising screening methods may, however, emerge far more often than every 10th year, and the knowledge gap may easily widen unless research is made a key responsibility for any ongoing cancer screening program. Previous lost battles on screening research may be won if accepting that scientific evidence may be obtained within the framework of screening programs - provided that they are designed as platforms for Comparative Effectiveness Research (CER). Accepting that CER-based screening programs should be preferred to non-CER programs and seriously compete for their funding sources, then CER screening programs may not be considered so much as contenders for ordinary clinical research funds. Also, CER within a screening framework may benefit patients in routine clinics as shown by screening research in Nordic countries. The Nordic countries have been early contributors to research on CRC screening, but slow in implementing screening programs.

  5. 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

  6. Integration of routine rapid HIV screening in an urban family planning clinic.

    PubMed

    Criniti, Shannon M; Aaron, Erika; Hilley, Amy; Wolf, Sandra

    2011-01-01

    Family planning centers can play an important role in HIV screening, education, and risk-reduction counseling for women who are sexually active. This article describes how 1 urban Title X-funded family planning clinic transitioned from using a designated HIV counselor for targeted testing to a model that uses clinic staff to provide integrated, routine, nontargeted, rapid HIV testing as standard of care. Representative clinic staff members developed an integrated testing model that would work within the existing clinic flow. Education sessions were provided to all staff, signs promoting routine HIV testing were posted, and patient and clinician information materials were developed. A review of HIV testing documentation in medical charts was performed after the new model of routine, nontargeted, rapid HIV testing was integrated, to determine any changes in patient testing rates. A survey was given to all staff members 6 months after the transition to full integration of HIV testing to evaluate the systems change process. Two years after the transition, the rate of patients with an HIV test in the medical chart within the last 12 months increased 25.5%. The testing acceptance rate increased 17%. Sixteen HIV seropositive individuals were identified and linked into medical care. All surveyed clinic staff agreed that offering routine HIV screening to all patients is very important, and 78% rated the integration efforts as successful. Integrating routine HIV screening into a family planning clinic can be critical to identifying new HIV infections in women. This initiative demonstrated that routine, nontargeted, rapid HIV screening can be offered successfully as a standard of care in a high-volume, urban, reproductive health care setting. This description and evaluation of the process of changing the model of HIV testing in a clinic setting is useful for clinicians who are interested in expanding routine HIV testing in their clinics. © 2011 by the American College of

  7. Effect of routine mental health screening in a low-resource pediatric primary care population.

    PubMed

    Berger-Jenkins, Evelyn; McCord, Mary; Gallagher, Trish; Olfson, Mark

    2012-04-01

    Despite evidence for its feasibility, the usage of mental health screening in primary care practices with overburdened providers and few referral options remains unclear. This study explores the effects of routine screening on mental health problem identification and management in a low-resource setting. Medical records of 5 to 12 year-old children presenting for well visits before and after screening was implemented were reviewed. Multivariate logistic regression was used to explore associations between study period and identification/management practices. Changes in the number of visits and wait times for a co-located referral service were assessed post hoc. Parents disclosed more mental health problems, and providers initiated more workups but referred fewer patients after screening was implemented. The proportion of new visits and wait times for the referral service did not change. Even in low-resource settings, screening may facilitate parental disclosure and increase clinical attention to mental health problems without overburdening referral services.

  8. Routine HIV Screening in an Urban Community Health Center: Results from a Geographically Focused Implementation Science Program.

    PubMed

    Nunn, Amy; Towey, Caitlin; Chan, Philip A; Parker, Sharon; Nichols, Emily; Oleskey, Patrick; Yolken, Annajane; Harvey, Julia; Banerjee, Geetanjoli; Stopka, Thomas; Trooskin, Stacey

    2016-01-01

    CDC has recommended routine HIV screening since 2006. However, few community health centers (CHCs) routinely offer HIV screening. Research is needed to understand how to implement routine HIV screening programs, particularly in medically underserved neighborhoods with high rates of HIV infection. A routine HIV screening program was implemented and evaluated in a Philadelphia, Pennsylvania, neighborhood with high rates of HIV infection. Implementation science is the study of methods to promote the integration of research findings and evidence into health-care policy and practice. Using an implementation science approach, the results of the program were evaluated by measuring acceptability, adoption, and penetration of routine HIV screening. A total of 5,878 individuals were screened during the program. HIV screening was highly accepted among clinic patients. In an initial needs assessment of 516 patients, 362 (70.2%) patients reported that they would accept testing if offered. Routine screening policies were adopted clinic-wide. Staff trainings, new electronic medical records that prompted staff members to offer screening and evaluate screening rates, and other continuing quality-improvement policies helped promote screenings. HIV screening offer rates improved from an estimated 5.0% of eligible patients at baseline in March 2012 to an estimated 59.3% of eligible patients in December 2014. However, only 5,878 of 13,827 (42.5%) patients who were offered screening accepted it, culminating in a 25.2% overall screening rate. Seventeen of the 5,878 patients tested positive, for a seropositivity rate of 0.3%. Routine HIV screening at CHCs in neighborhoods with high rates of HIV infection is feasible. Routine screening is an important tool to improve HIV care continuum outcomes and to address racial and geographic disparities in HIV infection.

  9. Routine HIV Screening in an Urban Community Health Center: Results from a Geographically Focused Implementation Science Program

    PubMed Central

    Towey, Caitlin; Chan, Philip A.; Parker, Sharon; Nichols, Emily; Oleskey, Patrick; Yolken, Annajane; Harvey, Julia; Banerjee, Geetanjoli; Stopka, Thomas; Trooskin, Stacey

    2016-01-01

    Objective CDC has recommended routine HIV screening since 2006. However, few community health centers (CHCs) routinely offer HIV screening. Research is needed to understand how to implement routine HIV screening programs, particularly in medically underserved neighborhoods with high rates of HIV infection. A routine HIV screening program was implemented and evaluated in a Philadelphia, Pennsylvania, neighborhood with high rates of HIV infection. Methods Implementation science is the study of methods to promote the integration of research findings and evidence into health-care policy and practice. Using an implementation science approach, the results of the program were evaluated by measuring acceptability, adoption, and penetration of routine HIV screening. Results A total of 5,878 individuals were screened during the program. HIV screening was highly accepted among clinic patients. In an initial needs assessment of 516 patients, 362 (70.2%) patients reported that they would accept testing if offered. Routine screening policies were adopted clinic-wide. Staff trainings, new electronic medical records that prompted staff members to offer screening and evaluate screening rates, and other continuing quality-improvement policies helped promote screenings. HIV screening offer rates improved from an estimated 5.0% of eligible patients at baseline in March 2012 to an estimated 59.3% of eligible patients in December 2014. However, only 5,878 of 13,827 (42.5%) patients who were offered screening accepted it, culminating in a 25.2% overall screening rate. Seventeen of the 5,878 patients tested positive, for a seropositivity rate of 0.3%. Conclusion Routine HIV screening at CHCs in neighborhoods with high rates of HIV infection is feasible. Routine screening is an important tool to improve HIV care continuum outcomes and to address racial and geographic disparities in HIV infection. PMID:26862228

  10. Immunoassay as a screening tool for industrial toxicants

    SciTech Connect

    Pierce, T.

    1986-08-01

    Immunoassay techniques may represent useful screening tools to assist analysts interested in the presence and amounts of organic toxicants in biological fluids. The widespread application of immunoassay methods in medicinal and forensic (drugs of abuse) chemistry has resulted in such screening methodologies. Four methodologies of potential benefit are considered: the free radical assay technique, the enzyme-mediated immunoassay technique, radioimmunoassay, and hemagglutination. Each of these immunoassays is based on the competitive displacement of the labeled drug (or toxicant) from the antibody complex by the unlabeled drug-toxicant in the sample.

  11. Routine Screening Radiography for Retained Wire Following Arch Bar Removal Is Not Indicated.

    PubMed

    Gelesko, Savannah; Wahlstrom, Devin; Engelstad, Mark

    2016-04-01

    To estimate the screening test value of routine radiography after arch bar wire removal by assessing the incidence of retained wires and the importance of their sequelae. This was a retrospective medical record review. Records of arch bar removal procedures were examined and divided into those screened with radiography after removal (screen group) and those that were not screened (comparison group). The incidence of retained wire was calculated for each group. Study variables included wire-related radiographic or clinical findings. Records of 546 mandible fractures were reviewed; 95 met the study criteria. Most exclusions were due to lack of arch bars, missing postoperative radiographs, or insufficient postoperative documentation. Of the 55 records in the screen group, 1 wire was detected (2%); of the 40 records in the comparison group, 1 wire was detected (3%). The total incidence of retained wire findings was not statistically different between the 2 groups and there were no adverse wire-related sequelae reported by any of the 95 patients. Because of the low incidence of retained wires and wire-related sequelae, routine imaging after wire removal is probably not an effective screening test for retained wire and should be limited to situations in which there is clinical suspicion of retained wire. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  12. 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

  13. 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.

  14. Routine Pre-cesarean Staphylococcus aureus Screening and Decolonization: A Cost-Effectiveness Analysis

    PubMed Central

    Lee, Bruce Y.; Wiringa, Ann E.; Mitgang, Elizabeth A.; McGlone, Sarah M.; Afriyie, Abena N.; Song, Yeohan; Beigi, Richard H.

    2013-01-01

    Objectives To estimate the economic value of screening pregnant women for Staphylococcus aureus carriage before cesarean delivery. Study Design Computer simulation model. Methods We used computer simulation to assess the cost-effectiveness, from the third-party payer perspective, of routine screening for S aureus (and subsequent decolonization of carriers) before planned cesarean delivery. Sensitivity analyses explored the effects of varying S aureus colonization prevalence, decolonization treatment success rate (for the extent of the puerperal period), and the laboratory technique (agar culture vs polymerase chain reaction [PCR]) utilized for screening and pathogen identification from wound isolates. Results Pre-cesarean screening and decolonization were only cost-effective when agar was used for both screening and wound cultures when the probability of decolonization success was ≥50% and colonization prevalence was ≥40%, or decolonization was ≥75% successful and colonization prevalence was ≥20%. The intervention was never cost-effective using PCR-based laboratory methods. The cost of agar versus PCR and their respective sensitivities and specificities, as well as the probability of successful decolonization, were important drivers of the economic and health impacts of preoperative screening and decolonization of pregnant women. The number needed to screen ranged from 21 to 2294, depending on colonization prevalence, laboratory techniques used, and the probability of successful decolonization. Conclusions Despite high rates of cesarean delivery, presurgical screening of pregnant women for S aureus and decolonization of carriers is unlikely to be cost-effective under prevailing epidemiologic circumstances. PMID:22106462

  15. HPV testing in routine cervical screening: cross sectional data from the ARTISTIC trial

    PubMed Central

    Kitchener, H C; Almonte, M; Wheeler, P; Desai, M; Gilham, C; Bailey, A; Sargent, A; Peto, J

    2006-01-01

    To evaluate the effectiveness of human papillomavirus (HPV) testing in primary cervical screening. This was a cross-sectional study from the recruitment phase of a prospective randomised trial. Women were screened for HPV in addition to routine cervical cytology testing. Greater Manchester, attendees at routine NHS Cervical Screening Programme. In all, 24 510 women aged 20–64 screened with liquid-based cytology (LBC) and HPV testing at entry. HPV testing in primary cervical screening. Type-specific HPV prevalence rates are presented in relation to age as well as cytological and histological findings at entry. In all, 24 510 women had adequate cytology and HPV results. Cytology results at entry were: 87% normal, 11% borderline or mild, 1.1% moderate and 0.6% severe dyskaryosis or worse. Prevalence of HPV decreased sharply with age, from 40% at age 20–24 to 12% at 35–39 and 7% or less above age 50. It increased with cytological grade, from 10% of normal cytology and 31% of borderline to 70% mild, 86% moderate, and 96% of severe dyskaryosis or worse. HPV 16 or HPV 18 accounted for 64% of infections in women with severe or worse cytology, and one or both were found in 61% of women with severe dyskaryosis but in only 2.2% of those with normal cytology. The majority of young women in Greater Manchester have been infected with a high-risk HPV by the age of 30. HPV testing is practicable as a primary routine screening test, but in women aged under 30 years, this would lead to a substantial increase in retesting and referral rates. HPV 16 and HPV 18 are more predictive of underlying disease, but other HPV types account for 30% of high-grade disease. PMID:16773068

  16. Routine screening of hospital patients for secondhand tobacco smoke exposure: a feasibility study.

    PubMed

    Kruse, Gina Rae; Rigotti, Nancy A

    2014-12-01

    Secondhand tobacco smoke (SHS) exposure causes over 40,000 deaths per year, but healthcare systems rarely address this risk factor. In September 2012, Massachusetts General Hospital initiated routine inpatient screening for SHS exposure by adding a question to the nurses' computerized admission assessment form ("Is smoking allowed in your home or car?"). We measured the implementation of this screening question over 1year. Multivariable analysis of hospital records of adult and pediatric admissions (N=35,701) from September 1, 2012 to August 31, 2013, to assess screening question completion and identify characteristics of nonsmokers who may be exposed to SHS. Nurses entered "Yes" or "No" to the screening question for 91% of 34,295 adult admissions and 86% of 1406 pediatric admissions. Among nonsmokers, smoking in the home or car was allowed for 3% of adult admissions and 4% of pediatric admissions. Adults admitted for psychiatric diagnoses, children admitted for asthma, and patients with Medicaid insurance had higher odds of exposure to SHS in their home or car. Routine screening of SHS among hospitalized patients by nurses is feasible. Doing so offers hospitals an opportunity to intervene and to promote smoke-free policies in patients' homes and cars. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Should home ipecac-induced emesis be routinely recommended in the management of toxic berry ingestions?

    PubMed

    Wax, P M; Cobaugh, D J; Lawrence, R A

    1999-12-01

    Poison center (PC) management of toxic berry ingestions may include recommendations to administer syrup of ipecac (SI) regardless of the number of berries ingested. We investigated whether the routine use of SI in the home management of asymptomatic single or few (< 6) berry ingestions may be unnecessary. A prospective, randomized clinical trial compared SI + home observation (HO) to HO alone for management of pediatric toxic berry ingestions. Subjects were children 9 mo to 5 y who ingested a small number (< 6) of Taxus sp (yew), Solanum americanus (nightshade), Ilex sp (holly) or unknown potentially toxic berries. Exclusions were symptomatic subjects, ingestion of more than 1 type of berry or other plant part, or contraindication to SI. Outcome variables consisting of symptom assessment and disposition were assessed 24 h following the ingestion. Over a 27-mo period 103 subjects were entered into the study; 45 received SI/HO and 51 received only HO. While 100% of the SI/HO group experienced vomiting, none of the HO group vomited. Diarrhea and sedation were more common in the SI/HO group. Use of SI in the home management of young children who ingest fewer than 6 toxic berries (yew, nightshade, holly or unknown) and who are asymptomatic when the PC is contacted may be responsible for the majority of symptoms. Ingestion of small amounts of berries may require no intervention beyond observation. Methodological limitations of this study included the lack of confirmed identification of the berries and the inability to confirm ingestion and absorption.

  18. Is Routine Screening for Intimate Partner Violence Feasible in Public Health Care Settings in Kenya?

    PubMed

    Undie, Chi-Chi; Maternowska, M Catherine; Mak'anyengo, Margaret; Askew, Ian

    2016-01-01

    More than a third of women worldwide have experienced either physical and/or sexual intimate partner violence (IPV) or non-partner sexual violence. The short- and long-term health effects of violence can be disabling if left undetected. A recent World Health Organization (WHO) report indicates that Africa is one of the regions with the highest prevalence of physical and/or sexual IPV among ever-partnered women. Routine screening for IPV can potentially improve the care and treatment of women suffering from violence. Although routine screening is commonplace in European and American countries, health systems barriers in developing countries have deterred introduction of this practice. Results from this feasibility study indicate that providers are willing and able to incorporate IPV screening into their practice and that IPV screening in a variety of health care settings in a public hospital is feasible and welcomed by clients. Referral uptake by women suffering from IPV was low compared with provider referral rates, but ways in which referral and management services could be improved were identified. © The Author(s) 2014.

  19. Routine screening for α-thalassaemia using an immunochromatographic strip assay for haemoglobin Bart's.

    PubMed

    Prayalaw, Patcharawadee; Fucharoen, Goonnapa; Fucharoen, Supan

    2014-09-01

    To evaluate an immunochromatographic (IC) strip assay for Hb Bart's as a routine screening test for α-thalassaemia in area with a high prevalence of thalassaemia and haemoglobinopathies. A total of 300 adult screen positive blood specimens were collected at an ongoing thalassaemia screening programme in northeast Thailand. Routine screening was done using red blood cell indices, osmotic fragility, and dichlorophenolindophenol tests. The IC strip assay for haemoglobin Bart's was performed on all samples. The result was evaluated against thalassaemia genotypes determined using standard haemoglobin and DNA analyses. Of 300 subjects investigated, Hb and DNA analyses identified 32 with normal genotype. The remaining subjects carried thalassaemia with as many as 16 different genotypes. Hb Bart's was detected in all cases, with several α(0)-thalassaemia (SEA type) related disorders. Of cases with α(+)-thalassaemia, 86.1% showed a positive result; 100 out of 103 Hb E carriers, all homozygous Hb E and β-thalassaemia trait were negative. Nine out of 17 cases with β-thalassaemia/Hb E disease, and one case of double heterozygote for Hb Q-Thailand and Hb E returned positive results. The overall sensitivity and specificity of the IC strip assay for detecting α(0)-thalassaemia were 100% and 73.1%, respectively. The results showed a high sensitivity for screening for α(0)-thalassaemia using IC strip assay for Hb Bart's. This simple method, used in combination with conventional screening protocols, should lead to a significant reduction in the number of referral cases for DNA analysis. Cost effectiveness in each population should be taken into consideration. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. Aquatic Toxicity Screening of Fire Fighting Agents; 2003 Report

    DTIC Science & Technology

    2003-06-02

    the Trimmed Spearman - Karber Method and the results were shown in parts per million (ppm). Typical program output is shown in Appendix C. 4 SECTION... Karber Method and the results are given in parts per million (ppm). RESULTS The first sample of FireAde 2000 had a pH of 12.4, which resulted in the...the Fathead Minnow (Pimephales promelas) as the screening organism. Aquatic toxicity screening offers an inexpensive, efficient and reliable method for

  1. Routine serum thyroid-stimulating hormone testing-optimizing pre-conception health or generating toxic knowledge?

    PubMed

    Maheshwari, Abha; Bhide, Priya; Pundir, Jyotsna; Bhattacharya, Siladitya

    2017-09-01

    Monitoring subclinical hypothyroidism (SCH) in women is believed to be important in terms of preventing overt hypothyroidism and optimizing the health and cognitive development of their children. Current systematic reviews have suggested an association between maternal SCH and adverse obstetric and neonatal outcomes. However, initiating the administration of thyroxine during pregnancy has failed to demonstrate appreciable health benefits. Hence there are calls by professional endocrine societies for optimizing serum thyroid-stimulating hormone (TSH) levels pre-conception. The strategy of ensuring that serum TSH levels are below 2.5 mIU/l during the pre-conception period has generated considerable uncertainty partly because the recommended level of <2.5 mIU/l is lower than those previously used to define the condition and partly due to uncertainty about the best screening programme clinicians can use in this context. Recalibrating the expected normal peri-conceptional range of serum TSH (<2.5 mIU/l), will have a significant impact on clinical services due to an inevitable increase in numbers of women diagnosed with SCH who will need to be investigated, treated and monitored. Serum TSH fulfils the criteria for a screening test and oral thyroxine is an inexpensive drug. Therefore, there is no reason to believe that screening cannot be undertaken in all women planning to conceive. Yet this approach will miss women whose pregnancies are unplanned and generate anxiety, further tests and many more prescriptions for thyroxine, coupled with the need for lifelong monitoring in affected women. A number of existing and ongoing randomized trials have evaluated the use of thyroxine in women with infertility or miscarriage with detectable thyroid auto-antibodies. These are unlikely to answer the question whether routine pre-conception testing for SCH in asymptomatic women is beneficial. Routine screening of women at risk of pregnancy and optimization of their thyroid status could

  2. 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.

  3. Setting the stage for universal financial distress screening in routine cancer care.

    PubMed

    Khera, Nandita; Holland, Jimmie C; Griffin, Joan M

    2017-08-17

    Financial burden from cancer treatment is increasingly being recognized as a threat to optimal access, quality, and outcomes of cancer care for patients. Although research in the area is moving at a fast pace, multiple questions remain unanswered, such as how to practically integrate the assessment and management of financial burden into routine health care delivery for patients with cancer. Although psychological distress screening for patients undergoing cancer treatment now is commonplace, the authors raise the provocative idea of universal screening for financial distress to identify and assist vulnerable groups of patients. Herein, the authors outline the arguments to support screening for financial burden in addition to psychological distress, examining it as an independent patient-reported outcome for all patients with cancer at various time points during their treatment. The authors describe the proximal and downstream impact of such a strategy and reflect on some challenges and potential solutions to help integrate this concept into routine cancer care delivery. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. Prevalence of intimate partner violence disclosed during routine screening in a large general practice.

    PubMed

    Higgins, Debs; Manhire, Kathy; Marshall, Bob

    2015-06-01

    Domestic violence in its myriad shapes and forms is a crime affecting every level of society. Gaining a true understanding of intimate partner violence (IPV) victimology allows for the meaningful provision of intervention services. To explore the prevalence of IPV disclosure during routine screening in a large general practice in provincial New Zealand. Data were collected from 13 October 2008 to 30 June 2014 from 6827 individuals screened for IPV on 10 062 occasions and were analysed relative to age, ethnicity, gender, screening outcome, screener and health centre enrolled status. Analysis indicated an overall ever-positive disclosure rate of IPV of 11.1%, lower than New Zealand studies that place ever-positive prevalence as high as 78%. Maori women disclosed an ever-positive rate of 21.6%, Pacific women 13.2%, compared to 8.9% for NZ European/Other women. Casual patients positively disclosed in 13.7% of instances as opposed to enrolled patients in 10.5%. Disclosure of past abuse was made 1.3 times more often than that of a current abusive situation. Those aged between 16 and 65 years disclosed an ever-positive rate ≥10%. While nurses screened 5.5 times more patients than doctors, the doctors facilitated a higher percentage of positive disclosures than the nurses. Disclosure rates from a general practice setting do not mirror those of population studies or administrative datasets due to differences in samples and data collection methods. Routine annual screening is effective, with both doctors and nurses providing support for approximately equal numbers of patients in immediate danger.

  5. Screening Breast MRI Outcomes in Routine Clinical Practice: Comparison to BI-RADS Benchmarks.

    PubMed

    Strigel, Roberta M; Rollenhagen, Jennifer; Burnside, Elizabeth S; Elezaby, Mai; Fowler, Amy M; Kelcz, Frederick; Salkowski, Lonie; DeMartini, Wendy B

    2017-04-01

    The BI-RADS Atlas 5th Edition includes screening breast magnetic resonance imaging (MRI) outcome benchmarks. However, the metrics are from expert practices and clinical trials of women with hereditary breast cancer predispositions, and it is unknown if they are appropriate for routine practice. We evaluated screening breast MRI audit outcomes in routine practice across a spectrum of elevated risk patients. This Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included all consecutive screening breast MRI examinations from July 1, 2010 to June 30, 2013. Examination indications were categorized as gene mutation carrier (GMC), personal history (PH) breast cancer, family history (FH) breast cancer, chest radiation, and atypia/lobular carcinoma in situ (LCIS). Outcomes were determined by pathology and/or ≥12 months clinical and/or imaging follow-up. We calculated abnormal interpretation rate (AIR), cancer detection rate (CDR), positive predictive value of recommendation for tissue diagnosis (PPV2) and biopsy performed (PPV3), and median size and percentage of node-negative invasive cancers. Eight hundred and sixty examinations were performed in 566 patients with a mean age of 47 years. Indications were 367 of 860 (42.7%) FH, 365 of 860 (42.4%) PH, 106 of 860 (12.3%) GMC, 14 of 860 (1.6%) chest radiation, and 8 of 22 (0.9%) atypia/LCIS. The AIR was 134 of 860 (15.6%). Nineteen cancers were identified (13 invasive, 4 DCIS, two lymph nodes), resulting in CDR of 19 of 860 (22.1 per 1000), PPV2 of 19 of 88 (21.6%), and PPV3 of 19 of 80 (23.8%). Of 13 invasive breast cancers, median size was 10 mm, and 8 of 13 were node negative (61.5%). Performance outcomes of screening breast MRI in routine clinical practice across a spectrum of elevated risk patients met the American College of Radiology Breast Imaging Reporting and Data System benchmarks, supporting broad application of these metrics. The indication

  6. 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

  7. Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment.

    PubMed

    Everds, Nancy E; Snyder, Paul W; Bailey, Keith L; Bolon, Brad; Creasy, Dianne M; Foley, George L; Rosol, Thomas J; Sellers, Teresa

    2013-01-01

    Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias. This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters

  8. 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

  9. The Efficacy of Routine Screening for High-Frequency Hearing Loss in Adults and Children.

    PubMed

    Serpanos, Yula C; Senzer, Deborah; Renne, Brittany; Langer, Rebecca; Hoffman, Roxanne

    2015-09-01

    This study was conducted to investigate the efficacy of routine screening for high-frequency hearing loss (HFHL) including 3000, 6000, and 8000 Hz frequencies with conventional test frequencies (1000, 2000, and 4000 Hz) in adults and children in a university outreach program. Screening outcomes were examined in 2 cohorts of adults (Cohort 1, N = 315, M = 66.2 years; Cohort 2, N = 67, M = 68.3 years) and children (Cohort 1, N = 177, M = 6.5 years; Cohort 2, N = 57, M = 6.9 years) with a high-frequency screen protocol (1000-8000 Hz at 25 dB HL for adults and 20 dB HL for children) using supra-aural headphones. A rescreen was conducted in Cohort 2 with a modified protocol using insert earphones and monitored ambient noise levels. Average total test time significantly increased (p < .0001) and nearly doubled with inclusion of 3000-, 6000-, and 8000-Hz frequencies, adding approximately 1 min. Rescreen referral rates decreased by approximately 2%-16% at 1000-8000 Hz (approximately 13%-16% at 6000 and 8000 Hz) using the modified protocol in adults and children, supporting false-positive responses using supra-aural headphones. Screening for HFHL should include insert earphones in order to prevent potential errors, particularly at 6000 and 8000 Hz.

  10. Factors Associated with Adherence to Routine Screening Mammography in HIV-Infected Women.

    PubMed

    Weinstein, Zoe M; Battaglia, Tracy A; Baranoski, Amy S

    2016-05-01

    Both HIV-infected women and minority women have historically lower rates of screening mammography. The objective of this study was to identify factors related to adherence to routine screening mammography in a diverse inner-city cohort of HIV-infected women, to inform future work on targeted interventions to address disparities. This retrospective cohort study reviewed the electronic medical record of HIV-infected women aged 40 and older engaged in care between October 1, 2003 and March 31, 2008 at a large urban safety-net HIV clinic. Analyses included chi square testing and multivariate logistic regression to assess for patient-specific factors associated with adherence to breast cancer screening, defined as obtaining a screening mammogram within 2 years of engaging in care. The 292 women were a racially diverse group, with 70% black, 11% Hispanic, and 42% foreign born. There was suboptimal HIV control, with only 33% having an undetectable viral load (VL). One hundred forty-six (50%) were adherent to screening mammography. In multivariate analysis, women who were foreign born (OR 2.65 [CI 1.52-4.64]) had not completed high school (OR 1.77 [CI 1.06-2.95]) or had an undetectable VL (OR 2.51 [CI 1.44-4.40]) had increased odds of obtaining a mammogram. Among a racially diverse urban population of HIV-infected women engaged in care, only half had a mammogram. Foreign-born women had higher odds of undergoing mammography, suggesting that nativity status and social determinants of health are under-recognized drivers of adherence in this population. Future programs targeting screening must be mindful of the multiple predictors of adherence.

  11. Should antibody to hepatitis B core antigen be tested in routine screening of donor corneas for transplant?

    PubMed

    Mattern, R M; Cavanagh, H D

    1997-03-01

    A review of the literature on transfusion-transmitted infectious diseases shows that antibody to hepatitis B core antigen (anti-HBc) is not presently viewed as helpful for hepatitis C or hepatitis non-ABC screening of blood donors. Its utility as a screen for hepatitis B or human immunodeficiency virus-1 (HIV-1) is controversial among experts. We compare relevant aspects of the screening of blood donations and the screening of cornea transplant donors to assess implications for the screening of donor corneas. We conclude that there is not sufficient evidence to warrant introducing anti-HBc as a routine screening test for cornea donors.

  12. Routine Use of Screening and Brief Intervention for College Students in a University Counseling Center

    PubMed Central

    Denering, Loretta L.; Spear, Suzanne E.

    2012-01-01

    This study provides preliminary evidence of the effectiveness of the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) and ASSIST-linked brief intervention in a college mental health clinic. Data are from a single group, pre-post evaluation study (2006–2009) at a university counseling center. Students deemed to be at risk for substance use problems were offered the ASSIST and the ASSIST-linked brief intervention. Staff therapists administered the ASSIST and intervention as part of routine care; 453 students (ages 18–24) participated in the evaluation and completed baseline and six-month follow-up interviews. Changes in alcohol and marijuana use were examined by McNemar’s test of proportions and by paired t-tests for means. Slight reductions in the rates and number of days (in the prior 30 days) of binge drinking and marijuana use were found. Routine screening and brief intervention procedures in a mental health setting may reduce problematic substance use among college students. PMID:23210380

  13. Routine screening for the presence of adulteration in raw materials using automated nuclear magnetic resonance spectroscopy.

    PubMed

    Meriage, David; Rogers, Gary; Phillips, Joseph

    2012-01-01

    In an effort to increase the security of the supply chain for raw materials used in the manufacture of human therapeutics, a routine screen to detect the presence of adulteration using fully automated nuclear magnetic resonance spectroscopy has been developed and qualified for use in quality control laboratories. The method involves the collection of one-dimensional (1)H and (13)C spectra, which are subsequently processed to identify and quantitate raw material constituents by comparison to a spectral database. The resulting method is an easy-to-use limit test that can automatically determine the integrity of incoming raw materials. The method is intended to be used in good manufacturing practice production facilities and is suitable for excipients and aqueous soluble raw materials used in biopharmaceutical processes. In an effort to increase the security of the supply chain for raw materials used in the manufacture of human therapeutics, a routine screen to detect the presence of adulteration using fully automated nuclear magnetic resonance (NMR) spectroscopy has been developed and qualified for use in quality control laboratories. The method involves the collection of NMR spectra, which are subsequently processed to identify and quantitate raw material constituents by comparison to a spectral database. The resulting method is an easy-to-use limit test that can automatically determine the integrity of incoming raw materials. The method is intended to be used in good manufacturing practice production facilities and is suitable for excipients and aqueous soluble raw materials used in biopharmaceutical processes.

  14. Is it worthwhile to routinely ultrasound screen children with idiopathic clubfoot for hip dysplasia?

    PubMed Central

    Mahan, Susan T.; Yazdy, Mahsa M; Kasser, James R.; Werler, Martha M

    2015-01-01

    Purpose Patients with idiopathic clubfoot are considered at increased risk for having developmental dysplasia of the hips (DDH). However, the studies showing this association have been relatively small. Many clinicians who treat idiopathic clubfoot routinely screen the hips of these patients with ultrasound or radiograph due to the concerns of increased risk of DDH. We evaluated a large clubfoot population to determine the risk of DDH and compare this to a population of children without clubfoot. We also evaluated if the clubfoot patients found to have DDH would have been discovered by standard DDH screening. Methods We identified infants in three states (MA, NY, NC) who were reported to each state’s birth defects registry as having a clubfoot. A second cohort of infants without clubfoot was also identified as a control group. Mothers of these children were contacted to be included in the study, and a computer-assisted telephone interview was administered by one of the study nurses, including questions about treatment of DDH. The child’s median age at interview was 7 months. Mothers of clubfoot cases were also contacted for follow-up at mean age of 3.3 years. Results Families of 677 patients with clubfoot and 2037 controls were interviewed. 5/677 (0.74%) patients with clubfoot and 5/2037 (0.25%) controls reported having their infant treated with a brace or harness for hip problems (p=0.134). Of the patients with clubfoot, two of them did not need treatment for their DDH and two would have been discovered by standard hip screening. Follow-up study at 3.3 years of age found no serious late hip dysplasia. Conclusions Treatment of DDH was uncommon in all children; the higher proportion in infants with clubfoot was not statistically different than controls. Of the patients with clubfoot and DDH, standard hip screening would have been appropriate and others did not need treatment. These data suggest that routine hip ultrasound or radiographic screening of idiopathic

  15. Is it worthwhile to routinely ultrasound screen children with idiopathic clubfoot for hip dysplasia?

    PubMed

    Mahan, Susan T; Yazdy, Mahsa M; Kasser, James R; Werler, Martha M

    2013-12-01

    Patients with idiopathic clubfoot are considered at increased risk for having developmental dysplasia of the hips (DDH). However, the studies showing this association have been relatively small. Many clinicians who treat idiopathic clubfoot routinely screen the hips of these patients with ultrasound or radiograph due to the concerns of increased risk of DDH. We evaluated a large clubfoot population to determine the risk of DDH and compare this to a population of children without clubfoot. We also evaluated if the clubfoot patients found to have DDH would have been discovered by standard DDH screening. We identified infants in 3 states (MA, NY, NC), who were reported to each state's birth defects registry as having a clubfoot. A second cohort of infants without clubfoot was also identified as a control group. Mothers of these children were contacted to be included in the study, and a computer-assisted telephone interview was administered by one of the study nurses, including questions about treatment of DDH. The child's median age at interview was 7 months. Mothers of clubfoot cases were also contacted for follow-up at mean age of 3.3 years. Families of 677 patients with clubfoot and 2037 controls were interviewed. A total of 5/677 (0.74%) patients with clubfoot and 5/2037 (0.25%) controls reported having their infant treated with a brace or harness for hip problems (P=0.134). Of the patients with clubfoot, 2 of them did not need treatment for their DDH and 2 would have been discovered by standard hip screening. Follow-up study at 3.3 years of age found no serious late hip dysplasia. Treatment of DDH was uncommon in all children; the higher proportion in infants with clubfoot was not statistically different than controls. Of the patients with clubfoot and DDH, standard hip screening would have been appropriate and others did not need treatment. These data suggest that routine hip ultrasound or radiographic screening of idiopathic clubfoot patients is not necessary

  16. Clinical outcomes of routine opt-out antenatal human immunodeficiency virus screening: a systematic review.

    PubMed

    Ibekwe, Everistus; Haigh, Carol; Duncan, Fiona; Fatoye, Francis

    2017-02-01

    To evaluate the clinical outcome of routine screening of human immunodeficiency virus in antenatal clinic settings. Despite the growing advances in human immunodeficiency virus management, nearly 30% of the estimated 1·5 million seropositive pregnant women are undiagnosed. Routine opt-out testing is a strategy endorsed by the World Health Organization in to increase testing rates in clinical settings. A systematic review of relevant published literature. A comprehensive electronic search for relevant studies in Science Direct, MEDLINE, SCOPUS, CINAHL and PubMed was conducted with search terms (Box 2). Hand searches were also conducted for additional resources. There were no geographical restrictions. Searches were restricted to English language and studies conducted between 1998-2015; totaling 1097 were retrieved and carefully appraised for review. Eighteen studies were eligible for review: eight from Africa, five from the United States, three from Europe, one from Australia and one from Asia. Fourteen studies reported increases in human immunodeficiency virus testing rate. Following the introduction of routine testing, human immunodeficiency virus testing rates increased from values ranging from 68-99·9% with median value of 88%. The comparison studies reported testing uptake of 22-93·5% with median value of 59%. Maternal human immunodeficiency virus case detection rates nearly doubled following adoption of routine testing at values of 99 and 45% during opt-in. Linkage to treatment and care for prevention of vertical transmission was reported on six studies, and results ranged between 12·9-77·2%. The findings show that irrespective of human immunodeficiency virus epidemiological scenarios, routine testing gave more women opportunity to learn their human immunodeficiency virus status and take measures for prevention of mother-to-child transmission of human immunodeficiency virus. Future studies should focus on identifying strategies to improving linkages to

  17. Economic impact of routine opt-out antenatal human immune deficiency virus screening: A systematic review.

    PubMed

    Ibekwe, Everistus; Haigh, Carol; Duncan, Fiona; Fatoye, Francis

    2017-03-02

    reporting format would facilitate comparison between studies and generalisability of economic evaluations. (i) Healthcare decision-makers should understand that routine antenatal screening for human immune deficiency virus is both cost-effective and cost saving. (ii) Addressing late identification of prenatal human immune deficiency virus is crucial to reducing mother-to-child transmission at minimal healthcare spending. © 2017 John Wiley & Sons Ltd.

  18. Efficacy of drug screening in forensic autopsy: retrospective investigation of routine toxicological findings.

    PubMed

    Tominaga, Mariko; Michiue, Tomomi; Inamori-Kawamoto, Osamu; Hishmat, Asmaa Mohammed; Oritani, Shigeki; Takama, Masashi; Ishikawa, Takaki; Maeda, Hitoshi

    2015-05-01

    Toxicological analysis is indispensable in forensic autopsy laboratories, but often depends on the limitations of individual institutions. The present study reviewed routine drug screening data of forensic autopsy cases (n=2996) during an 18.5-year period (January 1996-June 2014) at our institute to examine the efficacy of the procedures and findings in autopsy diagnosis and interpretation. Drug screening was performed using on-site immunoassay screening devices and gas chromatography/mass spectrometry (GC/MS) in all cases, followed by re-examination using GC/MS and liquid chromatography/tandem mass spectrometry (LC/MS/MS) at a cooperating institute in specific cases in the last 4 years. GC/MS detected drugs in 486 cases (16.2%), including amphetamines (n=160), major tranquilizers (n=72), minor tranquilizers (n=294), antidepressants (n=21), cold remedies (n=77), and other drugs (n=19). Among these cases, fatal intoxication (n=123) involved amphetamines (n=73), major tranquilizers (n=37), minor tranquilizers (n=86), antidepressants (n=3), and cold remedies (n=9); most cases involved self-administration, alleged suicide and accidental overdose, while homicide was not included. These drugs were also identified in other manners of death, including homicide (n=40/372), suicide (n=34/226), accidental falls (n=27/129), and natural death (n=72/514). In these cases, on-site immunoassay screening of drugs of abuse showed negative findings in 2440 cases (81.4% in all cases), while GC/MS detected other drugs in 218 cases (7.3% in all cases), including several antipsychotic drugs, acetaminophen and salicylic acid. Further analysis using LC/MS/MS detected low concentrations of benzodiazepines in 32 cases, and also anti-diabetic and hypertensive drugs in a case of fatal abuse. These observations indicate the efficacy of systematic routine toxicological analysis to investigate not only the cause of death but also the background of fatalities in forensic autopsy. The provision of

  19. Characteristics of U.S. emergency departments that offer routine human immunodeficiency virus screening.

    PubMed

    Berg, Laura J; Delgado, M Kit; Ginde, Adit A; Montoy, Juan Carlos; Bendavid, Eran; Camargo, Carlos A

    2012-08-01

    -out consent for testing (RR = 1.76, 95% CI = 1.01 to 2.74) were associated with increased availability of screening in multivariable analysis. EDs whose directors were concerned about added costs were associated with decreased availability of screening (RR = 0.45, 95% CI = 0.23 to 0.85). After adjusting for other ED operational and demographic characteristics, ED crowding and teaching hospital affiliation were not independently associated with the availability of HIV screening. EDs whose directors were concerned about the cost of preventive services were less likely to provide routine HIV screening. Addressing ED director's concerns about the added costs of ED preventive services, increasing social work availability, and implementing testing laws consistent with Centers for Disease Control and Prevention (CDC) recommendations may facilitate increased adoption of ED HIV screening. © 2012 by the Society for Academic Emergency Medicine.

  20. Acute toxicity screening of reservoir water and sediment

    SciTech Connect

    Moses, J.; Wade, D.C.

    1991-05-01

    Toxicological evaluation of forebay and transition area water column (overlying water) and sediment porewater (interstitial water) samples was initiated during the summer of 1990 as part of TVA's Reservoir Vital Signs monitoring. Twenty-four stations were identified for study using acute toxicity screening test methods with the freshwater rotifer Brachionus calyciflorus (Rotox{reg sign}) and light emitting bacteria Photobacterium phosphoreum (Microtox{reg sign}). No acute toxicity to rotifers was demonstrated in the first series of tests using water column and sediment samples from the locations selected for monitoring. Sediments from three locations indicated some toxicity based on Microtox{reg sign}, although all EC{sub 50} concentrations were greater than 100 percent sample.

  1. 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

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

    PubMed

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

    2015-03-01

    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.

  3. 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.

  4. 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.

  5. Harnessing Information Technology to Inform Patients Facing Routine Decisions: Cancer Screening as a Test Case.

    PubMed

    Krist, Alex H; Woolf, Steven H; Hochheimer, Camille; Sabo, Roy T; Kashiri, Paulette; Jones, Resa M; Lafata, Jennifer Elston; Etz, Rebecca S; Tu, Shin-Ping

    2017-05-01

    Technology could transform routine decision making by anticipating patients' information needs, assessing where patients are with decisions and preferences, personalizing educational experiences, facilitating patient-clinician information exchange, and supporting follow-up. This study evaluated whether patients and clinicians will use such a decision module and its impact on care, using 3 cancer screening decisions as test cases. Twelve practices with 55,453 patients using a patient portal participated in this prospective observational cohort study. Participation was open to patients who might face a cancer screening decision: women aged 40 to 49 who had not had a mammogram in 2 years, men aged 55 to 69 who had not had a prostate-specific antigen test in 2 years, and adults aged 50 to 74 overdue for colorectal cancer screening. Data sources included module responses, electronic health record data, and a postencounter survey. In 1 year, one-fifth of the portal users (11,458 patients) faced a potential cancer screening decision. Among these patients, 20.6% started and 7.9% completed the decision module. Fully 47.2% of module completers shared responses with their clinician. After their next office visit, 57.8% of those surveyed thought their clinician had seen their responses, and many reported the module made their appointment more productive (40.7%), helped engage them in the decision (47.7%), broadened their knowledge (48.1%), and improved communication (37.5%). Many patients face decisions that can be anticipated and proactively facilitated through technology. Although use of technology has the potential to make visits more efficient and effective, cultural, workflow, and technical changes are needed before it could be widely disseminated. © 2017 Annals of Family Medicine, Inc.

  6. Integrating Routine HIV Screening in the New York City Community Health Center Collaborative.

    PubMed

    Rodriguez, Vanessa; Lester, Deborah; Connelly-Flores, Alison; Barsanti, Franco A; Hernandez, Paloma

    2016-01-01

    One in seven of the 1.1 million people living in the United States infected with HIV are not aware of their HIV status. At the same time, many clinical settings have not adopted routine HIV screening, which promotes linkage to specialist medical care. We sought to improve HIV screening in a large community health center network by using a data-driven, collaborative learning approach and system-wide modifications, where counselor-based HIV screening and testing were replaced by health-care providers and medical assistants. Urban Health Plan, Inc., a network of federally qualified health centers in the boroughs of the Bronx and Queens in New York City, provided HIV screening training for its health-care providers. In January 2011, it modified its electronic medical record system to incorporate HIV test offering. This study compared the 2010 baseline year with the three-year implementation follow-up period (January 2011 through December 2013) to determine the number of eligible individuals for HIV testing, HIV tests offered and performed, HIV-positive individuals, and HIV cases linked to specialty care. A total of 26,853 individuals at baseline and 100,369 individuals in the implementation period were eligible for HIV testing. HIV testing was performed on 2,079 (8%) of 26,853 eligible individuals in 2010 and 49,646 (50%) of 100,369 eligible individuals from 2011 through 2013. HIV-positive status was determined in 19 (0.9%) of 2,079 tested individuals in 2010 and 166 (0.3%) of 49,646 tested individuals from 2011 through 2013. Linkage to care was observed in all 19 eligible individuals and 127 (77%) of 166 eligible individuals who tested HIV positive in 2010 and 2011-2013, respectively. This study enabled routine HIV implementation testing at a community health center network, which resulted in enhanced HIV testing, an increased number of HIV-positive cases identified, and a rise in the number of patients linked to HIV specialist care.

  7. Integrating Routine HIV Screening in the New York City Community Health Center Collaborative

    PubMed Central

    Lester, Deborah; Connelly-Flores, Alison; Barsanti, Franco A.; Hernandez, Paloma

    2016-01-01

    Objective One in seven of the 1.1 million people living in the United States infected with HIV are not aware of their HIV status. At the same time, many clinical settings have not adopted routine HIV screening, which promotes linkage to specialist medical care. We sought to improve HIV screening in a large community health center network by using a data-driven, collaborative learning approach and system-wide modifications, where counselor-based HIV screening and testing were replaced by health-care providers and medical assistants. Methods Urban Health Plan, Inc., a network of federally qualified health centers in the boroughs of the Bronx and Queens in New York City, provided HIV screening training for its health-care providers. In January 2011, it modified its electronic medical record system to incorporate HIV test offering. This study compared the 2010 baseline year with the three-year implementation follow-up period (January 2011 through December 2013) to determine the number of eligible individuals for HIV testing, HIV tests offered and performed, HIV-positive individuals, and HIV cases linked to specialty care. Results A total of 26,853 individuals at baseline and 100,369 individuals in the implementation period were eligible for HIV testing. HIV testing was performed on 2,079 (8%) of 26,853 eligible individuals in 2010 and 49,646 (50%) of 100,369 eligible individuals from 2011 through 2013. HIV-positive status was determined in 19 (0.9%) of 2,079 tested individuals in 2010 and 166 (0.3%) of 49,646 tested individuals from 2011 through 2013. Linkage to care was observed in all 19 eligible individuals and 127 (77%) of 166 eligible individuals who tested HIV positive in 2010 and 2011–2013, respectively. Conclusion This study enabled routine HIV implementation testing at a community health center network, which resulted in enhanced HIV testing, an increased number of HIV-positive cases identified, and a rise in the number of patients linked to HIV specialist

  8. 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. Copyright © 2016 Kremastinou et al.

  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. High Tuberculosis Prevalence in a South African Prison: The Need for Routine Tuberculosis Screening

    PubMed Central

    Telisinghe, Lilanganee; Fielding, Katherine L.; Malden, Justin L.; Hanifa, Yasmeen; Churchyard, Gavin J.; Grant, Alison D.; Charalambous, Salome

    2014-01-01

    , justifying routine screening for tuberculosis at entry into the prison, and intensified case finding among existing prisoners. PMID:24498059

  11. Implementation of routine screening for Lynch syndrome in university and safety-net health system settings: successes and challenges

    PubMed Central

    Marquez, Evelyn; Geng, Zhuo; Pass, Sarah; Summerour, Pia; Robinson, Linda; Sarode, Venetia; Gupta, Samir

    2016-01-01

    Purpose Routine screening for evidence of DNA mismatch repair abnormalities can identify colorectal cancer patients with Lynch syndrome, but impact in usual care settings requires study. After implementing routine screening at our university and safety-net health systems as usual practice, our aims were to determine outcomes, including screening process quality. Methods We conducted a retrospective cohort study from 1 May 2010 to 1 May 2011. Screening included reflexive immunohistochemistry to evaluate DNA mismatch repair protein expression for patients with colorectal cancer aged ≤70 years, with a cancer genetics team following up results. Screening outcomes, as well as challenges to a high-quality screening process were evaluated. Results We included 129 patients (mean age 56 years, 36% female); 100 had immunohistochemistry screening completed. Twelve patients had abnormal immunohistochemistry: four with definite Lynch syndrome, four with probable Lynch syndrome, and three without Lynch syndrome; one patient had an incomplete work-up. Lynch syndrome was confirmed for 6/13 asymptomatic relatives tested. Screening process quality was optimal for 77.5% of patients. Barriers to optimal quality screening included ensuring reflexive immunohistochemistry completion, complete follow-up of abnormal immunohistochemistry, and timely incorporation of results into clinical decision making. Conclusion Usual care implementation of routine screening for Lynch syndrome can result in significant rates of detection, even in a largely safety-net setting. To optimize implementation, challenges to high-quality Lynch syndrome screening, such as ensuring reflexive screening completion and clinically indicated genetic testing and follow-up for abnormal screens, must be identified and addressed. PMID:23598716

  12. Knowledge, Attitudes, and Ordering Patterns for Routine HIV Screening among Resident Physicians at an Urban Medical Center.

    PubMed

    Bares, Sara; Steinbeck, Jennifer; Bence, Lauren; Kordik, Abbe; Acree, Mary Ellen; Jih, Jane; Farnan, Jeanne; Watson, Sydeaka; Rasinski, Kenneth; Schneider, John; Pitrak, David

    2016-07-01

    We sought to measure resident physician knowledge of HIV epidemiology and screening guidelines, attitudes toward testing, testing practices, and barriers and facilitators to routine testing. Resident physicians in internal medicine, pediatrics, obstetrics and gynecology, and emergency medicine were surveyed. Overall response rate was 63% (162 of 259). Half knew details of the HIV screening guidelines, but few follow these recommendations. Less than one-third reported always or usually performing routine testing. A significant proportion reported only sometimes or never screening patients with risk factors. This was despite a strong belief that HIV screening improves patient care and public health. The most common barriers to testing were competing priorities and forgetting to order the test. Elimination of written consent and electronic reminders was identified as facilitators to routine testing. Although an institutional policy assigns responsibility for test notification and linkage of HIV-positive patients to care to the HIV care program, only 29% were aware of this. Few resident physicians routinely screen for HIV infection and some don't test patients with risk factors. While competing priorities remain a significant barrier, elimination of written consent form and electronic reminders has facilitated testing. Increasing the awareness of policies regarding test notification and linkage to care may improve screening. © The Author(s) 2014.

  13. Evolution and Escalation of an Emergency Department Routine, Opt-out HIV Screening and Linkage-to-Care Program.

    PubMed

    Galbraith, James W; Willig, James H; Rodgers, Joel B; Donnelly, John P; Westfall, Andrew O; Ross-Davis, Kelly L; Heath, Sonya L

    2016-01-01

    The Centers for Disease Control and Prevention has recommended emergency department (ED) opt-out HIV screening since 2006. Routine screening can prove challenging due to the ED's complexity and competing priorities. This study examined the implementation and evolution of a routine, integrated, opt-out HIV screening program at an urban academic ED in Alabama since August 2011. ED routine, opt-out HIV screening was implemented as a standard of care in September 2011. To describe the outcomes and escalation of the screening program, data analyses were performed from three separate data queries: (1) encounter-level HIV screening questionnaire and test results from September 21, 2011, through December 31, 2013; (2) test-level, fourth-generation HIV results from July 9 through December 31, 2013; and (3) daily HIV testing rates and trends from September 9, 2011, through June 30, 2014. Of the 46,385 HIV screening tests performed, 252 (0.5%) were confirmed to be positive. Acute HIV infection accounted for 11.8% of all HIV patients identified using the fourth-generation HIV screening assay. Seventy-six percent of confirmed HIV-positive patients had successful linkage to care. Implementation of fourth-generation HIV instrument-based testing resulted in a 15.0% decline in weekly HIV testing rates. Displacement of nursing provider HIV test offers from triage to the bedside resulted in a 31.6% decline in weekly HIV testing rates. This program demonstrated the capacity for high-volume, routine, opt-out HIV screening. Evolving ED challenges require program monitoring and adaptation to sustain scalable HIV screening in EDs.

  14. Evolution and Escalation of an Emergency Department Routine, Opt-out HIV Screening and Linkage-to-Care Program

    PubMed Central

    Willig, James H.; Rodgers, Joel B.; Donnelly, John P.; Westfall, Andrew O.; Ross-Davis, Kelly L.; Heath, Sonya L.

    2016-01-01

    Objective The Centers for Disease Control and Prevention has recommended emergency department (ED) opt-out HIV screening since 2006. Routine screening can prove challenging due to the ED's complexity and competing priorities. This study examined the implementation and evolution of a routine, integrated, opt-out HIV screening program at an urban academic ED in Alabama since August 2011. Methods ED routine, opt-out HIV screening was implemented as a standard of care in September 2011. To describe the outcomes and escalation of the screening program, data analyses were performed from three separate data queries: (1) encounter-level HIV screening questionnaire and test results from September 21, 2011, through December 31, 2013; (2) test-level, fourth-generation HIV results from July 9 through December 31, 2013; and (3) daily HIV testing rates and trends from September 9, 2011, through June 30, 2014. Results Of the 46,385 HIV screening tests performed, 252 (0.5%) were confirmed to be positive. Acute HIV infection accounted for 11.8% of all HIV patients identified using the fourth-generation HIV screening assay. Seventy-six percent of confirmed HIV-positive patients had successful linkage to care. Implementation of fourth-generation HIV instrument-based testing resulted in a 15.0% decline in weekly HIV testing rates. Displacement of nursing provider HIV test offers from triage to the bedside resulted in a 31.6% decline in weekly HIV testing rates. Conclusion This program demonstrated the capacity for high-volume, routine, opt-out HIV screening. Evolving ED challenges require program monitoring and adaptation to sustain scalable HIV screening in EDs. PMID:26862235

  15. 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

  16. 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.

  17. Using In Silico Fragmentation to Improve Routine Residue Screening in Complex Matrices

    NASA Astrophysics Data System (ADS)

    Kaufmann, Anton; Butcher, Patrick; Maden, Kathryn; Walker, Stephan; Widmer, Mirjam

    2017-09-01

    Targeted residue screening requires the use of reference substances in order to identify potential residues. This becomes a difficult issue when using multi-residue methods capable of analyzing several hundreds of analytes. Therefore, the capability of in silico fragmentation based on a structure database ("suspect screening") instead of physical reference substances for routine targeted residue screening was investigated. The detection of fragment ions that can be predicted or explained by in silico software was utilized to reduce the number of false positives. These "proof of principle" experiments were done with a tool that is integrated into a commercial MS vendor instrument operating software (UNIFI) as well as with a platform-independent MS tool (Mass Frontier). A total of 97 analytes belonging to different chemical families were separated by reversed phase liquid chromatography and detected in a data-independent acquisition (DIA) mode using ion mobility hyphenated with quadrupole time of flight mass spectrometry. The instrument was operated in the MSE mode with alternating low and high energy traces. The fragments observed from product ion spectra were investigated using a "chopping" bond disconnection algorithm and a rule-based algorithm. The bond disconnection algorithm clearly explained more analyte product ions and a greater percentage of the spectral abundance than the rule-based software (92 out of the 97 compounds produced ≥1 explainable fragment ions). On the other hand, tests with a complex blank matrix (bovine liver extract) indicated that the chopping algorithm reports significantly more false positive fragments than the rule based software. [Figure not available: see fulltext.

  18. In Vitro Toxicity Screening Technique for Volatile Substances ...

    EPA Pesticide Factsheets

    In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However the challenge is that many of these chemicals are volatile and not amenable to HTS robotic liquid handling applications. We assembled an in vitro cell culture apparatus capable of screening volatile chemicals for toxicity with potential for miniaturization for high throughput. BEAS-2B lung cells were grown in an enclosed culture apparatus under air-liquid interface (ALI) conditions, and exposed to an array of xenobiotics in 5% CO2. Use of ALI conditions allows direct contact of cells with a gas xenobiotic, as well as release of endogenous gaseous molecules without interference by medium on the apical surface. To identify potential xenobiotic-induced perturbations in cell homeostasis, we monitored for alterations of endogenously-produced gaseous molecules in air directly above the cells, termed “headspace”. Alterations in specific endogenously-produced gaseous molecules (e.g., signaling molecules nitric oxide (NO) and carbon monoxide (CO) in headspace is indicative of xenobiotic-induced perturbations of specific cellular processes. Additionally, endogenously produced volatile organic compounds (VOCs) may be monitored in a nonspecific, discovery manner to determine whether cell processes are

  19. Improved bacterial growth test for rapid water toxicity screening

    SciTech Connect

    Slabbert, J.L.

    1986-10-01

    Bacteria have several attributes which make them attractive as test organisms for the rapid screening of chemical pollution in natural waters. They have relatively short life cycles and, therefore, respond rapidly to environmental change. The degree of toxicity of chemicals to bacteria is normally established by measuring viability or growth. A very sensitive test has been described measuring cell multiplication inhibition of Pseudomonas putida, results being obtained after a 16 h incubation period. Because of their short generation time it is possible, however, that bacteria are capable of manifesting measurable growth within a shorter incubation period. In the present study P. putida was cultured under modified test conditions aiming at an equally sensitive but more rapid growth test. Subsequent to initial tests, using different growth media, a toxicity test procedure was developed which uses a medium with low complexing capacity, a standardized inoculum and a 6 h incubation period.

  20. 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.

  1. Contingent versus routine third-trimester screening for late fetal growth restriction.

    PubMed

    Triunfo, S; Crovetto, F; Scazzocchio, E; Parra-Saavedra, M; Gratacos, E; Figueras, F

    2016-01-01

    To evaluate the use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population. Maternal characteristics, fetal biometry and second-trimester uterine artery (UtA) Doppler were included in logistic regression analysis to estimate risk for late FGR (birth weight < 3(rd) percentile, or 3(rd) -10(th) percentile plus abnormal cerebroplacental ratio or UtA Doppler, with delivery ≥ 34 weeks). Based on the second-trimester risk, strategies for performing contingent third-trimester ultrasound examinations in 10%, 25% or 50% of the cohort were tested against a strategy of routine ultrasound scanning in the entire population at 32 + 0 to 33 + 6 weeks. Models were constructed based on 1393 patients and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At the second-trimester scan, the a-posteriori second-trimester risk (a-posteriori first-trimester risk (baseline a-priori risk and mean arterial blood pressure) combined with second-trimester abdominal circumference and UtA Doppler) yielded an area under the receiver-operating characteristics curve (AUC) of 0.81 (95% CI, 0.74-0.87) (detection rate (DR), 43.1% for a 10% false-positive rate (FPR)). The combination of a-posteriori second-trimester risk plus third-trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI, 0.88-0.96) (DR, 74% for a 10% FPR). Subjecting 10%, 25% or 50% of the study population to third-trimester ultrasound, based on a-posteriori second-trimester risk, gave AUCs of 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.78-0.91) and 0.89 (95% CI, 0.84-0.94), respectively. Only the 50% contingent model proved statistically equivalent to performing routine third-trimester ultrasound scans (AUC, 0.92 (95% CI, 0.88-0.96), P = 0.11). A strategy of selecting 50% of the study population to undergo third

  2. Full-screen ultrafast video modes over-clocked by simple VESA routines and registers reprogramming under MS-DOS.

    PubMed

    Liu, Zuxiang; Wang, Bo

    2002-05-01

    Fast full-screen presentation of stimuli is necessary in psychological research. Although Spitczok von Brisinski (1994) introduced a method that achieved ultrafast display by reprogramming the registers, he could not produce an acceptable full-screen display. In this report, the author introduces a new method combining VESA routine calling with registers reprogramming that can yield a display at 640 x 480 resolution, with a refresh rate of about 150 Hz.

  3. Evaluation of human papillomavirus DNA detection in samples obtained for routine Chlamydia trachomatis screening.

    PubMed

    Söderlund-Strand, Anna; Wikström, Arne; Dillner, Joakim

    2015-03-01

    The costs and logistics involved in obtaining samples is a bottleneck in large-scale studies of the circulation of human papillomavirus (HPV), which are useful for monitoring and optimisation of HPV-vaccination programs. Residual samples obtained after screening for Chlamydia trachomatis could constitute a convenient, low-cost solution. We evaluated HPV DNA detection and typing using (i) the residual samples routinely taken for C. trachomatis screening or (ii) the sample types used in large-scale phase III HPV vaccination trials (cervical, vulvar, labial, perineal, perianal, scrotal and penile shaft samples). Samples from 127 men and 110 women attending two sexual health clinics were analysed using PCR for HPV DNA, with typing using mass spectrometry. The HPV DNA prevalence was 7.1% in male urine samples, but 57.3% in female urine/vaginal samples, which was even higher than the HPV prevalence found in cervical samples (54.1%). The sensitivity for HPV DNA detection in the urine/vaginal samples was 7.9% (95% CI 3.0-16.4) for men and 78.9% (95% CI 67.6-87.7) for women, using detection in any one of the reference samples as reference. With cervical samples as reference, the sensitivity was 89.3 % (95% CI 78.1-95.9). Among men, low sensitivity of urine for HPV detection suggests limited usefulness. Among women, the high sensitivity of urine/vaginal samples for HPV detection suggests a useful low-cost solution for the study of HPV epidemiology. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Breast Cancer Risk in Sexual Minority Women during Routine Screening at an Urban LGBT Health Center.

    PubMed

    Clavelle, Kasey; King, Dana; Bazzi, Angela R; Fein-Zachary, Valerie; Potter, Jennifer

    2015-01-01

    Sexual minority women (SMW) may experience elevated breast cancer risk, yet limited research has assessed the utility of the Gail breast cancer risk model in this population. Using data from screening mammography patients at an urban health center specializing in sexual minority health, we calculated and compared Gail risk scores of SMW with heterosexual women and identified factors associated with elevated risk. This retrospective study reviewed medical records from all patients who underwent screening mammography during 12 months (2013-2014) at a federally qualified community health center in the Northeast United States. Descriptive statistics compared risk scores and other characteristics of patients reporting female only or female and male sex partners ("SMW") with patients reporting only male sex partners ("heterosexual"). Linear regression identified correlates of increased lifetime risk. Among 423 patients, SMW (n=162) were more likely to be nulliparous than heterosexual women (79% vs. 40%; p<.01) and had significantly higher lifetime Gail scores (10.7% vs. 8.9%; p<.01). In multivariable regression, being SMW was independently associated with 1.43% higher lifetime Gail scores (95% CI, 0.69%-2.17%), and having private health insurance was associated with 1.52% higher lifetime Gail scores (95% CI, 0.62-2.42). Using the Gail model to assess breast cancer risk routinely in a clinical setting is feasible. Risk scores may be higher among SMW, who are more likely to be nulliparous, and among patients who are privately insured. Additional research on breast cancer risk assessment among SMW is needed. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  5. Triple test as predictive screen for unilateral weakness on caloric testing in routine practice.

    PubMed

    Rohrmeier, Christian; Richter, Otto; Schneider, Michael; Wirsching, Kornelia; Fiedler, Isabella; Haubner, Frank; Strutz, Jürgen; Kühnel, Thomas S

    2013-02-01

    To investigate in vertigo patients in routine practice to what extent a rapid and straightforward triple bedside test (spontaneous nystagmus, head-shaking nystagmus, and the head impulse test) can predict a normal result on caloric testing. Prospective, single-blind, diagnostic study. Tertiary referral center. 151 patients (78 male and 73 female subjects; mean age, 52.5 +/- 16.4 yr) presenting with acute or recent symptoms of vertigo. Diagnostic evaluation. The negative predictive value (NPV) of the triple test in relation to a normal caloric test response. In unilateral weakness (UW) on caloric testing (UW, >=25%), the triple test had sensitivity of 63.6%, specificity of 85.4%, a positive predictive value (PPV) of 71.4%, and an NPV of 80.4%. In other words, 80.4% of patients with a negative triple test also had a normal response on caloric testing. In pronounced canal paresis (UW, >=50%), the triple test had sensitivity of 81.8%, specificity of 81.4%, a PPV of 55.1%, and an NPV of 94.1%. Significant differences were found between 2 subgroups assessed by examiners with differing levels of experience (p < 0.05). The triple test represents a good screening tool that quickly and reliably excludes unilateral weakness and in particular pronounced canal paresis on caloric testing. (C) 2013 Otology & Neurotology, Inc.

  6. Young pregnant women's views on the acceptability of screening for chlamydia as part of routine antenatal care

    PubMed Central

    2010-01-01

    Background In pregnancy, untreated chlamydia infection has been associated with adverse outcomes for both mother and infant. Like most women, pregnant women infected with chlamydia do not report genital symptoms, and are therefore unlikely to be aware of their infection. The aim of this study was to determine the acceptability of screening pregnant women aged 16-25 years for chlamydia as part of routine antenatal care. Methods As part of a larger prospective, cross-sectional study of pregnant women aged 16-25 years attending antenatal services across Melbourne, Australia, 100 women were invited to participate in a face-to-face, semi structured interview on the acceptability of screening for chlamydia during pregnancy. Women infected with chlamydia were oversampled (n = 31). Results Women had low levels of awareness of chlamydia before the test, retained relatively little knowledge after the test and commonly had misconceptions around chlamydia transmission, testing and sequelae. Women indicated a high level of acceptance and support for chlamydia screening, expressing their willingness to undertake whatever care was necessary to ensure the health of their baby. There was a strong preference for urine testing over other methods of specimen collection. Women questioned why testing was not already conducted alongside other antenatal STI screening tests, particularly in view of the risks chlamydia poses to the baby. Women who tested positive for chlamydia had mixed reactions, however, most felt relief and gratitude at having had chlamydia detected and reported high levels of partner support. Conclusions Chlamydia screening as part of routine antenatal care was considered highly acceptable among young pregnant women who recognized the benefits of screening and strongly supported its implementation as part of routine antenatal care. The acceptability of screening is important to the uptake of chlamydia screening in future antenatal screening strategies. PMID:20723264

  7. Young pregnant women's views on the acceptability of screening for chlamydia as part of routine antenatal care.

    PubMed

    Bilardi, Jade E; De Guingand, Deborah L; Temple-Smith, Meredith J; Garland, Suzanne; Fairley, Christopher K; Grover, Sonia; Wallace, Euan; Hocking, Jane S; Tabrizi, Sepehr; Pirotta, Marie; Chen, Marcus Y

    2010-08-19

    In pregnancy, untreated chlamydia infection has been associated with adverse outcomes for both mother and infant. Like most women, pregnant women infected with chlamydia do not report genital symptoms, and are therefore unlikely to be aware of their infection. The aim of this study was to determine the acceptability of screening pregnant women aged 16-25 years for chlamydia as part of routine antenatal care. As part of a larger prospective, cross-sectional study of pregnant women aged 16-25 years attending antenatal services across Melbourne, Australia, 100 women were invited to participate in a face-to-face, semi structured interview on the acceptability of screening for chlamydia during pregnancy. Women infected with chlamydia were oversampled (n = 31). Women had low levels of awareness of chlamydia before the test, retained relatively little knowledge after the test and commonly had misconceptions around chlamydia transmission, testing and sequelae. Women indicated a high level of acceptance and support for chlamydia screening, expressing their willingness to undertake whatever care was necessary to ensure the health of their baby. There was a strong preference for urine testing over other methods of specimen collection. Women questioned why testing was not already conducted alongside other antenatal STI screening tests, particularly in view of the risks chlamydia poses to the baby. Women who tested positive for chlamydia had mixed reactions, however, most felt relief and gratitude at having had chlamydia detected and reported high levels of partner support. Chlamydia screening as part of routine antenatal care was considered highly acceptable among young pregnant women who recognized the benefits of screening and strongly supported its implementation as part of routine antenatal care. The acceptability of screening is important to the uptake of chlamydia screening in future antenatal screening strategies.

  8. Assessment of Nurse Perspectives on an Emergency Department-Based Routine Opt-Out HIV Screening Program.

    PubMed

    Heinert, Sara; Carter, Julius; Mauntel-Medici, Cammeo; Lin, Janet

    2016-12-15

    Routine opt-out HIV screening is recommended for everyone between 13 and 64 years of age. An urban, academic emergency department implemented a nurse-driven routine opt-out HIV screening program. The aim of our study was to assess program uptake and opportunities to improve the program from the perspectives of emergency nurses. Emergency nurses completed a brief prediscussion questionnaire and then participated in a focus group or semi-structured one-on-one interview to elicit feedback on the routine opt-out HIV screening program. All 16 participants felt adequately prepared for the screening program. Several themes emerged from the discussions, including challenges of specific patient characteristics and overall nurse and patient support for the program. One thread across themes was the importance of good language and communication skills in such programs. While there are opportunities to improve nurse-driven routine opt-out HIV testing programs in emergency settings, this program was found to be accepted by emergency nurses.

  9. In vitro screening for population variability in chemical toxicity.

    PubMed

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

    2011-02-01

    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.

  10. Use of higher plants as screens for toxicity assessment.

    PubMed

    Kristen, U

    1997-01-01

    This review deals with the use of entire plants, seedlings, cell suspension cultures and pollen tubes for the estimation of potential toxicity in the environment, and for risk assessment of chemicals and formulations of human relevance. It is shown that the roots of onions and various crop seedlings, as well as in vitro growing pollen tubes of some mono- and dicotyledonous plants, are most frequently used to obtain toxicity data by determination of root and tube growth inhibition. Both roots and pollen tubes are chloroplast free, non-photosynthetic systems and, therefore, with regard to their cytotoxic reactions are closer to vertebrate tissues and cells than are chloroplast-containing plant organs. Root tips and anthers of flower buds are shown to be applicable to genotoxicity screening by microscopic analysis of mitotic or meiotic aberrations during cell division or microspore development, respectively. The processes of mitosis and meiosis are similar in plants and animals. Therefore, meristematic and sporogenic tissues of plants generally show patterns of cytotoxic response similar to those of embryogenic and spermatogenic tissues of vertebrates. The suitability of root tips, cell suspensions and pollen tubes for the investigation of mechanisms of toxic action and for the analysis of structure-activity relationships is also demonstrated. Two plant-based assays, the Allium test and the pollen tube growth test, both currently being evaluated alongside with established mammalian in vivo and in vitro protocols, are emphasized with regard to their potential use as alternatives to animal in vivo toxicity tests. For both assays, preliminary results indicate that the tips of growing roots and the rapidly elongating pollen tubes of certain higher plant species are as reliable as mammalian cell lines for detecting basal cytotoxicity. It is suggested that seeds and pollen grains, in particular, provide easily storable and convenient systems for inexpensive, relatively

  11. 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. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Extent of prevalence and size of flat neoplasms in a heterogeneous population undergoing routine colorectal cancer screening.

    PubMed

    Kim, J; Rami, P; O'Toole, J; Llor, X; Carroll, R E; Benya, R V

    2010-05-01

    The importance of identifying flat colorectal neoplasms is increasingly appreciated, although the extent of prevalence of these lesions in a general population is not known. To determine the extent of prevalence of flat neoplasms in a diverse population undergoing routine endoscopic screening for colorectal cancer. Patients referred to the Colorectal Cancer Screening Clinic over a 12-month period (n = 642). The patient population was 56% African American and 21% Caucasian; with a mean age of 59 + or - 9 years. Flat neoplasms were detected in 5.5% of all patients, similar to that reported elsewhere, with extent of prevalence being similar regardless of gender or race. Average size of flat neoplasms was of 2.8 + or - 2.3 mm (range 1-20 mm). However, there was no evidence of advanced pathology in any of the flat neoplasms identified. Flat neoplasms are common but may not be associated with advanced pathology in a population undergoing routine screening.

  13. Assessment of the use of the AVS concept for the routine toxicity monitoring of contaminated freshwater sediments

    SciTech Connect

    Vangheluwe, M.L.; Janssen, C.R.; Goyvaerts, M.P.; Cooman, P.

    1995-12-31

    Acid volatile sulfides (AVS) have been shown to be an important factor mediating the bioavailability of heavy metals in sediments and have consequently been suggested as a possible predictive tool for toxicity assessment of these matrices. The potential use and limitations of the AVS method for predictive toxicity screening and priority setting was assessed in a large scale sediment monitoring study (Flanders, Belgium). The acute toxicity of 50 metal contaminated freshwater sediments, with varying metal concentrations and sediment characteristics, were tested using the Microtox{reg_sign} Solid Phase test and the 10 day test with Chironomus riparius and Hyalella azteca. Uni and multivariate statistical techniques were used to asses the relations between acute toxicity and SEM/AVS ratio`s and to evaluate the influence of sediment characteristics on metal bioavailability and toxicity. In general, the results of this study indicate that the AVS-toxicity relationship proposed in literature does have certain limitations. Finally, the potential use of a concentration-addition model for predicting metal-mixture toxicity in sediments will be presented and discussed.

  14. Compliance with recommendations for routine HIV screening during pregnancy in Halifax

    PubMed Central

    Côté, Stephanie J; Halperin, Scott A

    2002-01-01

    BACKGROUND: The routine offering of testing for HIV during each pregnancy is recommended by various advisory bodies, including the Canadian Paediatric Society. OBJECTIVES: To determine the proportion of women in Nova Scotia who were counselled about HIV and HIV testing during their pregnancies and to determine the proportion of those who underwent the blood test after counselling. METHODS: A Self-administered survey at the IWK Health Centre, Halifax, Nova Scotia was performed. Questionnaires were distributed to 800 new mothers who delivered a child between March 10 and May 10, 2000. The questionnaire asked women for their ages, levels of education, history of previous deliveries, whether they had received counselling about HIV during their pregnancy, whether they were offered an HIV blood test and whether they underwent an HIV blood test. RESULTS: A total of 155 questionnaires were returned (response rate of 19.4%). The proportion of women who were counselled about HIV during their pregnancy was 65 of 155 (41.9%) (95% CI 34.1 to 49.7) and the proportion of those who were counselled who underwent the test was 47 of 65 (72.3%) (95% CI 65.3 to 79.3). There was a significant difference between the proportion counselled and history of previous deliveries (P=0.050), the proportion offered a test and their ages (P=0.028), and the proportion who had a test done and their ages (P=0.017). CONCLUSIONS: There is inadequate compliance with the recommendation that all women be offered HIV testing during each pregnancy at the IWK Health Centre. Health care professionals involved in obstetrics need to be reminded of the importance of HIV counselling and testing during pregnancy. Further evaluation throughout Canada of the effect of HIV screening recommendations during pregnancy is advisable. PMID:20046277

  15. Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy.

    PubMed

    Becerra, Lino; Aasted, Christopher M; Boas, David A; George, Edward; Yücel, Meryem A; Kussman, Barry D; Kelsey, Peter; Borsook, David

    2016-04-01

    Colonoscopy is an invaluable tool for the screening and diagnosis of many colonic diseases. For most colonoscopies, moderate sedation is used during the procedure. However, insufflation of the colon produces a nociceptive stimulus that is usually accompanied by facial grimacing/groaning while under sedation. The objective of this study was to evaluate whether a nociceptive signal elicited by colonic insufflation could be measured from the brain. Seventeen otherwise healthy patients (age 54.8 ± 9.1; 6 female) undergoing routine colonoscopy (ie, no history of significant medical conditions) were monitored using near-infrared spectroscopy (NIRS). Moderate sedation was produced using standard clinical protocols for midazolam and meperidine, titrated to effect. Near-infrared spectroscopy data captured during the procedure was analyzed offline to evaluate the brains' responses to nociceptive stimuli evoked by the insufflation events (defined by physician or observing patients' facial responses). Analysis of NIRS data revealed a specific, reproducible prefrontal cortex activity corresponding to times when patients grimaced. The pattern of the activation is similar to that previously observed during nociceptive stimuli in awake healthy individuals, suggesting that this approach may be used to evaluate brain activity evoked by nociceptive stimuli under sedation, when there is incomplete analgesia. Although some patients report recollection of procedural pain after the procedure, the effects of repeated nociceptive stimuli in surgical patients may contribute to postoperative changes including chronic pain. The results from this study indicate that NIRS may be a suitable technology for continuous nociceptive afferent monitoring in patients undergoing sedation and could have applications under sedation or anesthesia.

  16. In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System#

    EPA Science Inventory

    In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However the cha...

  17. 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.

  18. Diagnostic performance of guaiac-based fecal occult blood test in routine screening: state-wide analysis from Bavaria, Germany.

    PubMed

    Brenner, Hermann; Hoffmeister, Michael; Birkner, Berndt; Stock, Christian

    2014-03-01

    Randomized trials have shown that annual or biannual screening by guaiac-based fecal occult blood tests (gFOBTs) reduces colorectal cancer (CRC) mortality. Few clinical studies have evaluated diagnostic performance of gFOBT through validation by colonoscopy in all participants. We aimed for a comprehensive evaluation of diagnostic performance of gFOBT by age and sex under routine screening conditions. Our analysis is based on 20,884 colonoscopies following up a positive gFOBT and 182,956 primary screening colonoscopies documented in a state-wide quality assurance program in Bavaria, Germany, in 2007-2009. Positive likelihood ratios (LR+), which represent an integrative measure of diagnostic performance, were derived, by age groups (55-59, 60-64, 65-69, 70-74 years) and sex, from a joint and comparative analysis of prevalences of colorectal neoplasms in both groups. Overall LR+ (95% confidence intervals) were 1.11 (1.06-1.15), 1.80 (1.72-1.88), and 5.04 (4.64-5.47) for non-advanced adenoma, advanced adenoma, and cancer, respectively. Assuming a specificity of gFOBT of 95.2%, as recently observed in a German study among 2,235 participants of screening colonoscopy, these LR+ would translate to sensitivities of 5.3%, 8.6%, and 24.2% for the three outcomes, respectively. Diagnostic performance was similarly poor among women and men and across age groups. The performance of gFOBT under routine screening conditions is even worse than previously estimated from clinical studies. In routine screening application, gFOBTs are expected to miss more than 9 out of 10 advanced adenomas and 3 out of 4 cancers. These results underline the need and the potential for better noninvasive CRC screening tests.

  19. Experiences Implementing a Routine HIV Screening Program in Two Federally Qualified Health Centers in the Southern United States

    PubMed Central

    Arrezola, Erica; Brown, Emily H.; Brazzeal, Angela; Sanchez, Travis H.

    2016-01-01

    Objective The southern United States is highly affected by HIV, and community health centers play a key role in addressing the health-care needs of residents of southern cities. In 2012, Southside Medical Care Services (“Southside”) in Atlanta, Georgia, and Central Care Community Health Center (“Central Care”) in Houston, Texas, began comprehensive programs for routine HIV screening and linkage to HIV care. Methods We examined patient-level testing outcomes using medical record-derived data. We also compared the total number of HIV tests and HIV-positive tests in the most recent 12 months of the program with the number of HIV tests and HIV-positive tests during the 12 months prior to the program start. Results Southside saw 52,437 eligible patients from June 2012 through April 2014; 41,720 (80%) were offered an HIV test, 11,092 (27% of those offered a test) were tested, 75 (0.7% of those tested) had a positive result, and 74 (99% of those with a positive result) were linked to HIV care. Compared with the 12 months prior to the start of routine HIV screening implementation, Southside's routine HIV screening program conducted 5,955 more HIV tests (733% increase) and had 31 more patients who tested positive (238% increase). Central Care saw 22,658 eligible patients from July 2012 to April 2014; 10,904 (48%) were offered an HIV test, 9,909 (91% of those offered a test) were tested, 52 (0.5% of those tested) had a positive result, and 41 (79% of those with a positive result) were linked to HIV care. Compared with the 12 months before routine HIV screening was implemented, Central Care's routine HIV screening program conducted 4,559 more HIV tests (618% increase) and had 36 more patients who tested positive (600% increase). Conclusion Southside and Central Care effectively implemented routine HIV screening programs that dramatically increased their testing volume while also linking the majority of HIV-positive patients to care. Other community health centers

  20. Experiences Implementing a Routine HIV Screening Program in Two Federally Qualified Health Centers in the Southern United States.

    PubMed

    Crumby, Natasha S; Arrezola, Erica; Brown, Emily H; Brazzeal, Angela; Sanchez, Travis H

    2016-01-01

    The southern United States is highly affected by HIV, and community health centers play a key role in addressing the health-care needs of residents of southern cities. In 2012, Southside Medical Care Services ("Southside") in Atlanta, Georgia, and Central Care Community Health Center ("Central Care") in Houston, Texas, began comprehensive programs for routine HIV screening and linkage to HIV care. We examined patient-level testing outcomes using medical record-derived data. We also compared the total number of HIV tests and HIV-positive tests in the most recent 12 months of the program with the number of HIV tests and HIV-positive tests during the 12 months prior to the program start. Southside saw 52,437 eligible patients from June 2012 through April 2014; 41,720 (80%) were offered an HIV test, 11,092 (27% of those offered a test) were tested, 75 (0.7% of those tested) had a positive result, and 74 (99% of those with a positive result) were linked to HIV care. Compared with the 12 months prior to the start of routine HIV screening implementation, Southside's routine HIV screening program conducted 5,955 more HIV tests (733% increase) and had 31 more patients who tested positive (238% increase). Central Care saw 22,658 eligible patients from July 2012 to April 2014; 10,904 (48%) were offered an HIV test, 9,909 (91% of those offered a test) were tested, 52 (0.5% of those tested) had a positive result, and 41 (79% of those with a positive result) were linked to HIV care. Compared with the 12 months before routine HIV screening was implemented, Central Care's routine HIV screening program conducted 4,559 more HIV tests (618% increase) and had 36 more patients who tested positive (600% increase). Southside and Central Care effectively implemented routine HIV screening programs that dramatically increased their testing volume while also linking the majority of HIV-positive patients to care. Other community health centers should consider similar programs.

  1. Feasibility of integrating mental health screening and services into routine elder abuse practice to improve client outcomes.

    PubMed

    Sirey, Jo Anne; Berman, Jacquelin; Salamone, Aurora; DePasquale, Alyssa; Halkett, Ashley; Raeifar, Elmira; Banerjee, Samprit; Bruce, Martha L; Raue, Patrick J

    2015-01-01

    The goal of this pilot program was to test the feasibility of mental health screening among elder abuse victims and of offering those victims a brief psychotherapy for depression and anxiety. Elder abuse victims who sought assistance from a large, urban elder abuse service were screened for depression and anxiety using standardized measures. Clients with clinically significant depression (PHQ-9) or anxiety (GAD-7) were randomized to receive one of three different interventions concurrent with abuse resolution services. Staff were able to screen 315 individuals, with 34% of clients scoring positive for depression or anxiety. Of those with mental health needs, only 15% refused all services. The mental health intervention (PROTECT) was successfully implemented in two different formats with collaboration between staff workers. These findings support both the need for mental health care among elder abuse victims and the feasibility of integrating mental health screening and treatment into routine elder abuse practice.

  2. A vibrating screen maintenance plan combines the routine with special attention

    SciTech Connect

    Shields, M.W.

    2008-02-15

    To properly maintain a screening machine coal preparation plant operators need to choose the appropriate screening machine for the application and install it properly. The way the feed is distributed to the deck is also important. The screen motion has a big impact on how the machine operates. 1 fig., 4 photos.

  3. 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...

  4. Developing a UHPLC-QTOF-MS and Automated Library Search Method for Screening Drugs and Toxic Compounds in Postmortem Specimens.

    PubMed

    Liu, Hsiu-Chuan; Yang, Chu-An; Liu, Ray H; Lin, Dong-Liang

    2017-03-24

    Screening and confirming the presence of drugs and toxic compounds in various matrices are important and challenging tasks routinely faced by forensic and clinical laboratories. Recent advances in the liquid chromatographic and mass spectrometric technologies have provided an opportunity for the development of more specific and effective approaches to achieve the "screening" and "confirmation" goals in a single analytical step. The objectives of this study are: (i) the establishment of an ultra-high performance liquid chromatographic, quadrupole time-of-flight mass spectrometric mass spectrometric and MS-MS spectral database, including 1,200 compounds of interest; and (ii) the development of an effective protocol, using this database and three searching algorithms, for general unknown screening of these compounds. The established database and protocol were evaluated through the analysis of 30 external proficiency test and 100 postmortem samples and found to be significantly more effective than the LC-IT-MS and GC-MS approaches previously established in our laboratory.

  5. A qualitative study of the acceptability of routine screening of postnatal women using the Edinburgh Postnatal Depression Scale.

    PubMed Central

    Shakespeare, Judy; Blake, Fiona; Garcia, Jo

    2003-01-01

    BACKGROUND: Screening for postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS) has been widely recommended and implemented in primary care, although little is known about how acceptable it is to women. AIM: To explore the acceptability to women of postnatal screening by health visitors with the EPDS. DESIGN OF STUDY: Qualitative interview study. SETTING: Postnatal patients from 22 general practices within the area of Oxford City Primary Care Group. METHOD: Thirty-nine postnatal women from a purposive sample were interviewed, chosen on the basis of different general practices, EPDS results at eight weeks and eight months postnatal, and whether 'listening visits' were received. The interviews were analysed using the constant comparative method. RESULTS: Just over half of the women interviewed found screening with the EPDS less than acceptable, whatever their postnatal emotional health. The main themes identified were problems with the process of screening and, in particular, the venue, the personal intrusion of screening and stigma. The women interviewed had a clear preference for talking about how they felt, rather than filling out a questionnaire. CONCLUSION: For this sample, routine screening with the EPDS was less than acceptable for the majority of women. This is of concern, as universal screening with the EPDS for the detection of postnatal depression is already recommended and widespread in primary care. PMID:14601337

  6. HPV immunisation and increased uptake of cervical screening in Scottish women; observational study of routinely collected national data

    PubMed Central

    Palmer, T J; McFadden, M; Pollock, K G J; Kavanagh, K; Cuschieri, K; Cruickshank, M; Nicoll, S; Robertson, C

    2016-01-01

    Background: To measure the uptake of first invitation to cervical screening by vaccine status in a population-based cohort offered HPV immunisation in a national catch-up campaign. Methods: A retrospective observational study of routinely collected data from the Scottish Cervical Screening Programme. Data were extracted and linked from the Scottish Cervical Call Recall System, the Scottish Population Register and the Scottish Index of Multiple Deprivation. Records from 201 023 women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. Attendance for screening was within 12 months of the first invitation at age 20 years. Results: There was a significant decline in overall attendance from the 1988 cohort to the 1993 cohort with the adjusted attendance ratio of the 1988 cohort being 1.49 times (95% CI 1.46–1.52) that of the 1993 cohort. Immunisation compensated for this decrease in uptake with unvaccinated individuals having a reduced ratio of attendance compared with those fully vaccinated (RR=0.65, 95% CI 0.64–0.65). Not taking up the opportunity for HPV immunisation was associated with an attendance for screening below the trend line for all women before the availability of HPV immunisation. Conclusions: HPV immunisation is not associated with the reduced attendance for screening that had been feared. Immunised women in the catch-up cohorts appear to be more motivated to attend than unimmunised women, but this may be a result of a greater awareness of health issues. These results, while reassuring, may not be reproduced in routinely immunised women. Continued monitoring of attendance for the first smear and subsequent routine smears is needed. PMID:26794278

  7. Toxic endothelial cell destruction of the cornea after routine extracapsular cataract surgery.

    PubMed

    Breebaart, A C; Nuyts, R M; Pels, E; Edelhauser, H F; Verbraak, F D

    1990-08-01

    Eighteen patients developed an acute corneal decompensation following normal intraocular surgery (cataract extraction in 17 patients), characterized by star-shaped endothelial folds, a twofold increase in corneal thickness, and a visual acuity of counting fingers during several postoperative days. In some cases, there was an additional iritis and transient hypotony. There was no effect of topical and/or subconjunctival corticosteroids on the course of the decompensation. Endothelial morphometric analysis showed a mean endothelial cell loss of 72%. Endothelial wound healing, as determined by coefficient of variation and percentage hexagonals, stabilized 6 months postoperatively. We coined the term toxic endothelial cell destruction for this syndrome. Epidemiological evaluation revealed the toxic endothelial cell destruction syndrome to be linked with the 10-fold increase of a detergent solution in the ultrasonic bath for cleaning the surgical instruments.

  8. Routine meconium screening versus drug screening per physician order: detecting the true incidence of drug-exposed infants.

    PubMed

    Zenewicz, D; Kuhn, P J

    1998-01-01

    National statistics indicate that 11% of newborns are exposed to drugs of abuse in utero (Chasnoff, Burns, Schnoll, & Burns, 1985). From July through November of 1993, 0.2% (1/583) of infants in our hospital screened positive for exposure to drugs of abuse in utero, by blood and urine screens collected per physician's order. During the same 4 months in 1995, 0.2% (1/574) screened positive. In contrast, from July through November 1994, all newborns born at our institution were screened for in utero drug exposure using meconium samples; approximately 4.5% (22/493) were positive. Meconium screening of all infants, not just those per physician order, produced a dramatic increase in positive drug results. Of great concern in this study was that only two of the 22 mothers identified as having drug-screen positive babies during the 1994 meconium screening agreed to use rehabilitative services. This highlights the necessity of intervention through early educational programs stressing prevention.

  9. Validating automated screening for psychological distress by means of computer touchscreens for use in routine oncology practice.

    PubMed

    Cull, A; Gould, A; House, A; Smith, A; Strong, V; Velikova, G; Wright, P; Selby, P

    2001-12-14

    The aim of the study was to confirm the validity of using touchscreen computers for screening for clinically significant levels of distress among cancer patients in routine oncology practice. The Hospital Anxiety and Depression Scale (HADS), EORTC Quality of Life questionnaire (QLQ-C30), Mental Health Inventory-MHI5 and a Concerns Checklist were administered via touchscreen computer to 172 chemotherapy out-patients, twice, 2-4 weeks apart. A standard psychiatric interview (Present State Examination - PSE) was conducted within a week of the second assessment. On interview, 23% of patients were identified as 'cases'. Using the available data (questionnaires, sociodemographic details, self-reported past psychiatric history), the best screening strategy combined scores from MHI-5 and HADS from a single time-point with the following rules: if MHI-5 < 11 = non-case; if MHI-5 > or = 11 then use HADS; then, if HADS > or = 9 = 'case' (sensitivity 85%; specificity 71%; misclassification rate 26%; positive predictive value 47%). The computerized screening system enabled data to be collected, scored, collated and reported in real time to identify patients who warrant further clinical assessment. It offers the potential for improving 'case' detection in routine oncology practice while reducing the burden of questions put to 'non-cases'. Further work is needed to develop optimal choice of screening questions for this purpose.

  10. Validating automated screening for psychological distress by means of computer touchscreens for use in routine oncology practice

    PubMed Central

    Cull, A; Gould, A; House, A; Smith, A; Strong, V; Velikova, G; Wright, P; Selby, P

    2001-01-01

    The aim of the study was to confirm the validity of using touchscreen computers for screening for clinically significant levels of distress among cancer patients in routine oncology practice. The Hospital Anxiety and Depression Scale (HADS), EORTC Quality of Life questionnaire (QLQ-C30), Mental Health Inventory-MHI5 and a Concerns Checklist were administered via touchscreen computer to 172 chemotherapy out-patients, twice, 2–4 weeks apart. A standard psychiatric interview (Present State Examination – PSE) was conducted within a week of the second assessment. On interview, 23% of patients were identified as ‘cases’. Using the available data (questionnaires, sociodemographic details, self-reported past psychiatric history), the best screening strategy combined scores from MHI-5 and HADS from a single time-point with the following rules: if MHI-5 < 11 = non-case; if MHI-5 ≥ 11 then use HADS; then, if HADS ≥ 9 = ‘case’ (sensitivity 85%; specificity 71%; misclassification rate 26%; positive predictive value 47%). The computerized screening system enabled data to be collected, scored, collated and reported in real time to identify patients who warrant further clinical assessment. It offers the potential for improving ‘case’ detection in routine oncology practice while reducing the burden of questions put to ‘non-cases’. Further work is needed to develop optimal choice of screening questions for this purpose. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11747324

  11. Increasing Routine Cancer Screening Among Underserved Populations Through Effective Communication Strategies: Application of a Health Literacy Framework.

    PubMed

    Best, Alicia L; Vamos, Cheryl; Choi, Seul Ki; Thompson, Erika L; Daley, Ellen; Friedman, Daniela B

    2017-03-08

    Cancer prevention and control efforts serve as national priorities, as cancer is the second leading cause of death in the USA. In addition, cancer disparities exist, with racial/ethnic minority, low-income, and uninsured populations suffering the greatest burden. The goal of this paper is to describe the role that effective health communication can play in increasing routine cancer screening among medically underserved populations, thus decreasing persistent health disparities. For this paper, we applied Sorenson's integrated model of health literacy as a framework for identifying communication gaps and opportunities that can help improve cancer screening specifically at federally qualified health centers (FQHCs). This integrated model consists of four interrelated dimensions: access, understand, appraise, and apply. Employing communication strategies across this health literacy framework has the potential to facilitate improved decision making and cancer screening outcomes among the most underserved populations.

  12. Women's attitude towards routine human platelet antigen-screening in pregnancy.

    PubMed

    Winkelhorst, Dian; Loeff, Rosanne M; van den Akker-Van Marle, M Elske; de Haas, Masja; Oepkes, Dick

    2017-08-01

    Fetal and neonatal alloimmune thrombocytopenia is a potentially life-threatening disease with excellent preventative treatment available for subsequent pregnancies. To prevent index cases, the effectiveness of a population-based screening program has been suggested repeatedly. Therefore, we aimed to evaluate women's attitude towards possible future human platelet antigen-screening in pregnancy. We performed a cross-sectional questionnaire study among healthy pregnant women receiving prenatal care in one of seven participating midwifery practices. Attitude was assessed using a questionnaire based on the validated Multidimensional Measurement of Informed Choice model, containing questions assessing knowledge, attitude and intention to participate. A total of 143 of the 220 women (65%) completed and returned the questionnaire. A positive attitude towards human platelet antigen-screening was expressed by 91% of participants, of which 94% was based on sufficient knowledge. Attitude was more likely to be negatively influenced by the opinion that screening can be frightening. Informed choices were made in 87% and occurred significantly less in women from non-European origin, 89% in European women vs. 60% in non-European women (p = 0.03). Pregnant women in the Netherlands expressed a positive attitude towards human platelet antigen-screening in pregnancy. We therefore expect a high rate of informed uptake when human platelet antigen-screening is implemented. In future counseling on human platelet antigen-screening, ethnicity and possible anxiety associated with a screening test need to be specifically addressed. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  13. Beyond Trisomy 21: Additional Chromosomal Anomalies Detected through Routine Aneuploidy Screening

    PubMed Central

    Metcalfe, Amy; Hippman, Catriona; Pastuck, Melanie; Johnson, Jo-Ann

    2014-01-01

    Prenatal screening is often misconstrued by patients as screening for trisomy 21 alone; however, other chromosomal anomalies are often detected. This study aimed to systematically review the literature and use diagnostic meta-analysis to derive pooled detection and false positive rates for aneuploidies other than trisomy 21 with different prenatal screening tests. Non-invasive prenatal testing had the highest detection (DR) and lowest false positive (FPR) rates for trisomy 13 (DR: 90.3%; FPR: 0.2%), trisomy 18 (DR: 98.1%; FPR: 0.2%), and 45,X (DR: 92.2%; FPR: 0.1%); however, most estimates came from high-risk samples. The first trimester combined test also had high DRs for all conditions studied (trisomy 13 DR: 83.1%; FPR: 4.4%; trisomy 18 DR: 91.9%; FPR: 3.5%; 45,X DR: 70.1%; FPR: 5.4%; triploidy DR: 100%; FPR: 6.3%). Second trimester triple screening had the lowest DRs and highest FPRs for all conditions (trisomy 13 DR: 43.9%; FPR: 8.1%; trisomy 18 DR: 70.5%; FPR: 3.3%; 45,X DR: 77.2%; FPR: 9.3%). Prenatal screening tests differ in their ability to accurately detect chromosomal anomalies. Patients should be counseled about the ability of prenatal screening to detect anomalies other than trisomy 21 prior to undergoing screening. PMID:26237381

  14. Routine HIV screening in two health-care settings--New York City and New Orleans, 2011-2013.

    PubMed

    Lin, Xia; Dietz, Patricia M; Rodriguez, Vanessa; Lester, Deborah; Hernandez, Paloma; Moreno-Walton, Lisa; Johnson, Grant; Van Handel, Michelle M; Skarbinski, Jacek; Mattson, Christine L; Stratford, Dale; Belcher, Lisa; Branson, Bernard M

    2014-06-27

    Approximately 16% of the estimated 1.1 million persons living with human immunodeficiency virus (HIV) in the United States are unaware of their infection and thus unable to benefit from effective treatment that improves health and reduces transmission risk. Since 2006, CDC has recommended that health-care providers screen for HIV all patients aged 13-64 years unless prevalence of undiagnosed HIV infection in their patients has been documented to be <0.1%. This report describes novel HIV screening programs at the Urban Health Plan (UHP), Inc. in New York City and the Interim Louisiana Hospital (ILH) in New Orleans. Data were provided by the two programs. UHP screened a monthly average of 986 patients for HIV during January 2011-September 2013. Of the 32,534 patients screened, 148 (0.45%) tested HIV-positive, of whom 147 (99%) received their test result and 43 (29%) were newly diagnosed. None of the 148 patients with HIV infection were previously receiving medical care, and 120 (81%) were linked to HIV medical care. The ILH emergency department (ED) and the urgent-care center (UCC) screened a monthly average of 1,323 patients from mid-March to December 2013. Of the 12,568 patients screened, 102 (0.81%) tested HIV-positive, of whom 100 (98%) received their test result, 77 (75%) were newly diagnosed, and five (5%) had acute HIV infection. Linkage to HIV medical care was successful for 67 (74%) of 91 patients not already in care. Routine HIV screening identified patients with new and previously diagnosed HIV infection and facilitated their linkage to medical care. The two HIV screening programs highlighted in this report can serve as models that could be adapted by other health-care settings.

  15. Routine screening for CKD should be done in asymptomatic adults... selectively.

    PubMed

    Berns, Jeffrey S

    2014-11-07

    CKD is an important public health problem associated with substantial morbidity, impaired quality of life, shortened life expectancy, and excessive health care costs. Given its long preclinical latency, screening of asymptomatic individuals for CKD has been considered as a potentially useful means of early detection, with a goal of reducing CKD progression and its complications. A recent clinical practice guideline from the American College of Physicians that recommended against screening for CKD in asymptomatic adults without risk factors has reignited debate regarding CKD screening. Despite the lack of randomized controlled trial evidence showing benefits of CKD screening, even among individuals at increased risk for CKD, such as those with diabetes or hypertension or who are of certain high-risk racial or ethnic groups, a thoughtful and selective approach to CKD screening seems to be cost-effective and clinically valuable. CKD screening is recommended by several nephrology professional societies and appropriate in at-risk asymptomatic individuals with the intent of identifying and managing CKD, diagnosing the etiology of CKD, limiting or preventing CKD progression and its associated cardiovascular disease risk, and minimizing risk of AKI, inappropriate drug dosing, and nephrotoxic injury.

  16. Public attitudes towards genomic risk profiling as a component of routine population screening.

    PubMed

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

    2013-10-01

    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.

  17. Receipt of a false positive test result during routine screening for ovarian cancer: a teachable moment?

    PubMed

    Floyd, Andrea; Steffens, Rachel F; Pavlik, Edward; Andrykowski, Michael A

    2011-03-01

    The term "teachable moment" (TM) has been used to describe a life transition or event which motivates an individual to change a behavior or presents an opportunity to intervene to prompt behavior change. We examined whether receipt of a false positive ovarian cancer (OC) screening result may represent a TM. 403 women participating in an OC screening program completed questionnaires assessing demographic, clinical, behavioral, and psychosocial information. The TM was operationalized as expressed interest in receiving health-related information. We hypothesized that among women receiving a false positive screening test result, those women who had experienced greater personal perceived risk for OC as well as distress would be more interested in receiving health-related information than women receiving a normal result. Analyses revealed that women receiving a false positive screening result were less interested in receiving health-related information than women receiving a normal screening result. For women receiving a false positive result, expressed interest in receipt of health-related information was only modestly related to distress and related even less to perceptions of OC risk. Our data do not support viewing a false positive OC screening result as a TM. Potential explanations for the current findings as well as recommendations for future research investigating the TM are discussed.

  18. Sexually Transmitted Infections in Newly Arrived Refugees: Is Routine Screening for Neisseria gonorrheae and Chlamydia trachomatis Infection Indicated?

    PubMed Central

    Stauffer, William M.; Painter, John; Mamo, Blain; Kaiser, Robyn; Weinberg, Michelle; Berman, Stuart

    2012-01-01

    More than 340 million cases of bacterial and protozoal sexually transmitted infections (STIs) occur annually. Approximately 70,000 refugees arrive in the United States on a yearly basis. Refugees are a particularly disenfranchised and vulnerable population. The prevalence of Chlamydia and gonorrhea in refugee populations has not been described, and the utility of routine screening is unknown. We performed a descriptive evaluation of 25,779 refugees who completed a screening medical examination in Minnesota during 2003–2010. A total of 18,516 (72%) refugees were tested for at least one STI: 183 (1.1%) of 17,235 were seropositive for syphilis, 15 (0.6%) of 2,512 were positive for Chlamydia, 5 (0.2%) of 2,403 were positive for gonorrhea, 136 (2.0%) of 6,765 were positive for human immunodeficiency virus, and 6 (0.1%) of 5,873 were positive for multiple STIs. Overall prevalence of Chlamydia (0.6%) and gonorrhea (0.2%) infection was low, which indicated that routine screening may not be indicated. However, further research on this subject is encouraged. PMID:22302865

  19. Effects of Scanning—Routine Health Information Exposure—on Cancer Screening and Prevention Behaviors in the General Population

    PubMed Central

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

    2014-01-01

    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. We hypothesized that scanning from non-medical sources, both mediated and interpersonal, affects cancer screening and prevention decisions. A nationally representative longitudinal survey of adults 40 to 70 years (N=2,489) was used to analyze the effects of scanning on three cancer screening behaviors (mammography, PSA, colonoscopy) and three prevention behaviors (exercising, eating fruits and vegetables, dieting to lose weight). After adjustment for baseline behaviors and covariates, scanning at baseline predicted one year later weekly exercise days overall, as well as daily fruits and vegetables servings for those already higher on baseline consumption. 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. While 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 non-medical sources affects specific health behaviors. PMID:24083417

  20. 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.

  1. The Clinical Impact and Cost-Effectiveness of Routine, Voluntary HIV Screening in South Africa

    PubMed Central

    Walensky, Rochelle P.; Wood, Robin; Fofana, Mariam O.; Martinson, Neil A.; Losina, Elena; April, Michael D.; Bassett, Ingrid V.; Morris, Bethany L.; Freedberg, Kenneth A.; Paltiel, A. David

    2010-01-01

    Background Although 900,000 HIV-infected South Africans receive antiretroviral therapy (ART), the majority of South Africans with HIV remain undiagnosed. Methods We use a published simulation model of HIV case detection and treatment to examine three HIV screening scenarios, in addition to current practice: 1) one-time; 2) every five years; and 3) annually. South African model input data include: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including two sequential ART regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness. Results HIV screening one-time, every five years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6 and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every five years. Screening every five years and annually each have incremental cost-effectiveness ratios of $1,570/quality-adjusted life year (QALY) and $1,720/QALY. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case. Conclusions In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment. PMID:21068674

  2. Routine practice HCV infection screening with saliva samples: multicentric study in an intravenous drug user population.

    PubMed

    Lucidarme, Damien; Decoster, Anne; Fremaux, Didier; Harbonnier, Jean; Jacob, Claude; Vosgien, Véronique; Josse, Pascal; Villeger, Pierre; Henrio, Cécile; Prouvost-Keller, Bernard; Saccardy, Claire; Lemaire, Muriel; Vazeille, Gérard; Duchene, Claude; Thuillier, Michel; Colbeaux, Christian; Lefebvre, Anne-Marie; Forzy, Gérard; Filoche, Bernard

    2007-05-01

    The purpose of this randomized multicentric study was to evaluate the diagnostic contribution of screening for HCV infection on saliva samples in day-to-day practice in the intravenous drug-user (IVDU) population. Between January and May 2004, 274 presumably HCV-negative IVDU were screened for HCV infection in 15 centers in France (median age 29 years). After centralized randomization, screening tests were performed on blood samples (arm A) or saliva samples (arm B). Screening tests were performed in 78 subjects (28%) had never been screened before and in 196 subjects (72%) who had had a negative HCV screening test on average 12 months prior to the beginning of the study. In the event of a positive saliva test for anti-HCV Ab, a serum test for anti-HCV Ab was performed. In the event of a positive serum test for anti-HCV Ab, PCR was performed on serum to measure HCV-RNA. Fourteen individuals were positive for HCV RNA (7 in each arm). Six of these cases had not been detected before. In eight cases, the median time between the last negative screening test and study inclusion was 11 months (range 6-94 months). Viremia tests were positive in 5% percent of the target population, although one-third of the individuals in arm A (blood samples) were not tested. The saliva test may be a useful alternative in the event of refusal of a blood test or when poor venous conditions compromise venous puncture. A confirmatory blood test still remains difficult to obtain in nearly half of patients.

  3. Biochemical screening of 504,049 newborns in Denmark, the Faroe Islands and Greenland--experience and development of a routine program for expanded newborn screening.

    PubMed

    Lund, Allan Meldgaard; Hougaard, David Michael; Simonsen, Henrik; Andresen, Brage Storstein; Christensen, Mette; Dunø, Morten; Skogstrand, Kristin; Olsen, Rikke K J; Jensen, Ulrich Glümer; Cohen, Arieh; Larsen, Nanna; Saugmann-Jensen, Peter; Gregersen, Niels; Brandt, Niels Jacob; Christensen, Ernst; Skovby, Flemming; Nørgaard-Pedersen, Bent

    2012-11-01

    Expanded newborn screening for selected inborn errors of metabolism (IEM) in Denmark, the Faroe Islands and Greenland was introduced in 2002. We now present clinical, biochemical, and statistical results of expanded screening (excluding PKU) of 504,049 newborns during nine years as well as diagnoses and clinical findings in 82,930 unscreened newborns born in the same period. The frequencies of diagnoses made within the panel of disorders screened for are compared with the frequencies of the disorders in the decade preceding expanded newborn screening. The expanded screening was performed as a pilot study during the first seven years, and the experience obtained during these years was used in the development of the routine neonatal screening program introduced in 2009. Methods for screening included tandem mass spectrometry and an assay for determination of biotinidase activity. A total of 310 samples from 504,049 newborns gave positive screening results. Of the 310 results, 114 were true positive, including results from 12 newborns in which the disease in question was subsequently diagnosed in their mothers. Thus, the overall frequency of an IEM in the screening panel was 1:4942 (mothers excluded) or 1:4421 (mothers included). The false positive rate was 0.038% and positive predictive value 37%. Overall specificity was 99.99%. All patients with true positive results were followed in The Center for Inherited Metabolic Disorders in Copenhagen, and the mean follow-up period was 45 months (range 2109 months). There were no deaths among the 102 children, and 94% had no clinically significant sequelae at last follow-up. Our study confirms the higher frequency of selected IEM after implementation of expanded newborn screening and suggests an improved outcome for several disorders. We argue that newborn screening for these disorders should be standard of care, though unresolved issues remain, e.g. about newborns with a potential for remaining asymptomatic throughout life

  4. Oxidation of parenteral lipid emulsion by ambient and phototherapy lights: potential toxicity of routine parenteral feeding.

    PubMed

    Neuzil, J; Darlow, B A; Inder, T E; Sluis, K B; Winterbourn, C C; Stocker, R

    1995-05-01

    Vitamin E can be a prooxidant in isolated lipoprotein suspensions. Because lipid emulsions used in parenteral nutrition are lipoprotein-like suspensions rich in polyunsaturated fatty acids and vitamin E, we hypothesized that vitamin E may act as a prooxidant in lipid emulsions, as it is in lipoprotein suspensions. We therefore exposed an intravenously administered lipid emulsion (Intralipid) to a single spotlight commonly used in the treatment of neonatal jaundice, and measured the formation of triglyceride hydroperoxides by using high-performance liquid chromatography with postcolumn chemiluminescence detection. Concentrations of these hydroperoxides in different batches of fresh intralipid were usually approximately 10 mumol/L but increased up to 60 times after exposure to phototherapy light for a period of 24 hours, even though significant amounts of vitamin E were present at the end of the exposure. Triglyceride hydroperoxides were formed during phototherapy light exposure whether the intralipid was in plastic tubing used routinely for infusion or in glass containers. Ambient light also caused significant peroxidation of the formula lipids, although to a much lesser extent than observed with phototherapy light. For infants in the neonatal intensive care unit who were receiving intralipid but not phototherapy, solutions being infused at the end of 24 hours contained a mean of 40 mumol/L hydroperoxides. For infants receiving phototherapy, the mean was 97 mumol/L. Phototherapy light-induced formation of triglyceride hydroperoxides was prevented by covering the intralipid with aluminum foil or supplementation with sodium ascorbate before light exposure. We conclude that intralipid is highly susceptible to oxidation and that elevated levels of oxidized lipids can be formed during its clinical use, especially when intralipid infusion is combined with phototherapy. Because lipid hydroperoxides are cytotoxic and can cause adverse effects, inadvertent infusion of rancid

  5. Integrating HIV testing into cervical cancer screening in Tanzania: an analysis of routine service delivery statistics.

    PubMed

    Plotkin, Marya; Besana, Giulia V R; Yuma, Safina; Kim, Young Mi; Kulindwa, Yusuph; Kabole, Fatma; Lu, Enriquito; Giattas, Mary Rose

    2014-09-30

    While the lifetime risk of developing cervical cancer (CaCx) and acquiring HIV is high for women in Tanzania, most women have not tested for HIV in the past year and most have never been screened for CaCx. Good management of both diseases, which have a synergistic relationship, requires integrated screening, prevention, and treatment services. The aim of this analysis is to assess the acceptability, feasibility and effectiveness of integrating HIV testing into CaCx prevention services in Tanzania, so as to inform scale-up strategies. We analysed 2010-2013 service delivery data from 21 government health facilities in four regions of the country, to examine integration of HIV testing within newly introduced CaCx screening and treatment services, located in the reproductive and child health (RCH) section of the facility. Analysis included the proportion of clients offered and accepting the HIV test, reasons why testing was not offered or was declined, and HIV status of CaCx screening clients. A total of 24,966 women were screened for CaCx; of these, approximately one-quarter (26%) were referred in from HIV care and treatment clinics. Among the women of unknown HIV status (n = 18,539), 60% were offered an HIV test. The proportion of women offered an HIV test varied over time, but showed a trend of decline as the program expanded. Unavailability of HIV test kits at the facility was the most common reason for a CaCx screening client not to be offered an HIV test (71% of 6,321 cases). Almost all women offered (94%) accepted testing, and 5% of those tested (582 women) learned for the first time that they were HIV-positive. Integrating HIV testing into CaCx screening services was highly acceptable to clients and was an effective means of reaching HIV-positive women who did not know their status; effectiveness was limited, however, by shortages of HIV test kits at facilities. Integration of HIV testing into CaCx screening services should be prioritized in HIV

  6. Transient elastography improves detection of liver cirrhosis compared to routine screening tests

    PubMed Central

    Göbel, Thomas; Schadewaldt-Tümmers, Janine; Greiner, Lucas; Poremba, Christopher; Häussinger, Dieter; Erhardt, Andreas

    2015-01-01

    AIM: To investigate the diagnostic significance of transient elastography (TE) in a daily routine clinical setting in comparison to clinical signs, laboratory parameters and ultrasound. METHODS: TE, ultrasound, laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine. RESULTS: Sensitivity of TE for the detection of liver cirrhosis was 90.4%, compared to 80.1% for ultrasound, 58.0% for platelet count and 45.1% for cutaneous liver signs (P < 0.0001 for comparisons with histology). AUROC for TE was 0.760 (95%CI: 0.694-0.825). Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825 (95%CI: 0.768-0.882). TE correlated with laboratory parameters of cirrhosis progression like albumin (r = -0.43), prothrombin time (r = -0.44), and bilirubin (r = 0.34; P < 0.001 for each). Particularly, in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1% (P < 0.04) and 16.3% (P < 0.02), respectively. CONCLUSION: Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations. PMID:25624730

  7. Feasibility of Long-Term Patient Self-Reporting of Toxicities From Home via the Internet During Routine Chemotherapy

    PubMed Central

    Judson, Timothy J.; Bennett, Antonia V.; Rogak, Lauren J.; Sit, Laura; Barz, Allison; Kris, Mark G.; Hudis, CliffordA.; Scher, Howard I.; Sabattini, Paul; Schrag, Deborah; Basch, Ethan

    2013-01-01

    Purpose Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits. Patients and Methods Patients receiving chemotherapy for lung, gynecologic, genitourinary, or breast cancer at a tertiary cancer center, with access to a home computer and prior e-mail experience, were asked to self-report seven symptomatic toxicities via the Web between visits. E-mail reminders were sent to participants weekly; patient-reported high-grade toxicities triggered e-mail alerts to nurses; printed reports were provided to oncologists at visits. A priori threshold criteria were set to determine if this data collection approach merited further development based on monthly (≥ 75% participants reporting at least once per month on average) and weekly compliance rates (60% at least once per week). Results Between September 2006 and November 2010, 286 patients were enrolled (64% were women; 88% were white; median age, 58 years). Mean follow-up was 34 weeks (range, 2 to 214). On average, monthly compliance was 83%, and weekly compliance was 62%, without attrition until the month before death. Greater compliance was associated with older age and higher education but not with performance status. Compliance was greatest during the initial 12 weeks. Symptomatic illness and technical problems were rarely barriers to compliance. Conclusion Monthly compliance with home Web reporting was high, but weekly compliance was lower, warranting strategies to enhance compliance in routine care settings. PMID:23733753

  8. Feasibility of long-term patient self-reporting of toxicities from home via the Internet during routine chemotherapy.

    PubMed

    Judson, Timothy J; Bennett, Antonia V; Rogak, Lauren J; Sit, Laura; Barz, Allison; Kris, Mark G; Hudis, Clifford A; Scher, Howard I; Sabattini, Paul; Schrag, Deborah; Basch, Ethan

    2013-07-10

    Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits. Patients receiving chemotherapy for lung, gynecologic, genitourinary, or breast cancer at a tertiary cancer center, with access to a home computer and prior e-mail experience, were asked to self-report seven symptomatic toxicities via the Web between visits. E-mail reminders were sent to participants weekly; patient-reported high-grade toxicities triggered e-mail alerts to nurses; printed reports were provided to oncologists at visits. A priori threshold criteria were set to determine if this data collection approach merited further development based on monthly (≥ 75% participants reporting at least once per month on average) and weekly compliance rates (60% at least once per week). Between September 2006 and November 2010, 286 patients were enrolled (64% were women; 88% were white; median age, 58 years). Mean follow-up was 34 weeks (range, 2 to 214). On average, monthly compliance was 83%, and weekly compliance was 62%, without attrition until the month before death. Greater compliance was associated with older age and higher education but not with performance status. Compliance was greatest during the initial 12 weeks. Symptomatic illness and technical problems were rarely barriers to compliance. Monthly compliance with home Web reporting was high, but weekly compliance was lower, warranting strategies to enhance compliance in routine care settings.

  9. 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.

  10. 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

  11. Loeys-Dietz syndrome: life threatening aortic dissection diagnosed on routine family screening

    PubMed Central

    Martin, Claire A; Clowes, Virginia E; Cooper, John P

    2014-01-01

    A 52-year-old man was found to have a severely dilated aortic root and a Stanford type A dissection on familial screening echocardiography, following diagnosis of a dilated aorta in his son. The dissection required urgent surgical repair. Clinical examination suggested features of Loeys-Dietz syndrome type II, and subsequent demonstration of a mutation in the TGFBR1 gene in the patient and his son confirmed the diagnosis. This article highlights the high prevalence of inherited conditions in dilated aortic root presentations and the importance of family screening and surveillance to allow early surgical intervention. PMID:24495977

  12. A Novel Approach to Realizing Routine HIV Screening and Enhancing Linkage to Care in the United States: Protocol of the FOCUS Program and Early Results

    PubMed Central

    Sullivan, Patrick S; Rothman, Richard E; Brown, Emily H; Fitzpatrick, Lisa K; Wood, Angela F; Hernandez, Paloma I; Nunn, Amy S; Serota, Martin L; Moreno-Walton, Lisa

    2014-01-01

    Background The United States health care system remains far from implementing the Centers for Disease Control and Prevention's recommendation of routine human immunodeficiency virus (HIV) screening as part of health care for adults. Although consensus for the importance of screening has grown, innovations in implementing routine screening are still lacking. HIV on the Frontlines of Communities in the United States (FOCUS) was launched in 2010 to provide an environment for testing innovative approaches to routine HIV screening and linkage to care. Objective The strategy of the FOCUS program was to develop models that maximize the use of information systems, fully integrate HIV screening into clinical practice, transform basic perceptions about routine HIV screening, and capitalize on emerging technologies in health care settings and laboratories. Methods In 10 of the most highly impacted cities, the FOCUS program supports 153 partnerships to increase routine HIV screening in clinical and community settings. Results From program launch in 2010 through October 2013, the partnerships have resulted in a total of 799,573 HIV tests and 0.68% (5425/799,573) tested positive. Conclusions The FOCUS program is a unique model that will identify best practices for HIV screening and linkage to care. PMID:25093431

  13. Prevalence and related factors of psychological distress among cancer inpatients using routine Distress Thermometer and Chinese Health Questionnaire screening

    PubMed Central

    Chiou, Yu-Jie; Chiu, Nien-Mu; Wang, Liang-Jen; Li, Shau-Hsuan; Lee, Chun-Yi; Wu, Ming-Kung; Chen, Chien-Chih; Wu, Yi-Shan; Lee, Yu

    2016-01-01

    Background Clinical practice guidelines suggest routine screening for distress among cancer patients for immediate early psychiatric care. However, previous studies focusing on routine screening for psychological distress among cancer inpatients in Taiwan are scant. Thus, the aim of this study was to evaluate the prevalence and related factors of psychological distress and mental illness among cancer inpatients in Taiwan. Patients and methods This study was conducted as a retrospective chart review in a general hospital in southern Taiwan. Cancer inpatients were regularly screened by nursing staff using the Distress Thermometer and the 12-item Chinese Health Questionnaire. Positive screening results on either instrument were followed by a non-commanded referral to psychiatrists for clinical psychiatric diagnosis and treatment. Results Of the 810 participants in this study, 179 (22.1%) were recognized as having psychological distress. Younger age (odds ratio [OR] =1.82), having head and neck cancer (OR =2.43), and having not received chemotherapy (OR =1.58) were significantly related to psychological distress. Among the 56 patients (31.3%) with psychological distress who were referred to psychiatrists, the most common mental illness was adjustment disorder (n=22, 39.2%), followed by major depressive disorder (n=13, 23.2%), depressive disorder not otherwise specified (n=6, 10.7%), and anxiety disorder not otherwise specified (n=4, 7.1%). Conclusion Our study indicated that cancer inpatients with psychological distress were more likely to be younger in age, have head and neck cancer, and have not received chemotherapy. The most common psychiatric disorder was adjustment disorder. Early detection of psychological distress and prompt psychiatric consultation and management are very important for cancer inpatients. PMID:27822049

  14. Routine Laboratory Screening for Acute and Recent HIV Infection in Lima, Peru

    PubMed Central

    Clark, Jesse L.; Segura, Eddy R.; Montano, Silvia M.; Leon, Segundo R.; Kochel, Tadeusz; Salvatierra, Hector J.; Alcantara, Jorge; Cáceres, Carlos F.; Coates, Thomas J.; Klausner, Jeffrey D.

    2011-01-01

    Background Prior to implementing screening programs for acute HIV infection in developing countries, key issues including cost, feasibility, and public health impact must be determined. We compared fourth-generation enzyme immunoassay (EIA) with pooled HIV-1 RNA assays for the detection of acute and early HIV infection in counseling and testing populations in Lima, Peru. Methods Adults presenting for HIV testing at designated clinics in Lima-Callao, Peru were offered additional screening for acute HIV infection. All serum samples were tested with fourth-generation Ag/Ab EIA and confirmed by line immunoassay (LIA). Negative specimens were combined into 50-sample pools for HIV-1 RNA screening by PCR analysis in standard pooling algorithms. RNA-positive samples were re-tested with a third-generation EIA to evaluate the relative sensitivity of standard testing procedures. Results Between 2007 and 2008 we recruited 1,191 participants. The prevalence of HIV infection was 3.2% (38/1191; 2.2-4.2%) overall and 10.6% (25/237; CI=6.6-14.5%) among men who reported sex with men (MSM). The prevalence of acute or recent HIV infection was 0.2% (CI=0-0.4%) overall and 0.8% (CI=0-2.0%) among MSM. Compared with third generation EIA testing, both fourth generation EIA and RNA PCR increased the rate of HIV case identification by 5.6% overall and by 8.0% within the subpopulation of MSM. Conclusions Screening for acute HIV infection within Peru's resource-limited public health system was acceptable and detected a high prevalence of acute and recent HIV infection among MSM. Additional efforts are needed to screen for and prevent transmission of HIV among MSM in Peru during the acute seroconversion stage. PMID:21113069

  15. 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...

  16. 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...

  17. The Texas-Indiana Virtual STAR Center: Zebrafish Models for Developmental Toxicity Screening

    EPA Pesticide Factsheets

    The Texas-Indiana Virtual STAR Center: Zebrafish Models for Developmental Toxicity Screening (Presented by Maria Bondesson Bolin, Ph.D, University of Houston, Center for Nuclear Receptors and Cell Signaling) (3/22/2012)

  18. Picking Cell Lines for High-Throughput Transcriptomic Toxicity Screening (SOT)

    EPA Science Inventory

    High throughput, whole genome transcriptomic profiling is a promising approach to comprehensively evaluate chemicals for potential biological effects. To be useful for in vitro toxicity screening, gene expression must be quantified in a set of representative cell types that captu...

  19. Feasibility of Integrating Mental Health Screening and Services Into Routine Elder Abuse Practice to Improve Client Outcomes

    PubMed Central

    Sirey, Jo Anne; Berman, Jacquelin; Salamone, Aurora; DePasquale, Alyssa; Halkett, Ashley; Raeifar, Elmira; Banerjee, Samprit; Bruce, Martha L.; Raue, Patrick J.

    2015-01-01

    Objective The goal of this pilot program was to test the feasibility of mental health screening among elder abuse victims and enrolling those victims into a brief psychotherapy useful with both depression and anxiety. Methods Elder abuse victims who sought assistance from a large, urban elder abuse service were screened for depression and anxiety using standardized measures. Clients with clinically significant depression (PHQ-9) or anxiety (GAD-7) were randomized to receive one of three different mental health interventions concurrent with abuse resolution services. This design helped determine the acceptability of each intervention offered and thus the optimal format for service delivery. Results Staff were able to integrate mental health screening for 315 individuals, with 34% of clients scoring positive for depression or anxiety. Of those with mental health needs, only 15% refused all services. The mental health intervention (PROTECT) was able to be implemented in two different formats, with collaboration between elder abuse and mental health staff workers. Discussion These findings support both the need for mental health care among elder abuse victims and the feasibility of integrating mental health screening and treatment into routine elder abuse practice. PMID:25611116

  20. Routine ECG screening in infancy and early childhood should not be performed.

    PubMed

    Skinner, Jonathan R; Van Hare, George F

    2014-12-01

    For all of us working in the field of inherited heart conditions, our ultimate aim is the prevention of sudden cardiac death in young people in our communities. We share the passion and drive to this aim with our colleagues Saul et al, who write to advocate infant screening of infants for LQTS. Although Saul et al aimed to write an unbiased review of the subject, they present data that support screening while underrepresenting evidence against it. Their illustrative Figure 1 is arguably misleading, presenting a graph of freedom from any cardiac event in symptomatic individuals with familial LQTS. We know that 87% of deaths from LQTS occur in those who were previously symptomatic. This discussion, however, is not about symptomatic patients with LQTS; it is about the detection of presymptomatic individuals on a community level. Our aim is to present evidence that has led us to oppose the conclusions and suggestions of their article. Most pediatric cardiologists do not wish to see ECG screening in infancy, and we are among them. Saul et al state that there is sufficient evidence to propose ECG screening in infancy for LQTS. We disagree. We disagree with this view for a number of reasons: (1) The effectiveness of such a program has not been evaluated in terms of outcome. (2) The ECG is an unreliable diagnostic tool with unacceptable reproducibility, specificity, and sensitivity. (3) The adverse effects of overdiagnosing or underdiagnosing LQTS in thousands of individuals have not been evaluated. (4) There are no definitive criterion standard by which LQTS can be excluded once the possibility is raised, and in particular genetic testing is not sensitive or specific enough to do so. (5) There is a paucity of normative ECG and genetic data for non-Whites. We propose what we believe is a more attractive alternative: the detection of LQTS in the community through an active multidisciplinary program to detect probands and screen family members, based around a clinical

  1. Prevalence of obstructive sleep apnoea in acute coronary syndrome: Routine screening in intensive coronary care units.

    PubMed

    Morra, S; Bughin, F; Solecki, K; Aboubadra, M; Lattuca, B; Gouzi, F; Macia, J-C; Cung, T-T; Cade, S; Cransac, F; Davy, J-M; Dauvilliers, Y; Corrado, D; Roubille, F

    2017-09-01

    Increased evidence has shown that, despite the maximum care afforded to patients admitted with acute coronary syndromes (ACS), a residual risk of mortality remains, in which obstructive sleep apnoea (OSA) appears to be a largely undiagnosed factor, particularly in the intensive cardiac care unit (ICCU). The purpose of this study is to determine whether the systematic screening for sleep-disordered breathing (SDB) is feasible and may be recommended. The aims of our study are to determine: (1) The estimated prevalence of OSA in patients admitted to the ICCU for ACS determined by a validated, user-friendly portable screening device; (2) The feasibility of the screening in this context; (3) To assess any negative impact of OSA on the severity of ACS. This is an observational study of 101 patients admitted to the ICCU for ACS showing no clinical evidence of heart failure (HF). In the 24-72hours following admission, they underwent an overnight sleep study using a 3-channel portable screening device with automatic analysis. Sixty-two out of the 101 patients proved positive to the screening test, and its feasibility was acceptable. OSA patients tended to have greater peak levels of hs-cTnT (3685±3576ng/L versus 2830±3333ng/L, P=0.08) than the non-OSA group. Compared with the non-OSA group, OSA patients presented more severe ACS, with a greater average GRACE score at admission of 112.2±26.3 (versus 98.4±19.2, P<0.001). In the OSA group, we found a statistically significant inverse correlation between the apnoea-hypopnea index (AHI) and the left ventricular ejection fraction (LVEF) in the linear regression analysis (r=-0.26; P=0.037). A systematic screening of patients in the ICCU is acceptable. OSA is frequently found in the acute phase of ischaemic heart disease and its presence is associated with more severe ACS and a poorer left ventricle systolic function. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. The cost-effectiveness of cervical self-sampling to improve routine cervical cancer screening: The importance of respondent screening history and compliance

    PubMed Central

    Burger, Emily A; Sy, Stephen; Nygård, Mari; Kim, Jane J

    2016-01-01

    Background Human papillomavirus (HPV) testing allows women to self-collect cervico-vaginal cells at home (i.e., self-sampling). Using primary data from a randomized pilot study, we evaluated the long-term consequences and cost-effectiveness of using self-sampling to improve participation to routine cervical cancer screening in Norway. Methods We compared a strategy reflecting screening participation (using reminder letters) to strategies that involved mailing self-sampling device kits to women non-compliant to screening within a 5-year or 10-year period under two scenarios: A) self-sampling respondents had moderate under-screening histories, or B) respondents to self-sampling had moderate and severe under-screening histories. Model outcomes included quality-adjusted life-years (QALY) and lifetime costs. The ‘most cost-effective’ strategy was identified as the strategy just below $100,000 per QALY gained. Results Mailing self-sampling device kits to all women non-compliant to screening within a 5-year or 10-year period can be more effective and less costly than the current reminder letter policy; however, the optimal self-sampling strategy was dependent on the profile of self-sampling respondents. For example, ‘10-yearly self-sampling’ is preferred ($95,500 per QALY gained) if ‘5-yearly self-sampling’ could only attract moderate under-screeners; however, ‘5-yearly self-sampling’ is preferred if this strategy could additionally attract severe under-screeners. Conclusions Targeted self-sampling of non-compliers likely represents good value-for-money; however, the preferred strategy is contingent on the screening histories and compliance of respondents. Impact The magnitude of the health benefit and optimal self-sampling strategy is dependent on the profile and behavior of respondents. Health authorities should understand these factors prior to selecting and implementing a self-sampling policy. PMID:27624639

  3. The Cost-Effectiveness of Cervical Self-Sampling to Improve Routine Cervical Cancer Screening: The Importance of Respondent Screening History and Compliance.

    PubMed

    Burger, Emily A; Sy, Stephen; Nygård, Mari; Kim, Jane J

    2017-01-01

    Human papillomavirus (HPV) testing allows women to self-collect cervico-vaginal cells at home (i.e., self-sampling). Using primary data from a randomized pilot study, we evaluated the long-term consequences and cost-effectiveness of using self-sampling to improve participation to routine cervical cancer screening in Norway. We compared a strategy reflecting screening participation (using reminder letters) to strategies that involved mailing self-sampling device kits to women noncompliant to screening within a 5- or 10-year period under two scenarios: (A) self-sampling respondents had moderate under-screening histories, or (B) respondents to self-sampling had moderate and severe under-screening histories. Model outcomes included quality-adjusted life-years (QALY) and lifetime costs. The "most cost-effective" strategy was identified as the strategy just below $100,000 per QALY gained. Mailing self-sampling device kits to all women noncompliant to screening within a 5- or 10-year period can be more effective and less costly than the current reminder letter policy; however, the optimal self-sampling strategy was dependent on the profile of self-sampling respondents. For example, "10-yearly self-sampling" is preferred ($95,500 per QALY gained) if "5-yearly self-sampling" could only attract moderate under-screeners; however, "5-yearly self-sampling" is preferred if this strategy could additionally attract severe under-screeners. Targeted self-sampling of noncompliers likely represents good value-for-money; however, the preferred strategy is contingent on the screening histories and compliance of respondents. The magnitude of the health benefit and optimal self-sampling strategy is dependent on the profile and behavior of respondents. Health authorities should understand these factors prior to selecting and implementing a self-sampling policy. Cancer Epidemiol Biomarkers Prev; 26(1); 95-103. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. 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

  5. Self-collection tools for routine cervical cancer screening: a review.

    PubMed

    Othman, Nor Hayati; Mohamad Zaki, Fatma Hariati

    2014-01-01

    Sub-optimal participation is a major problem with cervical cancer screening in developing countries which have no organized national screening program. There are various notable factors such as 'embarrassment', 'discomfort' and 'no time' cited by women as they are often also the bread winners for the family. Implementation of self-sampling methods may increase their participation. The aim of this article was to provide a survey of various types of self-sampling tools which are commonly used in collection of cervical cells. We reviewed currently available self-sampling devices and collated the advantages and disadvantages of each in terms of its acceptance and its accuracy in giving desired results. In general, regardless of which device is used, self-sampling for cervical scrapings is highly acceptable to women in most of the studies cited.

  6. A cost/effective screening method for assessing the toxicity of nutrient rich effluents to algae.

    PubMed

    Carbonell, G; Fernández, C; Tarazona, J V

    2010-07-01

    Screening whole effluent toxicity tests are cost/effective methods for detecting the presence of toxic concentrations of unknown pollutants, but the application must solve the problem associated with the effect of high and variable concentrations of nutrients in the effluent on the results of algal toxicity tests. This work proposes a cost/effective test, based on three dilution levels measured at a single point time and a discriminant model for establishing if this kind of complex samples, with difficult interpretation of dilution-response curves, should be considered toxic to algae. This procedure identified properly around 85% of the samples considered toxic by expert judgement.

  7. An optimized method for routine HLA-B27 screening using flow cytometry.

    PubMed

    Hulstaert, F; Albrecht, J; Hannet, I; Lancaster, P; Buchner, L; Kunz, J; Falkenrodt, A; Tongio, M; De Keyser, F; Veys, E M

    1994-03-15

    Flow cytometry and monoclonal antibodies are promising tools for HLA-antigen detection. Previous approaches have been hampered by the lack of a carefully standardized system for calibration and sample analysis. A new system for HLA-B27 screening was developed using a FACScan flow cytometer, software for automated calibration and analysis, calibration beads, and the anti-HLA-B27-FITC/anti-Leu4-PE (CD3) monoclonal antibodies. The median fluorescence channel result for the HLA-B27-FITC signal of CD3+ T lymphocytes is compared to a decision marker. Values lower than this threshold are read as HLA-B27 negative and those above are recommended for retesting with the classic microcytotoxicity assay on the presumption of HLA-B27 positivity. The anti-HLA-B27 antibody reacts with all six HLA-B27 subtypes and shows a weaker binding to HLA-B7. The screening test results were compared with those from the microcytotoxicity assay for HLA-typing in studies involving several European centers. The observed sensitivity was 100% (95% Cl:98.6-100) and the specificity was 97.4% (95% Cl: 96.4-98.3). Other performance studies verified the reproducibility and reliability of results obtained with the screening system.

  8. Workbook of screening techniques for assessing impacts of toxic air pollutants (revised). Final report

    SciTech Connect

    Not Available

    1992-12-01

    The workbook provides a logical approach to the selection of appropriate screening techniques for estimating ambient concentrations due to various toxic/hazardous pollutant releases. Methods used in the workbook apply to situations where a release can be fairly well-defined, a condition typically associated with non-accidental toxic releases. The format of the workbook is built around a series of release scenarios which may be considered typical and representative of the means by which toxic chemicals become airborne.

  9. Development of an algorithm for phenotypic screening of carbapenemase-producing Enterobacteriaceae in the routine laboratory.

    PubMed

    Robert, Jérôme; Pantel, Alix; Merens, Audrey; Meiller, Elodie; Lavigne, Jean-Philippe; Nicolas-Chanoine, Marie-Hélène

    2017-01-17

    Carbapenemase-producing Enterobacteriaceae (CPE) are difficult to identify among carbapenem non-susceptible Enterobacteriaceae (NSE). We designed phenotypic strategies giving priority to high sensitivity for screening putative CPE before further testing. Presence of carbapenemase-encoding genes in ertapenem NSE (MIC > 0.5 mg/l) consecutively isolated in 80 French laboratories between November 2011 and April 2012 was determined by the Check-MDR-CT103 array method. Using the Mueller-Hinton (MH) disk diffusion method, clinical diameter breakpoints of carbapenems other than ertapenem, piperazicillin+tazobactam, ticarcillin+clavulanate and cefepime as well as diameter cut-offs for these antibiotics and temocillin were evaluated alone or combined to determine their performances (sensitivity, specificity, positive and negative likelihood ratios) for identifying putative CPE among these ertapenem-NSE isolates. To increase the screening specificity, these antibiotics were also tested on cloxacillin-containing MH when carbapenem NSE isolates belonged to species producing chromosomal cephalosporinase (AmpC) but Escherichia coli. Out of the 349 ertapenem NSE, 52 (14.9%) were CPE, including 39 producing OXA-48 group carbapenemase, eight KPC and five MBL. A screening strategy based on the following diameter cut offs, ticarcillin+clavulanate <15 mm, temocillin <15 mm, meropenem or imipenem <22 mm, and cefepime <26 mm, showed 100% sensitivity and 68.1% specificity with the better likelihood ratios combination. The specificity increased when a diameter cut-off <32 mm for imipenem (76.1%) or meropenem (78.8%) further tested on cloxacillin-containing MH was added to the previous strategy for AmpC-producing isolates. The proposed strategies that allowed for increasing the likelihood of CPE among ertapenem-NSE isolates should be considered as a surrogate for carbapenemase production before further CPE confirmatory testing.

  10. Feasibility of implementing routine nutritional screening for older adults in Australian general practices: a mixed-methods study.

    PubMed

    Hamirudin, Aliza Haslinda; Charlton, Karen; Walton, Karen; Bonney, Andrew; Potter, Jan; Milosavljevic, Marianna; Hodgkins, Adam; Albert, George; Ghosh, Abhijeet; Dalley, Andrew

    2014-11-25

    Nutrition screening in older adults is not routinely performed in Australian primary care settings. Low awareness of the extent of malnutrition in this patient group, lack of training and time constraints are major barriers that practice staff face. This study aimed to demonstrate the feasibility of including a validated nutrition screening tool and accompanying nutrition resource kit for use with older patients attending general practice. Secondary aims were to assess nutrition-related knowledge of staff and to identify the extent of malnutrition in this patient group. Nine general practitioners, two general practice registrars and 11 practice nurses from three participating general practices in a rural, regional and metropolitan area within a local health district of New South Wales, Australia were recruited by convenience sampling. Four key themes were determined regarding the feasibility of performing MNA -SF: ease of use; incorporation into existing practice; benefit to patients' health; and patients' perception of MNA-SF. Two key themes related to the nutrition resource kit: applicability and improvement. These findings were supported by open ended questionnaire responses. Knowledge scores of staff significantly improved from baseline (52% to 66%; P < 0.05). Of the 143 patients that had been screened, 4.2% (n = 6) were classified as malnourished, 26.6% (n = 38) 'at risk' of malnutrition and 69.2% (n = 99) as well-nourished. It is feasible to include the MNA-SF and a nutrition resource kit within routine general practice, but further refinement of patients' electronic clinical records in general practice software would streamline this process.

  11. Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified?

    PubMed Central

    2013-01-01

    Vitamin B12 is an essential micronutrient required for optimal hemopoetic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, sub acute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia. This review article offers a current perspective on the physiological roles of vitamin B12, proposed pathophysiological mechanisms of vitamin B12 deficiency, screening for vitamin B12 deficiency and vitamin B12 supplementation among patients with diabetes mellitus. PMID:23651730

  12. 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

  13. 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-...

  14. 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-...

  15. Rapid screening for Native American mitochondrial and Y-chromosome haplogroups detection in routine DNA analysis.

    PubMed

    Zuccarelli, Gala; Alechine, Evguenia; Caputo, Mariela; Bobillo, Cecilia; Corach, Daniel; Sala, Andrea

    2011-03-01

    Aiming to detect individuals of Native American maternal or paternal ancestry a rapid screening approach has been developed. Its strategy was based on SNP typing by Real Time PCR (rt-PCR) followed by High Resolution Melting analysis (HRM). After extraction, DNA was quantitated by rt-PCR using commercial kits; samples were then submitted to two multiplex reactions in order to determine the major Native American mtDNA and Y-chromosome haplogroups by HRM. One cocktail included primers flanking nucleotide substitutions that define mtDNA haplogroup C and sub-haplogroups A2, B2, and D1. The other included primers flanking Y-SNPs M3, M269 and U179 that allowed discriminating Q and non-Q haplogroups. In all cases amplicons were <125 nucleotides long in order to increase the peak resolution. The accuracy of the results obtained was established by means of sequencing analysis of the amplicons. The new working-flow here proposed facilitates and speeds-up the screening process that may preclude a detailed sequencing analysis of particular samples, or for further molecular epidemiological investigations in which continental origin influences might be relevant.

  16. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. On the value of routine prothrombin time screening in elective neurosurgical procedures.

    PubMed

    Dützmann, Stephan; Gessler, Florian; Marquardt, Gerhard; Seifert, Volker; Senft, Christian

    2012-11-01

    The authors performed a study to evaluate whether preoperative assessment of prothrombin time (PT) is mandatory in patients undergoing routinely planned neurosurgical procedures. The charts of all patients admitted to general wards of the authors' department for routinely planned surgery (excluding trauma and ICU patients) between 2006 and 2010 were retrospectively reviewed. The authors assessed preoperative PT and the clinical courses of all patients, with special consideration for patients receiving coagulation factor substitution. All cases involving hemorrhagic complications were analyzed in detail with regard to pre- and postoperative PT abnormalities. Prothrombin time was expressed as the international normalized ratio, and values greater than 1.28 were regarded as elevated. Clinical courses and PT values of 4310 patients were reviewed. Of these, 33 patients (0.7%) suffered hemorrhagic complications requiring repeat surgery. Thirty-one patients (94%) had a normal PT before the initial operation, while 2 patients had slightly elevated PT values of 1.33 and 1.65, which were anticipated based on the patient's history. In the latter 2 cases, surgery was performed without prior correction of PT. Preoperatively, PT was elevated in 78 patients (1.8%). In 73 (93.6%) of the 78 patients, the PT elevation was expected and explained by each patient's medical history. In only 5 (0.1%) of 4310 patients did we find an unexpected PT elevation (mean 1.53, range 1.37-1.74). All 5 patients underwent surgery without complications, while 2 had received coagulation factor substitution preoperatively, as requested by the surgeon, because of an estimated risk of bleeding complications. None of the 5 patients received coagulation factor substitution postoperatively, and later detailed laboratory studies ruled out single coagulation factor deficiencies. There was no statistically significant association between preoperatively elevated PT levels and the occurrence of hemorrhagic

  18. Feasibility of implementing an automated culture system for bacteria screening in platelets in the blood bank routine.

    PubMed

    Castro, E; Bueno, J L; Barea, L; González, R

    2005-06-01

    Bacterial contamination of blood components is the principal infectious complication linked to transfusion. The aim of the study was to evaluate the applicability of an automated culture system for platelets. 10 141 platelet concentrates were cultured individually and in pools of five on storage days 1 and 7 using Bact/Alert system aerobic bottles. A modified collection bag was used for improved sampling. Five-millilitre samples were cultured at 37 degrees C for 7 days. Only those samples where the same bacteria were identified in reculture were considered true positives (TP). Homogeneity of proportions was tested by Fisher's exact test. The rate of TP was 30 per 100 000 (95% CI, 6.1-86.4) sampling on day 1; 33 per 100 000 (95% CI, 7-96) on day 7; and 40 per 100 000 (95% CI, 1.28-122.4) if the screening was based on taking both samples (day 1 and 7). Only one TP was detected in the pool testing. The time for detection among TPs on day 1 ranged between 30 and 134 h. The system is not considered practical for use as a routine screening method, as the time for detection is too long. Pool testing is insensitive. Faster screening methods or pathogen-inactivation systems are needed.

  19. Detecting re-infection in patients after an initial diagnosis of gonorrhoea: is routine recall for re-screening useful?

    PubMed

    Fernando, K A; Fowler, T; Harding, J; Flew, S; Caley, M; Phattey, J; Ross, Jdc

    2015-08-01

    To assess the outcome of routine sexually transmitted infection re-screening after a three-month interval in unselected patients diagnosed with gonorrhoea, we sought to assess whether this active approach would result in an increase in the number of people attending clinic and subsequently diagnosed with gonorrhoea re-infection, compared with normal re-presentation rates. A recall group of patients were invited for re-screening three months after their initial diagnosis of gonorrhoea. Permission was sought to send a reminder two weeks prior to their scheduled recall appointment. Comparisons were made with a historical control group of patients with gonorrhoea in the absence of any formal recall. Of the 242 patients in the intervention arm, 96 (40%) re-attended within six months, and 15 (6%) tested gonorrhoea positive. Two hundred and two patients were assessed in the control group, of whom 45 (22%) re-attended within six months, and 13 (6%) tested gonorrhoea positive. Women were more likely than men to re-attend following active recall, but they were not at higher risk of re-attending while re-infected with gonorrhoea. Active recall following a gonorrhoea diagnosis significantly increases re-attendance rates for repeat screening but did not result in an increased number of subsequent gonorrhoea diagnoses.

  20. A human pluripotent stem cell platform for assessing developmental neural toxicity screening

    PubMed Central

    2013-01-01

    A lack of affordable and effective testing and screening procedures mean surprisingly little is known about the health hazards of many of the tens of thousands of chemicals in use in the world today. The recent rise in the number of children affected by neurological disorders such as autism has stirred valuable debate about the role chemicals play in our daily life, highlighting the need for improved methods of assessing chemicals for developmental neural toxicity. Current methods of testing chemicals for developmental neural toxicity include animal testing with rats or mice and in vitro testing using cultured primary cells or cell lines. Here, we review the current state of neural toxicity screening, analyze the limitations of these methods and, under the National Institutes of Health's new Microphysiological Systems initiative, describe a human pluripotent stem cell-based platform for developmental neural toxicity screens. PMID:24565336

  1. Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone.

    PubMed

    Syed, Husnain; Som, Sumit; Khan, Nazia; Faltas, Wael

    2009-01-01

    The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving.

  2. Exposure-based validation list for developmental toxicity screening assays.

    PubMed

    Daston, George P; Beyer, Bruce K; Carney, Edward W; Chapin, Robert E; Friedman, Jan M; Piersma, Aldert H; Rogers, John M; Scialli, Anthony R

    2014-12-01

    Validation of alternative assays requires comparison of the responses to toxicants in the alternative assay with in vivo responses. Chemicals have been classified as "positive" or "negative" in vivo, despite the fact that developmental toxicity is conditional on magnitude of exposure. We developed a list of positive and negative developmental exposures, with exposure defined by toxicokinetic data, specifically maternal plasma Cmax . We selected a series of 20 chemicals that caused developmental toxicity and for which there were appropriate toxicokinetic data. Where possible, we used the same chemical for both positive and negative exposures, the positive being the Cmax at a dose level that produced significant teratogenicity or embryolethality, the negative being the Cmax at a dose level not causing developmental toxicity. It was not possible to find toxicokinetic data at the no-effect level for all positive compounds, and the negative exposure list contains Cmax values for some compounds that do not have developmental toxicity up to the highest dose level tested. This exposure-based reference list represents a fundamentally different approach to the evaluation of alternative tests and is proposed as a step toward application of alternative tests in quantitative risk assessment.

  3. 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.

  4. Routine radiographer screening for fetal abnormalities by ultrasound in an unselected low risk population.

    PubMed

    Shirley, I M; Bottomley, F; Robinson, V P

    1992-07-01

    A screening programme for fetal abnormalities began at The Hillingdon Hospital in July 1986. Second trimester ultrasound scans are performed by radiographers. A combined prospective and retrospective study of the ultrasound findings and outcome in all pregnancies delivered in 1989-1990 was undertaken. 6412 babies were born during this period, of whom 6183 (96%) were examined by ultrasound in the second trimester; 29 pregnancies were terminated for fetal abnormality. Of the 89 fetuses who were abnormal at birth or at induced termination of the pregnancy (1.4%), 84 were scanned in the second trimester. In 51 cases the abnormality was detected before 22 weeks gestation (sensitivity, 60.7%). 56 of these 84 abnormal fetuses scanned had potentially lethal or major handicapping abnormalities of which 41 were detected by ultrasound before 22 weeks gestation (sensitivity, 73%). There was one false positive diagnosis of abnormality which did not affect outcome. 6352 babies were normal at delivery or on discharge from hospital (specificity, 99.98%).

  5. Electrocardiography and the preparticipation physical examination: is it time for routine screening?

    PubMed

    Donnelly, Diane K; Howard, Thomas M

    2006-04-01

    The preparticipation physical examination (PPE) is a screening tool endorsed by numerous organizations and used to evaluate young athletes prior to competition for both medical and musculoskeletal conditions that may predispose them to injury. The cardiac portion of the examination, as recommended by the American Heart Association, is detailed specifically to detect signs or symptoms consistent with certain congenital heart conditions that may increase a young athlete's risk of sudden cardiac death (SCD). Much controversy has erupted over the years as to whether this examination has the diagnostic sensitivity to detect these conditions and prevent SCD, and whether additional modalities, such as the 12-lead electrocardiograph (ECG), should be incorporated. Given the rarity of SCD events, the large population of young athletes that would qualify yearly for the examination, and the limitations that an ECG would present, it would not be efficient to add the ECG to the standard PPE on the symptomatic athlete. More efforts should be spent in standardizing the PPE on a national level to further improve its efficiency.

  6. Adequacy of cellular material in split-sampling of cervical scrapings for routine cancer screening: an analysis of 702 smears.

    PubMed

    Othman, Norodiyah; Othman, Nor Hayati

    2012-12-01

    The aim of this study was to examine cells (split-sample) that were retained on sampling devices used to collect conventional Pap smears (primary smears) in order to evaluate specimen adequacy and cytological diagnosis of scrapings that are routinely discarded. Cervical scrapings from women attending routine cervical cancer screening were obtained using a cervical brush. Following primary conventional smear preparation, the same sampling devices were rinsed in Preservcyt solution (Cytyc) for subsequent monolayered thin smear (split-sample/discarded sample). The smears (conventional and ThinPrep monolayer) were examined independently by pathologists and classified using the Bethesda System. The diagnoses from discarded samples (split-sample smears) were then compared with the diagnoses made on primary conventional Pap smears. 702 samples were studied. Cell abnormalities was found in 14/702 conventional smear and 12/702 split-sample thin smear. The adequacy of sampling in primary smears was 94.7% compared to 88.9% in split-sample smears. Six cases of Human Papillomavirus infection was found in split-sample smear, whereas only 5 cases found in primary smear. Cohen's Kappa was 0.61 showing substantial agreement between both sampling cytological results. The cervical brush discarded after conventional smear retain adequate number of cells for diagnostic purposes.

  7. 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.

  8. 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.

  9. 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...

  10. Evaluating the Zebrafish Embryo Toxicity Test for Pesticide Hazard Screening

    EPA Science Inventory

    Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more reso...

  11. 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...

  12. 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...

  13. 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...

  14. Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.

    PubMed

    Takayama, Kazuo; Mizuguchi, Hiroyuki

    2017-02-01

    Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicity screening. To apply human ES/iPS-HLCs to various applications including drug toxicity screening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs.

  15. Routine coagulation tests are not useful as a screening tool for the FII G20210A polymorphism.

    PubMed

    Rolla, Roberta; Pergolini, Patrizia; Vidali, Matteo; Pollarolo, Paola; Appiani, Alice; Cerutti, Chiara; Manzini, Matteo; Crisci, Alice; Bellomo, Giorgio

    2014-01-01

    The identification of prothrombin G20210A polymorphism (PT20210) is normally included in the thrombophilia laboratory panel and evaluated by DNA-based molecular analysis. To date, a routine coagulation test that helps to identify PT20210 carriers has not been set, in contrast to the FV Leiden mutation, for which a functional coagulation test, the Activated Protein C Resistance test (APCR), is available as a screening tool. More- over the molecular tests are expensive and are used inappropriately. The aim of the study is to characterize the effects of the prothrombin G20210A mutation on routine clotting assays in order to identify, if any, coagulation tests that can be used as a first-line cost-effective assay for prothrombin G20210A polymorphism. Our cohort consisted of 80 PT20210 polymorphism carriers and 82 age and gender matched controls. All subjects were investigated for PT-INR, aPTT, dRVVT, FII (%), and Endogenous Thrombin Potential (EPT) parameters. In heterozygotes and wild-type, PT, aPTT, and dRVVT values were not significantly different. The plasma activity of Factor II (%), AUC TG (%), and C max (%) of EPT were significantly higher in heterozygotes than in controls (p < 0.0001, Mann-Whitney test). In the absence of oral anticoagulant therapy and/or heparin, lupus anticoagulants, and liver disease, the discriminating abilities of the FII, AUC TG, and C max (%) to separate properly the study population into carriers and controls were equal to 0.99 (95% CI 0.98 to 1.00); 0.97 (95% CI 0.94 to 0.99), and 0.84 (95% CI 0.77 to 0.90), respectively. All routine clotting assays performed in the present work are not useful as a screening tool for the G20210A prothrombin gene allele in a general population. Definitely, to date, the exclusive possible approach to identify the PT20210 mutation is molecular genetic testing, but unfortunately it is used inappropriately, contributing significantly to an uncontrolled waste of resources. It is mandatory to restrict the

  16. 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...

  17. 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...

  18. Microcytic hypochromic anemia: should high performance liquid chromatography be used routinely for screening anemic and antenatal patients?

    PubMed

    Philip, Joseph; Sarkar, Ravi Shankar; Kushwaha, Neerja

    2013-01-01

    Hemoglobinopathies are the most common inherited red cell disorders worldwide. Identification of these disorders is immensely important epidemiologically and for improved management protocols. Our aim was to determine the prevalence of hemoglobinopathies in patients with microcytic hypochromic anemia and to assess the suitability of using high performance liquid chromatography (HPLC) routinely for screening antenatal cases and patients with anemia. A total of 4335 cases received from Mar 2007 to Nov 2011 were studied for various hemoglobinopathies and variants on BIO RAD 'VARIANT' analyzer. Of the 4335 cases studied, 2119 were antenatal cases, 1710 patients with other disorders and 506 family studies. Of these, 688 cases displayed abnormal hemoglobin fractions on HPLC of which 140 were antenatal women. There were 455 cases of β thalassemia trait, 24 β thalassemia major, 20 thalassemia inter-media, 54 sickle cell trait, fivesickle cell disease, 21 double heterozygous β thalassemia-sickle cell trait, nineand 4 Hb D- Punjab heterozygous and homozygous respectively, three Hb D β Thalassemia trait, 20 and 37 Hb E homozygous and heterozygous respectively, three Hb E β Thalassemia trait and four cases of Hb Q India. Twenty nine adults had isolated HbF elevation. Our study found a high prevalence (15.8%) of hemoglobinopathies amongst microcytic hypochromic anemia and antenatal cases. An accurate diagnosis helps in preventing unnecessary iron loading. Screening all antenatal cases with anemia helps in timely antenatal counseling, thus preventing the psychological trauma of bearing a transfusion dependent child for life.

  19. 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

  20. 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

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

    PubMed

    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.

  2. 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

  3. Screening for PTSD symptoms in unaccompanied refugee minors: a test of the CRIES-8 questionnaire in routine care.

    PubMed

    Salari, Raziye; Malekian, Cariz; Linck, Linda; Kristiansson, Robert; Sarkadi, Anna

    2017-08-01

    The dramatic increase in the number of refugees in Europe presents a major public health challenge. The limited existing evidence indicates that the mental health needs of refugees are significant; unaccompanied refugee minors (URMs) constitute a particularly vulnerable group. In this study, we aimed to investigate whether a short questionnaire (Children's Revised Impact of Event Scale; CRIES-8) could be used as a screening tool for PTSD symptoms in URMs, 8-18 years old, during their routine health check-up. Data were collected at the healthcare centre for asylum-seekers in Uppsala, Sweden. In total, 208 URMs completed the CRIES-8 during their health assessment. The CRIES-8 was feasible to use, showed good internal consistency and its factor structure was confirmed. Children with less than four years of education often had difficulties completing the questionnaire by themselves and needed help reading the questions. Almost all the respondents were male (98%), aged 9-18 years. The majority (81%) came from Afghanistan. About 76% scored above the cut-off and therefore were considered to be at risk of PTSD. The proportion of children who screened positive did not differ based on age, country of origin or current living arrangements. The CRIES-8 is a useful tool in clinical settings, however, children should be provided with reading support and instructions about how to complete the questionnaire. The high number of children who screened positive for PTSD symptoms indicates the need for a more thorough mental health assessment, and early prevention/intervention programmes to address URMs' mental health issues.

  4. 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.

  5. 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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Incidence of caffeine in serum of patients undergoing dipyridamole myocardial perfusion stress test by an intensive versus routine caffeine history screening.

    PubMed

    Banko, Lesan T; Haq, Salman A; Rainaldi, Debroah A; Klem, Igor; Siegler, Jason; Fogel, Joshua; Sacchi, Terrence J; Heitner, John F

    2010-05-15

    The coronary vasodilatory effect of dipyridamole is competitively blocked by caffeine. The purposes of this study were to (1) assess the incidence of having detectable serum caffeine and (2) evaluate whether an intensive caffeine history screening strategy was superior to routine history screening before dipyridamole myocardial perfusion imaging. One hundred ninety-four patients who were randomized to an intensive or a routine screening history strategy were prospectively evaluated. Serum caffeine levels were determined in all patients. Outcomes data, including death, nonfatal myocardial infarction, and history of revascularization, were obtained at 24 months. Nearly 1 in 5 patients (19%) who screened negative by history had detectable serum caffeine. In patients who screened negative by history, there was no statistically significant difference in the percentage of caffeine seropositivity between the intensive and routine arms (16% vs 22%, respectively, p = 0.31). The incidence of combined end points of death, myocardial infarction, or revascularization was 22.9% and 7.3% in patients with and without detectable serum caffeine, respectively (p = 0.01). In conclusion, despite initial negative results on screening by history, a considerably high percentage of patients had positive serum caffeine levels. These results do not support the use of an intensive screening strategy. Detectable serum caffeine was associated with a higher incidence of adverse outcomes.

  7. 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.

  8. Preventive health care, 2001 update: Should women be routinely taught breast self-examination to screen for breast cancer?

    PubMed Central

    Baxter, Nancy

    2001-01-01

    Objectives To evaluate the evidence relating to the effectiveness of breast self-examination (BSE) to screen for breast cancer and to provide recommendations for routine teaching of BSE to women in various age groups as part of a periodic health examination. Options Routine teaching of BSE to women. Evidence The electronic databases MEDLINE, PreMEDLINE, CINAHL, HealthSTAR, Current Contents and the Cochrane Library were searched for abstracts and full reports of studies published from 1966 to October 2000 that evaluated the effectiveness of BSE in reducing breast cancer mortality. In addition, references of key papers were searched and experts consulted to ensure that all relevant articles had been identified. Outcomes Prevention of death from breast cancer was viewed as the most important outcome; other outcomes examined included the stage of cancer detected, the rate of benign biopsy results, the number of patient visits for breast complaints, and psychological benefits and harms. Values The recommendations of this report reflect the commitment of the Canadian Task Force on Preventive Health Care to provide a structured, evidence-based appraisal of whether a manoeuvre should be included in the periodic health examination. Benefits, harms and costs Breast cancer is the most frequently diagnosed cancer among Canadian women, accounting for 30% of all new cancer cases each year. In 2000 an estimated 19 200 Canadian women would have been diagnosed with breast cancer, and 5500 would have died from the disease. To date, 2 large randomized controlled trials, a quasi-randomized trial, a large cohort study and several case–control studies have failed to show a benefit for regular performance of BSE or BSE education, compared with no BSE. In contrast, there is good evidence of harm from BSE instruction, including significant increases in the number of physician visits for the evaluation of benign breast lesions and significantly higher rates of benign biopsy results

  9. Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review.

    PubMed

    Geamănu Pancă, A; Popa-Cherecheanu, A; Marinescu, B; Geamănu, C D; Voinea, L M

    2014-09-15

    Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.

  10. Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review

    PubMed Central

    Geamănu (Pancă), A; Popa-Cherecheanu, A; Marinescu, B; Geamănu, CD; Voinea, LM

    2014-01-01

    Abstract Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects. PMID:25408748

  11. Parent Reports of Mental Health Concerns and Functional Impairment on Routine Screening with the Strengths and Difficulties Questionnaire

    PubMed Central

    Biel, Matthew G.; Kahn, Nicole F.; Srivastava, Anjuli; Mete, Mihriye; Banh, My K.; Wissow, Lawrence S.; Anthony, Bruno J.

    2015-01-01

    Objective This study used the Strengths and Difficulties Questionnaire (SDQ) to describe the prevalence of parent-reported mental health (MH) concerns in youth presenting for primary care appointments and to examine relationships between children’s MH issues and functional impairment. We hypothesized that increased MH symptomology would be associated with increased impairment and family burden. Methods Parents of 4–17 years old children were approached at routine visits in 13 primary care sites. Chi-square tests, independent samples t-tests, and a one-way analysis of variance (ANOVA) were used to make comparisons between demographic groups. Age-, sex-, and race-adjusted ordered logistic regression models and ANOVAs examined relationships between impact and SDQ scales. Results Boys had higher total Hyperactivity and Peer Problems. Adolescents showed higher Emotional Symptoms, while younger children showed more Hyperactivity. Latinos reported more Conduct Problems, Hyperactivity, and Peer Problems. Latinos also indicated less distress on the child, impairment at home and school, and family burden. Regression analyses indicated increased odds of impairment with higher scale scores. MH symptoms identified with the SDQ in pediatric primary care settings were associated with parent-reported impairment affecting youth and their families. Conclusions The presence of significant impairment suggests that parents’ concerns identified by screening are likely to be clinically important and worthy of practice strategies designed to promote assessment, treatment, and referral for these common problems. Identifying and exploring parents’ concerns with strategic use of screening tools may allow PCPs to directly engage families around the MH issues that affect them most. PMID:25922333

  12. 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.

  13. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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

  15. Screening housing to prevent lead toxicity in children.

    PubMed

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

    2005-01-01

    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). 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. 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%. 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.

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

    SciTech Connect

    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.

  17. 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...

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

    Treesearch

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

    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...

  19. Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

    EPA Science Inventory

    Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive signature was constructed from U.S. EPA ToxCast high-throughput screening (HTS) assays that map to...

  20. 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...

  1. Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems.

    PubMed

    Woehrling, E K; Hill, E J; Coleman, M D

    2010-02-01

    Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.

  2. An in vitro screening paradigm for extracts of whole foods for detection of potential toxicants.

    PubMed

    Charles, G D; Linscombe, V A; Tornesi, B; Mattsson, J L; Gollapudi, B B

    2002-10-01

    The application of organic, conventional and biotechnology techniques can alter the intrinsic levels of natural toxicants in crop foods and methods are needed to screen for unexpected changes in toxicant levels. We evaluated crude, aqueous preparations of 37 foods purchased from a local market in a battery of four in vitro mammalian toxicity screens. The foods were evaluated in one or more of the following tests: (1) cytotoxicity (37 foods) and (2) chromosomal aberration test (nine foods), both in Chinese hamster ovary cells, (3) limb bud micromass assay (nine foods) using 11-day old CD-1 mouse embryos and (4) estrogenicity (MCF-7 cells transfected with estrogen receptor and lucerifase reporter constructs, 12 foods). IC50s for cellular proliferation ranged from < 1% (v/v, garlic) to > 10% (v/v, 18 foods), the maximal concentration tested. Five of nine preparations (soybeans, broccoli, garlic, snow peas and corn) were clastogenic and two (soybeans and snow peas) inhibited chrondrogenesis in the limb bud micromass assay. Five of nine preparations (soybeans, snow peas, cumin, asparagus and bean sprouts) produced significant estrogenic responses. Overall, the 12 foods evaluated in two or more of the tests showed different patterns of response. These preliminary data indicate that screening for potential toxicants is possible with fast, relatively inexpensive in vitro tests. These in vitro tests, while potentially useful to detect unexpected toxicants in plants that may signal the need for further evaluation, are not directly useful to predict human or animal risk from eating these plants.

  3. 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.

  4. 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

  5. Evaluation of the smoke density chamber as an apparatus for fire toxicity screening tests

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Labossiere, L. A.

    1976-01-01

    The smoke density chamber is perhaps the most widely used apparatus for smoke measurements. Because of its availability, it has been proposed as an apparatus for evaluating fire toxicity. The standard apparatus and procedure were not found suitable for toxicity screening tests using laboratory animals, because not enough materials of interest produced animal mortality or even incapacitation under standard test conditions. With modifications, the chamber offers greater promise as a screening tool, but other tests specifically designed to measure relative toxicity may be more cost-effective. Where one-dimensional heat flux is a requirement, the chamber is the most suitable apparatus available. It should be improved in regard to visibility of animals and ease of cleaning.

  6. 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...

  7. 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...

  8. 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 ...

  9. 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 ...

  10. Sensitive bromine-based screening of potential toxic furanoids in Dioscorea bulbifera L.

    PubMed

    Zhang, Zhengyu; Lin, Dongju; Li, Weiwei; Gao, Huiyuan; Peng, Ying; Zheng, Jiang

    2017-07-01

    Numerous furanoids have been reported to be toxic, and many of them were found in herbal medicines. Toxicities of furanoids are suggested to result from the generation of cis-enedials via biotransformation. The detection of the electrophilic metabolic intermediates is a challenge. Earlier, we developed a selective approach to screen potential toxic furanoids, through which we found two major furanoids, diosbulbin B and 8-epidiosbulbin E acetate, in Dioscorea bulbifera L., a known furanoid-containing and hepatotoxic herbal medicine. In the present study, we improved the approach to analyze furanoids in D. bulbifera L., which allowed us to detect additional six potential furanoids, including diosbulbin A, diosbulbin D, diosbulbin E, diosbulbin F, diosbulbin M, and diosbulbin D glycoside. The achievements of this study enhanced the sensitivity to screen potential toxic furanoids through elevating S/N values by approximately 3 times. This will facilitate the understanding of mechanisms of toxic actions of D. bulbifera L. and other furanoid-containing toxic herbal medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Routine Drug Screening for Patients in the Emergency Department of a State Psychiatric Hospital: A Naturalistic Cohort Study.

    PubMed

    Margolis, Anatoly; Rosca, Paola; Kurs, Rena; Sznitman, Sharon R; Grinshpoon, Alexander

    2016-01-01

    -40), male sex, fewer years of education, single marital status, and ICD-10 diagnosis of substance-related, personality, and nonpsychotic disorders were indicators of higher likelihood of positive urine drug test findings. Results suggest that routine urine toxicology screening is not necessary in the psychiatric emergency department as an adjunct to a thorough psychiatric clinical examination. However, urine drug tests should be performed when the clinical evaluation cannot determine whether the mental disorder is the result of illicit drug use or clearly non-drug-related.

  12. Phytochemical Screening and Toxicity Studies on the Leaves of Capparis sepiaria Linn. (Capparidaceae)

    PubMed Central

    Rajesh, P.; Latha, S.; Selvamani, P.; Kannan, V. Rajesh

    2009-01-01

    Capparis sepiaria Linn. (Family: Capparidaceae) is a rare indigenous in South India but has widespread distribution in many tropical and sub-tropical countries. The present study intended with various phytochemical screening and toxicity studies were carried out on the leaves of the Capparis sepiaria. Preliminary phytochemical evaluation of the ethanolic extract of revealed that the presence of reducing sugar, flavonoids, steroids, tannins, glycosides, alkaloids, gums, resins, amino acids, proteins and anthraquinones. The toxicity studies were performed as acute, sub-acute and chronic toxicity determined the LD50 value of 300-5000 mg/kg body weight 4-6 weeks. The results of the various phytochemical tests indicated that the plant to be rich in various biologically active compounds which could serve as potential source of the crude drugs and in addition the plant is not toxic to the experimental model. PMID:25206253

  13. Large-Scale Screen for Modifiers of Ataxin-3-Derived Polyglutamine-Induced Toxicity in Drosophila

    PubMed Central

    Voßfeldt, Hannes; Butzlaff, Malte; Prüßing, Katja; Ní Chárthaigh, Róisín-Ana; Karsten, Peter; Lankes, Anne; Hamm, Sabine; Simons, Mikael; Adryan, Boris

    2012-01-01

    Polyglutamine (polyQ) diseases represent a neuropathologically heterogeneous group of disorders. The common theme of these disorders is an elongated polyQ tract in otherwise unrelated proteins. So far, only symptomatic treatment can be applied to patients suffering from polyQ diseases. Despite extensive research, the molecular mechanisms underlying polyQ-induced toxicity are largely unknown. To gain insight into polyQ pathology, we performed a large-scale RNAi screen in Drosophila to identify modifiers of toxicity induced by expression of truncated Ataxin-3 containing a disease-causing polyQ expansion. We identified various unknown modifiers of polyQ toxicity. Large-scale analysis indicated a dissociation of polyQ aggregation and toxicity. PMID:23139745

  14. Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila.

    PubMed

    VoSSfeldt, Hannes; Butzlaff, Malte; PrüSSing, Katja; Ní Chárthaigh, Róisín-Ana; Karsten, Peter; Lankes, Anne; Hamm, Sabine; Simons, Mikael; Adryan, Boris; Schulz, Jörg B; Voigt, Aaron

    2012-01-01

    Polyglutamine (polyQ) diseases represent a neuropathologically heterogeneous group of disorders. The common theme of these disorders is an elongated polyQ tract in otherwise unrelated proteins. So far, only symptomatic treatment can be applied to patients suffering from polyQ diseases. Despite extensive research, the molecular mechanisms underlying polyQ-induced toxicity are largely unknown. To gain insight into polyQ pathology, we performed a large-scale RNAi screen in Drosophila to identify modifiers of toxicity induced by expression of truncated Ataxin-3 containing a disease-causing polyQ expansion. We identified various unknown modifiers of polyQ toxicity. Large-scale analysis indicated a dissociation of polyQ aggregation and toxicity.

  15. Light catalytically cracked naphtha: subchronic toxicity of vapors in rats and mice and developmental toxicity screen in rats.

    PubMed

    Dalbey, W E; Feuston, M H; Yang, J J; Kommineni, C V; Roy, T A

    1996-01-01

    Both a subchronic inhalation study and a developmental toxicity screen were performed with vapors of light catalytically cracked naphtha (LCCN). In the subchronic study, four groups of mice and rats (10 animals per sex per species) were exposed for approximately 13 wk (6 h/d, 5 d/wk) to concentrations of LCCN vapors of 0, 530, 2060, or 7690 mg/m3. An untreated control group was also included. Animals were observed daily and body weights were taken weekly. No significant treatment-related changes were found in clinical signs, body weight, serum chemistry, hematology, histopathology of 24 tissues, or weights of 12 organs. A marginal decrease was noted in the number of sperm per gram of epididymis. In the developmental toxicity screen, presumed-pregnant Sprague-Dawley rats were exposed to 0, 2150, or 7660 mg/m3 of LCCN vapors, 6 h/d on d 0-19 of gestation. Females were sacrificed on d 20; dams and fetuses were examined grossly and fetuses were later evaluated for skeletal and visceral effects. The number of resorptions was increased by approximately 140% in the group receiving 7660 mg/m3; no other definite treatment-related changes were observed. Overall, the effects of exposure to partially vaporized LCCN were minimal.

  16. Quantitative high-throughput screening for chemical toxicity in a population-based in vitro model.

    PubMed

    Lock, Eric F; Abdo, Nour; Huang, Ruili; Xia, Menghang; Kosyk, Oksana; O'Shea, Shannon H; Zhou, Yi-Hui; Sedykh, Alexander; Tropsha, Alexander; Austin, Christopher P; Tice, Raymond R; Wright, Fred A; Rusyn, Ivan

    2012-04-01

    A shift in toxicity testing from in vivo to in vitro may efficiently prioritize compounds, reveal new mechanisms, and enable predictive modeling. Quantitative high-throughput screening (qHTS) is a major source of data for computational toxicology, and our goal in this study was to aid in the development of predictive in vitro models of chemical-induced toxicity, anchored on interindividual genetic variability. Eighty-one human lymphoblast cell lines from 27 Centre d'Etude du Polymorphisme Humain trios were exposed to 240 chemical substances (12 concentrations, 0.26nM-46.0μM) and evaluated for cytotoxicity and apoptosis. qHTS screening in the genetically defined population produced robust and reproducible results, which allowed for cross-compound, cross-assay, and cross-individual comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited interindividual differences in cytotoxicity. Specifically, the qHTS in a population-based human in vitro model system has several unique aspects that are of utility for toxicity testing, chemical prioritization, and high-throughput risk assessment. First, standardized and high-quality concentration-response profiling, with reproducibility confirmed by comparison with previous experiments, enables prioritization of chemicals for variability in interindividual range in cytotoxicity. Second, genome-wide association analysis of cytotoxicity phenotypes allows exploration of the potential genetic determinants of interindividual variability in toxicity. Furthermore, highly significant associations identified through the analysis of population-level correlations between basal gene expression variability and chemical-induced toxicity suggest plausible mode of action hypotheses for follow-up analyses. We conclude that as the improved resolution of genetic profiling can now be matched with high-quality in vitro screening data, the evaluation of the toxicity pathways and the effects of

  17. 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.

  18. Use of biosensors to screen urine samples for potentially toxic chemicals.

    PubMed

    Horswell, Jacqui; Dickson, Stuart

    2003-09-01

    Forensic toxicology laboratories are often required to implicate or exclude poisoning as a factor in a death or unexplained illness. An analytical tool which enables toxicologists to screen a wide variety of common poisons would be extremely useful. In this paper, we describe the use of a bacterial biosensor for detecting the presence of commonly encountered potentially toxic chemicals in urine. The biosensor responds to any chemical that causes metabolic stress to the bacterial cell and the response is in direct proportion to the concentration of the stressor. This allows a measure of the concentration of a toxicant in urine, without knowing exactly what the toxic compound(s) may be. This affords a distinct advantage over conventional analytical techniques, which require an extensive screening program before it is even known that a toxic compound is present. This preliminary investigation has shown that this biosensor can indicate the presence, in urine, of herbicides such as glyphosate, 2,4-dichlorophenoxyacetic acid, and 2,4,5-trichlorophenoxyacetic acid; the biocide pentachlorophenol; or inorganic poisons such as arsenic, mercury, and cyanide. The biosensor was also shown to be sensitive to a concentration range of these toxicants likely to be found in samples submitted for toxicological analysis.

  19. Evaluation of the annual killifish Nothobranchius guentheri as a tool for rapid acute toxicity screening

    SciTech Connect

    Shedd, T.R.; Widder, M.W.; Toussaint, M.W.; Sunkel, M.C.; Hull, E.

    1999-10-01

    This study evaluated the use of Nothobranchius guentheri as a novel organism for rapid acute toxicity screening. A major advantage of the species is that there is no need to maintain a continuous culture to have organisms immediately available for testing. Rather, the embryos are viable under long-term storage conditions and can be hatched within a few hours. The tests require only 24 h with standard laboratory equipment. Sensitivity levels for 11 representative toxicants were comparable to those reported for five of the standard US Environmental Protection Agency test species requiring continuous culture.

  20. Use of field-portable XRF analyzers for rapid screening of toxic elements in FDA-regulated products.

    PubMed

    Palmer, Peter T; Jacobs, Richard; Baker, Peter E; Ferguson, Kelly; Webber, Siri

    2009-04-08

    compared to existing methods such as ICP-MS. It concludes with a discussion of a number of different FDA applications and case studies in which XRF has been used to screen, identify, and in some cases quantify toxic elements in various products. This work clearly demonstrates that XRF analyzers are an exceedingly valuable tool for routine and nonroutine elemental analysis investigations, both in the laboratory and in the field. In the future, it is hoped that both field-portable and laboratory-grade XRF analyzers will see more widespread use for investigational and forensic-type applications of food and other regulated consumer products.

  1. Toxicity screening of materials from buildings with fungal indoor air quality problems (Stachybotrys chartarum).

    PubMed

    E, J; M, G; S, Y C; E-L, H; M, N; B, J; R, D

    1998-06-01

    Samples of building materials visibly contaminated with moisture-related fungi (drywall, fiberglass, wallpaper, wood) were tested with indirect (FFL) and direct (MTT) cytotoxicity screening tests that are particularly sensitive toStachybotrys chartarum toxins. In addition, microscopic, chemical, immunochemical (Roridin A enzyme immunoassay) and mycological culture analyses were performed. In all cases in which building occupants had reported verifiable skin, mucous membrane, respiratory, central nervous system or neuropsychological abnormalities, cytotoxicity was identified. Results of a cytotoxicity screening test of field samples, such as the direct MTT test method, will give investigators of health problems related to indoor air quality problems important toxicity information.

  2. Statistical studies of animal response data from USF toxicity screening test method

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Machado, A. M.

    1978-01-01

    Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

  3. Statistical studies of animal response data from USF toxicity screening test method

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Machado, A. M.

    1978-01-01

    Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

  4. The submitochondrial particle assay as a screening test for acute aquatic toxicity of surfactant molecules

    SciTech Connect

    Bookland, E.A.; Bettermann, A.D.

    1995-12-31

    Two complementary protocols of the submitochondrial particle assay (SMP) were evaluated as screening tools for predicting the acute aquatic toxicity of various classes and chain lengths of surfactant molecules. SMP contain the functionally intact mitochondrial enzyme systems responsible for electron transport and oxidative phosphorylation. Both the Electron Transfer Assay (ETR) and the Reverse Electron Transfer Assay (RET) have been shown in prior work to generally be sensitive to agents capable of membrane and protein interactions, both suspected mechanisms of action for surfactants. The toxicity of ten compounds; four anionic surfactants, C{sub 12} alkyl sulfate (C{sub 12}AS), C{sub 12} and C{sub 15} alkyl ethoxy sulfate (C{sub 12}E{sub 4}S, C{sub 15}E{sub 4}S), linear alkyl benzene sulfonate (C{sub 12.3}LAS); one nonionic surfactant, alkyl ethoxylate (C{sub 12}E{sub 3}); three cationic surfactants, C{sub 8}, C{sub 12}, and C{sub 16} alkyl trimethyl ammonium chloride (C{sub 8}TMAC, C{sub 12}TMAC, C{sub 16}TMAC); an alcohol (C{sub 12}OH); and an amine, alkyl dimethylamine (C{sub 12}DMA); was determined. In all cases, both the ETR and the RET gave results showing equal or greater sensitivity than previously reported acute fish and invertebrate LC{sub 50}`s. In addition, increasing toxicity with increasing alkyl chain length was observed. As a rapid screening tool, the SMP bioassay avoids exposure concerns such as degradation of test material, a common concern for acute in vivo toxicity testing with rapidly degradable materials. Results indicate that the SMP bioassay can be useful as a predictive screening tool for the aquatic toxicity of surfactants.

  5. Acute toxicity screening of reservoir water and sediment. Reservoir vital signs monitoring, 1990

    SciTech Connect

    Moses, J.; Wade, D.C.

    1991-05-01

    Toxicological evaluation of forebay and transition area water column (overlying water) and sediment porewater (interstitial water) samples was initiated during the summer of 1990 as part of TVA`s Reservoir Vital Signs monitoring. Twenty-four stations were identified for study using acute toxicity screening test methods with the freshwater rotifer Brachionus calyciflorus (Rotox{reg_sign}) and light emitting bacteria Photobacterium phosphoreum (Microtox{reg_sign}). No acute toxicity to rotifers was demonstrated in the first series of tests using water column and sediment samples from the locations selected for monitoring. Sediments from three locations indicated some toxicity based on Microtox{reg_sign}, although all EC{sub 50} concentrations were greater than 100 percent sample.

  6. Evaluation of Electrochemiluminescent Metabolic Toxicity Screening Arrays Using a Multiple Compound Set

    PubMed Central

    Pan, Shenmin; Zhao, Linlin; Schenkman, John B.; Rusling, James F.

    2011-01-01

    Arrays for screening metabolite-generated toxicity utilizing spots containing DNA, enzyme and electroluminescent (ECL) polymer ([Ru(bpy)2PVP10]2+) were extended to include a fully representative set of metabolic enzymes from human and rat liver microsomes, human and rat liver cytosol, and mouse liver S9 fractions. Array use involves two steps: (1) enzyme activation of the test chemical, and metabolite reaction with DNA, then (2) capture of ECL resulting from DNA damage using a CCD camera. Plots of ECL increase vs. enzyme reaction time monitor relative rates of DNA damage, and were converted into turnover rates for enzymic production of DNA-reactive metabolites. ECL turnover rates were defined by R, the initial slope of ECL increase versus enzyme reaction time normalized for amounts of enzyme and test chemical. R-values were used to establish correlations for 11 toxic compounds with the standard toxicity metrics rodent liver TD50 and LD50, Ames tests, and Comet assays for in vitro DNA damage. Results support the value of the ECL genotoxicity arrays together with toxicity bioassays for early screening of new chemicals and drug candidates. PMID:21395325

  7. Implementation of Routine Postpartum Depression Screening and Care Initiation Across a Multispecialty Health Care Organization: An 18-Month Retrospective Analysis.

    PubMed

    Lind, April; Richter, Sara; Craft, Cheryl; Shapiro, Alice C

    2017-02-01

    Objectives Postpartum depression (PPD) affects approximately 10-20% of all mothers after giving birth. Adequate screening and follow-up care for the postpartum mother with depression is an essential component of quality care in this population. The purpose of this quality improvement project was to evaluate the quality and quantity of a postnatal PPD screening program and the subsequent initiation of needed PPD treatment in an integrated health system. Methods After implementing a standardized PPD screening process, we conducted an 18-month retrospective study of patient visits that required a PPD screen. Data were abstracted from medical records and analyzed to determine if postnatal PPD screening occurred, what quality of the screening was, and what follow-up measures were taken. Results Within the study timeframe, 28,389 postpartum and well-child visits were eligible for PPD screening. PPD screening occurred at 88% of eligible visits for approximately 5000 unique women. PPD was identified in 8.1% of screened women. Conclusions Of women with PPD, at least 44.8% were prescribed an SSRI and 21.4% attended a visit with a mental health professional, which is consistent with other studies. Screening can be successful through collaboration, although ongoing evaluation and process modification are necessary.

  8. 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.

  9. 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.

  10. Using molecular similarity to highlight the challenges of routine immunoassay-based drug of abuse/toxicology screening in emergency medicine

    PubMed Central

    Krasowski, Matthew D; Pizon, Anthony F; Siam, Mohamed G; Giannoutsos, Spiros; Iyer, Manisha; Ekins, Sean

    2009-01-01

    Background Laboratory tests for routine drug of abuse and toxicology (DOA/Tox) screening, often used in emergency medicine, generally utilize antibody-based tests (immunoassays) to detect classes of drugs such as amphetamines, barbiturates, benzodiazepines, opiates, and tricyclic antidepressants, or individual drugs such as cocaine, methadone, and phencyclidine. A key factor in assay sensitivity and specificity is the drugs or drug metabolites that were used as antigenic targets to generate the assay antibodies. All DOA/Tox screening immunoassays can be limited by false positives caused by cross-reactivity from structurally related compounds. For immunoassays targeted at a particular class of drugs, there can also be false negatives if there is failure to detect some drugs or their metabolites within that class. Methods Molecular similarity analysis, a computational method commonly used in drug discovery, was used to calculate structural similarity of a wide range of clinically relevant compounds (prescription and over-the-counter medications, illicit drugs, and clinically significant metabolites) to the target ('antigenic') molecules of DOA/Tox screening tests. These results were compared with cross-reactivity data in the package inserts of immunoassays marketed for clinical testing. The causes for false positives for phencyclidine and tricyclic antidepressant screening immunoassays were investigated at the authors' medical center using gas chromatography/mass spectrometry as a confirmatory method. Results The results illustrate three major challenges for routine DOA/Tox screening immunoassays used in emergency medicine. First, for some classes of drugs, the structural diversity of common drugs within each class has been increasing, thereby making it difficult for a single assay to detect all compounds without compromising specificity. Second, for some screening assays, common 'out-of-class' drugs may be structurally similar to the target compound so that they

  11. Experience of Routine Live-birth Screening for Galactosaemia in a British Hospital, with Emphasis on Heterozygote Detection

    PubMed Central

    Ellis, Graham; Wilcock, A. Ross; Goldberg, David M.

    1972-01-01

    Results are reported of a screening programme for galactosaemia covering a period of 2½ years and 6415 births. The gene frequency for galactosaemia estimated from the data of the screening programme was 0·002. This conflicted with the known live-birth incidence of at least 1: 50,000 during this same period. 2 of the 4 galactosaemic infants concerned died under circumstances that were preventable had they been screened at birth. The need to screen all sick infants for galactosaemia is emphasized, as is the requirement for reliable information on its incidence in Great Britain. The screening test employed (Beutler and Baluda, 1966a) seemed appropriate for this purpose. It was simple to perform and apparently accurate in galactosaemic infants. Its accuracy in detecting heterozygotes is uncertain. This test should be available in all hospitals receiving sick neonates. PMID:4401641

  12. A randomised controlled trial and cost effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in the over 65s: (SAFE) [ISRCTN19633732].

    PubMed

    Swancutt, Dawn; Hobbs, Richard; Fitzmaurice, David; Mant, Jonathan; Murray, Ellen; Jowett, Sue; Raftery, James; Bryan, Stirling; Davies, Michael; Lip, Gregory

    2004-07-29

    Atrial fibrillation (AF) has been recognised as an important independent risk factor for thromboembolic disease, particularly stroke for which it provides a five-fold increase in risk. This study aimed to determine the baseline prevalence and the incidence of AF based on a variety of screening strategies and in doing so to evaluate the incremental cost-effectiveness of different screening strategies, including targeted or whole population screening, compared with routine clinical practice, for detection of AF in people aged 65 and over. The value of clinical assessment and echocardiography as additional methods of risk stratification for thromboembolic disease in patients with AF were also evaluated. The study design was a multi-centre randomised controlled trial with a study population of patients aged 65 and over from 50 General Practices in the West Midlands. These purposefully selected general practices were randomly allocated to 25 intervention practices and 25 control practices. GPs and practice nurses within the intervention practices received education on the importance of AF detection and ECG interpretation. Patients in the intervention practices were randomly allocated to systematic (n = 5000) or opportunistic screening (n = 5000). Prospective identification of pre-existing risk factors for AF within the screened population enabled comparison between high risk targeted screening and total population screening. AF detection rates in systematically screened and opportunistically screened populations in the intervention practices were compared to AF detection rate in 5,000 patients in the control practices.

  13. A randomised controlled trial and cost effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in the over 65s: (SAFE) [ISRCTN19633732

    PubMed Central

    Swancutt, Dawn; Hobbs, Richard; Fitzmaurice, David; Mant, Jonathan; Murray, Ellen; Jowett, Sue; Raftery, James; Bryan, Stirling; Davies, Michael; Lip, Gregory

    2004-01-01

    Background Atrial fibrillation (AF) has been recognised as an important independent risk factor for thromboembolic disease, particularly stroke for which it provides a five-fold increase in risk. This study aimed to determine the baseline prevalence and the incidence of AF based on a variety of screening strategies and in doing so to evaluate the incremental cost-effectiveness of different screening strategies, including targeted or whole population screening, compared with routine clinical practice, for detection of AF in people aged 65 and over. The value of clinical assessment and echocardiography as additional methods of risk stratification for thromboembolic disease in patients with AF were also evaluated. Methods The study design was a multi-centre randomised controlled trial with a study population of patients aged 65 and over from 50 General Practices in the West Midlands. These purposefully selected general practices were randomly allocated to 25 intervention practices and 25 control practices. GPs and practice nurses within the intervention practices received education on the importance of AF detection and ECG interpretation. Patients in the intervention practices were randomly allocated to systematic (n = 5000) or opportunistic screening (n = 5000). Prospective identification of pre-existing risk factors for AF within the screened population enabled comparison between high risk targeted screening and total population screening. AF detection rates in systematically screened and opportunistically screened populations in the intervention practices were compared to AF detection rate in 5,000 patients in the control practices. PMID:15283871

  14. 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

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

    PubMed

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

    2013-05-07

    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.

  16. Screening of drugs and toxic compounds with liquid chromatography-linear ion trap tandem mass spectrometry.

    PubMed

    Sauvage, François-Ludovic; Saint-Marcoux, Franck; Duretz, Bénédicte; Deporte, Didier; Lachatre, Gérard; Marquet, Pierre

    2006-09-01

    In clinical and forensic toxicology, general unknown screening is used to detect and identify exogenous compounds. In this study, we aimed to develop a comprehensive general unknown screening method based on liquid chromatography coupled with a hybrid triple-quadrupole linear ion trap mass spectrometer. After solid-phase extraction, separation was performed using gradient reversed-phase chromatography. The mass spectrometer was operated in the information-dependent acquisition mode, switching between a survey scan acquired in the Enhanced Mass Spectrometry mode with dynamic subtraction of background noise and a dependent scan obtained in the enhanced product ion scan mode. The complete cycle time was 1.36 s. A library of 1000 enhanced product ion-tandem mass spectrometry spectra in positive mode and 250 in negative mode, generated using 3 alternated collision tensions during each scan, was created by injecting pure solutions of drugs and toxic compounds. Comparison with HPLC-diode array detection and gas chromatography-mass spectrometry for the analysis of 36 clinical samples showed that linear ion trap tandem mass spectrometry could identify most of the compounds (94% of the total). Some compounds were detected only by 1 of the other 2 techniques. Specific clinical cases highlighted the advantages and limitations of the method. A unique combination of new operating modes provided by hybrid triple-quadrupole linear ion trap mass spectrometers and new software features allowed development of a comprehensive and efficient method for the general unknown screening of drugs and toxic compounds in blood or urine.

  17. Estimated Prevalence of Cryptococcus Antigenemia (CrAg) among HIV-Infected Adults with Advanced Immunosuppression in Namibia Justifies Routine Screening and Preemptive Treatment

    PubMed Central

    Makumbi, Boniface; Purfield, Anne; Ndjavera, Christophine; Mutandi, Gram; Maher, Andrew; Kaindjee-Tjituka, Francina; Kaplan, Jonathan E.; Park, Benjamin J.; Lowrance, David W.

    2016-01-01

    Background Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4+ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies. Methods The study design was cross-sectional. De-identified plasma specimens collected for routine CD4+ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4+ counts <200 cells/μL were sampled and tested for CrAg using the IMMY® Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4+ count. Results A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32–46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/μL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/μL and 100–200 cells/μL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/μL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/μL 50–200 (2.2%). Conclusion This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4+<100 cells/μL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/μL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in

  18. Estimated Prevalence of Cryptococcus Antigenemia (CrAg) among HIV-Infected Adults with Advanced Immunosuppression in Namibia Justifies Routine Screening and Preemptive Treatment.

    PubMed

    Sawadogo, Souleymane; Makumbi, Boniface; Purfield, Anne; Ndjavera, Christophine; Mutandi, Gram; Maher, Andrew; Kaindjee-Tjituka, Francina; Kaplan, Jonathan E; Park, Benjamin J; Lowrance, David W

    2016-01-01

    Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4+ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies. The study design was cross-sectional. De-identified plasma specimens collected for routine CD4+ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4+ counts <200 cells/μL were sampled and tested for CrAg using the IMMY® Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4+ count. A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32-46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/μL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/μL and 100-200 cells/μL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/μL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/μL 50-200 (2.2%). This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4+<100 cells/μL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/μL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in Namibia now recommend routine screening for CrAg.

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

    USDA-ARS?s Scientific Manuscript database

    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. 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…

  1. 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…

  2. 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...

  3. 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...

  4. 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.

  5. 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

  6. In vivo antimalarial activity, toxicity and phytochemical screening of selected antimalarial plants.

    PubMed

    Musila, M F; Dossaji, S F; Nguta, J M; Lukhoba, C W; Munyao, J M

    2013-03-27

    Malaria continues to kill over a million people each year and in many populations affected by malaria, conventional drugs are often unaffordable or inaccessible. Historically, plants have been a prominent source of antimalarial drugs. Those plants currently used by indigenous people to treat malaria should be documented and investigated as potential sources of new antimalarial drugs. To investigate in vivo antimalarial activity, toxicity and carry out phytochemical screening of selected plants which have been used in traditional medicine for the treatment of malaria. Organic and water extracts of four medicinal plants used for the treatment of malaria in traditional health systems of Msambweni people in Kenya were tested for antimalarial activity against Plasmodium berghei and brine shrimp lethality. They were also screened for their major phytochemical constituents. Aqueous extract of the stem bark of Adansonia digitata exhibited highest chemosuppression of parasitaemia, >60% in a murine model of Plasmodium berghei infected mice. Aqueous and organic extracts of Launaea cornuta and Zanthoxylum chalybeum were toxic to the brine shrimp (LD50<1000μg/ml) while aqueous and organic extracts of Adansonia digitata and aqueous extracts of Canthium glaucum were not toxic to brine shrimp (LD50>1000μg/ml). Phytochemical screening revealed the presence of alkaloids and flavonoids in all the crude extracts of the selected plant species studied. Sesquiterpene lactones and saponis were present in organic extracts but absent in the aqueous extracts of Adansonia digitata, Canthium glaucum, Launaea cornuta and Zanthoxylum chalybeum. The results showed that the crude extracts of Adansonia digitata and Canthium glaucum demonstrated promising antimalarial activity and there is potential for isolation of lead compounds from their extracts. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Does routine psychosocial screening improve referral to psychosocial care providers and patient-radiotherapist communication? A cluster randomized controlled trial.

    PubMed

    Braeken, Anna P B M; Lechner, Lilian; Eekers, Daniëlle B P; Houben, Ruud M A; van Gils, Francis C J M; Ambergen, Ton; Kempen, Gertrudis I J M

    2013-11-01

    This study tests whether using a screening instrument improves referral to psychosocial care providers (e.g. psychologist) and facilitates patient-radiotherapist communication. A cluster randomized controlled trial was used. Fourteen radiotherapists were randomly allocated to the experimental or control group and 568 of their patients received care in accordance with the group to which their radiotherapist was allocated. Patients in the experimental group were asked to complete a screening instrument before and at the end of the radiation treatment period. All patients were requested to complete questionnaires concerning patient-physician communication after the first consultation and concerning psychosocial care 3 and 12 months post-intervention. Patients who completed the screening instrument were referred to social workers at an earlier stage than patients who did not (P<0.01). No effects were observed for numbers of referred patients, or for improved patient-radiotherapist communication. Our results suggest that a simple screening procedure can be valuable for the timely treatment of psychosocial problems in patients. Future efforts should be directed at appropriate timing of screening and enhancing physicians' awareness regarding the importance of identifying, discussing and treating psychosocial problems in cancer patients. Psychosocial screening can be enhanced by effective radiotherapist-patient communication. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. 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.

  11. Framework for use of toxicity screening tools in context-based decision-making.

    PubMed

    Doull, John; Borzelleca, Joseph F; Becker, Richard; Daston, George; DeSesso, John; Fan, Anna; Fenner-Crisp, Penelope; Holsapple, Michael; Holson, Joseph; Craig Llewellyn, G; MacGregor, James; Seed, Jennifer; Walls, Isabel; Woo, Yin-tak; Olin, Stephen

    2007-05-01

    One of the principal applications of toxicology data is to inform risk assessments and support risk management decisions that are protective of human health. Ideally, a risk assessor would have available all of the relevant information on (a) the toxicity profile of the agent of interest; (b) its interactions with living systems; and (c) the known or projected exposure scenarios: to whom, how much, by which route(s), and how often. In practice, however, complete information is seldom available. Nonetheless, decisions still must be made. Screening-level assays and tools can provide support for many aspects of the risk assessment process, as long as the limitations of the tools are understood and to the extent that the added uncertainty the tools introduce into the process can be characterized and managed. Use of these tools for decision-making may be an end in itself for risk assessment and decision-making or a preliminary step to more extensive data collection and evaluation before assessments are undertaken or completed and risk management decisions made. This paper describes a framework for the application of screening tools for human health decision-making, although with some modest modification, it could be made applicable to environmental settings as well. The framework consists of problem formulation, development of a screening strategy based on an assessment of critical data needs, and a data analysis phase that employs weight-of-evidence criteria and uncertainty analyses, and leads to context-based decisions. Criteria for determining the appropriate screening tool(s) have been identified. The choice and use of the tool(s) will depend on the question and the level of uncertainty that may be appropriate for the context in which the decision is being made. The framework is iterative, in that users may refine the question(s) as they proceed. Several case studies illustrate how the framework may be used effectively to address specific questions for any endpoint

  12. Metabolic toxicity screening using electrochemiluminescence arrays coupled with enzyme-DNA biocolloid reactors and liquid chromatography-mass spectrometry.

    PubMed

    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.

  13. 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

  14. 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.

  15. Longitudinal lactate levels from routine point-of-care monitoring in adult Malawian antiretroviral therapy patients: associations with stavudine toxicities.

    PubMed

    Chagoma, Newton; Mallewa, Jane; Kaunda, Symon; Njalale, Yasin; Kampira, Elizabeth; Mukaka, Mavuto; Heyderman, Robert S; van Oosterhout, Joep J

    2013-10-01

    Stavudine is still widely used in under-resourced settings such as Malawi due to its low price. It frequently causes peripheral neuropathy and lipodystrophy and increases the risk of lactic acidosis and other high lactate syndromes. We studied the association of longitudinal lactate levels, obtained by routine, 3-monthly point-of-care monitoring, with peripheral neuropathy, lipodystrophy and high lactate syndromes in adult Malawians who were in the second year of stavudine containing antiretroviral therapy (ART). Point-of-care lactate measurements were feasible in a busy urban ART clinic. Of 1170 lactate levels collected from 253 patients over the course of one year, 487 (41.8%) were elevated (>2.2mg/dl), 58 (5.0%) were highly elevated (>3.5mg/dl). At least one elevated lactate level occurred in 210 (83.0%) of patients and sustained hyperlactatemia in 65 (26.4%). In random effects analyses lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Only five patients developed high lactate syndromes (one lactic acidosis) of whom no preceding lactate measurements were available because events had started before enrolment. Lactate levels significantly decreased over time and no high lactate syndromes were observed after the 15th month on ART. Lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Lactate levels decreased over time, coinciding with absence of new high lactate syndromes after the 15th month on ART.

  16. The use of routine non density calibrated clinical computed tomography data as a potentially useful screening tool for identifying patients with osteoporosis

    PubMed Central

    Burke, Christopher John; Didolkar, Manjiri M.; Barnhart, Huiman X.; Vinson, Emily N.

    2016-01-01

    Summary Objectives To evaluate whether lumbar vertebral body density CT attenuation values measured in Hounsfield Units (HUs) on routine Computed Tomography (CT) examinations can be reliably measured with limited variability, and to evaluate for a correlation between HUs and bone mineral density as measured by dual energy X-ray absorptiometry (DXA) scan. Methods Retrospective review of a total of 249 routine MDCT examinations, performed to measure HUs at the first non-rib bearing lumbar vertebral body on axial images, cross-referenced to the lateral scout image. Results The overall ICC and RC for intra-reader variability on CT HU were 0.987 (95% CI 0.973 – 0.999) and 15.664 (95% CI 11.66–16.97). The overall ICC and RDC for inter-reader variability on CT HU were 0.952 (95% CI 0.892 – 0.999) and 30.20 (95% CI 23.73 – 34.48). The ICC and RC for interscanner variability were 0.98 (95% CI 0.95 – 0.99) and 16.67 (95% CI 13.13 – 22.85). The correlation between the L1 HUs and L1 BMD, L1 t-score, and overall t-score was 0.437, 0.392, and 0.400, respectively. Conclusions CT attenuation values of the first lumbar vertebra can be measured on routine abdomen CTs with limited variability despite multiple readers and scanners. Correlation between HU and BMD as measured by DXA scan was only weakly positive, and by this method measuring the density of a lumbar vertebral body from a routine MDCT scan does not provide the sensitivity or specificity necessary for a screening test. However above a certain measured value (180 HU), patients have a low chance of osteoporosis and therefore may not need additional screening, potentially limiting radiation exposure and cost. PMID:27920811

  17. Routine Use of an Antenatal Infection Screen-and-Treat Program to Prevent Preterm Birth: Long-Term Experience at a Tertiary Referral Center.

    PubMed

    Farr, Alex; Kiss, Herbert; Hagmann, Michael; Marschalek, Julian; Husslein, Peter; Petricevic, Ljubomir

    2015-06-01

    Vaginal infection in early pregnancy is associated with preterm birth. This study evaluates long-term results after integrating an antenatal screen-and-treat program for asymptomatic vaginal infections into routine pregnancy care. We retrospectively analyzed data of all women with singleton high-risk pregnancies delivering at our tertiary referral center between 2005 and 2014. The intervention group included women who presented for a prenatal visit for a planned birth between 10 + 0 and 16 + 0 gestational weeks. Women were routinely screened for asymptomatic infections using Gram stain. In cases of bacterial vaginosis, candidiasis or trichomoniasis, women were treated according to our clinical protocol. The control group included women who did not undergo the program. Prenatal care was equal in both groups. Preterm birth served as the primary outcome variable. Of the 20,052 women with singleton pregnancies, 8,490 (42.3%) participated in the antenatal prevention program. The mean gestational age at birth was 38.8 ± 2.6 weeks and 37.5 ± 4.3 weeks in the intervention and control groups, respectively (p < 0.001). The incidence of preterm birth was significantly lower in the intervention group than in the control group (9.7% vs 22.3%; p < 0.001). Low-birthweight neonates, stillbirths, and late miscarriages were less frequent in the intervention group (p < 0.001). Long-term results support the use of an antenatal infection screen-and-treat program to prevent preterm birth. If integrated into routine pregnancy care at a high-risk obstetrical setting, this simple public health intervention could lead to a significant reduction in preterm birth, low infant birthweight, and adverse pregnancy outcomes. © 2015 Wiley Periodicals, Inc.

  18. 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.

  19. Routine Self-administered, Touch-Screen Computer Based Suicidal Ideation Assessment Linked to Automated Response Team Notification in an HIV Primary Care Setting

    PubMed Central

    Lawrence, Sarah T.; Willig, James H.; Crane, Heidi M.; Ye, Jiatao; Aban, Inmaculada; Lober, William; Nevin, Christa R.; Batey, D. Scott; Mugavero, Michael J.; McCullumsmith, Cheryl; Wright, Charles; Kitahata, Mari; Raper, James L.; Saag, Micheal S.; Schumacher, Joseph E.

    2010-01-01

    Summary The implementation of routine computer-based screening for suicidal ideation and other psychosocial domains through standardized patient reported outcome instruments in two high volume urban HIV clinics is described. Factors associated with an increased risk of self-reported suicidal ideation were determined. Background HIV/AIDS continues to be associated with an under-recognized risk for suicidal ideation, attempted as well as completed suicide. Suicidal ideation represents an important predictor for subsequent attempted and completed suicide. We sought to implement routine screening of suicidal ideation and associated conditions using computerized patient reported outcome (PRO) assessments. Methods Two geographically distinct academic HIV primary care clinics enrolled patients attending scheduled visits from 12/2005 to 2/2009. Touch-screen-based, computerized PRO assessments were implemented into routine clinical care. Substance abuse (ASSIST), alcohol consumption (AUDIT-C), depression (PHQ-9) and anxiety (PHQ-A) were assessed. The PHQ-9 assesses the frequency of suicidal ideation in the preceding two weeks. A response of “nearly every day” triggered an automated page to pre-determined clinic personnel who completed more detailed self-harm assessments. Results Overall 1,216 (UAB= 740; UW= 476) patients completed initial PRO assessment during the study period. Patients were white (53%; n=646), predominantly males (79%; n=959) with a mean age of 44 (± 10). Among surveyed patients, 170 (14%) endorsed some level of suicidal ideation, while 33 (3%) admitted suicidal ideation nearly every day. In multivariable analysis, suicidal ideation risk was lower with advancing age (OR=0.74 per 10 years;95%CI=0.58-0.96) and was increased with current substance abuse (OR=1.88;95%CI=1.03-3.44) and more severe depression (OR=3.91 moderate;95%CI=2.12-7.22; OR=25.55 severe;95%CI=12.73-51.30). Discussion Suicidal ideation was associated with current substance abuse and

  20. 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.

  1. Cadmium in aquatic microcosms: implications for screening the ecological effects of toxic substances

    SciTech Connect

    Hendrix, P.F.; Langner, C.L.; Odum, E.P.

    1982-11-01

    A two-phase set of experiments was conducted to address some of the problems inherent in ecological screening of toxic substances in aquatic microcosms. Phase I was a 4 x 4 factorial experiment dealing with the interactive effects of cadmium and nutrients in static microcosms. Phase II was a 2 x 4 factorial experiment using flowthrough microcosms to study temporal aspects of system behavior in response to nutrient loading and chronic versus acute cadmium perturbations. Nutrient enrichment resulted in increased biomass and metabolic activity in both static and flowthrough microcosms. Cadmium treatments generally resulted in a decrease in abundance of grazing crustaceans and a subsequent increase in community respiration, suggesting a change in community structure from a grazing to a detritus food chain. Of the variables measured, community metabolism, community composition, and output/input ratios of nitrate-nitrogen were the most useful indicators of system response to cadmium. Nutrient enrichment reduced the effects of cadmium. For screening the ecological effects of toxic chemicals, a series of experiments is proposed, including 1) relatively simple static microcosms, 2) flow through microcosms, and 3) more detailed but selective studies in microcosms derived from specific ecosystems. Each step yields increasingly more information and serves as a guide for subsequent experiments; in addition, each step more closely approximates natural ecosystems.

  2. Cadmium in aquatic microcosms: Implications for screening the ecological effects of toxic substances

    NASA Astrophysics Data System (ADS)

    Hendrix, Paul F.; Langner, Christine L.; Odum, Eugene P.

    1982-11-01

    A two-phase set of experiments was conducted to address some of the problems inherent in ecological screening of toxic substances in aquatic microcosms. Phase I was a 4×4 factorial experiment dealing with the interactive effects of cadmium and nutrients in static microcosms. Phase II was a 2×4 factorial experiment using flowthrough microcosms to study temporal aspects of system behavior in response to nutrient loading and chronic versus acute cadmium perturbations. Nutrient enrichment resulted in increased biomass and metabolic activity in both static and flowthrough microcosms. Cadmium treatments generally resulted in a decrease in abundance of grazing crustaceans and a subsequent increase in community respiration, suggesting a change in community structure from a grazing to a detritus food chain. Of the variables measured, community metabolism, community composition, and output/input ratios of nitrate-nitrogen were the most useful indicators of system response to cadmium. Nutrient enrichment significantly influenced cadmium effects with respect to most of the variables measured; high levels of enrichment reduced the effects of cadmium. For screening the ecological effects of toxic chemicals, a series of experiments is proposed, including 1) relatively simple static microcosms, 2) flow through microcosms, and 3) more detailed but selective studies in microcosms derived from specific ecosystems. Each step yields increasingly more information and serves as a guide for subsequent experiments; in addition, each step more closely approximates natural ecosystems.

  3. Detection of X chromosome aneuploidy using Southern blot analysis during routine population-based screening for fragile X syndrome.

    PubMed

    Adir, Vardit; Shahak, Elena; Dar, Hanna; Borochowitz, Zvi U

    2003-01-01

    We report herein two cases where detection of X chromosome aneuploidy (cytogenetically proved 45,X/46XX and 47,XXX) was made possible by molecular diagnosis during population-based carrier screening for Fragile X syndrome, using Southern blot analysis. This study emphasizes the value of molecular analysis for gene dosage to suggest chromosomal aneuploidy.

  4. 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

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

    PubMed Central

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

    2016-01-01

    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 vitroto-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

  6. Fluorescence-based assay as a new screening tool for toxic chemicals

    PubMed Central

    Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

    2016-01-01

    Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

  7. Fluorescence-based assay as a new screening tool for toxic chemicals

    NASA Astrophysics Data System (ADS)

    Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

    2016-09-01

    Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

  8. Fluorescence-based assay as a new screening tool for toxic chemicals.

    PubMed

    Moczko, Ewa; Mirkes, Evgeny M; Cáceres, César; Gorban, Alexander N; Piletsky, Sergey

    2016-09-22

    Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

  9. Should routine screening by mammography be replaced by a more selective service of risk assessment/risk management?

    PubMed

    Baum, Michael

    2010-01-01

    The NHS screening program was launched 20 years ago and, until recently, has been accepted in an uncritical way. However, emerging data have suggested that the reduction in breast cancer mortality owing to screening is much less than it has been credited for. Furthermore, the harms from false-positive results and the overdiagnosis of indolent disease, which includes the detection of a cancer that is not destined to present clinically in that patient's lifetime, are now perceived as much greater than ever anticipated. This article suggests that it is complacent to continue with the program unchecked, a program that has so far denied women an informed choice. It is also suggested that a more efficient use of scarce resources that may reduce all-cause mortality might be to shift from a 'one size fits all' approach, to a risk assessment/risk management scheme.

  10. Design and implementation of a controlled clinical trial to evaluate the effectiveness and efficiency of routine opt-out rapid human immunodeficiency virus screening in the emergency department.

    PubMed

    Haukoos, Jason S; Hopkins, Emily; Byyny, Richard L; Conroy, Amy A; Silverman, Morgan; Eisert, Sheri; Thrun, Mark; Wilson, Michael; Boyett, Brian; Heffelfinger, James D

    2009-08-01

    In 2006, the Centers for Disease Control and Prevention (CDC) released revised recommendations for performing human immunodeficiency virus (HIV) testing in health care settings, including implementing routine rapid HIV screening, the use of an integrated opt-out consent, and limited prevention counseling. Emergency departments (EDs) have been a primary focus of these efforts. These revised CDC recommendations were primarily based on feasibility studies and have not been evaluated through the application of rigorous research methods. This article describes the design and implementation of a large prospective controlled clinical trial to evaluate the CDC's recommendations in an ED setting. From April 15, 2007, through April 15, 2009, a prospective quasi-experimental equivalent time-samples clinical trial was performed to compare the clinical effectiveness and efficiency of routine (nontargeted) opt-out rapid HIV screening (intervention) to physician-directed diagnostic rapid HIV testing (control) in a high-volume urban ED. In addition, three nested observational studies were performed to evaluate the cost-effectiveness and patient and staff acceptance of the two rapid HIV testing methods. This article describes the rationale, methodologies, and study design features of this program evaluation clinical trial. It also provides details regarding the integration of the principal clinical trial and its nested observational studies. Such ED-based trials are rare, but serve to provide valid comparisons between testing approaches. Investigators should consider similar methodology when performing future ED-based health services research.

  11. Twenty-four mini-pool HCV RNA screening in a routine clinical virology laboratory setting: a six-year prospective study.

    PubMed

    Seme, Katja; Mocilnik, Tina; Poljak, Mario

    2011-01-01

    The usefulness of combined anti-HCV and 24 mini-pool HCV RNA screening strategy was re-evaluated after a six-year continuous routine use in a clinical virology laboratory, at which more than half of newly diagnosed hepatitis C patients are intravenous drug users. Pools of 24 samples were prepared from 20,448 anti-HCV negative serum samples and tested using an automated commercial PCR assay with a lower limit of detection of 50 IU/ml. After detection of anti-HCV negative/HCV RNA positive patients, responsible physicians provided follow-up samples. Thirty-eight (0.19%) anti-HCV negative/HCV RNA positive samples from 30 patients (28 intravenous drug users) were detected. Follow-up samples were available for 27/30 patients. Twenty, six and one patient seroconverted in the second, third and fourth available samples, respectively. The interval between the first HCV RNA positive and the first available anti-HCV positive sample was 17-517 days. The costs of detecting a single anti-HCV negative/HCV RNA positive patient were 1227 Euros. Combined anti-HCV and 24 mini-pool HCV RNA screening is a useful and cost effective strategy, not only in blood-transfusion settings but also in a routine clinical virology laboratory, at which a significant proportion of the tested population belongs to a high-risk population.

  12. Routine HIV Screening in North Carolina in the Era of the Affordable Care Act: Update on Laws, Reimbursement, and Tests

    PubMed Central

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

    2013-01-01

    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

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

    PubMed

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

    1989-07-01

    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

  14. 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

  15. A Novel Marker for Screening Paroxysmal Nocturnal Hemoglobinuria Using Routine Complete Blood Count and Cell Population Data

    PubMed Central

    Kahng, Jimin; Kim, Yonggoo; Kim, Jung Ok; Koh, Kwangsang; Lee, Jong Wook

    2015-01-01

    Background Final diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) may take years demanding a quick diagnosis measure. We used the facts that PNH cells are damaged in acid, and reagents for measuring reticulocytes in Coulter DxH800 (Beckman Coulter, USA) are weakly acidic and hypotonic, to create a new PNH screening marker. Methods We analyzed 979 complete blood counts (CBC) data from 963 patients including 57 data from 44 PNH patients. Standard criteria for PNH assay for population selection were followed: flow cytometry for CD55 and CD59 on red blood cells (RBCs) to a detection level of 1%; and fluorescent aerolysin, CD24 and CD15 in granulocytes to 0.1%. Twenty-four PNH minor clone-positive samples (minor-PNH+) were taken, in which the clone population was <5% of RBCs and/or granulocytes. Excluding PNH and minor-PNH+ patients, the population was divided into anemia, malignancy, infection, and normal groups. Parameters exhibiting a distinct demarcation between PNH and non-PNH groups were identified, and each parameter cutoff value was sought that includes the maximum [minimum] number of PNH [non-PNH] patients. Results Cutoff values for 5 selected CBC parameters (MRV, RDWR, MSCV, MN-AL2-NRET, and IRF) were determined. Positive rates were: PNH (86.0%), minor-PNH+ (33.3%), others (5.0%), anemia (13.4%), malignancy (5.3%), infection (3.7%), normal (0.0%); within anemia group, aplastic anemia (40.0%), immune hemolytic anemia (11.1%), iron deficiency anemia (1.6%). Sensitivity (86.0%), specificity (95.0%), PPV (52.1%), and NPV (99.1%) were achieved in PNH screening. Conclusion A new PNH screening marker is proposed with 95% specificity and 86% sensitivity. The flag identifies PNH patients, reducing time to final diagnosis by flow cytometry. PMID:25553278

  16. How Compliance Measures, Behavior Modification, and Continuous Quality Improvement Led to Routine HIV Screening in an Emergency Department in Brooklyn, New York

    PubMed Central

    Sanchez, Travis H.; Brown, Emily H.; Thompson, Gina; Sanchez, Christina; Fils-Aime, Stephany; Maria, Jose

    2016-01-01

    Objective New York State adopted a new HIV testing law in 2010 requiring medical providers to offer an HIV test to all eligible patients aged 13–64 years during emergency room or ambulatory care visits. Since then, Wyckoff Heights Medical Center (WHMC) in Brooklyn, New York, began implementing routine HIV screening organization-wide using a compliance, behavior-modification, and continuous quality-improvement process. Methods WHMC first implemented HIV screening in the emergency department (ED) and evaluated progress with the following monthly indicators: HIV tests offered, HIV tests accepted, HIV tests ordered (starting in December 2013), HIV tests administered, positive HIV tests, and linkage to HIV care. Compliance with the delivery of HIV testing was determined by the proportion of patients who, after accepting a test, received one. Results During August 2013 through July 2014, of 57,852 eligible patients seen in the WHMC ED, a total of 31,423 (54.3%) were offered an HIV test. Of those, 8,229 (26.2%) patients accepted a test. Of those, 6,114 (74.3%) underwent a test. A total of 26 of the 6,114 patients tested (0.4%) had a positive test, and 24 of the 26 HIV-positive patients were linked to HIV medical care. By July 2014, the monthly proportion of patients offered a test was 62%; the proportion of those offered a test who had a test ordered was 98%, and the proportion of those with a test ordered who were tested was 81%. Testing compliance increased substantially at the WHMC ED, from 77% in December 2013 to >98% in July 2014. Conclusion Using compliance-monitoring, behavior-modification, and continuous quality-improvement processes produced substantial increases in offers and HIV test completion. WHMC is replicating this approach across departments, and other hospitals implementing routine HIV screening programs should consider this approach as well. PMID:26862231

  17. Factors impacting the results of interferon-γ release assay and tuberculin skin test in routine screening for latent tuberculosis in patients with inflammatory bowel diseases.

    PubMed

    Papay, Pavol; Eser, Alexander; Winkler, Stefan; Frantal, Sophie; Primas, Christian; Miehsler, Wolfgang; Novacek, Gottfried; Vogelsang, Harald; Dejaco, Clemens; Reinisch, Walter

    2011-01-01

    Screening for latent tuberculosis (LTB) including chest x-ray, tuberculin skin test (TST), and facultative whole blood interferon-γ assay (IGRA) is part of routine management in inflammatory bowel disease (IBD) patients before starting therapy with tumor necrosis factor (TNF)-α inhibitors. However, in patients with immunomodulators (IM) TST and IGRA might show limitations. We aimed to evaluate the results from an IGRA (QuantiFERON-TB Gold in Tube) and TST as well as their concordance in 208 consecutive IBD patients with indications for anti-TNF-α therapy. Associations of both tests with risk factors for LTB were determined by logistic regression. During screening, 149 patients (71.6%) were under IM therapy. In 26 (12.5%) patients TST was positive, whereas 15 (7.2%) patients showed a positive result from IGRA. IGRA failed on samples from 16/208 (7.7%) patients, resulting in 192/208 (92.3%) patients in whom results from both screening tests were available. Correlation between IGRA and TST results was fair (84.9%, κ = 0.21). The presence of risk factors for LTB showed association with positive results of TST (odds ratio [OR] 3.7, 1.5-9.6) and IGRA (OR 3.5, 1.2-11.3). TST was associated furthermore with age (OR 1.06, 1.02-1.10) and signs indicative of LTB in chest x-ray (OR 4.9, 1.1-19.9). The IGRA was negatively influenced by IM therapy (OR 0.3, 0.1-0.9). Our study reveals that results of IGRA are negatively affected by IM therapy. Thus, current guidelines for TB screening prior anti-TNF-α therapy appear inaccurate in patients under IM. Therefore, LTB screening might be best performed prior to initiation of IM treatment. Copyright © 2010 Crohn's & Crohn's & Colitis Foundation of America, Inc.

  18. A combined enrichment/polymerase chain reaction based method for the routine screening of Streptococcus agalactiae in pregnant women

    PubMed Central

    Munari, F.M.; De-Paris, F.; Salton, G.D.; Lora, P.S.; Giovanella, P.; Machado, A.B.M.P.; Laybauer, L.S.; Oliveira, K.R.P.; Ferri, C.; Silveira, J.L.S.; Laurino, C.C.F.C.; Xavier, R.M.; Barth, A.L.; Echeverrigaray, S.; Laurino, J.P.

    2012-01-01

    Group B Streptococcus (GBS) is the most common cause of life-threatening infection in neonates. Guidelines from CDC recommend universal screening of pregnant women for rectovaginal GBS colonization. The objective of this study was to compare the performance of a combined enrichment/PCR based method targeting the atr gene in relation to culture using enrichment with selective broth medium (standard method) to identify the presence of GBS in pregnant women. Rectovaginal GBS samples from women at ≥36 weeks of pregnancy were obtained with a swab and analyzed by the two methods. A total of 89 samples were evaluated. The prevalence of positive results for GBS detection was considerable higher when assessed by the combined enrichment/PCR method than with the standard method (35.9% versus 22.5%, respectively). The results demonstrated that the use of selective enrichment broth followed by PCR targeting the atr gene is a highly sensitive, specific and accurate test for GBS screening in pregnant women, allowing the detection of the bacteria even in lightly colonized patients. This PCR methodology may provide a useful diagnostic tool for GBS detection and contributes for a more accurate and effective intrapartum antibiotic and lower newborn mortality and morbidity. PMID:24031826

  19. 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.

  20. 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.

  1. Screening for toxic phorbol esters in jerky pet treat products using LC–MS

    PubMed Central

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

    2016-01-01

    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

  2. Clinical implementation of routine screening for fetal trisomies in the UK NHS: cell-free DNA test contingent on results from first-trimester combined test.

    PubMed

    Gil, M M; Revello, R; Poon, L C; Akolekar, R; Nicolaides, K H

    2016-01-01

    Cell-free DNA (cfDNA) analysis of maternal blood for detection of trisomies 21, 18 and 13 is superior to other methods of screening but is expensive. One strategy to maximize performance at reduced cost is to offer cfDNA testing contingent on the results of the first-trimester combined test that is used currently. The objectives of this study were to report the feasibility of implementing such screening, to examine the factors affecting patient decisions concerning their options for screening and decisions on the management of affected pregnancies and to report the prenatal diagnosis of fetal trisomies and outcome of affected pregnancies following the introduction of contingent screening. We examined routine clinical implementation of contingent screening in 11,692 singleton pregnancies in two National Health Service (NHS) hospitals in the UK. Women with a risk ≥ 1 in 100 (high-risk group) were offered options of invasive testing, cfDNA testing or no further testing, and those with a risk between 1 in 101 and 1 in 2500 (intermediate-risk group) were offered cfDNA testing or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or by examination of the neonates. In the study population of 11,692 pregnancies, there were 47 cases of trisomy 21 and 28 of trisomies 18 or 13. Screening with the combined test followed by invasive testing for all patients in the high-risk group potentially could have detected 87% of trisomy 21 and 93% of trisomies 18 or 13, at a false-positive rate of 3.4%; the respective values for cfDNA testing in the high- and intermediate-risk groups were 98%, 82% and 0.25%. However, in the high-risk group, 38% of women chose invasive testing and 60% chose cfDNA testing; in the intermediate-risk group 92% opted for cfDNA testing. A prenatal diagnosis was made in 43 (91.5%) pregnancies with trisomy 21 and all pregnancies with trisomies 18 or 13. In many affected pregnancies the parents chose

  3. Paired image- and FACS-based toxicity assays for high content screening of spheroid-type tumor cell cultures.

    PubMed

    Trumpi, Kari; Egan, David A; Vellinga, Thomas T; Borel Rinkes, Inne H M; Kranenburg, Onno

    2015-01-01

    Novel spheroid-type tumor cell cultures directly isolated from patients' tumors preserve tumor characteristics better than traditionally grown cell lines. However, such cultures are not generally used for high-throughput toxicity drug screens. In addition, the assays that are commonly used to assess drug-induced toxicity in such screens usually measure a proxy for cell viability such as mitochondrial activity or ATP-content per culture well, rather than actual cell death. This generates considerable assay-dependent differences in the measured toxicity values. To address this problem we developed a robust method that documents drug-induced toxicity on a per-cell, rather than on a per-well basis. The method involves automated drug dispensing followed by paired image- and FACS-based analysis of cell death and cell cycle changes. We show that the two methods generate toxicity data in 96-well format which are highly concordant. By contrast, the concordance of these methods with frequently used well-based assays was generally poor. The reported method can be implemented on standard automated microscopes and provides a low-cost approach for accurate and reproducible high-throughput toxicity screens in spheroid type cell cultures. Furthermore, the high versatility of both the imaging and FACS platforms allows straightforward adaptation of the high-throughput experimental setup to include fluorescence-based measurement of additional cell biological parameters.

  4. Screening of Toxic Effects of Bisphenol A and Products of Its Degradation: Zebrafish (Danio rerio) Embryo Test and Molecular Docking.

    PubMed

    Makarova, Katerina; Siudem, Pawel; Zawada, Katarzyna; Kurkowiak, Justyna

    2016-10-01

    Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated. The docking experiments showed that 4-isopropylphenol could have similar toxicity to that of BPA due to its high affinity to ERRγ and ERRγB and high octanol-water partitioning coefficient. The least toxic compounds were hydroquinone and phenol. Those compounds as well as BPA were screened in the zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA caused the delay in development, multiple deformations, and low heartbeats (30 bps), whereas hydroquinone had no impact on the development of the zebrafish embryo. Thus, the results of zebrafish screening are in good agreement with our docking experiment. The molecular docking could be used to screen the toxicity of other xenoestrogens and their products of degradation.

  5. Toxicity of electronic waste leachates to Daphnia magna: screening and toxicity identification evaluation of different products, components, and materials.

    PubMed

    Lithner, Delilah; Halling, Maja; Dave, Göran

    2012-05-01

    Electronic waste has become one of the fastest growing waste problems in the world. It contains both toxic metals and toxic organics. The aim of this study was to (1) investigate to what extent toxicants can leach from different electronic products, components, and materials into water and (2) identify which group of toxicants (metals or hydrophobic organics) that is causing toxicity. Components from five discarded electronic products (cell phone, computer, phone modem, keyboard, and computer mouse) were leached in deionised water for 3 days at 23°C in concentrations of 25 g/l for metal components, 50 g/l for mixed-material components, and 100 g/l for plastic components. The water phase was tested for acute toxicity to Daphnia magna. Eighteen of 68 leachates showed toxicity (with immobility of D. magna ≥ 50% after 48 h) and came from metal or mixed-material components. The 8 most toxic leachates, with 48 h EC(50)s ranging from 0.4 to 20 g/l, came from 2 circuit sheets (key board), integrated drive electronics (IDE) cable clips (computer), metal studs (computer), a circuit board (computer mouse), a cord (phone modem), mixed parts (cell phone), and a circuit board (key board). All 5 electronic products were represented among them. Toxicity identification evaluations (with C18 and CM resins filtrations and ethylenediaminetetraacetic acid addition) indicated that metals caused the toxicity in the majority of the most toxic leachates. Overall, this study has shown that electronic waste can leach toxic compounds also during short-term leaching with pure water.

  6. 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. © 2015 Wiley Periodicals, Inc.

  7. 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

  8. Routine bacterial screening of platelet concentrates by flow cytometry and its impact on product safety and supply.

    PubMed

    Müller, B; Walther-Wenke, G; Kalus, M; Alt, T; Bux, J; Zeiler, T; Schottstedt, V

    2015-04-01

    Bacterial contamination represents the major infectious hazard associated with transfusion of platelet concentrates (PCs). As bacterial screening of PCs is not mandatory in Germany, the BactiFlow flow cytometry test has been introduced as a rapid detection method to increase product safety. During a period of 25 months, a total of 34 631 PCs (26 411 pooled and 8220 apheresis-derived PCs) were tested at the end of day 3 of their shelf life using the BactiFlow system. PCs initially reactive in BactiFlow testing and expired PCs not reactive in BactiFlow on day 3 were also investigated by the BacT/ALERT system and by microbiological cultivation in order to identify the contaminating bacterial species and to confirm reactive BactiFlow results. Two hundred and twenty-eight PCs (0.7%) had an initially reactive result, 24 of them remained reactive in a second test run. Out of these reproducible reactive BactiFlow results, 12 could not be verified by parallel BacT/ALERT culturing, resulting in a confirmed false-positive rate of 0.03%. The bacterial species were identified as S. aureus, S. epidermidis, S. dysgalactiae ssp. equisimilis and B. cereus. In 10 out of 9017 expired PCs (0.11%), a confirmed-positive result was obtained in the BacT/ALERT system which had a negative result in the BactiFlow system. Testing of PCs by BactiFlow was successfully implemented in our blood donation service and proved sufficient as a rapid and reliable screening method. False reactive results are in an acceptable range since the transfusion of 12 bacterially contaminated PCs was prevented. © 2014 International Society of Blood Transfusion.

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

    PubMed

    Roura, Esther; Iftner, Thomas; Vidart, José Antonio; Kjaer, Susanne Krüger; Bosch, F Xavier; Muñoz, Nubia; Palacios, Santiago; Rodriguez, Maria San Martin; Morillo, Carmen; Serradell, Laurence; Torcel-Pagnon, Laurence; Cortes, Javier; Castellsagué, Xavier

    2012-06-26

    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. 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. 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). 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.

  10. 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.

  11. [Prevention of severe toxicity from capecitabine, 5-fluorouracil and tegafur by screening for DPD-deficiency].

    PubMed

    Deenen, Maarten J; Cats, Annemieke; Mandigers, Caroline M P W; Soesan, Marcel; Terpstra, Wim E; Beijnen, Jos H; Schellens, Jan H M

    2012-01-01

    Capecitabine, 5-fluorouracil and tegafur form the group called the fluoropyrimidines, which is one of the most frequently prescribed group of anti-cancer drugs for the treatment of (metastatic) colorectal, gastric and breast cancer. The primary enzyme responsible for the inactivation of the fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD). Consequently, patients with an inborn partial DPD deficiency, induced, for example by the polymorphism DPYD*2A, are highly prone to severe, potentially lethal toxicity following a standard dose of fluoropyrimidines. In this article, based on three representative case reports and our prospective study in patients with cancer, we demonstrate the clinical value of prospective screening for DPD deficiency in patients being treated with fluoropyrimidine-based anti-cancer therapy. The results show that upfront genotyping for DPYD*2A followed by a fluoropyrimidine dose reduction of 50% (on average) in patients heterozygous polymorphic for DPYD*2A, significantly reduces the incidence of severe to potentially lethal toxicity compared to historical control patients given full-dose therapy.

  12. Toxicological assessment of refined naphthenic acids in a repeated dose/developmental toxicity screening test.

    PubMed

    McKee, Richard H; North, Colin M; Podhasky, Paula; Charlap, Jeffrey H; Kuhl, Adam

    2014-01-01

    Naphthenic acids (NAs) are primarily cycloaliphatic carboxylic acids with 10 to 16 carbons. To characterize the potential of refined NAs (>70% purity) to cause reproductive and/or developmental effects, Sprague-Dawley rats (12/group) were given oral doses of 100, 300, or 900 mg/kg/d, beginning 14 days prior to mating, then an additional 14 days for males or through lactation day 3 for females (up to 53 days) in a repeated dose/reproductive toxicity test (Organization for Economic Cooperation and Development [OECD] 422). Potential mutagenic effects were assessed using Salmonella (OECD 471) and in in vivo micronucleus tests (OECD 474) using bone marrow taken from treated animals in the screening study described previously. Systemic effects included reduced terminal body weights, increased liver weights, and changes in a number of blood cell parameters. The overall no effect level for all target organ effects was 100 mg/kg/d. In the reproductive/developmental toxicity assessment, there were significant reductions in numbers of live born offspring in groups exposed to 300 and 900 mg/kg/d. The overall no effect level for developmental effects was 100 mg/kg/d. The data from the Salmonella and micronucleus tests provide evidence that refined NAs are not genotoxic.

  13. The accuracy and effectiveness of routine population screening with mammography, prostate-specific antigen, and prenatal ultrasound: a review of published scientific evidence.

    PubMed

    Woolf, S H

    2001-01-01

    . Even for the most established screening tests, the appropriateness of routine testing depends on subjective value judgments about the quality of supporting evidence and about the trade-offs between benefits and harms. Individuals, clinicians, policy makers, and governments must weigh the evidence in light of these values and the constraints imposed by available resources.

  14. Predicting Future Hip Fractures on Routine Abdominal CT Using Opportunistic Osteoporosis Screening Measures: A Matched Case-Control Study.

    PubMed

    Lee, Scott J; Anderson, Paul A; Pickhardt, Perry J

    2017-08-01

    Hip fracture is a major consequence of low bone mineral density, which is treatable but underdiagnosed. The purpose of this case-control study is to determine whether lumbar vertebral trabecular attenuation, vertebral compression fractures, and femoral neck T scores readily derived from abdominopelvic CT scans obtained for various indications are associated with future hip fragility fracture. A cohort of 204 patients with hip fracture (130 women and 74 men; mean age, 74.3 years) who had undergone abdominopelvic CT before fracture occurred (mean interval, 24.8 months) was compared with an age- and sex-matched control cohort without hip fracture. L1 trabecular attenuation, vertebral compression fractures of grades 2 and 3, and femoral neck T scores derived from asynchronous quantitative CT were recorded. The presence of one or more clinical risk factor for fracture was also recorded. Multivariate logistic regression models were used to determine the association of each measurement with the occurrence of hip fracture. The mean L1 trabecular attenuation value, the presence of one or more vertebral compression fracture, and CT-derived femoral neck T scores were all significantly different in patients with hip fracture versus control subjects (p < 0.01). Logistic regression models showed a significant association of all measurements with hip fracture outcome after adjustments were made for age, sex, and the presence of one or more clinical risk factor. L1 trabecular attenuation and CT-derived femoral neck T scores showed moderate accuracy in differentiating case and control patients (AUC, 0.70 and 0.78, respectively). L1 trabecular attenuation, CT-derived femoral neck T scores, and the presence of at least one vertebral compression fracture on CT are all associated with future hip fragility fracture in adults undergoing routine abdominopelvic CT for a variety of conditions.

  15. Text-message reminders increase uptake of routine breast screening appointments: a randomised controlled trial in a hard-to-reach population

    PubMed Central

    Kerrison, R S; Shukla, H; Cunningham, D; Oyebode, O; Friedman, E

    2015-01-01

    Background: There is a need for interventions to promote uptake of breast screening throughout Europe. Methods: We performed a single-blind randomised controlled trial to test whether text-message reminders were effective. Two thousand two hundred and forty women receiving their first breast screening invitation were included in the study and randomly assigned in a 1 : 1 ratio to receive either a normal invitation only (n=1118) or a normal invitation plus a text-message reminder 48 h before their appointment (n=1122). Findings: In the intention-to-treat analysis, uptake of breast screening was 59.1% among women in the normal invitation group and 64.4% in the text-message reminder group (χ2=6.47, odds ratio (OR): 1.26, 95% confidence intervals (CI): 1.05–1.48, P=0.01). Of the 1122 women assigned to the text-message reminder group, only 456 (41%) had a mobile number recorded by their GP and were thereby sent a text. In the per-protocol analysis, uptake by those in the control group who had a mobile number recorded on the GP system was 59.77% and by those in the intervention group who were sent a reminder 71.7% (χ2=14.12, OR=1.71, 95% CI=1.29–2.26, P<0.01). Interpretation: Sending women a text-message reminder before their first routine breast screening appointment significantly increased attendance. This information can be used to allocate resources efficiently to improve uptake without exacerbating social inequalities. PMID:25668008

  16. Text-message reminders increase uptake of routine breast screening appointments: a randomised controlled trial in a hard-to-reach population.

    PubMed

    Kerrison, R S; Shukla, H; Cunningham, D; Oyebode, O; Friedman, E

    2015-03-17

    There is a need for interventions to promote uptake of breast screening throughout Europe. We performed a single-blind randomised controlled trial to test whether text-message reminders were effective. Two thousand two hundred and forty women receiving their first breast screening invitation were included in the study and randomly assigned in a 1 : 1 ratio to receive either a normal invitation only (n=1118) or a normal invitation plus a text-message reminder 48 h before their appointment (n=1122). In the intention-to-treat analysis, uptake of breast screening was 59.1% among women in the normal invitation group and 64.4% in the text-message reminder group (χ(2)=6.47, odds ratio (OR): 1.26, 95% confidence intervals (CI): 1.05-1.48, P=0.01). Of the 1122 women assigned to the text-message reminder group, only 456 (41%) had a mobile number recorded by their GP and were thereby sent a text. In the per-protocol analysis, uptake by those in the control group who had a mobile number recorded on the GP system was 59.77% and by those in the intervention group who were sent a reminder 71.7% (χ(2)=14.12, OR=1.71, 95% CI=1.29-2.26, P<0.01). Sending women a text-message reminder before their first routine breast screening appointment significantly increased attendance. This information can be used to allocate resources efficiently to improve uptake without exacerbating social inequalities.

  17. Screening for chest disease in college students: policies of student health services regarding the use of routine screening chest radiographs and tuberculin skin tests

    SciTech Connect

    Fager, S.S.; Slap, G.B.; Kitz, D.S.; Eisenberg, J.M.

    1984-02-01

    A survey of college health services was conducted to determine their policies regarding the use of screening chest radiographs and tuberculin skin tests. Pre-enrollment chest radiographs are prescribed for all incoming students by 24% of the 531 respondents and for health professions students, foreign students, and intercollegiate athletes only by an additional 20%, 19%, and 6%, respectively. Periodic chest radiography is conducted for all students by 7% of the respondents and for health professions students, foreign students, and intercollegiate athletes only by an additional 22%, 16%, and 8%, respectively. Pre-enrollment tuberculin skin tests are prescribed for all incoming students by 52% of the respondents and for health professions students, foreign students, and intercollegiate athletes only by an additional 48%, 29%, and 9%, respectively. Periodic tuberculin skin testing is conducted for all students by 27% of the respondents and for health professions students, foreign students, and intercollegiate athletes only by an additional 48%, 23%, and 16%, respectively. It is estimated from these data that 723,000 incoming students in the United States received screening chest radiographs in 1979 with estimated charges totaling between $7 million and $27 million. There may be 0.05 to 0.33 induced cases of lung cancer, leukemia, thyroid cancer, and female breast cancer over a 20-year period among this group of students exposed to ionizing radiation.

  18. 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

  19. Social Withdrawal Among Individuals Receiving Psychiatric Care: Derivation of a Scale Using Routine Clinical Assessment Data to Support Screening and Outcome Measurement.

    PubMed

    Rios, Sebastian; Perlman, Christopher M

    2017-04-24

    Social withdrawal is a symptom experienced by individuals with an array of mental health conditions, particularly those with schizophrenia and mood disorders. Assessments of social withdrawal are often lengthy and may not be routinely integrated within the comprehensive clinical assessment of the individual. This study utilized item response and classical test theory methods to derive a Social Withdrawal Scale (SWS) using items embedded within a routine clinical assessment, the RAI-Mental Health (RAI-MH). Using data from 60,571 inpatients in Ontario, Canada, a common factor analysis identified seven items from the RAI-MH that measure social withdrawal. A graded response model found that six items had acceptable discrimination parameters: lack of motivation, reduced interaction, decreased energy, flat affect, anhedonia, and loss of interest. Summing these items, the SWS was found to have strong internal consistency (Cronbach's alpha = 0.82) and showed a medium to large effect size (d = 0.77) from admission to discharge. Fewer individuals with high SWS scores participated in social activity or reported having a confidant compared to those with lower scores. Since the RAI-MH is available across clinical subgroups in several jurisdictions, the SWS is a useful tool for screening, clinical decision support, and evaluation.

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

    PubMed

    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

    2016-05-01

    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. 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. 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. 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.

  1. 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

  2. Payer Status, Race/Ethnicity, and Acceptance of Free Routine Opt-Out Rapid HIV Screening Among Emergency Department Patients

    PubMed Central

    Hopkins, Emily; Sasson, Comilla; Al-Tayyib, Alia; Bender, Brooke; Haukoos, Jason S.

    2012-01-01

    Objectives. We estimated associations between payer status, race/ethnicity, and acceptance of nontargeted opt-out rapid HIV screening in the emergency department (ED). Methods. We analyzed data from a prospective clinical trial between 2007 and 2009 at Denver Health. Patients in the ED were offered free HIV testing. Patient demographics and payer status were collected, and we used multivariable logistic regression to estimate associations with HIV testing acceptance. Results. A total of 31 525 patients made 44 765 unique visits: 40% were White, 37% Hispanic, 14% Black, 1% Asian, and 7% unknown race/ethnicity. Of all visits, 10 237 (23%) agreed to HIV testing; 27% were self-pay, 23% state-sponsored, 18% Medicaid, 13% commercial insurance, 12% Medicare, and 8% another payer source. Compared with commercial insurance patients, self-pay patients (odds ratio [OR] = 1.63; 95% confidence interval [CI] = 1.51, 1.75), state-sponsored patients (OR = 1.64; 95% CI = 1.52, 1.77), and Medicaid patients (OR = 1.24; 95% CI = 1.14, 1.34) had increased odds of accepting testing. Compared with White patients, Black (OR = 1.29; 95% CI = 1.21, 1.38) and Hispanic (OR = 1.17; 95% CI = 1.11, 1.23) patients had increased odds of accepting testing. Conclusions. Many ED patients are uninsured or subsidized through government programs and are more likely to consent to free rapid HIV testing. PMID:22420816

  3. Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

    EPA Pesticide Factsheets

    Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

  4. 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...

  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. Is routine viral screening useful in patients with recent-onset polyarthritis of a duration of at least 6 weeks? Results from a nationwide longitudinal prospective cohort study.

    PubMed

    Varache, Sophie; Narbonne, Valérie; Jousse-Joulin, Sandrine; Guennoc, Xavier; Dougados, Maxime; Daurès, Jean Pierre; Devauchelle-Pensec, Valerie; Saraux, Alain

    2011-11-01

    To study the contribution of routine viral screening tests in patients with early rheumatoid arthritis (RA) or a potential for progressing to RA. Eight hundred thirteen patients with swelling of at least 2 joints for at least 6 weeks and a symptom duration of less than 6 months in the ESPOIR cohort were screened for parvovirus B19 (IgG and IgM anti-parvovirus B19 antibodies), hepatitis B virus (HBV; hepatitis B surface antigen), hepatitis C virus (HCV; anti-HCV antibodies), and human immunodeficiency virus (HIV; anti-HIV-1 and -2 antibodies). Parvovirus B19 testing was performed in 806 patients and showed longstanding immunity in 574 (71.2%) and no antibodies in 223 (27.7%). Among the 9 remaining patients (7 IgG positive/IgM positive, 1 IgG negative/IgM positive, and 1 IgG indeterminate/IgM positive), only 2 (0.25%; 95% confidence interval [95% CI] 0-0.99%) had a positive polymerase chain reaction test for parvovirus B19; these patients (women ages 34 and 40 years) had no extraarticular signs. HIV seroprevalence was 0.12% (n = 1 of 813; 95% CI 0.01-0.8%) and HCV seroprevalence was 0.86% (n = 7 of 808, 95% CI 0.38-1.86%). HCV-related arthritis was diagnosed in 4 patients (0.5%). HCV-seropositive patients had significantly higher transaminase levels than the other patients (P = 0.001), with no significant differences for the other laboratory data. HBV seroprevalence was 0.12% (n = 1 of 808; 95% CI 0.01-0.8%); the positive HBV status was known before study inclusion, and the patient had no diagnosis of HBV-related arthritis. Finally, routine viral testing identified 2 patients with parvovirus B19 infection and 3 with HBV infection (0.6%; 95% CI 0.2-1.5%). Cost was €85.05 per patient (total €68,720). Routine serologic testing did not contribute substantially to the diagnosis in this context. Copyright © 2011 by the American College of Rheumatology.

  7. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study.

    PubMed

    Hobbs, F D R; Fitzmaurice, D A; Mant, J; Murray, E; Jowett, S; Bryan, S; Raftery, J; Davies, M; Lip, G

    2005-10-01

    cases (incidence 1.1% per year). Of these, 31 were detected by targeted screening and a further 21 by total population screening. A further 22 cases were detected outside the screening programme (overall incidence 1.62% per year). In terms of ECG interpretation, computerised decision support software (CDSS) gave a sensitivity of 87.3%, a specificity of 99.1% and a positive predictive value (PPV) of 89.5% compared with the gold standard (cardiologist reporting). GPs and practice nurses performed less well. The only difference in performance between intervention populations and controls was that practice nurses from the control arm performed less well than with intervention practice nurses on interpretation of limb-lead (PPV 38.8% versus 20.8%) and single-lead (PPV 37.7% versus 24.0%) ECGs. The within-trial economic evaluation results showed the lowest incremental cost to be for the opportunistic arm, with an incremental cost-effectiveness ratio of 337 pounds Sterling for each additional case detected compared to the control arm. Opportunistic screening dominated both more intensive screening strategies. Model-based analyses showed small differences in cost and quality-adjusted life-years for different methods and intensities of screening, but annual opportunistic screening resulted in the lowest number of ischaemic strokes and greatest proportion of cases of AF diagnosed. Probabilistic sensitivity results indicated that there was a probability of approximately 60% that screening from the age of 65 years was cost-effective in both men and women. The results of the study indicated that in terms of a screening programme for atrial fibrillation in patients 65 and over, the only strategy that improved on routine practice was opportunistic screening, model-based analyses indicated that there was a probability of approximately 60% of annual opportunistic screening being cost effective. It is suggested that the following topics are worthy of further investigation: the effect of

  8. 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.

  9. 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.

  10. 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.

  11. Predicting late-onset sepsis by routine neonatal screening for colonisation by gram-negative bacteria in neonates at intensive care units: a protocol for a systematic review

    PubMed Central

    Harder, Thomas; Seidel, Juliane; Eckmanns, Tim; Weiss, Bettina; Haller, Sebastian

    2017-01-01

    Introduction Hospitals conduct extensive screening procedures to assess colonisation of the body surface of neonates by gram-negative bacteria to avoid complications like late-onset sepsis. However, the benefits of these procedures are controversially discussed. Until now, no systematic review has investigated the value of routine screening for colonisation by gram-negative bacteria in neonates for late-onset sepsis prediction. Methods and analysis We will conduct a systematic review, considering studies of any design that include infants up to an age of 12 months. We will search MEDLINE and EMBASE (inception to 2016), reference lists and grey literature. Screening of titles, abstracts and full texts will be conducted by two independent reviewers. We will extract data on study characteristics and study results. Risk of bias will be assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Quality in Prognosis Studies (QUIPS) tools. Subgroup analyses are planned according to characteristics of studies, participants, index tests and outcome. For quantitative data synthesis on prognostic accuracy, sensitivity and specificity of screening to detect late-onset sepsis will be calculated. If sufficient data are available, we will calculate summary estimates using hierarchical summary receiver operating characteristics and bivariate models. Applying a risk factor approach, pooled summary estimates will be calculated as relative risk or OR, using fixed-effects and random-effects models. I-squared will be used to assess heterogeneity. All calculations will be performed in Stata V14.1 (College Station, Texas, USA). The results will be used to calculate positive and negative predictive value and number needed to be screened to prevent one case of sepsis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess certainty in the evidence. The protocol follows the Preferred Reporting Items for Systematic Review and

  12. Evaluation of a hepatitis C virus (HCV) antigen assay for routine HCV screening among men who have sex with men infected with HIV.

    PubMed

    Vanhommerig, Joost W; van de Laar, Thijs J W; Koot, Maarten; van Rooijen, Martijn S; Schinkel, Janke; Speksnijder, Arjen G C L; Prins, Maria; de Vries, Henry J; Bruisten, Sylvia M

    2015-03-01

    For detection of early HCV infection and reinfection, commercial HCV-RNA tests are available. However, these tests are relatively time-consuming and expensive. A commercially available test that may supplement current screening methods, targets the HCV core protein. During five waves of anonymous surveys at the Amsterdam STI clinic between 2009-2012, all HIV-infected MSM (N=439) were tested for HCV-antibodies (AxSYM HCV 3.0, Abbott), and HCV-RNA (TMA Versant, Siemens). To evaluate the potential value of the ARCHITECT HCV antigen (HCV-Ag) assay (Abbott), all HCV-RNA-positive sera (N=31) were tested with this assay, as well as two HIV-infected HCV-RNA-negative controls. In addition, all included samples were tested for alanine aminotransferase (ALT). Among 439 HIV-infected MSM, 31 (7.1%) tested positive for HCV-RNA; the HCV-Ag assay showed concordant positive results for 31/31 (100%). A substantial number of MSM, i.e., 5/31 (16.1%), had detectable HCV-RNA but were HCV-seronegative at the time of screening and were presumed to have been recently infected. Concordant HCV-RNA-negative results were obtained in 57/60 control-samples. Specificity was 95.0% (95% CI: 86.1-99.0). The detection limit was between 3.0 and 3.7 Log10 IU/mL, irrespective of HCV genotype/subtype. ALT concentrations were elevated (i.e.,>40 U/L) in 9/31 (29.0%) HCV-RNA positive MSM, including 1/5 (20.0%) MSM with recent HCV-infection. The HCV-Ag assay proved a valuable screening tool for detection of active HCV infection among HIV-infected MSM with and without anti-HCV. Adding ALT to current screening methods would improve case finding marginally. We therefore recommend implementation of routine HCV-Ag screening for populations at risk for HCV-(re)infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

    PubMed

    Kurz, Ella; Davis, Deborah

    2015-04-17

    Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

  14. 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.

  15. Toxicity profiling of marine surface sediments: A case study using rapid screening bioassays of exhaustive total extracts, elutriates and passive sampler extracts.

    PubMed

    Vethaak, A Dick; Hamers, Timo; Martínez-Gómez, Concepción; Kamstra, Jorke H; de Weert, Jasperien; Leonards, Pim E G; Smedes, Foppe

    2017-03-01

    This study was carried out in the framework of the ICON project (Integrated Assessment of Contaminant Impacts on the North Sea) (Hylland et al., 2015) and aimed (1) to evaluate the toxicity of marine sediments using a battery of rapid toxicity bioassays, and; (2) to explore the applicability and data interpretation of in vitro toxicity profiling of sediment extracts obtained from ex situ passive sampling. Sediment samples were collected at 12 selected (estuarine, coastal, offshore) sites in the North Sea, Icelandic waters (as reference sites), south-western Baltic Sea and western Mediterranean during autumn 2008. Organic extracts using a mild non-destructive clean-up procedure were prepared from total sediment and silicone passive samplers and tested with five in vitro bioassays: DR-Luc bioassay, ER-Luc bioassay, AR-EcoScreen bioassay, transthyretin (TTR) binding assay, and Vibrio fischeri bioluminescence bioassay. In vitro toxicity profiling of total sediment and silicone passive sampler extracts showed the presence of multiple organic contaminations by arylhydrocarbon receptor agonists (e.g. polycyclic aromatic hydrocarbons) and endocrine-active compounds, as well as non-specific toxicity caused by organic contaminants, at virtually all sampling sites. In vitro responses to total sediment extracts from coastal/estuarine sites were significantly different from those in offshore sites (p < 0.05). Several bioassays of passive sampler extracts showed highest activity in some offshore sediment samples. Impact on embryogenesis success and larval growth in undiluted sediment elutriates was shown at some sites using the in vivo sea urchin embryo test. The observed toxicity profiles could only partially be explained by the chemical target analysis, indicating the presence of unknown or unanalysed biologically-active compounds in the sediments. In vitro bioassay testing with silicone passive sampler extracts of sediments is a promising tool to assess the toxic

  16. Screening for Small Molecule Inhibitors of Statin-Induced APP C-terminal Toxic Fragment Production.

    PubMed

    Poksay, Karen S; Sheffler, Douglas J; Spilman, Patricia; Campagna, Jesus; Jagodzinska, Barbara; Descamps, Olivier; Gorostiza, Olivia; Matalis, Alex; Mullenix, Michael; Bredesen, Dale E; Cosford, Nicholas D P; John, Varghese

    2017-01-01

    Alzheimer's disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model. Thus, inhibition of this cleavage is a reasonable target for new therapeutic development. In order to identify small molecules that inhibit the generation of APP-C31, we first used an APPΔC31 cleavage site-specific antibody to develop an AlphaLISA to screen several chemical compound libraries for the level of N-terminal fragment production. This antibody was also used to develop an ELISA for validation studies. In both high throughput screening (HTS) and validation testing, the ability of compounds to inhibit simvastatin- (HTS) or cerivastatin- (validation studies) induced caspase cleavage at the APP-D720 cleavage site was determined in Chinese hamster ovary (CHO) cells stably transfected with wildtype (wt) human APP (CHO-7W). Several compounds, as well as control pan-caspase inhibitor Q-VD-OPh, inhibited APPΔC31 production (measured fragment) and rescued cell death in a dose-dependent manner. The effective compounds fell into several classes including SERCA inhibitors, inhibitors of Wnt signaling, and calcium channel antagonists. Further studies are underway to evaluate the efficacy of lead compounds - identified here using cells and tissues expressing wt human APP - in mouse models of AD expressing mutated human APP, as well as to identify additional compounds and determine the mechanisms by which they exert their effects.

  17. Screening for Small Molecule Inhibitors of Statin-Induced APP C-terminal Toxic Fragment Production

    PubMed Central

    Poksay, Karen S.; Sheffler, Douglas J.; Spilman, Patricia; Campagna, Jesus; Jagodzinska, Barbara; Descamps, Olivier; Gorostiza, Olivia; Matalis, Alex; Mullenix, Michael; Bredesen, Dale E.; Cosford, Nicholas D. P.; John, Varghese

    2017-01-01

    Alzheimer’s disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model. Thus, inhibition of this cleavage is a reasonable target for new therapeutic development. In order to identify small molecules that inhibit the generation of APP-C31, we first used an APPΔC31 cleavage site-specific antibody to develop an AlphaLISA to screen several chemical compound libraries for the level of N-terminal fragment production. This antibody was also used to develop an ELISA for validation studies. In both high throughput screening (HTS) and validation testing, the ability of compounds to inhibit simvastatin- (HTS) or cerivastatin- (validation studies) induced caspase cleavage at the APP-D720 cleavage site was determined in Chinese hamster ovary (CHO) cells stably transfected with wildtype (wt) human APP (CHO-7W). Several compounds, as well as control pan-caspase inhibitor Q-VD-OPh, inhibited APPΔC31 production (measured fragment) and rescued cell death in a dose-dependent manner. The effective compounds fell into several classes including SERCA inhibitors, inhibitors of Wnt signaling, and calcium channel antagonists. Further studies are underway to evaluate the efficacy of lead compounds – identified here using cells and tissues expressing wt human APP – in mouse models of AD expressing mutated human APP, as well as to identify additional compounds and determine the mechanisms by which they exert their effects. PMID:28261092

  18. 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.

  19. Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

    PubMed

    Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

    2017-09-01

    Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Fractionation of extracts from paper and board food contact materials for in vitro screening of toxicity.

    PubMed

    Bengtström, Linda; Trier, Xenia; Granby, Kit; Rosenmai, Anna Kjerstine; Petersen, Jens Højslev

    2014-01-01

    Paper and board used as food contact materials (FCMs) are chemically complex matrices, partly due to the naturally occurring substances in paper and board, but also due to the chemical treatment of the paper used to make it suitable for food contact. In order to assure the safety of packaging materials, information on the exposure as well as on the toxicity of substances in the packaging must be obtained. This study describes a comprehensive method for the extraction and fractionation of substances present in paper and board FCMs for further investigation by in vitro testing and chemical analysis. The extraction efficiency and the fractionation process were validated by determining recoveries in extracts from paper and board fortified with five surrogates of known concentration. The recoveries for the five surrogates were between 20% and 104% in the raw extract and between 21% and 109% after extraction and fractionation. The fractionation both reduces the number of compounds to be identified and works as a sample clean-up by reducing matrix effects. Raw extracts and fractions from two paper and board FCMs were furthermore tested in the aryl hydrocarbon receptor (AhR) reporter gene assay. Both raw extracts and two of the fractions of the raw extracts gave a positive response in the AhR assay. The strategy of extraction followed by fractionation offers a powerful tool in order to make the workflow for screening FCMs for potentially adverse effects more efficient.

  1. Plant toxicity testing to derive ecological soil screening levels for cobalt and nickel.

    PubMed

    Kapustka, Lawrence A; Eskew, David; Yocum, Joan M

    2006-03-01

    Phytotoxicity tests were performed to set ecological soil screening levels for cobalt (Co) and nickel (Ni) following the American Society for Testing and Materials international E1963-98 Standard Guide for Conducting Terrestrial Plant Toxicity Tests. Two soils (a modified artificial soil mixed with 5% organic matter, pH 5.01, and a native riverine sandy soil with 0.1% organic matter, pH 6.3) were treated with cobalt(II) chloride or nickel chloride and allowed to age for four weeks before initiating tests. Alfalfa, barley, radish, perennial rye, and brassica were used to determine the appropriate range of concentrations and to select the most sensitive plant species for definitive tests. The tests were designed to have one to three test concentrations below the 20% effects concentration (EC20), and five to six test concentrations above the EC20. Definitive tests for each chemical used two soil matrices, three plant species, and replicates at 10 nominal concentrations, including negative control. Soil chemical concentrations were determined before planting and on completion of the phytotoxicity tests. Threshold responses interpreted as the EC20 for each species endpoint were calculated from regression analyses. The geometric mean of the EC20 values (excluding emergence, mortality, and nodule numbers) for each species resulted in values of 30.6 mg/kg for Co and 27.9 mg/kg for Ni.

  2. Improvement of Physical Activity by a Kiosk-based Electronic Screening and Brief Intervention in Routine Primary Health Care: Patient-Initiated Versus Staff-Referred.

    PubMed

    Leijon, Matti; Arvidsson, Daniel; Nilsen, Per; Stark Ekman, Diana; Carlfjord, Siw; Andersson, Agneta; Johansson, Anne Lie; Bendtsen, Preben

    2011-11-22

    Interactive behavior change technology (eg, computer programs, Internet websites, and mobile phones) may facilitate the implementation of lifestyle behavior interventions in routine primary health care. Effective, fully automated solutions not involving primary health care staff may offer low-cost support for behavior change. We explored the effectiveness of an electronic screening and brief intervention (e-SBI) deployed through a stand-alone information kiosk for promoting physical activity among sedentary patients in routine primary health care. We further tested whether its effectiveness differed between patients performing the e-SBI on their own initiative and those referred to it by primary health care staff. The e-SBI screens for the physical activity level, motivation to change, attitudes toward performing the test, and physical characteristics and provides tailored feedback supporting behavior change. A total of 7863 patients performed the e-SBI from 2007 through 2009 in routine primary health care in Östergötland County, Sweden. Of these, 2509 were considered not sufficiently physically active, and 311 of these 2509 patients agreed to participate in an optional 3-month follow-up. These 311 patients were included in the analysis and were further divided into two groups based on whether the e-SBI was performed on the patient´s own initiative (informed by posters in the waiting room) or if the patient was referred to it by staff. A physical activity score representing the number of days being physically active was compared between baseline e-SBI and the 3-month follow-up. Based on physical activity recommendations, a score of 5 was considered the cutoff for being sufficiently physically active. In all, 137 of 311 patients (44%) were sufficiently physically active at the 3-month follow-up. The proportion becoming sufficiently physically active was 16/55 (29%), 40/101 (40%), and 81/155 (52%) for patients with a physical activity score at baseline of 0, 1 to

  3. Improvement of Physical Activity by a Kiosk-based Electronic Screening and Brief Intervention in Routine Primary Health Care: Patient-Initiated Versus Staff-Referred

    PubMed Central

    Nilsen, Per; Stark Ekman, Diana; Carlfjord, Siw; Andersson, Agneta; Johansson, Anne Lie; Bendtsen, Preben

    2011-01-01

    Background Interactive behavior change technology (eg, computer programs, Internet websites, and mobile phones) may facilitate the implementation of lifestyle behavior interventions in routine primary health care. Effective, fully automated solutions not involving primary health care staff may offer low-cost support for behavior change. Objectives We explored the effectiveness of an electronic screening and brief intervention (e-SBI) deployed through a stand-alone information kiosk for promoting physical activity among sedentary patients in routine primary health care. We further tested whether its effectiveness differed between patients performing the e-SBI on their own initiative and those referred to it by primary health care staff. Methods The e-SBI screens for the physical activity level, motivation to change, attitudes toward performing the test, and physical characteristics and provides tailored feedback supporting behavior change. A total of 7863 patients performed the e-SBI from 2007 through 2009 in routine primary health care in Östergötland County, Sweden. Of these, 2509 were considered not sufficiently physically active, and 311 of these 2509 patients agreed to participate in an optional 3-month follow-up. These 311 patients were included in the analysis and were further divided into two groups based on whether the e-SBI was performed on the patient´s own initiative (informed by posters in the waiting room) or if the patient was referred to it by staff. A physical activity score representing the number of days being physically active was compared between baseline e-SBI and the 3-month follow-up. Based on physical activity recommendations, a score of 5 was considered the cutoff for being sufficiently physically active. Results In all, 137 of 311 patients (44%) were sufficiently physically active at the 3-month follow-up. The proportion becoming sufficiently physically active was 16/55 (29%), 40/101 (40%), and 81/155 (52%) for patients with a physical

  4. Interspecies quantitative structure-activity relationships (QSARs) for eco-toxicity screening of chemicals: the role of physicochemical properties.

    PubMed

    Furuhama, A; Hasunuma, K; Aoki, Y

    2015-01-01

    In addition to molecular structure profiles, descriptors based on physicochemical properties are useful for explaining the eco-toxicities of chemicals. In a previous study we reported that a criterion based on the difference between the partition coefficient (log POW) and distribution coefficient (log D) values of chemicals enabled us to identify aromatic amines and phenols for which interspecies relationships with strong correlations could be developed for fish-daphnid and algal-daphnid toxicities. The chemicals that met the log D-based criterion were expected to have similar toxicity mechanisms (related to membrane penetration). Here, we investigated the applicability of log D-based criteria to the eco-toxicity of other kinds of chemicals, including aliphatic compounds. At pH 10, use of a log POW - log D > 0 criterion and omission of outliers resulted in the selection of more than 100 chemicals whose acute fish toxicities or algal growth inhibition toxicities were almost equal to their acute daphnid toxicities. The advantage of log D-based criteria is that they allow for simple, rapid screening and prioritizing of chemicals. However, inorganic molecules and chemicals containing certain structural elements cannot be evaluated, because calculated log D values are unavailable.

  5. Rapid bioassay-guided screening of toxic substances in vegetable oils that shorten the life of SHRSP rats.

    PubMed

    Ratnayake, Sunil; Lewandowski, Paul

    2010-02-02

    It has been consistently reported that vegetable oils including canola oil have a life shortening effect in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) and this toxic effect is not due to the fatty acid composition of the oil. Although it is possible that the phytosterol content or type of phytosterol present in vegetable oils may play some role in the life shortening effect observed in SHRSP rats this is still not completely resolved. Furthermore supercritical CO2 fractionation of canola oil with subsequent testing in SHRSP rats identified safe and toxic fractions however, the compounds responsible for life shortening effect were not characterised. The conventional approach to screen toxic substances in oils using rats takes more than six months and involves large number of animals. In this article we describe how rapid bioassay-guided screening could be used to identify toxic substances derived from vegetable oils and/or processed foods fortified with vegetable oils. The technique incorporates sequential fractionation of oils/processed foods and subsequent treatment of human cell lines that can be used in place of animal studies to determine cytotoxicity of the fractions with structural elucidation of compounds of interest determined via HPLC-MS and GC-MS. The rapid bioassay-guided screening proposed would require two weeks to test multiple fractions from oils, compared with six months if animal experiments were used to screen toxic effects. Fractionation of oil before bio-assay enhances the effectiveness of the detection of active compounds as fractionation increases the relative concentration of minor components.

  6. 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

  7. 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...

  8. 40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... biochemistry. (i) Clinical biochemistry determinations to investigate major toxic effects in tissues and... hematological and clinical biochemistry variables before dosing commences. (11) Pathology—(i) Gross necropsy. (A... assessments. (F) Hematological tests with relevant baseline values, (G) Clinical biochemistry tests with...

  9. 40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... biochemistry. (i) Clinical biochemistry determinations to investigate major toxic effects in tissues and... hematological and clinical biochemistry variables before dosing commences. (11) Pathology—(i) Gross necropsy. (A... assessments. (F) Hematological tests with relevant baseline values, (G) Clinical biochemistry tests with...

  10. 40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... biochemistry. (i) Clinical biochemistry determinations to investigate major toxic effects in tissues and... hematological and clinical biochemistry variables before dosing commences. (11) Pathology—(i) Gross necropsy. (A... assessments. (F) Hematological tests with relevant baseline values, (G) Clinical biochemistry tests with...

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

    PubMed

    Louie, 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.

  12. Rapid screening and confirmation of drugs and toxic compounds in biological specimens using liquid chromatography/ion trap tandem mass spectrometry and automated library search.

    PubMed

    Liu, Hsiu-Chuan; Liu, Ray H; Lin, Dong-Liang; Ho, Hsiu-O

    2010-01-01

    Recent advances in liquid chromatography/tandem mass spectrometry (LC/MS/MS) technology have provided an opportunity for the development of more specific approaches to achieve the 'screen' and 'confirmation' goals in a single analytical step. For this purpose, this study adapts the electrospray ionization ion trap LC/MS/MS instrumentation (LC/ESI-MS/MS) for the screening and confirmation of over 800 drugs and toxic compounds in biological specimens. Liquid-liquid and solid-phase extraction protocols were coupled to LC/ESI-MS/MS using a 1.8-microm particle size analytical column operated at 50 degrees C. Gradient elution of the analytes was conducted using a solvent system composed of methanol and water containing 0.1% formic acid. Positive-ion ESI-MS/MS spectra and retention times for each of the 800 drugs and toxic compounds were first established using 1-10 microg/mL standard solutions. This spectra and retention time information was then transferred to the library and searched by the identification algorithm for the confirmation of compounds found in test specimens - based on retention time matches and scores of fit, reverse fit, and purity resulting from the searching process. The established method was found highly effective when applied to the analyses of postmortem specimens (blood, urine, and hair) and external proficiency test samples provided by the College of American Pathology (CAP). The development of this approach has significantly improved the efficiency of our routine laboratory operation that was based on a two-step (immunoassay and GC/MS) approach in the past.

  13. Routine DNA testing

    USDA-ARS?s Scientific Manuscript database

    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...

  14. 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.

  15. Application of land-use data and screening tests for evaluating pesticide runoff toxicity in surface waters

    NASA Astrophysics Data System (ADS)

    Wilcock, Robert J.

    1993-05-01

    Survey information on pesticide usage in New Zealand during 1985-1989 is summarized by regions and principal applications. Two screening tests, one based on a simple water-balance method and the other based on a semiempirical runoff formula, have been used to identify 18 pesticides with application rates that may yield runoff concentrations that are harmful to aquatic fauna. These are predominantly associated either with intensive applications in horticulture or extensive applications to cereal crops and pasture. The purpose of the screening tests was to calculate typical edge-of-field concentrations in runoff and, by comparing them with known aquatic toxicity values, determine which compounds are applied at rates that may yield toxic runoff. While it may be possible to extend these methods to calculate typical surface water concentrations, further studies will be needed to evaluate pesticide persistence and assimilation in stream channels.

  16. Set-up and routine use of a database of 10,555 genotyped blood donors to facilitate the screening of compatible blood components for alloimmunized patients.

    PubMed

    Perreault, J; Lavoie, J; Painchaud, P; Côté, M; Constanzo-Yanez, J; Côté, R; Delage, G; Gendron, F; Dubuc, S; Caron, B; Lemieux, R; St-Louis, M

    2009-07-01

    Large-scale genotyping of blood donors for red blood cell and platelet antigens has been predicted to replace phenotyping assays in the screening of compatible blood components for alloimmunized patients. Although several genotyping platforms have been described, novel procedures and processes are needed to perform genotyping efficiently and to maximize its benefits for blood banks. Here we describe the processes and procedures developed to introduce large-scale genotyping in our routine operations. Preliminary cost-benefit analysis indicated that genotyping must target frequent blood donors (> 3 donations/year) to be efficiently used. A custom-designed computer application was developed to manage the whole project. It selects frequent donors among recent donations, prints coded labels to identify blood samples sent to the external genotyping laboratory, and stores genotyping results. It can search for donors compatible for any combination of the 22 genotyped antigens as well as consult the current inventory for the presence of the corresponding blood components. The phenotype of recovered components is confirmed by standard serology techniques prior to shipment to hospitals. Since October 2007, 10 555 blood donors have been genotyped. The database is used on a regular basis to find compatible blood components with a genotype-phenotype concordance of 99.6%.

  17. Screening toxicity evaluation of Wheeler Reservoir sediments using juvenile freshwater mussels (Anodonta imbecillis say) exposed to sediment interstitial water

    SciTech Connect

    Wade, D.C.

    1990-12-01

    Reservoir sediments (porewater) near several wastewater outfalls at Decatur, Alabama, were screened for acute (9-day) toxicity to 8-day old freshwater mussels. Sampling locations corresponded to four of five sites previously surveyed by the Alabama Wildlife Federation and Alabama mussel divers. A site located on the opposite (north) overbank where mussels are abundant was chosen as the study control. Reference sediments from an outdoor channel at TVA's Aquatic Research Laboratory (ARL) with flow-through Wheeler Reservoir water and from a downstream (Kentucky) reservoir were included in the study for comparative purposes. Toxicity was observed at two of the Decatur sites, and in the ARL channel. Sediments from the other two Decatur sites, the north overbank (control), and Kentucky Reservoir were not toxic to the test animals. Toxicity at station Alpha and from the ARL channel was correlated with un-ionized ammonia present in porewater during the test. Toxicity at station Delta was above the level explained by the regression model examined for ammonia. The site at Decatur having the greatest toxicity and ammonia concentration (Alpha) was located in the Dry Branch Embayment. Elevated ammonia in sediment collected from ARL was attributed to natural events. 13 refs., 4 figs., 6 tabs.

  18. 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.

  19. Prospects for the development of validated screening tests that measure developmental toxicity potential: view of one skeptic.

    PubMed

    Mirkes, P E

    1996-06-01

    Humans are exposed to a variety of potential developmental toxicants. This fact, combined with the knowledge that human development can be disrupted by "environmental" agents, has led to the development of methods designed to identify potential developmental toxicants. Currently, the principal method used to screen drugs and chemicals that are potential human developmental toxicants is the segment II study (i.e., a study in which prospective drugs and chemicals are tested in pregnant animals). Because of the cost and time involved in such studies and the pressure to reduce the number of animals used in such testing, alternative methods for developmental toxicity testing have been sought. This has resulted in a number of in vitro tests whose aim is to screen large numbers of agents quickly and inexpensively. Although numerous in vitro tests of developmental toxicity have been developed during the last 15 years, no one system or combination of tests have been validated for the purpose intended. Nonetheless, two systems--the limb bud/CNS micromass, and the chick embryo neural retina cell culture (CERC)--continue to be advanced as viable in vitro developmental toxicology tests. The purpose of this commentary is to evaluate the prospects for the development of an in vitro test system(s) that can screen the universe of drugs and chemicals and reliably identify those that require further study and those that do not. The conclusion of this investigator is that the prospects for validating such in vitro tests are not promising. This conclusion is based primarily on the lack of basic knowledge regarding the relevance of end points assayed in the micromass and CERC test systems to those end points known or thought to be critical for normal development.

  20. A high throughput pharmaceutical screen identifies compounds with specific toxicity against BRCA2-deficient tumors

    PubMed Central

    Evers, Bastiaan; Schut, Eva; van der Burg, Eline; Braumuller, Tanya M.; Egan, David A.; Holstege, Henne; Edser, Pauline; Adams, David J.; Wade-Martins, Richard; Bouwman, Peter; Jonkers, Jos

    2009-01-01

    Purpose: Hereditary breast cancer is partly explained by germline mutations in BRCA1 and BRCA2. While patients carry heterozygous mutations, their tumors have typically lost the remaining wild-type allele. Selectively targeting BRCA-deficiency may therefore constitute an important therapeutic approach. Clinical trials applying this principle are underway, but it is unknown whether the compounds tested are optimal. It is therefore important to identify alternative compounds that specifically target BRCA-deficiency and to test new combination therapies to establish optimal treatment strategies. Experimental Design: We performed a high-throughput pharmaceutical screen on BRCA2-deficient mouse mammary tumor cells and isogenic controls with restored BRCA2 function. Subsequently, we validated positive hits in vitro and in vivo using mice carrying BRCA2-deficient mammary tumors. Results: Three alkylators – chlorambucil, melphalan and nimustine – displayed strong and specific toxicity against BRCA2-deficient cells. In vivo, these showed heterogeneous but generally strong BRCA2-deficient antitumor activity, with melphalan and nimustine outperforming cisplatin and the poly-(ADP-ribose)-polymerase (PARP) inhibitor olaparib (AZD2281) in this small study. In vitro drug combination experiments showed synergistic interactions between the alkylators and olaparib. Tumor intervention studies combining nimustine and olaparib resulted in recurrence-free survival exceeding 330 days in 3 out of 5 animals tested. Conclusions: We generated and validated a platform for identification of compounds with specific activity against BRCA2-deficient cells that translates well to the preclinical setting. Our data call for the re-evaluation of alkylators – especially melphalan and nimustine – alone or in combination with PARP inhibitors for the treatment of breast cancers with a defective BRCA pathway. PMID:20008842

  1. Toxicity screening of diclofenac, propranolol, sertraline and simvastatin using Danio rerio and Paracentrotus lividus embryo bioassays.

    PubMed

    Ribeiro, Sílvia; Torres, Tiago; Martins, Rosário; Santos, Miguel M

    2015-04-01

    Early life-stage bioassays have been used as an alternative to short-term adult toxicity tests since they are cost-effective. A single couple can produce hundreds or thousands of embryos and hence can be used as a simple high-throughput approach in toxicity studies. In the present study, zebrafish and sea urchin embryo bioassays were used to test the toxicity of four pharmaceuticals belonging to different therapeutic classes: diclofenac, propranolol, simvastatin and sertraline. Simvastatin was the most toxic tested compound for zebrafish embryo, followed by diclofenac. Sertraline was the most toxic drug to sea urchin embryos, inducing development abnormalities at the ng/L range. Overall, our results highlight the potential of sea urchin embryo bioassay as a promising and sensitive approach for the high-throughput methods to test the toxicity of new chemicals, including pharmaceuticals, and identify several drugs that should go through more detailed toxicity assays.

  2. The effect of changes in the USF/NASA toxicity screening test method on data from some cellular polymers

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Miller, C. M.

    1976-01-01

    Rankings of relative toxicity can be markedly affected by changes in test variables. Revision of the USF/NASA toxicity screening test procedure to eliminate the connecting tube and supporting floor and incorporate a 1.0 g sample weight, 200 C starting temperature, and 800 C upper limit temperature for pyrolysis, reversed the rankings of flexible polyurethane and polychloroprene foams, not only in relation to each other, but also in relation to cotton and red oak. Much of the change is attributed to reduction of the distance between the sample and the test animals, and reduction of the sample weight charged. Elimination of the connecting tube increased the relative toxicity of the polyurethane foams. The materials tested were flexible polyurethane foam, without and with fire retardant; rigid polyurethane foam with fire retardant; flexible polychloroprene foam; cotton, Douglas fir, red oak, hemlock, hardboard, particle board, polystyrene, and polymethyl methacrylate.

  3. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Metabolic Enzyme Microarray Coupled with Miniaturized Cell-Culture Array Technology for High-Throughput Toxicity Screening

    PubMed Central

    Lee, Moo-Yeal; Dordick, Jonathan S.; Clark, Douglas S.

    2017-01-01

    Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug candidates to pharmaceuticals, it is important to develop high-throughput tools that can provide early-stage predictive toxicology data. In particular, in vitro cell-based systems that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process. The in vitro techniques that provide a high degree of human toxicity prediction will be perhaps more important in cosmetic and chemical industries in Europe, as animal toxicity testing is being phased out entirely in the immediate future. We have developed a metabolic enzyme microarray (the Metabolizing Enzyme Toxicology Assay Chip, or MetaChip) and a miniaturized three-dimensional (3D) cell-culture array (the Data Analysis Toxicology Assay Chip, or DataChip) for high-throughput toxicity screening of target compounds and their metabolic enzyme-generated products. The human or rat MetaChip contains an array of encapsulated metabolic enzymes that is designed to emulate the metabolic reactions in the human or rat liver. The human or rat DataChip contains an array of 3D human or rat cells encapsulated in alginate gels for cell-based toxicity screening. By combining the DataChip with the complementary MetaChip, in vitro toxicity results are obtained that correlate well with in vivo rat data. PMID:20217581

  5. Metabolic enzyme microarray coupled with miniaturized cell-culture array technology for high-throughput toxicity screening.

    PubMed

    Lee, Moo-Yeal; Dordick, Jonathan S; Clark, Douglas S

    2010-01-01

    Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug candidates to pharmaceuticals, it is important to develop high-throughput tools that can provide early-stage predictive toxicology data. In particular, in vitro cell-based systems that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process. The in vitro techniques that provide a high degree of human toxicity prediction will be perhaps more important in cosmetic and chemical industries in Europe, as animal toxicity testing is being phased out entirely in the immediate future.We have developed a metabolic enzyme microarray (the Metabolizing Enzyme Toxicology Assay Chip, or MetaChip) and a miniaturized three-dimensional (3D) cell-culture array (the Data Analysis Toxicology Assay Chip, or DataChip) for high-throughput toxicity screening of target compounds and their metabolic enzyme-generated products. The human or rat MetaChip contains an array of encapsulated metabolic enzymes that is designed to emulate the metabolic reactions in the human or rat liver. The human or rat DataChip contains an array of 3D human or rat cells encapsulated in alginate gels for cell-based toxicity screening. By combining the DataChip with the complementary MetaChip, in vitro toxicity results are obtained that correlate well with in vivo rat data.

  6. The Future of Toxicity Testing: A Focus on In Vitro Methods Using a Quantitative High Throughput Screening Platform

    PubMed Central

    Shukla, Sunita J.; Huang, Ruili; Austin, Christopher P.; Xia, Menghang

    2010-01-01

    The U.S. Tox21 collaborative program represents a paradigm shift in toxicity testing of chemical compounds from traditional in vivo tests to less expensive and higher throughput in vitro methods to prioritize compounds for further study, identify mechanisms of action, and ultimately develop predictive models for adverse health effects in humans. The NIH Chemical Genomics Center (NCGC) is an integral component of the Tox21 collaboration due to its quantitative high throughput screening (qHTS) paradigm, in which titration-based screening is used to profile hundreds of thousands of compounds per week. Here, we describe the Tox21 collaboration, qHTS-based compound testing, and the various Tox21 screening assays that have been validated and tested at the NCGC to date. PMID:20708096

  7. Simple screening method for gram-positive bacterial beta-lactam antibiotic tolerance on routine laboratory Bauer-Kirby antibiogram plates.

    PubMed

    Traub, W H

    1982-01-01

    A simple screening method served to detect beta-lactam antibiotic-tolerant variants of clinical isolates and laboratory control strains of staphylococcus aureus, S. epidermis, group B beta-hemolytic streptococci, and Listeria monocytogenes. The beta-lactamase(s) of a multiple drug-resistant strain of Enterobacter cloacae (isolate No. 19) yielded most consistent results as compared with several other beta-lactamase producers; the E. cloacae beta-lactamase(s) was neutralized by clavulanic acid. Spot inocula of E. cloacae isolate No. 19, following overnight "induction" with 1 microgram/ml of ampicillin and 3 microgram/ml of cephalothin in tryptic soya broth, were applied centrally to beta-lactam antibiotic inhibition zones of Bauer-Kirby antibiogram plates (Mueller-Hinton agar, MHA, and diagnostic sensitivity test agar, DSTA) following removal of the appropriate disks. The spot-inoculated plates were incubated overnight at 35 degrees C and inspected for satellite growths of tolerant variants around the E. cloacae spot inocula. Satellite growths of less than or equal to 10 colonies were interpreted to indicate tolerance of the relevant cell wall synthesis inhibitor. The method readily permitted detection of variants tolerant for ampicillin, cephalothin, penicillin G, piperacillin, azlocillin, and mezlocillin. However, strains documented by minimal inhibitory and minimal bactericidal concentrations to be tolerant for cefotaxime, cefoxitin, fosfomycin, and vancomycin only rarely gave rise to respective satellite growths. DSTA proved superior to MHA with respect to "rescue" of inhibited tolerant staphylococcal variants; furthermore, the diameters of inhibition zones obtained on DSTA correlated well with those on MHA. Therefore, DSTA was adopted as the routine test medium for clinical staphylococcal isolates.

  8. 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.

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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 ...

  14. 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...

  15. 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...

  16. 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.

  17. Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening.

    PubMed

    Nel, Andre; Xia, Tian; Meng, Huan; Wang, Xiang; Lin, Sijie; Ji, Zhaoxia; Zhang, Haiyuan

    2013-03-19

    The production of engineered nanomaterials (ENMs) is a scientific breakthrough in material design and the development of new consumer products. While the successful implementation of nanotechnology is important for the growth of the global economy, we also need to consider the possible environmental health and safety (EHS) impact as a result of the novel physicochemical properties that could generate hazardous biological outcomes. In order to assess ENM hazard, reliable and reproducible screening approaches are needed to test the basic materials as well as nanoenabled products. A platform is required to investigate the potentially endless number of biophysicochemical interactions at the nano/bio interface, in response to which we have developed a predictive toxicological approach. We define a predictive toxicological approach as the use of mechanisms-based high-throughput screening in vitro to make predictions about the physicochemical properties of ENMs that may lead to the generation of pathology or disease outcomes in vivo. The in vivo results are used to validate and improve the in vitro high-throughput screening (HTS) and to establish structure-activity relationships (SARs) that allow hazard ranking and modeling by an appropriate combination of in vitro and in vivo testing. This notion is in agreement with the landmark 2007 report from the US National Academy of Sciences, "Toxicity Testing in the 21st Century: A Vision and a Strategy" (http://www.nap.edu/catalog.php?record_id=11970), which advocates increased efficiency of toxicity testing by transitioning from qualitative, descriptive animal testing to quantitative, mechanistic, and pathway-based toxicity testing in human cells or cell lines using high-throughput approaches. Accordingly, we have implemented HTS approaches to screen compositional and combinatorial ENM libraries to develop hazard ranking and structure-activity relationships that can be used for predicting in vivo injury outcomes. This

  18. 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...

  19. 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...

  20. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    PubMed

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  1. A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents.

    PubMed

    Datta, Sandipan; Sahdeo, Sunil; Gray, Jennifer A; Morriseau, Christophe; Hammock, Bruce D; Cortopassi, Gino

    2016-11-01

    Mitochondrial toxicity is emerging as a major mechanism underlying serious human health consequences. This work performs a high-throughput screen (HTS) of 176 environmental chemicals for mitochondrial toxicity utilizing a previously reported biosensor platform. This established HTS confirmed known mitochondrial toxins and identified novel mitotochondrial uncouplers such as 2, 2'-Methylenebis(4-chlorophenol) and pentachlorophenol. It also identified a mitochondrial 'structure activity relationship' (SAR) in the sense that multiple environmental chlorophenols are mitochondrial inhibitors and uncouplers. This study demonstrates proof-of-concept that a mitochondrial HTS assay detects known and novel environmental mitotoxicants, and could be used to quickly evaluate human health risks from mitotoxicants in the environment. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  2. 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.

  3. A comparison of the daphnids Ceriodaphnia dubia and Daphnia ambigua for their utilization in routine toxicity testing in the Southeastern United States.

    PubMed

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

    2003-07-01

    U.S. regulatory agencies commonly require effluent toxicity testing with Ceriodaphnia dubia--a practice that has led to the criticism that this species and test protocol often does not reflect local taxa or 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) but 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, whereas 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.

  4. A new technique for screening chemical toxicity to the pulp from dental restorative materials and procedures.

    PubMed

    Hume, W R

    1985-11-01

    An in vitro test system is described which allows for quick and relatively inexpensive examination of the potential for chemical toxicity to the pulp of materials and procedures used in the restoration of single teeth. The test system consisted of two sequential steps. First, a restorative procedure was carried out on a freshly-extracted human tooth crown, to the pulpal surface of which had been attached a chamber filled with sterile tissue-culture medium. The preparation was kept at 37 degrees C. The culture medium was removed at day one and replaced with fresh medium, which was removed at day 3. In the second step, we used a standard tissue-culture toxicity assessment technique to examine both culture medium samples for the presence of chemical toxins. In use, this system gave results which correlated well with the known clinical potential for pulpal toxicity of various dental materials and techniques. For example, zinc oxide-eugenol used as temporary filling or base had no apparent potential for toxicity. Sealing a cotton pellet containing phenol into a cavity was of high apparent potential toxicity. Acrylic resin as intracoronal or extracoronal fillings showed potential for toxicity; this potential was decreased by lining with calcium hydroxide cement. Composite resin placed onto etched dentin had apparent toxic potential, but had less such potential when placed onto unetched dentin. The technique had some advantages over previously described in vitro toxicity test for restorative materials, because it included a step requiring diffusion of potential toxins into and through human dentin, and because it allowed for examination of variations in technique which mimic clinical behavior, and of materials used in sequence or in combination.

  5. 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.

  6. An Interactive Plotting Routine

    NASA Technical Reports Server (NTRS)

    Bowdish, D. W.

    1985-01-01

    Routine called CRTRPM meets needs of applications programer to plot data in interactive environment on Tektronix graphics terminal. CRTRPM designed specifically for applications where data is viewed and responded to at terminal. CRTRPM produces from one to four grids on terminal screen at one time, with from one to ten plots of X-Y data on each grid. CRTRPM written in FORTRAN V for interactive execution.

  7. Rapid, Cell-Based Toxicity Screen of Potentially Therapeutic Post-Transcriptional Gene Silencing Agents

    PubMed Central

    Kolniak, Tiffany A.; Sullivan, Jack M.

    2011-01-01

    Post-transcriptional gene silencing (PTGS) agents such as antisense, ribozymes and RNA interference (RNAi) have great potential as therapeutics for a variety of eye diseases including retinal and macular degenerations, glaucoma, corneal degenerations, inflammatory and viral conditions. Despite their great potential and over thirty years of academic and corporate research only a single PTGS agent is currently approved for human therapy for a single disease. Substantial challenges exist to achieving both efficacious and safe PTGS agents. Efficacy, as measured in specific target mRNA and protein knockdown, depends upon a number of complex factors including the identification of rare regions of target mRNA accessibility, cellular colocalization of the PTGS agent in sufficient concentration with the target mRNA, and stability of the PTGS agent in the target cells in which it is delivered or expressed. Safety is commonly measured by lack of cytotoxicity or other deleterious cellular responses in cells in which the PTGS agent is delivered or expressed. To relieve major bottlenecks in RNA drug discovery novel, efficient, inexpensive, and rapid tools are needed to facilitate lead identification of the most efficacious PTGS agent, rational optimization of efficacy of the lead agent, and lead agent safety determinations. We have developed a technological platform using cell culture expression systems that permits lead identification and efficacy optimization of PTGS agents against arbitrary disease target mRNAs under relatively high throughput conditions. Here, we extend the technology platform to include PTGS safety determinations in cultured human cells that are expected to represent the common cellular housekeeping microenvironment. We developed a high throughput screening (HTS) cytotoxicity assay in 96-well plate format based around the SYTOX Green dye which is excluded from healthy viable cells and becomes substantially fluorescent only after entering cells and binding

  8. What Makes Me Screen for HIV? Perceived Barriers and Facilitators to Conducting Recommended Routine HIV Testing among Primary care Physicians in the Southeastern United States

    PubMed Central

    White, Becky L.; Walsh, Joan; Rayasam, Swati; Pathman, Donald E.; Adimora, Adaora A.; Golin, Carol E.

    2015-01-01

    The Centers for Disease Control and Prevention have recommended routinely testing patients (aged 13–64) for HIV since 2006. However, many physicians do not routinely test. From January 2011- March 2012, we conducted 18 in-depth individual interviews and explored primary care physicians’ perceptions of barriers and facilitators to implementing routine HIV testing in North Carolina. Physicians’ comments were categorized thematically and fell into five groups: policy, community, practice, physician and patient. Lack of universal reimbursement was identified as the major policy barrier. Participants believed endorsement from the United States Preventive Services Tasks Force would facilitate adoption of routine HIV testing policies. Physicians reported HIV/AIDS stigma, socially conservative communities, lack of confidentiality, and rural geography as community barriers. Physicians believed public HIV testing campaigns would legitimize testing and decrease stigma in communities. Physicians cited time constraints and competing clinical priorities as physician barriers that could be overcome by delegating testing to nursing staff. HIV test refusal, low HIV risk perception, and stigma emerged as patient barriers. Physicians recommended adoption of routine HIV testing for all patients to facilitate and destigmatize testing. Physicians continue to experience a variety of barriers when implementing routine HIV testing in primary care settings. Our findings support multilevel approaches to enhance physician routine HIV testing in primary care settings. PMID:24643412

  9. Prediction and classification of drug toxicity using probabilistic modeling of temporal metabolic data: the consortium on metabonomic toxicology screening approach.

    PubMed

    Ebbels, Timothy M D; Keun, Hector C; Beckonert, Olaf P; Bollard, Mary E; Lindon, John C; Holmes, Elaine; Nicholson, Jeremy K

    2007-11-01

    sensitivities to liver and kidney toxicity were 67 and 41%, respectively, whereas the corresponding specificities were 77 and 100%. In some cases, it was not possible to make predictions because of interference by drug-related metabolite signals (18%), an inconsistent histopathological or urinary response (11%), genuine class overlap (8%), or lack of similarity to any other treatment (2%). This study constitutes the largest validation to date of the metabonomic approach to preclinical toxicology assessment, confirming that the methodology offers practical utility for rapid in vivo drug toxicity screening.

  10. Assessment of the routine, occupation-based gonorrhea and syphilis screening program in Moscow, Russia: an analysis of sexually transmitted infection prevalence and cost-effectiveness.

    PubMed

    Kourbatova, Ekaterina V; Akovbyan, Vagan A; Chesson, Harrell W; Lytkina, Irina N; Dmitriev, Georgyi A; Tikhonova, Lilia I; Koubanova, Anna A; Petukhova, Irina I; Latypova, Munira F; Aboymova, Olga A; Lewis, Joel S; Ryan, Caroline A; Shakarishvili, Anna

    2008-05-01

    In the Russian Federation, large sectors of the population regularly undergo mandatory occupational screening for sexually transmitted infections (STIs). Objectives of our study were to determine the prevalence of syphilis and gonorrhea in the screened occupational groups in Moscow and to conduct a cost-effectiveness evaluation of the occupational screening program. Serum samples from 4 main occupational groups (food handlers and other food industry workers, market salespersons, education and health care providers, and hotel and other public utility workers) were tested for syphilis and gonorrhea. We conducted a cost-effectiveness analysis (in 2003 rubles) of the screening program using decision analysis models. In the total sample of 1000 study participants, overall prevalence for syphilis was 1.2% with the highest rate in market salespersons (4.4%) and for gonorrhea 0.3%. The incremental cost per case of STI treated was 8409 rubles ($252) for syphilis screening (compared with no screening) with higher incremental costs associated with expanding the program to include gonorrhea screening. The relatively low STI prevalence in the screened groups and the poor performance of the diagnostic tests used were important factors in the estimated cost-effectiveness of occupation-based screening. Modifications to occupation-based screening, including an increased focus on higher risk population and the adoption of more current diagnostic technologies, could help to use prevention resources more effectively.

  11. Application of time-of-flight mass spectrometry for screening of crude glycerins for toxic phorbol ester contaminants.

    PubMed

    Herath, Kithsiri; Girard, Lauren; Reimschuessel, Renate; Jayasuriya, Hiranthi

    2017-03-01

    Since 2007, the U.S. Food and Drug Administration (FDA) has received numerous complaints of pet illnesses that may be related to the consumption of jerky pet treats. Many of those treats include glycerin as an ingredient. Glycerin can be made directly from oils such as palm seed oil, but can also be derived from the seed oil of toxic Jatropha plant during biodiesel production. If crude glycerin from biodiesel production from Jatropha curcas is used in the manufacture of animal feed, toxic tigliane diterpene phorbol esters (PEs), namely Jatropha factors (JFs), may be present and could lead to animal illnesses. Considering the numerous uses of glycerin in consumer products there is a need for a rapid method to screen crude glycerin for JF toxins and other PE contaminants. We describe the development of an ultra-high pressure liquid chromatography/quadrupole time of flight (UHPLC/Q-TOF) method for screening crude glycerin for PEs. An exact mass database, developed in-house, of previously identified PEs from Jatropha curcas as well as putative compounds was used to identify possible contaminants.

  12. 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.

  13. In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System

    EPA Science Inventory

    In 2007 the National Research Council envisioned the need for inexpensive, rapid, cell based toxicity testing methods relevant to human health. Recent advances in robotics, automation, and miniaturization have been used to address these problems. However, one challenge is that ma...

  14. Growth-Based Bacterial Viability Assay for Interference-Free and High-Throughput Toxicity Screening of Nanomaterials.

    PubMed

    Qiu, Tian A; Nguyen, Thu Ha Thi; Hudson-Smith, Natalie V; Clement, Peter L; Forester, Dona-Carla; Frew, Hilena; Hang, Mimi N; Murphy, Catherine J; Hamers, Robert J; Feng, Z Vivian; Haynes, Christy L

    2017-02-07

    Current high-throughput approaches evaluating toxicity of chemical agents toward bacteria typically rely on optical assays, such as luminescence and absorbance, to probe the viability of the bacteria. However, when applied to toxicity induced by nanomaterials, scattering and absorbance from the nanomaterials act as interferences that complicate quantitative analysis. Herein, we describe a bacterial viability assay that is free of optical interference from nanomaterials and can be performed in a high-throughput format on 96-well plates. In this assay, bacteria were exposed to various materials and then diluted by a large factor into fresh growth medium. The large dilution ensured minimal optical interference from the nanomaterial when reading optical density, and the residue left from the exposure mixture after dilution was confirmed not to impact the bacterial growth profile. The fractions of viable cells after exposure were allowed to grow in fresh medium to generate measurable growth curves. Bacterial viability was then quantitatively correlated to the delay of bacterial growth compared to a reference regarded as 100% viable cells; data analysis was inspired by that in quantitative polymerase chain reactions, where the delay in the amplification curve is correlated to the starting amount of the template nucleic acid. Fast and robust data analysis was achieved by developing computer algorithms carried out using R. This method was tested on four bacterial strains, including both Gram-negative and Gram-positive bacteria, showing great potential for application to all culturable bacterial strains. With the increasing diversity of engineered nanomaterials being considered for large-scale use, this high-throughput screening method will facilitate rapid screening of nanomaterial toxicity and thus inform the risk assessment of nanoparticles in a timely fashion.

  15. Filaricidal activities on Onchocerca ochengi and Loa loa, toxicity and phytochemical screening of extracts of Tragia benthami and Piper umbellatum.

    PubMed

    Cho-Ngwa, Fidelis; Monya, Elvis; Azantsa, Boris K; Manfo, Faustin Pascal T; Babiaka, Smith B; Mbah, James A; Samje, Moses

    2016-08-30

    Onchocerciasis is the world's second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L. loa microfilariae (mf). Fourteen extracts from two medicinal plants, Tragia benthami and Piper umbellatum were screened in vitro against Onchocerca ochengi parasite and L. loa mf. Activities of extracts on male worms and microfilariae were assessed by motility reduction, while MTT/Formazan assay was used to assess biochemically the death of female worms. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney cells and Balb/c mice, respectively. At 500 μg/mL, all extracts showed 100 % activity on Onchocerca ochengi males and microfilariae, while 9 showed 100 % activity on female worms. The methylene chloride extract of Piper umbellatum leaves was the most active on adult male and female worms (IC50s: 16.63 μg/mL and 35.65 μg/mL, respectively). The three most active extracts on Onchocerca ochengi females were also highly active on Loa loa microfilariae, with IC50s of 35.12 - 13.9 μg/mL. Active extracts were generally more toxic to the worms than to cells and showed no acute toxicity to Balb/c mice. Phytochemical screening revealed the presence of saponins, steroids, tannins and flavanoids in the promising extracts. These results unfold potential sources of novel anti-Onchocerca lead compounds and validate the traditional use of the plants in onchocerciasis treatment.

  16. 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

  17. Primary screening of the bioactivity of brackishwater cyanobacteria: toxicity of crude extracts to Artemia salina larvae and Paracentrotus lividus embryos.

    PubMed

    Lopes, Viviana R; Fernández, Nuria; Martins, Rosário F; Vasconcelos, Vitor

    2010-03-05

    Cyanobacteria are a diverse group of Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against vertebrates, invertebrates, plants, microalgae, fungi, bacteria, viruses and cell lines. The aim of this study was to assess the toxic effects of aqueous, methanolic and hexane crude extracts of benthic and picoplanktonic cyanobacteria isolated from estuarine environments, towards the nauplii of the brine shrimp Artemia salina and embryos of the sea urchin Paracentrotus lividus. The A. salina lethality test was used as a frontline screen and then complemented by the more specific sea urchin embryo-larval assay. Eighteen cyanobacterial isolates, belonging to the genera Cyanobium, Leptolyngbya, Microcoleus, Phormidium, Nodularia, Nostoc and Synechocystis, were tested. Aqueous extracts of cyanobacteria strains showed potent toxicity against A. salina, whereas in P. lividus, methanolic and aqueous extracts showed embryo toxicity, with clear effects on development during early stages. The results suggest that the brackishwater cyanobacteria are producers of bioactive compounds with toxicological effects that may interfere with the dynamics of invertebrate populations.

  18. Primary Screening of the Bioactivity of Brackishwater Cyanobacteria: Toxicity of Crude Extracts to Artemia salina Larvae and Paracentrotus lividus Embryos

    PubMed Central

    Lopes, Viviana R.; Fernández, Nuria; Martins, Rosário F.; Vasconcelos, Vitor

    2010-01-01

    Cyanobacteria are a diverse group of Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against vertebrates, invertebrates, plants, microalgae, fungi, bacteria, viruses and cell lines. The aim of this study was to assess the toxic effects of aqueous, methanolic and hexane crude extracts of benthic and picoplanktonic cyanobacteria isolated from estuarine environments, towards the nauplii of the brine shrimp Artemia salina and embryos of the sea urchin Paracentrotus lividus. The A. salina lethality test was used as a frontline screen and then complemented by the more specific sea urchin embryo-larval assay. Eighteen cyanobacterial isolates, belonging to the genera Cyanobium, Leptolyngbya, Microcoleus, Phormidium, Nodularia, Nostoc and Synechocystis, were tested. Aqueous extracts of cyanobacteria strains showed potent toxicity against A. salina, whereas in P. lividus, methanolic and aqueous extracts showed embryo toxicity, with clear effects on development during early stages. The results suggest that the brackishwater cyanobacteria are producers of bioactive compounds with toxicological effects that may interfere with the dynamics of invertebrate populations. PMID:20411110

  19. 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...

  20. 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...

  1. Larval Behavioral Toxicity Screening: Light Intensity and the Order of Stimulus Presentation Affect the Outcome

    EPA Science Inventory

    The U.S. Environmental Protection Agency is screening large numbers of chemicals using 6 day old zebrafish (Danio rerio). We use a behavioral testing paradigm that simultaneously tests individual zebrafish under both light and dark conditions in a 96-well plate using a video tr...

  2. 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...

  3. 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...

  4. Larval Behavioral Toxicity Screening: Light Intensity and the Order of Stimulus Presentation Affect the Outcome

    EPA Science Inventory

    The U.S. Environmental Protection Agency is screening large numbers of chemicals using 6 day old zebrafish (Danio rerio). We use a behavioral testing paradigm that simultaneously tests individual zebrafish under both light and dark conditions in a 96-well plate using a video tr...

  5. 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...

  6. 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...

  7. 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...

  8. STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies

    EPA Science Inventory

    The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

  9. STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies

    EPA Science Inventory

    The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

  10. 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

  11. 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.

  12. Subchronic and reproductive/developmental (screening level) toxicity of complexation products of iron trichloride and sodium tartrate (FemTA).

    PubMed

    Lynch, Barry; Emmen, Harry; van Otterdijk, Francois; Lau, Annette

    2013-09-01

    A complexation/reaction product, termed FemTA, of sodium tartrate [D(-)- and L(+)-tartaric acid and mesotartaric acid], sodium hydroxide, and iron trichloride may have use as an anticaking agent in salt preparations. FemTA is composed of about 4% sodium tartrate, approximately 10% mesotartaric acid, approximately 7% chloride, approximately 4% iron, approximately 7% sodium, approximately 0.3% sodium oxalate, and approximately 65% water. FemTA was tested in a 90-d oral toxicity study, which included a screening level reproductive/developmental toxicity phase, in Harlan Wistar rats. FemTA was administered by oral gavage at 500, 1000, and 2000 mg/kg body weight/d prior to and during mating, or about 20, 40, or 80 mg of iron/kg body weight/d, such that males received 90/91 d of treatment and females 104 to 109 d. Treatment was associated with inflammatory lesions of the lower GI tract at the mid- and high-dose levels, increased liver and kidney weights, increased serum bile acids and blood urea nitrogen, decreased chloride, and changes to hematological parameters consistent with inflammation. The effects were considered the result of iron overload. There were no effects on reproductive/developmental toxicity parameters. The no-observed-adverse-effect level (NOAEL), based on gastrointestinal tract effects was 500 mg/kg body weight/d. The NOAEL for reproductive/developmental toxicity was 2000 mg/kg body weight/d, the highest dose tested. © 2013 Institute of Food Technologists®

  13. Human Umbilical Cord Blood-Derived Neural Stem Cell Line as a Screening Model for Toxicity.

    PubMed

    Patnaik, Rajashree; Padhy, Rabindra Nath

    2017-04-01

    The aim was to investigate whether a human neural stem cell (NSC) line derived from human umbilical cord blood (hUCB) can be used for toxicity study. Toxicity of both neurotoxic environmental xenobiotics, methyl mercury chloride (CH3HgCl), lead acetate (CH3COOPb), and chlorpyrifos (CP), and non-neurotoxic insecticide, dichlorvos, as well as non-neurotoxic drugs, theophylline and acetaminophen were assessed. Additionally, differentiation of neuronal and glial cell lines derived from hUCB was elucidated. It was observed that CH3HgCl was more toxic to human NSCs in comparison to CH3COOPb and CP. The minimum inhibitory concentration (MIC) value against NSCs was 3, 10, and 300 mg/L, in each staining process, acridine orange/ethidium bromide (AO/EB) staining, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay, and Hoechst staining, for CH3HgCl, CP, and CH3COOPb, respectively. CH3HgCl had the LC25 value as 10.0, 14.4, and 12.7 mg/L, by staining method mentioned in succession. CP had the LC25 value as 21.9, 23.7, and 18.4 mg/L; similarly, CH3COOPb had LC25 values, successively as 616.9, 719.2, and 890.3 mg/L. LC50 values ranged from 18.2 to 21.7 mg/L for CH3HgCl, 56.4 to 60.2 mg/L for CP, and 1000 to 1460.1 for CH3COOPb. Theophylline, acetaminophen, and dichlorvos had no impact on the viability of NSCs. This work justified that hUCB-NSC model can be used for toxicity study.

  14. LuxCDABE—Transformed Constitutively Bioluminescent Escherichia coli for Toxicity Screening: Comparison with Naturally Luminous Vibrio fischeri

    PubMed Central

    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 EC50) 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 EC50 values highly correlated (log-log R2 = 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 EC50 values for Hg (0.04–0.05 mg/L) and highest EC50 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 R2 = 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 in

  15. Screening the Toxicity of Selected Personal Care Products Using Embryo Bioassays: 4-MBC, Propylparaben and Triclocarban

    PubMed Central

    Torres, Tiago; Cunha, Isabel; Martins, Rosário; Santos, Miguel M.

    2016-01-01

    Recently, several emerging pollutants, including Personal Care Products (PCPs), have been detected in aquatic ecosystems, in the ng/L or µg/L range. Available toxicological data is limited, and, for certain PCPs, evidence indicates a potential risk for the environment. Hence, there is an urgent need to gather ecotoxicological data on PCPs as a proxy to improve risk assessment. Here, the toxicity of three different PCPs (4-Methylbenzylidene Camphor (4-MBC), propylparaben and triclocarban) was tested using embryo bioassays with Danio rerio (zebrafish) and Paracentrotus lividus (sea urchin). The No Observed Effect Concentration (NOEC) for triclocarban was 0.256 µg/L for sea urchin and 100 µg/L for zebrafish, whereas NOEC for 4-MBC was 0.32 µg/L for sea urchin and 50 µg/L for zebrafish. Both PCPs impacted embryo development at environmentally relevant concentrations. In comparison with triclocarban and 4-MBC, propylparaben was less toxic for both sea urchin (NOEC = 160 µg/L) and zebrafish (NOEC = 1000 µg/L). Overall, this study further demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing the toxicity of emerging pollutants. PMID:27775672

  16. Screening the Toxicity of Selected Personal Care Products Using Embryo Bioassays: 4-MBC, Propylparaben and Triclocarban.

    PubMed

    Torres, Tiago; Cunha, Isabel; Martins, Rosário; Santos, Miguel M

    2016-10-21

    Recently, several emerging pollutants, including Personal Care Products (PCPs), have been detected in aquatic ecosystems, in the ng/L or µg/L range. Available toxicological data is limited, and, for certain PCPs, evidence indicates a potential risk for the environment. Hence, there is an urgent need to gather ecotoxicological data on PCPs as a proxy to improve risk assessment. Here, the toxicity of three different PCPs (4-Methylbenzylidene Camphor (4-MBC), propylparaben and triclocarban) was tested using embryo bioassays with Danio rerio (zebrafish) and Paracentrotus lividus (sea urchin). The No Observed Effect Concentration (NOEC) for triclocarban was 0.256 µg/L for sea urchin and 100 µg/L for zebrafish, whereas NOEC for 4-MBC was 0.32 µg/L for sea urchin and 50 µg/L for zebrafish. Both PCPs impacted embryo development at environmentally relevant concentrations. In comparison with triclocarban and 4-MBC, propylparaben was less toxic for both sea urchin (NOEC = 160 µg/L) and zebrafish (NOEC = 1000 µg/L). Overall, this study further demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing the toxicity of emerging pollutants.

  17. 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

  18. Parents' Opinion About a Routine Head-to-Toe Examination of Children as a Screening Instrument for Child Abuse and Neglect in Children Visiting the Emergency Department.

    PubMed

    Teeuw, Arianne Hélène; Hoytema van Konijnenburg, Eva M; Sieswerda-Hoogendoorn, Tessa; Molenaar, Sjaak; Heymans, Hugo S; van Rijn, Rick R

    2016-03-01

    To improve detection of child abuse and neglect (CAN), many emergency departments use screening methods. Apart from diagnostic accuracy, possible harms of screening methods are important to consider, especially because most children are not abused and do not benefit from screening. We performed a systematic literature review to assess parents' opinions about CAN screening, in which we could only include 7 studies, all reporting that the large majority of participating parents favor screening. Recently, a complete physical examination (called "top-toe" inspection [TTI], a fully undressed inspection of the child) was implemented as a CAN screening method at the emergency department of a teaching hospital in The Netherlands. This study describes parents' opinions about the TTI. We used a questionnaire to assess parents' opinions about the TTI of their children when visiting the emergency department. During the study period, 1000 questionnaires were distributed by mail. In total, 372 questionnaires were returned (37%). A TTI was performed for 194 children (52%). The overall attitude of parents whose children underwent a TTI was positive; 77.3% of the respondents found the TTI acceptable, and 1.5% (N = 3) found it unacceptable. Seventy percent of the respondents agreed with the theorem that all children who visit the emergency department should have a TTI performed, and 7.3% (N = 14) disagreed. Contrary to what is commonly believed, both in our systematic literature review and in our questionnaire study, the majority of participating parents agree with screening for CAN in general and with the TTI specifically. Sharing the results of this study with ED personnel and policy makers could take away prejudices about perceived disagreement of parents, thereby improving implementation of and adherence to CAN screening. Copyright © 2016 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

  19. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Aquatic Toxicity Screening of an ACWA Secondary Waste, GB-Hydrolysate

    DTIC Science & Technology

    2009-01-01

    survival and reproduction of freshwater organism Ceriodaphnia dubia were used to investigate the aquatic toxicities of ACWA GB-hydrolysate or the...nominal concentrations of 1.2, 2.3, 4.6, 9.3, 18.6, 37.2, and 74.3% vol/vol. 2.3 Ceriodaphnia 7-Day Survival and Reproduction Assay Ceriodaphnia 7-day... ceriodaphnia . The test media were renewed and fresh food added daily, for 7 d. Mortality, reproduction , pH, and dissolved oxygen measurements were

  1. A Short-Term Toxicity Screening Test Using Photobacteria -- A Feasibility Study.

    DTIC Science & Technology

    1980-06-01

    static 96-hour LC50 was determined inL i Ptmephales promelas and a 48-hour EC50 in Daphnia magna . These data, first summarized by earson et al., 31 are...of the nine chemicals. A comparison of the bacterial ECSO values and the toxic response in minnows (96-hour LCSO) and daphnia (48-hour EC5O) did not...result in a high degree of correspondence. Thus, i t was concluded that the photobacterlal test system was not highly predictive of minnow or daphnia

  2. Organ-on-a-chip technology and microfluidic whole-body models for pharmacokinetic drug toxicity screening.

    PubMed

    Lee, Jong Bum; Sung, Jong Hwan

    2013-11-01

    Microscale cell culture platforms better mimic the in vivo cellular microenvironment than conventional, macroscale systems. Microscale cultures therefore elicit a more authentic response from cultured cells, enabling physiologically realistic in vitro tissue models to be constructed. The fabrication of interconnecting microchambers and microchannels allows drug absorption, distribution, metabolism and elimination to be simulated, and enables precise manipulation of fluid flow to replicate blood circulation. Complex, multi-organ interactions can be investigated using "organ-on-a-chip" toxicology screens. By reproducing the dynamics of multi-organ interaction, the dynamics of various diseases and drug activities can be studied in mechanistic detail. In this review, we summarize the current status of technologies related to pharmacokinetic-based drug toxicity testing, and the use of microtechnology for reproducing the interaction between multiple organs. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. One-year routine opportunistic screening for hypertension in formal medical settings and potential improvements in hypertension awareness among older persons in developing countries: evidence from the Study on Global Ageing and Adult Health (SAGE).

    PubMed

    Maurer, Jürgen; Ramos, Alejandra

    2015-02-01

    Hypertension is a leading risk factor in the global disease burden. Limited hypertension awareness is a major determinant of widespread gaps in hypertension treatment and control, especially in developing countries. We analyzed data on persons aged 50 years or older from 6 low- and middle-income countries participating in the first wave (2007-2010) of the World Health Organization's Survey of Global Ageing and Adult Health (SAGE). Our estimates suggest that just 1 year of routine opportunistic hypertension screening during formal visits to medical-care providers could yield significant increases in hypertension awareness among seniors in the developing world. We also show that eliminating missed opportunities for hypertension screening in medical settings would not necessarily exacerbate existing socioeconomic differences in hypertension awareness, despite requiring at least occasional contact with a formal health-care provider for obtaining a hypertension diagnosis. Thus, routine opportunistic screening for hypertension in formal medical settings may provide a simple but reliable way to increase hypertension awareness. Moreover, the proposed approach has the added advantage of leveraging existing resources and infrastructures, as well as facilitating a direct transition from the point of diagnosis to subsequent expert counseling and clinical care for newly identified hypertension patients.

  4. The use of a genetically engineered Pseudomonas species (Shk1) as a bioluminescent reporter for heavy metal toxicity screening in wastewater treatment plant influent.

    PubMed

    Ren, Shijin; Frymier, Paul D

    2003-01-01

    Heavy metals are known to be inhibitory and toxic to the activated-sludge microbial community in biological wastewater treatment plants. Toxicity screening of aqueous mixtures of these heavy metal ions in plant influent could use both chemical and biological methods. As a biological method, luminescent bacterial bioreporters offer the advantages of a simple test procedure and rapid response. Current biologically based methods for screening aqueous streams for toxicity are labor-intensive, inaccurate, or difficult to use in continuous monitoring applications. In the present study, a system was developed that is simple and easily automated. This system is based on the bacterium Shk1, a genetically engineered bioluminescent Pseudomonad whose parent strain was originally isolated from activated sludge. Compared with other bioluminescence-based systems (specifically, the Microtox assay), the system of the present study more accurately reflects the effects of the toxicity of common metal ions on activated-sludge respirometry without being overly sensitive to typical constituents of wastewater. The use of Shk1 as a bioluminescent reporter for heavy metal toxicity testing for the application of wastewater treatment influent toxicity screening is presented in this study.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. In vitro relative toxicity screening of combined particulate and semivolatile organic fractions of gasoline and diesel engine emissions.

    PubMed

    Seagrave, JeanClare; Mauderly, Joe L; Seilkop, Steven K

    2003-06-27

    Engine technology modifications designed to reduce engine emissions are likely to alter the physicochemical characteristics of the emissions. These changes may alter the biological effects of the emissions, but these effects cannot currently be predicted from the physical and chemical properties. Rapid in vitro toxicity screening techniques to compare the biological effects of emission samples would be useful as preliminary guides to assess the relative health impact of modified technology. Here, we demonstrate that selected responses of cultured human lung epithelial cells and rat alveolar macrophages can discriminate among combined particulate matter (PM) and semivolatile organic compound (SVOO fractions of emissions collected from normal- and high-emitter, in-use gasoline and diesel vehicles. Macrophages were more susceptible to cytotoxicity than epithelial cells. Samples from gasoline vehicles (except a vehicle that produced visible white smoke) generally caused greater effects than the diesel engine samples. However, low concentrations of diesel emission samples were more potent stimulators of peroxide production than gasoline emission samples. The same rank order of potency applied to suppression of this response at high concentrations. A diesel PM fraction was much less toxic to both types of cells than the combined PM +SVOC fractions, consistent with a role for the SVOC fraction in cytotoxicity. However, the rank order of potency from the in vitro assays in general did not correspond with the previous rankings from in vivo comparisons of the same samples. Thus, while the in vitro assays may provide mechanistic information, revealing cell type-specific responses, they did not accurately reflect in vivo comparative toxicity in their current form.

  10. Routine echocardiography screening for left-ventricular dysfunction in childhood cancer survivors: a model-based estimation of the clinical and economic impacts

    PubMed Central

    Yeh, Jennifer M.; Nohria, Anju; Diller, Lisa

    2014-01-01

    Background Childhood cancer survivors treated with cardiotoxic therapies are recommended to undergo routine cardiac assessment every 1 to 5 years, yet the long-term benefits are uncertain. Objective To estimate the cost-effectiveness of routine cardiac assessment to detect asymptomatic left-ventricular dysfunction (ALVD) and angiotensin-converting enzyme inhibitor (ACEI) and beta-adrenergic blocking (BB) treatment to reduce congestive heart failure (CHF) in childhood cancer survivors. Design Simulation model. Data Sources Literature, including Childhood Cancer Survivor Study data. Target Population Childhood cancer survivors Time horizon Lifetime. Perspective Societal. Interventions Interval-based echocardiography assessment every 1, 2, 5 or 10 years, with subsequent ACEI/BB treatment for positive results. Outcome Measures Lifetime systolic CHF risk, lifetime costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis The lifetime CHF risk among 15-year-old 5-year childhood cancer survivors was 18.8% without routine cardiac assessment (average onset age 58.8 years). Routine echocardiography reduced lifetime CHF risk by 2.3% (with assessment every 10 years) to 8.7% (annual assessment). Compared to no assessment, the ICER for assessment every 10 years was $111,600/QALY. Assessment every 5 years had an ICER of $117,900/QALY, and the ICER for more frequent assessment exceeded >$165,000/QALY. For individuals exposed to ≥250 mg/m2 total anthracycline, the ICER for assessment every 2 years was $83,600/QALY. Results of Sensitivity Analysis Results were sensitive to treatment effectiveness, absolute excess CHF risk, and ALVD asymptomatic period. For the overall cohort, the probability that assessment every 10 or 5 years was preferred at a $100,000/QALY threshold was 0.33. Limitations Treatment effectiveness based on adult data. Conclusions Current recommendations for cardiac assessment may reduce CHF incidence, but

  11. 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

  12. 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.

  13. Endocrine modulation and toxic effects of two commonly used UV screens on the aquatic invertebrates Potamopyrgus antipodarum and Lumbriculus variegatus.

    PubMed

    Schmitt, Claudia; Oetken, Matthias; Dittberner, Olaf; Wagner, Martin; Oehlmann, Jörg

    2008-03-01

    The two UV screens 3-benzylidene-camphor (3-BC) and 3-(4'-methylbenzylidene)-camphor (4-MBC) were tested regarding their toxicity and estrogenic activity. The Yeast Estrogen Screen (YES) and two sediment assays with the freshwater invertebrates Lumbriculus variegatus and Potamopyrgus antipodarum were performed. In the YES, both substances activated the human estrogen receptor alpha with EC50 values of 44.2 microM for 3-BC and 44.3 microM for 4-MBC, whereby 4-MBC attained only 8% of the maximal response of 17beta-estradiol. For P. antipodarum embryo production increased after exposure to both substances (EC50 of 4.60 microM 4-MBC=1.17 mg kg(-1)dw) while mortality increased at high concentrations. The reproduction of L. variegatus was decreased by 3-BC with an EC50 of 5.95 microM (=1.43 mg kg(-1)dw) and also by 4-MBC, where no EC50 could be calculated. While reproduction decreased, the worms' weight increased after exposure to 3-BC with an EC50 of 26.9 microM (=6.46 mg kg(-1) dw), hence the total biomass remained unaffected.

  14. 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.

  15. The biofilm electrode sensor system for acute toxicity and viral screening

    SciTech Connect

    Holodnick, S.E.

    1988-01-01

    The biofilm electrode sensor (BFE) is designed for the rapid and sensitive detection of toxic and pathogenic environmental contaminants and industrial effluents. It includes a dissolved oxygen electrode which senses respiration changes induced in a biomass film. This study assessed the effects of five chemical on biofilms of Saccharomyces cerevisiae, and polio virus on biofilms of Buffalo Green Monkey kidney cells (BGMk). Acute toxicity was assessed in 30 min, and viral infectivity in 15-20 hr. Potassium cyanide and cupric nitrate inhibited respiration in a similar manner, 2.5-68.2 %I and 30.2-68.8 %I, respectively. The response of the BFE to cyanide and cupric ions occurred within 5-20 sec. Cadmium ions affected the BFE over the range of 50.0-1000 mg/l, but complexed with components in the support medium at lower concentrations. 2,4-dinitrophenol enhanced respiration in the concentration range of 10.0-50.0 mg/l and inhibited respiration in the concentration range of 85.0-100.0 mg/l. A maximum response of 19 %I was noted at 1200 mg/l phenol, before dissolution of the polysulfone membrane filter occurred. Detection of viruses utilized BGMk cells exposed to 4.7 {times} 10{sup 4}{minus}4.7 {times} 10{sup 8} ID{sub 50}/ml poliovirus for 2 hr prior to immobilization. The response of the BFE was optimal at 15-20 hr, with a %I range of 5-40%.

  16. 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

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

    PubMed

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

    2014-10-01

    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.

  18. 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.

  19. 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.

  20. Routine Responses to Disruption of Routines

    ERIC Educational Resources Information Center

    Guha, Mahua

    2015-01-01

    "Organisational routines" is a widely studied research area. However, there is a dearth of research on disruption of routines. The few studies on disruption of routines discussed problem-solving activities that are carried out in response to disruption. In contrast, this study develops a theory of "solution routines" that are a…

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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. 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...

  3. 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...

  4. Microcosms as potential screening tools for evaluating transport and effects of toxic substances

    SciTech Connect

    Ausmus, B.S.; Eddlemon, G.K.; Draggan, S.J.; Giddhings, J.M.; Jackson, D.R.; Luxmoore, R.J.; O'Neill, E.G.; O'Neill, R.V.; Ross-Todd, M.; Van Voris, P.

    1980-06-01

    Terrestrial and aquatic microcosms were evaluated for use in research on environmental contaminants. Research completed in this project attempted to: (1) evaluate relationships among size, complexity, stability, and replicability; (2) assess the simularity between microcosm results and actual environmental transport and effects; (3) identify and quantify system-level parameters that might be sensitive indicators of effects of chemical contaminants; (4) determine the relationship between system-level parameters measured in microcosms and in natural ecosystems; and (5) suggest protocols for establishing, maintaining, and interpreting results from microcosms. A number of experimental approaches using several microcosm designs and contaminants are reported. The use of terrestrial microcosm results was evaluated in conjunction with mathematical simulation models as a means of extending short-term exprimental results to interpret conditions as they might occur in the natural ecosystem. Although microcosms offer an excellent experimental system, their application to toxic substance testing is not a straightforward matter. They are characterized by complex dynamics and counterintuitive responses just as is the ecosystem to which they are an analog. These factors notwithstanding, microcosms do offer an excellent means of studying specific aspects of contaminant behavior and ecosystem processes. With appropriate attention to the design of specific questions, answers to which are relevant to interpreting ecological transport and effects of contaminants, microcosms can be useful tools.

  5. 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

  6. Reproductive and Developmental Toxicity Screening Test of Ethyl Hydrogen Adipate in Rats

    PubMed Central

    Nam, Chunja; Hwang, Jae-Sik; Han, Kyoung-Goo; Jo, Eunhye; Yoo, Sun-kyoung; Eom, Ig-Chun; Kang, Jong-Koo

    2016-01-01

    This study aimed to evaluate the potential toxicity and safety of ethyl hydrogen adipate (EHA) by determining its effect on the reproductive function and development of Sprague-Dawley (SD) rats at dose levels of 0 (control), 200, 400, and 800 mg/kg/day. One male and five females of the 800 mg/kg/day died. Body weight loss was observed in the males of the 800 mg/kg/day and in females of the 400 and 800 mg/kg/day. In addition, mating indices decreased and pre-implantation loss rates increased in parental animals of the 400 and 800 mg/kg/day. The gestation index decreased in the male and female rats of the 800 mg/kg/day. Moreover, the body weight of the pups from the 800 mg/kg/day group decreased on post-parturition day 4. These results indicated that the no-observed-adverse-effect level of EHA for parental males and females was 400 mg/kg/day and 200 mg/kg/day, respectively, and that for pups was 400 mg/kg/day. PMID:27818735

  7. 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.

  8. 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

  9. Test of tree core sampling for screening of toxic elements in soils from a Norwegian site.

    PubMed

    Algreen, Mette; Rein, Arno; Legind, Charlotte N; Amundsen, Carl Einar; Karlson, Ulrich Gosewinkel; Trapp, Stefan

    2012-04-01

    Tree core samples have been used to delineate organic subsurface plumes. In 2009 and 2010, samples were taken at trees growing on a former dump site in Norway and analyzed for arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), and zinc (Zn). Concentrations in wood were in averages (dw) 30 mg/kg for Zn, 2 mg/kg for Cu, and < 1 mg/kg for Cd, Cr, As and Ni. The concentrations in wood samples from the polluted test site were compared to those derived from a reference site. For all except one case, mean concentrations from the test site were higher than those from the reference site, but the difference was small and not always significant. Differences between tree species were usually higher than differences between reference and test site. Furthermore, all these elements occur naturally, and Cu, Ni, and Zn are essential minerals. Thus, all trees will have a natural background of these elements, and the occurrence alone does not indicate soil pollution. For the interpretation of the results, a comparison to wood samples from an unpolluted reference site with same species and similar soil conditions is required. This makes the tree core screening method less reliable for heavy metals than, e.g., for chlorinated solvents.

  10. 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

  11. Evaluation of Xpert MRSA Gen 3 and BD MAX MRSA XT for meticillin-resistant Staphylococcusaureus screening in a routine diagnostic setting in a low-prevalence area.

    PubMed

    Nielsen, Xiaohui Chen; Madsen, Tina Vasehus; Engberg, Jørgen

    2017-01-01

    Screening and pre-emptive isolation of at-risk patients are important aspects of the Danish approach to the prevention of meticillin-resistant Staphylococcusaureus (MRSA) infection, but screening with conventional culture can take up to 3 days for results to become available with attendant costs and disadvantages of prolonged isolation. We sought to evaluate the accuracy, time to availability of results and potential economic benefits of two next-generation MRSA screening assays, Xpert MRSA Gen 3 (GX MRSA) and BD MAX MRSA XT, in a setting of a consolidated laboratory serving a number of hospitals with a low prevalence of MRSA and using enrichment culture as a reference method. Four hundred and forty-seven screening samples together with 49 previously positive MRSA samples were evaluated. Xpert MRSA Gen 3 demonstrated sensitivity, specificity, positive predictive value and negative predictive value of 88.2, 97.9, 62.5 and 99.5 %, respectively, and for BD MAX MRSA XT, they were 88.2, 97.4, 57.7 and 99.5 %, respectively. Hands-on time was 8.8 and 21.6 min, respectively, for the Xpert MRSA Gen 3 and BD MAX MRSA XT PCR assays when five samples were handled simultaneously. The mean laboratory turnaround time was 2.9 (1-6) hours for the Xpert MRSA Gen 3 assay, 6.5 (2-46) hours for BD MAX MRSA XT and 49.6 (42-122) hours for enriched culture. Despite laboratory costs being higher for the rapid PCR assays, when the costs of isolation are taken into account, the assays offer the potential for significant cost savings.

  12. Sediment toxicity in the Duluth-Superior Harbor: Use of Microtox{reg_sign} and Mutatox{reg_sign} as screening assays

    SciTech Connect

    Schubauer-Berigan, M.; Hubbard, C.; Schubauer-Berigan, J.; Tesser, G.

    1995-12-31

    Sediment toxicity tests were conducted in the Duluth-Superior Harbor at 40 sites as part of an integrated sediment assessment during the fall of 1993. Two rapid assays conducted with Photobacterium phosphoreum (Microtox{reg_sign} and Mutatox{reg_sign}) were compared with three standard US EPA sediment toxicity tests: Hyalella azteca (acute tests) and Chironomus tentans (acute and sub-lethal tests). The response in the two microbial assays was also evaluated for sensitivity to various contaminants analyzed simultaneously in the Duluth-Superior Harbor sediments. Microtox{reg_sign} and Mutatox{reg_sign} were found to be sensitive to approximately one-third and one-half the sediments, respectively; Chironomus tentans was sensitive to 15% of the sediments (either acutely or sub-lethally), while Hyalella azteca was not sensitive to any of the sediments. In almost all cases, Microtox{reg_sign} and Mutatox{reg_sign} correctly identified samples that were toxic to the chironomid, making it useful as a screening tool for toxicity, to reduce the number of sites to be tested with the benthic organisms. The subsequent application of Microtox{reg_sign} as a screen for sediment toxicity in an EMAP survey in the St. Louis River (MN) estuary will be discussed. Correlation of Microtox{reg_sign} and Mutatox{reg_sign} toxicity to environmental contaminants found in the sediments will be presented.

  13. 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

  14. Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients.

    PubMed

    Vinken, Mathieu; Pauwels, Marleen; Ates, Gamze; Vivier, Manon; Vanhaecke, Tamara; Rogiers, Vera

    2012-03-01

    Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

  15. A Novel Genetic Screen Identifies Modifiers of Age-Dependent Amyloid β Toxicity in the Drosophila Brain

    PubMed Central

    Belfiori-Carrasco, Lautaro F.; Marcora, María S.; Bocai, Nadia I.; Ceriani, M. Fernanda; Morelli, Laura; Castaño, Eduardo M.

    2017-01-01

    The accumulation of amyloid β peptide (Aβ) in the brain of Alzheimer’s disease (AD) patients begins many years before clinical onset. Such process has been proposed to be pathogenic through the toxicity of Aβ soluble oligomers leading to synaptic dysfunction, phospho-tau aggregation and neuronal loss. Yet, a massive accumulation of Aβ can be found in approximately 30% of aged individuals with preserved cognitive function. Therefore, within the frame of the “amyloid hypothesis”, compensatory mechanisms and/or additional neurotoxic or protective factors need to be considered and investigated. Here we describe a modifier genetic screen in Drosophila designed to identify genes that modulate toxicity of Aβ42 in the CNS. The expression of Aβ42 led to its accumulation in the brain and a moderate impairment of negative geotaxis at 18 days post-eclosion (d.p.e) as compared with genetic or parental controls. These flies were mated with a collection of lines carrying chromosomal deletions and negative geotaxis was assessed at 5 and 18 d.p.e. Our screen is the first to take into account all of the following features, relevant to sporadic AD: (1) pan-neuronal expression of wild-type Aβ42; (2) a quantifiable complex behavior; (3) Aβ neurotoxicity associated with progressive accumulation of the peptide; and (4) improvement or worsening of climbing ability only evident in aged animals. One hundred and ninety-nine deficiency (Df) lines accounting for ~6300 genes were analyzed. Six lines, including the deletion of 52 Drosophila genes with human orthologs, significantly modified Aβ42 neurotoxicity in 18-day-old flies. So far, we have validated CG11796 and identified CG17249 as a strong candidate (whose human orthologs are HPD and PRCC, respectively) by using RNAi or mutant hemizygous lines. PRCC encodes proline-rich protein PRCC (ppPRCC) of unknown function associated with papillary renal cell carcinoma. HPD encodes 4-hydroxyphenylpyruvate dioxygenase (HPPD), a key

  16. Updates: Routine screening for antibodies to HIV-1, civilian applicants for U.S. military service and U.S. Armed Forces, active and reserve components.

    PubMed

    2011-08-01

    During routine testing of civilian applicants for U.S. military service, the overall seroprevalence of antibodies to HIV-1 was lower in 2010 than in any year since 1990. Among members of the active components of the U.S. Army and Air Force, HIV-1 seroprevalences were higher in 2008-2010 than in recent prior years. Among members of the active components of the U.S. Navy and Marine Corps, the Marine Corps Reserve, and the Army National Guard, HIV-1 seroprevalences have slightly declined or remained relatively stable for at least ten years. In the reserve components of most of the service branches, it is difficult to discern long-term trends because of instability of seroprevalences observed in the relatively small numbers of reserve component members tested each year.

  17. Modification of the in vitro hydra assay developmental toxicity screen for evaluation of airborne toxicants: Assessment of ammonium perchlorate and vapor expos. Final report, 15 December 1995-30 September 1996

    SciTech Connect

    Wolfe, R.E.

    1996-12-01

    When the Combat Exclusion Law was repealed, military women`s duties were expanded to include duties that formally were exclusively performed by men. These military women are occupationally exposed to chemicals, including airborne toxicants, for which no developmental or reproductive toxicity testing has been performed. The reproductive toxicity of these chemical compounds needs serious consideration so that military women can continue to perform their mission responsibilities and remain healthy. An in vitro developmental toxicity screen was performed to determine the developmental hazard index (A/D ratio) for ammonium perchlorate (AP), tricresyl phosphate vapor phase lubricant (TCP), and diethyleneglycol monomethylether (DGME) using the hydra assay. The screen employed exposing both adult Hydra attenuate and `artificial embryos` composed of disassociated hydra cells to these military compounds to investigate potential developmental toxicity. AID ratios of 1.71, <0.055, and 1.75, obtained for AP, TCP, and DGME, respectively, would indicate that these military compounds should not be considered primary developmental toxins in the context of this assay.

  18. Nasal swabs collected routinely to screen for colonization by methicillin-resistant Staphylococcus aureus in intensive care units are a sensitive screening test for the organism in clinical cultures.

    PubMed

    Byrnes, Matthew C; Adegboyega, Titi; Riggle, Andrew; Chipman, Jeffrey; Beilman, Greg; Reicks, Patty; Boeser, Kim; Irwin, Eric

    2010-12-01

    Many hospitals screen patients for methicillin-resistant Staphylococcus aureus (MRSA) on admission to the intensive care unit (ICU). We hypothesized that this screening information could be used to assist with empiric antibiotic decisions. The medical records of patients admitted to a university-affiliated community hospital as well as a tertiary-care university hospital were reviewed. Patients admitted to the ICU were screened for MRSA colonization with a nasal swab that was analyzed with either chromogenic medium (hospital 1) or polymerase chain reaction (PCR) (hospital 2). The results of the nasal swab were compared with clinical culture results. There were 141 patients, and 167 cultures were obtained. The majority of the cultures (70%) were performed on sputum specimens in an effort to diagnose pneumonia. The remaining cultures were performed on blood (10.1%), incisions (21.5%), and urine (3.4%). The overall sensitivity of nasal swab results was 69.5%. However, the sensitivity was significantly higher for nasal swab screening performed within six days of clinical cultures compared with screening performed seven days or more before cultures were obtained. (79% vs. 46%; p < 0.0001). Sensitivity also differed significantly depending on the surveillance method, being significantly higher among patients screened with PCR within six days of developing an infection than in patients screened with chromogenic medium (88% vs. 65.5%; p = 0.006). Screening with PCR analysis of nasal swab specimens is a highly sensitive test for MRSA in clinical cultures. Clinicians may be able to use the swab results to tailor more appropriate empiric antimicrobial regimens. The results with chromogenic medium screening are markedly poorer, which suggests that clinicians should view them with caution.

  19. Has universal screening with Xpert® MTB/RIF increased the proportion of multidrug-resistant tuberculosis cases diagnosed in a routine operational setting?

    PubMed

    Naidoo, Pren; Dunbar, Rory; Caldwell, Judy; Lombard, Carl; Beyers, Nulda

    2017-01-01

    Primary health services in Cape Town, South Africa where the introduction of Xpert® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases. To compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms. TB cases identified in a previous stepped-wedge study of TB yield in five sub-districts over seven one-month time-points prior to, during and after the introduction of the Xpert-based algorithm were analysed. We used a combination of patient identifiers to identify all drug susceptibility tests undertaken from electronic laboratory records. Differences in the proportions of DST undertaken and MDR-TB cases diagnosed between algorithms were estimated using a binomial regression model. Pre-treatment, the probability of having a DST undertaken (RR = 1.82)(p<0.001) and being diagnosed with MDR-TB (RR = 1.42)(p<0.001) was higher in the Xpert-based algorithm than in the smear/culture-based algorithm. For cases evaluated during the course of 1st-line TB treatment, there was no significant difference in the proportion with DST undertaken (RR = 1.02)(p = 0.848) or MDR-TB diagnosed (RR = 1.12)(p = 0.678) between algorithms. Universal screening for drug susceptibility in all presumptive TB cases in the Xpert-based algorithm resulted in a higher overall proportion of MDR-TB cases being diagnosed and is an important strategy in reducing transmission. The previous strategy of only screening new TB cases when 1st line treatment failed did not compensate for cases missed pre-treatment.

  20. Has universal screening with Xpert® MTB/RIF increased the proportion of multidrug-resistant tuberculosis cases diagnosed in a routine operational setting?

    PubMed Central

    Dunbar, Rory; Caldwell, Judy; Lombard, Carl; Beyers, Nulda

    2017-01-01

    Setting Primary health services in Cape Town, South Africa where the introduction of Xpert® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases. Study aim To compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms. Methods TB cases identified in a previous stepped-wedge study of TB yield in five sub-districts over seven one-month time-points prior to, during and after the introduction of the Xpert-based algorithm were analysed. We used a combination of patient identifiers to identify all drug susceptibility tests undertaken from electronic laboratory records. Differences in the proportions of DST undertaken and MDR-TB cases diagnosed between algorithms were estimated using a binomial regression model. Results Pre-treatment, the probability of having a DST undertaken (RR = 1.82)(p<0.001) and being diagnosed with MDR-TB (RR = 1.42)(p<0.001) was higher in the Xpert-based algorithm than in the smear/culture-based algorithm. For cases evaluated during the course of 1st-line TB treatment, there was no significant difference in the proportion with DST undertaken (RR = 1.02)(p = 0.848) or MDR-TB diagnosed (RR = 1.12)(p = 0.678) between algorithms. Conclusion Universal screening for drug susceptibility in all presumptive TB cases in the Xpert-based algorithm resulted in a higher overall proportion of MDR-TB cases being diagnosed and is an important strategy in reducing transmission. The previous strategy of only screening new TB cases when 1st line treatment failed did not compensate for cases missed pre-treatment. PMID:28199375

  1. 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

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

    2015-07-01

    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. 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. 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. 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. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  2. 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

  3. General practitioners' and nurses' experiences of using computerised decision support in screening for diabetic foot disease: implementing Scottish Clinical Information - Diabetes Care in routine clinical practice.

    PubMed

    Crawford, Fay; Bekker, Hilary L; Young, Matthew; Sheikh, Aziz

    2010-01-01

    The Scottish Care Information - Diabetes Collaboration (SCI-DC) developed a computer-based information system to create a shared electronic record for use by all involved in the care of patients with diabetes mellitus. The objectives of this study were to understand primary care practitioners' views towards screening for diabetic foot disease and their experience of the SCI-DC system. We conducted an exploratory study using qualitative methods. Semi-structured interviews were audiotape-recorded, transcribed and subjected to thematic analysis. Seven practice nurses and six general practitioners (GPs) with special responsibility for diabetes care in NHS Lothian participated. Primary care clinicians reported good systems in place to screen for diabetes-related complications and to refer their patients to specialist care. Foot ulceration was rarely observed; other diabetes related conditions were seen as a higher priority. Most had heard of the SCI-DC foot assessment tool, but its failure to integrate with other primary care information technology (IT) systems meant it was not used in these general practices. Adoption of the SCI-DC foot assessment tool in primary care is not perceived as clinically necessary. Although information recorded by specialist services on SCI-DC is helpful, important structural barriers to its implementation mean the potential benefits associated with its use are unlikely to be realised; greater engagement with primary care priorities for diabetes management is needed to assist its successful implementation and adoption.

  4. Protective efficacy of phosphodiesterase-1 inhibition against alpha-synuclein toxicity revealed by compound screening in LUHMES cells.

    PubMed

    Höllerhage, Matthias; Moebius, Claudia; Melms, Johannes; Chiu, Wei-Hua; Goebel, Joachim N; Chakroun, Tasnim; Koeglsperger, Thomas; Oertel, Wolfgang H; Rösler, Thomas W; Bickle, Marc; Höglinger, Günter U

    2017-09-13

    α-synuclein-induced neurotoxicity is a core pathogenic event in neurodegenerative synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. There is currently no disease-modifying therapy available for these diseases. We screened 1,600 FDA-approved drugs for their efficacy to protect LUHMES cells from degeneration induced by wild-type α-synuclein and identified dipyridamole, a non-selective phosphodiesterase inhibitor, as top hit. Systematic analysis of other phosphodiesterase inhibitors identified a specific phosphodiesterase 1 inhibitor as most potent to rescue from α-synuclein toxicity. Protection was mediated by an increase of cGMP and associated with the reduction of a specific α-synuclein oligomeric species. RNA interference experiments confirmed PDE1A and to a smaller extent PDE1C as molecular targets accounting for the protective efficacy. PDE1 inhibition also rescued dopaminergic neurons from wild-type α-synuclein induced degeneration in the substantia nigra of mice. In conclusion, this work identifies inhibition of PDE1A in particular as promising target for neuroprotective treatment of synucleinopathies.

  5. Screening of Bacillus thuringiensis serotypes by polymerase chain reaction (PCR) for insecticidal crystal genes toxic against coffee berry borer.

    PubMed

    Naidu, M M; Rang, C; Frutos, R; Sreenivasan, C S; Naidu, R

    2001-02-01

    Using PCR,257 isolates of Bacillus thuringiensis(Bt) were screened for cry-type genes. Of 257 isolates/strains, 60 isolates were identified as cry7/8, 10 isolates as cry3 and 36 isolates as cry 1I. One specific strain of B. thuringiensis (sumiyoshiensis; T03B 001) was investigated for the presence of cry7 and cry8 genes. Genes Cry7 and cry8 were first detected in this strain using family primers prior to analysis by exclusion polymerase chain reaction (E-PCR) using specific type primers. E-PCR conducted with the above said primers led to the identification by agarose gel electrophoresis of a remaining 1.5 Kb family band indicating a potentially novel gene. This PCR product, (1.5 Kb), was purified from the gel and cloned in pGEM-T Easy vector. Twenty recombinant colonies bearing 1.5 Kb insert were identified and three randomly selected representatives of the group, clones 7, 8 and 10, were sequenced and compared to all cry7 and cry8 sequences available from Gene Bank. Alignments with available DNA and protein sequences showed that all these clones contained a gene related to cry8Aa1. Analysis using protein sequence alignment showed that the sequence from clone 7 differed from the closest relative, known under the new nomenclature as cry 8Aa1, by 44%. The crystal proteins from B. thuringiensis sumiyoshiensis (T03B 001) was toxic to coffee berry borer larvae.

  6. In vitro antimicrobial and antiprotozoal activities, phytochemical screening and heavy metals toxicity of different parts of Ballota nigra.

    PubMed

    Ullah, Najeeb; Ahmad, Ijaz; Ayaz, Sultan

    2014-01-01

    The study was done to assess the phytochemicals (flavonoids, terpenoids, saponins, tannin, alkaloids, and phenol) in different parts (root, stem, and leaves) of Ballota nigra and correlated it to inhibition of microbes (bacteria and fungi), protozoan (Leishmania), and heavy metals toxicity evaluation. In root and stem flavonoids, terpenes and phenols were present in ethanol, chloroform, and ethyl acetate soluble fraction; these were found to be the most active inhibiting fractions against all the tested strains of bacteria, fungi, and leishmania. While in leaves flavonoids, terpenes, and phenols were present in ethanol, chloroform, and n-butanol fractions which were the most active fractions against both types of microbes and protozoan (leishmania) in in vitro study. Ethanol and chloroform fractions show maximum inhibition against Escherichia coli (17 mm). The phytochemical and biological screenings were correlated with the presence of heavy metals in selected plant Ballota nigra. Cr was found above permissible value (above 1.5 mg/kg) in all parts of the plant. Ni was above WHO limit in B. nigra root and leaves (3.35 ± 1.20 mg/kg and 5.09 ± 0.47 mg/kg, respectively). Fe was above permissible value in all parts of B. nigra (above 20 mg/kg). Cd was above permissible value in all parts of the plant (above 0.3 mg/kg). Pb was above WHO limit (above 2 mg/kg) in all parts of Ballota nigra.

  7. High-content analysis in toxicology: screening substances for human toxicity potential, elucidating subcellular mechanisms and in vivo use as translational safety biomarkers.

    PubMed

    O'Brien, Peter J

    2014-07-01

    High-content analysis (HCA) of in vitro biochemical and morphological effects of classic (small molecule) drugs and chemicals is concordant with potential for human toxicity. For hepatotoxicity, concordance is greater for cytotoxic effects assessed by HCA than for conventional cytotoxicity tests and for regulatory animal toxicity studies. Additionally, HCA identifies chronic toxicity potential, and drugs producing idiosyncratic adverse reactions and/or toxic metabolites are also identified by HCA. Mechanistic information on the subcellular basis for the toxicity is frequently identified, including various mitochondrial effects, oxidative stress, calcium dyshomeostasis, phospholipidosis, apoptosis and antiproliferative effects, and a fingerprinting of the sequence and pattern of subcellular events. As these effects are frequently non-specific and affect many cell types, some toxicities may be detected and monitored by HCA of peripheral blood cells, such as for anticancer and anti-infective drugs. Critical methodological and interpretive features are identified that are critical to the effectiveness of the HCA cytotoxicity assessment, including the need for multiple days of exposure of cells to drug, use of a human hepatocyte cell line with metabolic competence, assessment of multiple pre-lethal effects in individual live cells, consideration of hormesis, the need for interpretation of relevance of cytotoxicity concentration compared to efficacy concentration and quality management. Limitations of the HCA include assessment of drugs that act on receptors, transporters or processes not found in hepatocytes. HCA may be used in a) screening lead candidates for potential human toxicity in drug discovery alongside of in vitro assessment of efficacy and pharmacokinetics, b) elucidating mechanisms of toxicity and c) monitoring in vivo toxicity of drugs with known toxicity of known mechanism. © 2014 Nordic Association for the Publication of BCPT (former Nordic

  8. Microelectrophoretic study of environmentally induced DNA damage in fish and its use for early toxicity screening of freshwater bodies.

    PubMed

    Hussain, Bilal; Sultana, Tayyaba; Sultana, Salma; Al-Ghanim, K A; Masood, Shahreef; Ali, Muhammad; Mahboob, Shahid

    2017-03-01

    This study investigates the potential of the comet and micronucleus assays of fish DNA as a means of screening the toxicity of aquatic environments. Catla catla and Cirrhinus mrigala collected from the River Chenab in Pakistan were used as a case study for the application of comet and micronucleus techniques. Comet and micronucleus assays were used to compare DNA damage in C. catla and C. mrigala collected from polluted areas of the River Chenab and farmed fish. Atomic absorption spectrophotometry showed an acute level of toxicity from Cd, Cu, Mn, Zn, Pb, Cr, Sn, and Hg in river water. Comet assay showed significant (p < 0.05) DNA damage in C. catla representing 17.33 ± 2.42, 11.53 ± 2.14, and 14.17% DNA in the comet tail, averaged from three sites of the polluted area of the river. Tail moment was observed as 10.06 ± 2.71, 3.11 ± 0.74, and 14.70 ± 1.89, while olive moment was 8.85 ± 1.84, 3.83 ± 0.76, and 7.11 ± 0.73, respectively. Highly significant (p < 0.01) damage was reported in C. mrigala as 37.29 ± 2.51, 34.96 ± 2.53, and 38.80 ± 2.42% DNA in comet tail, tail moment was 23.48 ± 3.90, 19.78 ± 4.26, and 14.30 ± 1.82, and olive moment was 16.22 ± 2.04, 13.83 ± 1.96, and10.99 ± 0.90. Significant (p < 0.05) differences were observed in genotoxicity between farmed and polluted area fish. Micronucleus assay showed a similar picture of significant difference in respect to single and double micronucleus induction: i.e., 23.20 ± 4.19 and 2.80 ± 1.07‰ in C. catla and 44.80 ± 3.73 and 06.20 ± 0.97‰, respectively, in C. mrigala. Nuclear abnormalities were found as 6.00 ± 0.84 and 09.60 ± 1.72/thousand cells, respectively, in both species. The results of this study suggest that these novel fish DNA damage assays can be used as an expedient toxicity screening for aquatic environments.

  9. Incorporating Acute HIV Screening into Routine HIV Testing at Sexually Transmitted Infection Clinics, and HI