Direct Antiglobulin Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Immunoreactive Trypsinogen (IRT) Influenza Tests Insulin Insulin-like Growth Factor-1 ... Hormone (LH) Lyme Disease Tests Magnesium Maternal Serum Screening, ...

Rheumatoid Factor

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Immunoreactive Trypsinogen (IRT) Influenza Tests Insulin Insulin-like Growth Factor-1 ... Hormone (LH) Lyme Disease Tests Magnesium Maternal Serum Screening, ...

Indication of prenatal diagnosis in pregnancies complicated by undetectable second-trimester maternal serum estriol levels.

PubMed

Minsart, Anne-Frédérique; Van Onderbergen, Anne; Jacques, Francotte; Kurt, Crener; Gillerot, Yves

2008-07-01

Undetectable maternal serum unconjugated estriol levels in the second-trimester screening test have been associated with congenital pathology and an adverse pregnancy outcome. We reviewed outcomes of pregnancies with undetectable levels of estriol (<0.25 ng/ml) in the triple-marker screening test and assessed the clinical value of this finding. We studied estriol values in 6,018 pregnant patients who underwent a triple-marker screening test during a seven-year period. 26 women had estriol levels at or below the sensitivity of the assay. The most common explanations were dating errors, prematurity, growth restriction and X-linked ichthyosis. We also observed one fetal death at 16 weeks, one severe threatened fetal abortion, one case of multiple congenital anomalies and one case of isolated adrenocorticotropin hormone deficiency. There were 6 women remaining with unexplained undetectable estriol. Undetectable maternal estriol values may indicate a severe fetal pathology and should lead to further investigations.

TB Screening Tests

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

Management options for echogenic intracardiac focus and choroid plexus cysts: a review including Australian Association of Obstetrical and Gynaecological Ultrasonologists consensus statement.

PubMed

Bethune, M

2007-08-01

Echogenic intracardiac focus and choroid plexus cysts are common findings at the midtrimester ultrasound. These findings have been linked with an increased risk of Down syndrome and trisomy 18. Most fetuses with these findings will, however, not have chromosomal abnormalities, especially when these findings are isolated. Patients experience considerable anxiety when informed of these findings and require extensive counselling in order to minimize anxiety not only about aneuploidy but also about the structure and development of the heart and brain. Although early studies showed an association with aneuploidies, several recent studies have cast doubt on this association. Many of the early studies were carried out in high-risk populations or in populations that had not had the benefit of other screening tests. Many Australian and New Zealand patients will access screening tests designed to detect these aneuploidies before presenting for a midtrimester ultrasound. Patients who have been screened by nuchal translucency, maternal serum screening or some combination of the two will already have had most cases of Down syndrome and trisomy 18 detected, and any soft marker found will almost certainly be a false positive. It is time to rethink the management of these markers. Recent evidence indicates that if these markers are found in isolation in an otherwise low-risk pregnancy, then there is minimal or no increase in the risk of Down syndrome or trisomy 18: these markers should be considered normal variants. The Australian Association of Obstetrical and Gynaecological Ultrasonologists consensus statement on these markers is included.

Molecular markers of neuropsychological functioning and Alzheimer's disease.

PubMed

Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O'Bryant, Sid

2015-03-01

The current project sought to examine molecular markers of neuropsychological functioning among elders with and without Alzheimer's disease (AD) and determine the predictive ability of combined molecular markers and select neuropsychological tests in detecting disease presence. Data were analyzed from 300 participants (n = 150, AD and n = 150, controls) enrolled in the Texas Alzheimer's Research and Care Consortium. Linear regression models were created to examine the link between the top five molecular markers from our AD blood profile and neuropsychological test scores. Logistical regressions were used to predict AD presence using serum biomarkers in combination with select neuropsychological measures. Using the neuropsychological test with the least amount of variance overlap with the molecular markers, the combined neuropsychological test and molecular markers was highly accurate in detecting AD presence. This work provides the foundation for the generation of a point-of-care device that can be used to screen for AD.

Individual identification of Sitka black-tailed deer (Odocoileus hemionus sitkensis) using DNA from fecal pellets

Treesearch

Todd J. Brinkman; David K. Person; Michael K. Schwartz; Kristine L. Pilgrim; Kevin E. Colson; Kris J. Hundertmark

2010-01-01

We tested a protocol for extracting DNA from fecal pellets from Sitka black-tailed deer (Odocoileus hemionus sitkensis) and evaluated genotyping performance of previously developed microsatellite markers as well as a suite of new markers designed specifically for this study. We screened 30 microsatellites, and identified 7 (23%) loci including 4 new markers, that fit...

[A comparison study of hpt and bar as selection marker gene of transgenic rice].

PubMed

Zhang, Chun-Yu; Li, Hong-Yu; Liu, Bin

2012-12-01

The decision of using selection marker is one of the key factors for success of plant genetic transformation and offspring screening. As two commonly used selection markers, hpt and bar genes are widely used in tissue culture-based rice transformation. To experimentally compare their performance, we investigated the efficiency of two transformation systems using Hygromycin and Bialaphos as the selection agents, respectively. The result indicated that the system using hpt gene as the selection marker saved 10 days and had double transformation efficiency and lower transgene copy number in comparison to the system using bar gene. Then, we assessed the feasibility of screening transgenic rice in the field by soaking the wild-type and transgenic seeds in a series of solutions containing step diluted hygromycin for two days. We targeted the suitable concentration for distinguishing the transgenic seeds from WT Kitaake seeds was 167 mg L(-1). However, the cost of screening by hygromycin is still much higher than that of Basta in field test. Therefore, this study experimentally demonstrated the advantages and disadvantages of the hpt and bar gene as the selection markers and thus provided a reference for choose of an appropriate selection marker according to the practical applications.

Replacing Alpha-Fetoprotein With Alpha-Fetoprotein-L3 Increases the Sensitivity of Prenatal Screening for Trisomy 21.

PubMed

Huai, Lei; Leng, Jianhang; Ma, Shenglin; Huang, Fang; Shen, Junya; Ding, Yu

This study aimed to investigate the serum concentration of alpha-fetoprotein (AFP)-L3 in midterm pregnancies and its potential application in prenatal trisomy screening. The serum samples from 27 women with trisomy 21 fetuses and 800 women with normal fetuses were examined to measure the concentrations of AFP, AFP-L3, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The screening results of various tests consisting of these markers were analyzed. In normal pregnancies within 15-20 weeks of gestation, the medians of serum AFP-L3 were 4.63, 5.70, 5.78, 6.58, 7.03, and 7.25 pg/mL. The median of AFP-L3 MoM in the trisomy 21 group was 0.46, which was significantly lower than the value of 1 in the normal group (P < 0.05). When using a cutoff value of 1/270, the sensitivity of the triple marker test (AFP, hCG, uE3) was improved from 74% to 81% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 5.4% to 6.8%. Similarly, the sensitivity of the quad marker test (AFP, hCG, uE3, inhibin-A) was improved from 81% to 89% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 4.6% to 5.6%. Serum AFP-L3 concentration increases along with more weeks of gestation in the midterm pregnancies. Trisomy 21 screening tests with AFP replaced by AFP-L3 have higher sensitivities at the expense of slightly increased false-positive rates. This improvement in screening may help to better prepare the parents and caregivers for the special needs of newborns with trisomy 21.

Fecal immunochemical tests in combination with blood tests for colorectal cancer and advanced adenoma detection—systematic review

PubMed Central

Niedermaier, Tobias; Weigl, Korbinian; Hoffmeister, Michael; Brenner, Hermann

2017-01-01

Background Colorectal cancer (CRC) is a common but largely preventable cancer. Although fecal immunochemical tests (FITs) detect the majority of CRCs, they miss some of the cancers and most advanced adenomas (AAs). The potential of blood tests in complementing FITs for the detection of CRC or AA has not yet been systematically investigated. Methods We conducted a systematic review of performance of FIT combined with an additional blood test for CRC and AA detection versus FIT alone. PubMed and Web of Science were searched until June 9, 2017. Results Some markers substantially increased sensitivity for CRC when combined with FIT, albeit typically at a major loss of specificity. For AA, no relevant increase in sensitivity could be achieved. Conclusion Combining FIT and blood tests might be a promising approach to enhance sensitivity of CRC screening, but comprehensive evaluation of promising marker combinations in screening populations is needed. PMID:29435309

First trimester serum tests for Down's syndrome screening.

PubMed

Alldred, S Kate; Takwoingi, Yemisi; Guo, Boliang; Pennant, Mary; Deeks, Jonathan J; Neilson, James P; Alfirevic, Zarko

2015-11-30

Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. However, no test can predict the severity of problems a person with Down's syndrome will have. The aim of this review was to estimate and compare the accuracy of first trimester serum markers for the detection of Down's syndrome in the antenatal period, both as individual markers and as combinations of markers. Accuracy is described by the proportion of fetuses with Down's syndrome detected by screening before birth (sensitivity or detection rate) and the proportion of women with a low risk (normal) screening test result who subsequently had a baby unaffected by Down's syndrome (specificity). We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 25 August 2011), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (Archived 2007), Health Services Research Projects in Progress database (25 August 2011). We did forward citation searching ISI citation indices, Google Scholar and PubMed 'related articles'. We did not apply a diagnostic test search filter. We also searched reference lists and published review articles.   We included studies in which all women from a given population had one or more index test(s) compared to a reference standard (either chromosomal verification or macroscopic postnatal inspection). Both consecutive series and diagnostic case-control study designs were included. Randomised trials where individuals were randomised to different screening strategies and all verified using a reference standard were also eligible for inclusion. Studies in which test strategies were compared head-to-head either in the same women, or between randomised groups were identified for inclusion in separate comparisons of test strategies. We excluded studies if they included less than five Down's syndrome cases, or more than 20% of participants were not followed up. We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC meta-analytical methods or random-effects logistic regression methods to analyse test performance and compare test accuracy as appropriate. Analyses of studies allowing direct and indirect comparisons between tests were undertaken. We included 56 studies (reported in 68 publications) involving 204,759 pregnancies (including 2113 with Down's syndrome). Studies were generally of good quality, although differential verification was common with invasive testing of only high-risk pregnancies. We evaluated 78 test combinations formed from combinations of 18 different tests, with or without maternal age; ADAM12 (a disintegrin and metalloprotease), AFP (alpha-fetoprotein), inhibin, PAPP-A (pregnancy-associated plasma protein A, ITA (invasive trophoblast antigen), free βhCG (beta human chorionic gonadotrophin), PlGF (placental growth factor), SP1 (Schwangerschafts protein 1), total hCG, progesterone, uE3 (unconjugated oestriol), GHBP (growth hormone binding protein), PGH (placental growth hormone), hyperglycosylated hCG, ProMBP (proform of eosinophil major basic protein), hPL (human placental lactogen), (free αhCG, and free ßhCG to AFP ratio. Direct comparisons between two or more tests were made in 27 studies.Meta-analysis of the nine best performing or frequently evaluated test combinations showed that a test strategy involving maternal age and a double marker combination of PAPP-A and free ßhCG significantly outperformed the individual markers (with or without maternal age) detecting about seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). Limited evidence suggested that marker combinations involving PAPP-A may be more sensitive than those without PAPP-A. Tests involving two markers in combination with maternal age, specifically PAPP-A, free βhCG and maternal age are significantly better than those involving single markers with and without age. They detect seven out of 10 Down's affected pregnancies for a fixed 5% FPR. The addition of further markers (triple tests) has not been shown to be statistically superior; the studies included are small with limited power to detect a difference.The screening blood tests themselves have no adverse effects for the woman, over and above the risks of a routine blood test. However some women who have a 'high risk' screening test result, and are given amniocentesis or chorionic villus sampling (CVS) have a risk of miscarrying a baby unaffected by Down's. Parents will need to weigh up this risk when deciding whether or not to have an amniocentesis or CVS following a 'high risk' screening test result.

Identification and characterization of dinucleotide repeat (CA)[sub n] markers for genetic mapping in dog

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

Ostrander, E.A.; Sprague, G.F. Jr.; Rine, J.

1993-04-01

A large block of simple sequence repeat (SSR) polymorphisms for the dog genome has been isolated and characterized. Screening of primary libraries by conventional hybridization methods as well as by screening of enriched marker-selected libraries led to the isolation of a large number of genomic clones that contained (CA)[sub n] repeats. The sequences of 101 clones showed that the size and complexity of (CA)[sub n] repeats in the dog genome were similar to those reported for these markers in the human genome. Detailed analysis of a representative subset of these markers revealed that most markers were moderately to highly polymorphic,more » with PIC values exceeding 0.70 for 33% of the markers tested. An association between higher PIC values and markers containing longer (CA)[sub n] repeats was observed in these studies, as previously noted for similar markers in the human genome. A list of primer sequences that tag each characterized marker is provided, and a comprehensive system of nomenclature for the dog genome is suggested. 28 refs., 4 figs., 2 tabs.« less

Applying a new mammographic imaging marker to predict breast cancer risk

NASA Astrophysics Data System (ADS)

Aghaei, Faranak; Danala, Gopichandh; Hollingsworth, Alan B.; Stoug, Rebecca G.; Pearce, Melanie; Liu, Hong; Zheng, Bin

2018-02-01

Identifying and developing new mammographic imaging markers to assist prediction of breast cancer risk has been attracting extensive research interest recently. Although mammographic density is considered an important breast cancer risk, its discriminatory power is lower for predicting short-term breast cancer risk, which is a prerequisite to establish a more effective personalized breast cancer screening paradigm. In this study, we presented a new interactive computer-aided detection (CAD) scheme to generate a new quantitative mammographic imaging marker based on the bilateral mammographic tissue density asymmetry to predict risk of cancer detection in the next subsequent mammography screening. An image database involving 1,397 women was retrospectively assembled and tested. Each woman had two digital mammography screenings namely, the "current" and "prior" screenings with a time interval from 365 to 600 days. All "prior" images were originally interpreted negative. In "current" screenings, these cases were divided into 3 groups, which include 402 positive, 643 negative, and 352 biopsy-proved benign cases, respectively. There is no significant difference of BIRADS based mammographic density ratings between 3 case groups (p < 0.6). When applying the CAD-generated imaging marker or risk model to classify between 402 positive and 643 negative cases using "prior" negative mammograms, the area under a ROC curve is 0.70+/-0.02 and the adjusted odds ratios show an increasing trend from 1.0 to 8.13 to predict the risk of cancer detection in the "current" screening. Study demonstrated that this new imaging marker had potential to yield significantly higher discriminatory power to predict short-term breast cancer risk.

Prenatal diagnosis of 47,XXX.

PubMed

Khoury-Collado, Fady; Wehbeh, Ammar N; Fisher, Allan J; Bombard, Allan T; Weiner, Zeev

2005-05-01

We report 2 cases of 47,XXX that were diagnosed prenatally and were screened positive for trisomy 21 by biochemical and ultrasound markers. These cases underline the importance of discussing the sex chromosome abnormalities during the genetic counseling after an abnormal triple screen test or ultrasound examination.

Gene Expression Changes in Developing Zebrafish as Potential Markers for Rapid Developmental Neurotoxicity Screening

EPA Science Inventory

Sparse information exists on many chemicals to guide developmental neurotoxicity (DNT) risk assessments. As DNT testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for toxicity screening. Assessing the DNT potential of chem...

Genetic and epigenetic markers in colorectal cancer screening: recent advances.

PubMed

Singh, Manish Pratap; Rai, Sandhya; Suyal, Shradha; Singh, Sunil Kumar; Singh, Nand Kumar; Agarwal, Akash; Srivastava, Sameer

2017-07-01

Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.

Development of the Grammar and Phonology Screening (GAPS) test to assess key markers of specific language and literacy difficulties in young children.

PubMed

Gardner, Hilary; Froud, Karen; McClelland, Alastair; van der Lely, Heather K J

2006-01-01

Despite a large body of evidence regarding reliable indicators of language deficits in young children, there has not been a standardized, quick screen for language impairment. The Grammar and Phonology Screening (GAPS) test was therefore designed as a short, reliable assessment of young children's language abilities. GAPS was designed to provide a quick screening test to assess whether pre- and early school entry children have the necessary grammar and pre-reading phonological skills needed for education and social development. This paper reports the theoretical background to the test, the pilot study and reliability, and the standardization. This 10-min test comprises 11 test sentences and eight test nonsense words for direct imitation and is designed to highlight significant markers of language impairment and reading difficulties. To standardize the GAPS, 668 children aged 3.4-6.6 were tested across the UK, taking into account population distribution and socio-economic status. The test was carried out by a range of health and education professionals as well as by students and carers using only simple, written instructions. GAPS is effective in detecting a range of children in need of further in-depth assessment or monitoring for language difficulties. The results concur with those from much larger epidemiological studies using lengthy testing procedures. The GAPS test (1) provides a successful screening tool; (2) is designed to be administered by professionals and non-professionals alike; and (3) facilitates identification of language impairment or at-risk factors of reading impairment in the early educational years. Thus, the test affords a first step in a process of assessment and targeted intervention to enable children to reach their potential.

Urine tests for Down's syndrome screening.

PubMed

Alldred, S Kate; Guo, Boliang; Takwoingi, Yemisi; Pennant, Mary; Wisniewski, Susanna; Deeks, Jonathan J; Neilson, James P; Alfirevic, Zarko

2015-12-10

Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. To estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome. We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles. Studies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses. We included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies).In direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR). Tests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available.

Strategies for Implementing Cell-Free DNA Testing.

PubMed

Cuckle, Howard

2016-06-01

Maternal plasma cell-free (cf) DNA testing has higher discriminatory power for aneuploidy than any conventional multi-marker screening test. Several strategies have been suggested for introducing it into clinical practice. Secondary cfDNA, restricted only to women with positive conventional screening test, is generally cost saving and minimizes the need for invasive prenatal diagnosis but leads to a small loss in detection. Primary cfDNA, replacing conventional screening or retaining the nuchal translucency scan, is not currently cost-effective for third-party payers. Contingent cfDNA, testing about 20% of women with the highest risks based on a conventional test, is the preferred approach. Copyright © 2016 Elsevier Inc. All rights reserved.

A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

PubMed

Cho, Sung Jin; Lee, Jihoo; Lee, Hyun Jae; Jo, Hyun-Young; Sinniah, Mangalam; Kim, Hak-Yong; Chong, Chom-Kyu; Song, Hyun-Ok

2016-01-01

Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas. However, only a few malaria antibody tests are available in the microwell-based assay format and these are not suitable for field application. A novel malaria antibody (Ab)-based RDT using a differential diagnostic marker for falciparum and vivax malaria was developed as a suitable high-throughput assay that is sensitive and practical for blood screening. The marker, merozoite surface protein 1 (MSP1) was discovered by generation of a Plasmodium-specific network and the hierarchical organization of modularity in the network. Clinical evaluation revealed that the novel Malaria Pf/Pv Ab RDT shows improved sensitivity (98%) and specificity (99.7%) compared with the performance of a commercial kit, SD BioLine Malaria P.f/P.v (95.1% sensitivity and 99.1% specificity). The novel Malaria Pf/Pv Ab RDT has potential for use as a cost-effective blood-screening tool for malaria and in turn, reduces TTM risk in endemic areas.

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...

Laboratory and clinical aspects of human papillomavirus testing

PubMed Central

Chan, Paul K.S.; Picconi, María Alejandra; Cheung, Tak Hong; Giovannelli, Lucia; Park, Jong Sup

2012-01-01

Human papillomavirus (HPV) infection is associated with a wide spectrum of disease that ranges from self-limited skin warts to life-threatening cancers. Since HPV plays a necessary etiological role in cervical cancer, it is logical to use HPV as a marker for early detection of cervical cancer and precancer. Recent advances in technology enable the development of high-throughput HPV assays of different formats, including DNA-based, mRNA-based, high-risk group-specific and type-specific methods. The ultimate goal of these assays is to improve the accuracy and cost-effiectiveness of cervical screening programs. HPV testing has several potential advantages compared to cytology-based screening. However, since the cancer to transient infection ratio is always low in the general population, HPV test results are bound to have a low positive predictive value that may subject women to unnecessary follow-up investigations. The wide-spread administration of prophylactic HPV vaccine will substantially decrease the incidence of cancer and precancer. This poses a number of challenges to cytology-based screening, and the role of HPV testing is expected to increase. Finally, apart from technical and cost-effiectiveness considerations, one should also keep in mind the psycho-social impact of using sexually-transmitted agents as a marker for cancer screening. PMID:22913405

Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer

PubMed Central

Yokoi, Keigo; Yamashita, Keishi; Watanabe, Masahiko

2017-01-01

Epigenetic alterations by promoter DNA hypermethylation and gene silencing in cancer have been reported over the past few decades. DNA hypermethylation has great potential to serve as a screening marker, a prognostic marker, and a therapeutic surveillance marker in cancer clinics. Some bodily fluids, such as stool or urine, were obtainable without any invasion to the body. Thus, such bodily fluids were suitable samples for high throughput cancer surveillance. Analyzing the methylation status of bodily fluids around the cancer tissue may, additionally, lead to the early detection of cancer, because several genes in cancer tissues are reported to be cancer-specifically hypermethylated. Recently, several studies that analyzed the methylation status of DNA in bodily fluids were conducted, and some of the results have potential for future development and further clinical use. In fact, a stool DNA test was approved by the U.S. Food and Drug Administration (FDA) for the screening of colorectal cancer. Another promising methylation marker has been identified in various bodily fluids for several cancers. We reviewed studies that analyzed DNA methylation in bodily fluids as a less-invasive cancer screening. PMID:28358330

[Studies of marker screening efficiency and corresponding influencing factors in QTL composite interval mapping].

PubMed

Gao, Yong-Ming; Wan, Ping

2002-06-01

Screening markers efficiently is the foundation of mapping QTLs by composite interval mapping. Main and interaction markers distinguished, besides using background control for genetic variation, could also be used to construct intervals of two-way searching for mapping QTLs with epistasis, which can save a lot of calculation time. Therefore, the efficiency of marker screening would affect power and precision of QTL mapping. A doubled haploid population with 200 individuals and 5 chromosomes was constructed, with 50 markers evenly distributed at 10 cM space. Among a total of 6 QTLs, one was placed on chromosome I, two linked on chromosome II, and the other three linked on chromosome IV. QTL setting included additive effects and epistatic effects of additive x additive, the corresponding QTL interaction effects were set if data were collected under multiple environments. The heritability was assumed to be 0.5 if no special declaration. The power of marker screening by stepwise regression, forward regression, and three methods for random effect prediction, e.g. best linear unbiased prediction (BLUP), linear unbiased prediction (LUP) and adjusted unbiased prediction (AUP), was studied and compared through 100 Monte Carlo simulations. The results indicated that the marker screening power by stepwise regression at 0.1, 0.05 and 0.01 significant level changed from 2% to 68%, the power changed from 2% to 72% by forward regression. The larger the QTL effects, the higher the marker screening power. While the power of marker screening by three random effect prediction was very low, the maximum was only 13%. That suggested that regression methods were much better than those by using the approaches of random effect prediction to identify efficient markers flanking QTLs, and forward selection method was more simple and efficient. The results of simulation study on heritability showed that heightening of both general heritability and interaction heritability of genotype x environments could enhance marker screening power, the former had a greater influence on QTLs with larger main and/or epistatic effects, while the later on QTLs with small main and/or epistatic effects. The simulation of 100 times was also conducted to study the influence of different marker number and density on marker screening power. It is indicated that the marker screening power would decrease if there were too many markers, especially with high density in a mapping population, which suggested that a mapping population with definite individuals could only hold limited markers. According to the simulation study, the reasonable number of markers should not be more than individuals. The simulation study of marker screening under multiple environments showed high total power of marker screening. In order to relieve the problem that marker screening power restricted the efficiency of QTL mapping, markers identified in multiple environments could be used to construct two search intervals.

Patch testing with the European baseline series fragrance markers: a 2016 update.

PubMed

Ung, C Y; White, J M L; White, I R; Banerjee, P; McFadden, J P

2018-03-01

Fragrance contact allergy is common and is currently screened for using the following European baseline series fragrance markers: fragrance mix (FM)I, FMII, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde. To investigate the validity of patch testing using these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory within the European Union. We conducted a retrospective review of the patch test records of all patients with eczema who underwent testing using the European baseline series, extended with the individual fragrance substances during the period from 2015 to 2016. Overall, 359 patients (17·2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidized linalool [n = 154; 7·4%, 95% confidence interval (CI) 6·3-8·6], oxidized limonene (n = 89; 4·3%, 95% CI 3·4-5·2) and Evernia furfuracea (n = 44; 2·1%, 95% CI 1·5-2·8). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40·8%) also reacted to a baseline series fragrance marker. The sensitivity of our history-taking for detecting fragrance allergy was 25·7%. Given the evolving trends in fragrance allergy, patch testing with FMI, FMII, M. pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde is no longer sufficient for screening for fragrance allergy. © 2017 British Association of Dermatologists.

Is screening for fetal anomalies reliable in HIV-infected pregnant women? A multicentre study.

PubMed

Brossard, Philippe; Boulvain, Michel; Coll, Oriol; Barlow, Patricia; Aebi-Popp, Karoline; Bischof, Paul; Martinez de Tejada, Begoña

2008-10-01

To assess the impact of HIV infection on the reliability of the first-trimester screening for Down syndrome, using free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency, and of the second-trimester screening for neural tube defects, using alpha-fetoprotein. Multicentre study comparing the multiples of the median of markers for Down syndrome and neural tube defect screening among 214 HIV-infected pregnant women and 856 HIV-negative controls undergoing a first-trimester Down syndrome screening test, and 209 HIV-positive women and 836 HIV-negative controls with a risk evaluation for neural tube defect. The influence of treatment, chronic hepatitis and HIV disease characteristics were also evaluated. Multiples of the median medians for pregnancy-associated plasma protein-A and beta-human chorionic gonadotrophin were lower in HIV-positive women than controls (0.88 vs. 1.05 and 0.84 vs. 1.09, respectively; P < 0.005), but these differences had no impact on risk estimation; no differences were observed for the other markers. No association was found between HIV disease characteristics, antiretroviral treatment use at the time of screening or chronic hepatitis and marker levels. Screening for Down syndrome during the first trimester and for neural tube defect during the second trimester is accurate for HIV-infected women and should be offered, similar to HIV-negative women.

Microsatellites for Oenothera gayleana and O. hartwegii subsp. filifolia (Onagraceae), and their utility in section Calylophus.

PubMed

Lewis, Emily M; Fant, Jeremie B; Moore, Michael J; Hastings, Amy P; Larson, Erica L; Agrawal, Anurag A; Skogen, Krissa A

2016-02-01

Eleven nuclear and four plastid microsatellite markers were screened for two gypsum endemic species, Oenothera gayleana and O. hartwegii subsp. filifolia, and tested for cross-amplification in the remaining 11 taxa within Oenothera sect. Calylophus (Onagraceae). Microsatellite markers were tested in two to three populations spanning the ranges of both O. gayleana and O. hartwegii subsp. filifolia. The nuclear microsatellite loci consisted of both di- and trinucleotide repeats with one to 17 alleles per population. Several loci showed significant deviation from Hardy-Weinberg equilibrium, which may be evidence of chromosomal rings. The plastid microsatellite markers identified one to seven haplotypes per population. The transferability of these markers was confirmed in all 11 taxa within Oenothera sect. Calylophus. The microsatellite loci characterized here are the first developed and tested in Oenothera sect. Calylophus. These markers will be used to assess whether pollinator foraging distance influences population genetic parameters in predictable ways.

EDRN Breast and Ovary Cancer CVC, Study 3: Phase 3 Validation of screening decision rules in preclinical UKCTOCS serial samples — EDRN Public Portal

Cancer.gov

We will collaborate with investigators from University College London to test a screening decision rule in preclinical serial samples from the U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to learn if the panel can do better than CA125 alone. The UKCTOCS is an ideal setting for retrospective validation of an early detection marker panel and decision rule because it offers serial samples collected annually and use of imaging in women with rising CA125. Multi-modal strategies using serum markers HE4, MSLN, MMP7, and CA125 will be compared to strategies relying exclusively on CA125 and transvaginal sonography (TVS).

Acceptability of screening for early detection of liver disease in hazardous/harmful drinkers in primary care.

PubMed

Eyles, Caroline; Moore, Michael; Sheron, Nicholas; Roderick, Paul; O'Brien, Wendy; Leydon, Geraldine M

2013-08-01

It is estimated that one-quarter of adults in the UK drink at harmful/hazardous levels leading to increased mortality and alcohol liver disease (ALD). The Alcohol Liver Disease Detection Study (ALDDeS) aimed to test out in primary care the feasibility of alcohol misuse screening in adults, using the AUDIT questionnaire, and to assess screening harmful/hazardous alcohol users for ALD using newer non-invasive serum markers of fibrosis. To explore patients' experiences of taking part in ALDDeS and understanding of the delivery and process of screening for ALD using self-report questionnaires and feedback of liver fibrosis risk using levels of non-invasive serum markers. A nested qualitative study based in five primary care practices in the UK. From a sample of patients who were identified as drinking at harmful/hazardous levels, 30 participants were identified by maximum variation sampling for qualitative in-depth interviews. Using the principles of constant comparison the transcribed interviews were thematically analysed. Receiving a postal AUDIT questionnaire was viewed as acceptable by participants. For some completing the AUDIT increased awareness of their hazardous alcohol use and a positive blood test indicating liver fibrosis was a catalyst for behaviour change. For others, a negative blood test result provided a licence to continue drinking at hazardous levels. A limited understanding of safe drinking and of ALD was common. Educational and training needs of primary care professionals must be taken into account, so that patients with marker levels indicating low risk of fibrosis are correctly informed about the likely risks of continuing to drink at the same levels.

[Strategy for molecular testing in pulmonary carcinoma].

PubMed

Penault-Llorca, Frédérique; Tixier, Lucie; Perrot, Loïc; Cayre, Anne

2016-01-01

Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening. Copyright © 2016. Published by Elsevier Masson SAS.

Serum ALT levels as a surrogate marker for serum HBV DNA levels in HBeAg-negative pregnant women.

PubMed

Sangfelt, Per; Von Sydow, Madeleine; Uhnoo, Ingrid; Weiland, Ola; Lindh, Gudrun; Fischler, Björn; Lindgren, Susanne; Reichard, Olle

2004-01-01

In Stockholm, Sweden, the majority of pregnant women positive for hepatitis B surface antigen (HBsAg) are hepatitis Be antigen (HBeAg) negative. Newborns to HBeAg positive mothers receive vaccination and hepatitis B immunoglobulin (HBIg). Newborns to HBeAg negative mothers receive vaccine and HBIg only if the mothers have elevated ALT levels. The aim of this study was to retrospectively evaluate ALT levels as a surrogate marker for HBV DNA levels in HBeAg negative carrier mothers. Altogether 8947 pregnant women were screened for HBV markers from 1999 to 2001 at the Virology Department, Karolinska Hospital. Among mothers screened 192 tested positive for HBsAg (2.2%). 13 of these samples could not be retrieved. Of the remaining 179 sera, 8 (4%) tested positive for HBeAg and 171 (95.5%) were HBeAg negative. Among the HBeAg negative mothers, 9 had HBV DNA levels > 10(5) copies/ml, and of these 7 had normal ALT levels indicating low sensitivity of an elevated ALT level as a surrogate marker for high HBV DNA level. Furthermore, no correlation was found between ALT and HBV DNA levels. Hence, it is concluded that the use of ALT as a surrogate marker for high viral replication in HBeAg negative mothers could be questioned.

Early Pregnancy Biochemical Predictors of Gestational Diabetes Mellitus.

PubMed

Powe, Camille E

2017-02-01

Universal oral glucose tolerance-based screening is employed to identify pregnant women with gestational diabetes mellitus (GDM), as treatment of this condition decreases the risk of associated complications. A simple and accurate blood test which identifies women at low or high risk for GDM in the first trimester would have the potential to decrease costs and improve outcomes through prevention or treatment. This review summarizes published data on early pregnancy biomarkers which have been tested as predictors of GDM. A large number of first-trimester biochemical predictors of GDM have been reported, mostly in small case-control studies. These include glycemic markers (fasting glucose, post-load glucose, hemoglobin A1C), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha), insulin resistance markers (fasting insulin, sex hormone-binding globulin), adipocyte-derived markers (adiponectin, leptin), placenta-derived markers (follistatin-like-3, placental growth factor, placental exosomes), and others (e.g., glycosylated fibronectin, soluble (pro)renin receptor, alanine aminotransferase, ferritin). A few large studies suggest that first-trimester fasting glucose or hemoglobin A1C may be useful for identifying women who would benefit from early GDM treatment. To translate the findings from observational studies of first-trimester biomarkers for GDM to clinical practice, trials or cost-effectiveness analyses of screening and treatment strategies based on these novel biomarkers are needed.

Genome-Scale Screen for DNA Methylation-Based Detection Markers for Ovarian Cancer

PubMed Central

Houshdaran, Sahar; Shen, Hui; Widschwendter, Martin; Daxenbichler, Günter; Long, Tiffany; Marth, Christian; Laird-Offringa, Ite A.; Press, Michael F.; Dubeau, Louis; Siegmund, Kimberly D.; Wu, Anna H.; Groshen, Susan; Chandavarkar, Uma; Roman, Lynda D.; Berchuck, Andrew; Pearce, Celeste L.; Laird, Peter W.

2011-01-01

Background The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer. Methodology/Principal Findings We used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels. We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients. Conclusions/Significance We implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers. PMID:22163280

Diagnostic accuracy of blood centers in the screening of blood donors for viral markers

PubMed Central

Dogbe, Elliot Eli; Arthur, Fareed

2015-01-01

Introduction Blood transfusion still remains a life saving intervention in almost all healthcare facilities worldwide. Screening of blood donors/blood units is done in almost every blood bank facility before the blood units/blood components are transfused to prevent transfusion-transmissible infections. The kind of testing kits or the methods used by a facility and the technical expertise of the personnel greatly affects the screening results of a facility. This study was aimed at evaluating the diagnostic accuracy of five hospital-based blood bank testing facilities (Komfo Anokye Teaching Hospital KNUST, Kwame Nkrumah University of Science and Technology, Agogo, Bekwai and Sunyani) that used rapid immunochromatograhic assays (RIA) in screening blood donors/blood units in Ghana. Methods Blood samples (300) from the five testing facilities and their screening results for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (HCV) and human immunodeficiency virus (HIV) using RIAs were obtained. All the samples were then analysed for the three viral markers using 3rd generational enzyme linked immunosorbent assay (ELISA) kit as the gold standard. Results The mean false positive for HBsAg was 2.2% with Bekwai testing facility having the highest of 4.4%. For HCV, the mean false positive was 2.8% with Agogo and Bekwai testing facilities having the highest of 8.7% respectively. For HIV screening, the mean false positive was 11.1% with Bekwai testing facility having the highest of 28.0%. The mean false negative for the facilities were 3.0% for HBV, 75.0% for HCV and 0.0% for HIV with KATH having the highest of 6.3% for HBV, Bekwai having the highest of 100% for HCV and no facility showing false negative for HIV. Mean sensitivity of the screening procedure for the facilities was 97.0%, 25.0% and 100.0% whilst the mean specificity was 97.8%, 97.2% and 88.9% for HBV, HCV and HIV respectively. Statistical comparison among the testing facilities showed no significant differences among the various testing centres for HBV screening; however, significant differences were obtained for HCV and HIV screening. Conclusion This study has shown that there is no standardised screening procedure for blood bank testing facilities in the country. There is therefore an urgent need for an internal and external control body to oversee screening procedures in blood banks across the country. PMID:26090067

Evaluation of markers out of the steroid profile for the screening of testosterone misuse. Part I: Transdermal administration.

PubMed

Kotronoulas, Aristotelis; Gomez-Gómez, Àlex; Fabregat, Andreu; Segura, Jordi; Yang, Sheng; Xing, Yanyi; Moutian, Wu; Marcos, Josep; Joglar, Jesús; Ventura, Rosa; Pozo, Oscar J

2018-05-01

Although the introduction by the World Anti-Doping Agency (WADA) of the steroid module of the athlete biological passport (ABP) marked an important step forward in the screening of testosterone (T) misuse, it still remains one of the most difficult challenges in doping control analysis. The urinary determination of alternative markers has been recently reported as a promising tool for improving the screening of T oral administration. However, their evaluation for other, commonly used, administration routes is still required. The main goal of this study is the evaluation of the potential of 2 groups of metabolites (cysteinyl conjugated and glucuronoconjugated) after transdermal and intramuscular administration of T. Their suitability was evaluated in individuals with both low basal (L-T/E) and medium basal (M-T/E) values of T/E. In this Part I, we evaluated the urinary excretion profile of these 2 groups of T metabolites after the administration of 3 doses of T gel to 12 volunteers (6 L-T/E and 6 M-T/E) for 3 consecutive days. For this purpose, 9 different concentration ratios (5 cysteinyl conjugated and 4 glucuronoconjugated markers) were studied. Both, the intra-individual variability and the detection windows (DW) obtained by each ratio were evaluated. Cysteinyl conjugates showed a general low intra-individual variability and DWs that were shorter than any other tested marker. Despite the relatively large intra-individual variability, the DWs reached by glucuronoconjugates (2-3 days) were similar to those obtained by markers currently included in the ABP. Overall; this evaluation advises for the introduction of additional glucuronoconjugated markers in the screening of transdermal T administration. Copyright © 2017 John Wiley & Sons, Ltd.

Screening for chromosomal anomalies in the first trimester: does repeat maternal serum screening improve detection rates?

PubMed

Spencer, Kevin; Cuckle, Howard S

2002-10-01

To assess the within person biological variability of first trimester maternal serum biochemical markers of trisomy 21 across the 10-14 week gestational period. To evaluate whether repeat sampling and testing of free beta-hCG and PAPP-A during this period would result in an improved detection rate. Women presenting at the first trimester OSCAR clinic have blood collected prior to ultrasound dating and nuchal translucency measurement. All samples are analysed for free beta-hCG and PAPP-A before an accurate estimate of gestation is available. In 10% of cases the gestation is prior to the minimum time for NT measurement (11 weeks) and these women are rebooked for a repeat visit to the clinic at the appropriate time. Our fetal database was interrogated to obtain cases in which two maternal blood samples had been collected and analysed in the 10-14 week period. Using data from the marker correlations and statistical modelling, the impact of repeat testing on detection rate for trisomy 21 at a fixed 5% false positive rate, was assessed. 261 pairs of data were available for analysis collected over a 3 year period. The correlation between free beta-hCG in sample 1 and sample 2 was 0.890 and that for PAPP-A was 0.827. The average within person biological variation for free beta-hCG was 21% and 32% for PAPP-A. The increase in detection rate when using both sets of marker data was 3.5% when using serum biochemistry and maternal age, and 1.3% when using nuchal translucency, serum biochemistry and maternal age. Repeat sampling and testing of maternal serum biochemical markers is unlikely to substantially improve first trimester screening performance. Copyright 2002 John Wiley & Sons, Ltd.

First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing.

PubMed

Nicolaides, K H; Syngelaki, A; Poon, L C; Gil, M M; Wright, D

2014-01-01

To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers. In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in about 35, 20 and 11% of cases identified by first-line screening with the combined test alone (age, NT, FHR, β-hCG, PAPP-A), the combined test plus PLGF and AFP and the combined test plus PLGF, AFP and DV PIV, respectively. Effective first-trimester screening for trisomies can be achieved by contingent screening incorporating biomarkers and cfDNA testing. © 2013 S. Karger AG, Basel.

Detection and identification of occult HBV in blood donors in Taiwan using a commercial, multiplex, multi-dye nucleic acid amplification technology screening test.

PubMed

Lin, K T; Chang, C L; Tsai, M H; Lin, K S; Saldanha, J; Hung, C M

2014-02-01

The ability of a new generation commercial, multiplex, multi-dye test from Roche, the cobas TaqScreen MPX test, version 2.0, to detect and identify occult HBV infections was evaluated using routine donor samples from Kaohsiung Blood Bank, Taiwan. A total of 5973 samples were tested by nucleic acid amplification technology (NAT); 5898 in pools of six, 66 in pools of less than six and nine samples individually. NAT-reactive samples were retested with alternative NAT tests, and follow-up samples from the donors were tested individually by NAT and for all the HBV serological markers. Eight NAT-only-reactive donors were identified, and follow-up samples were obtained from six of the donors. The results indicated that all eight donors had an occult HBV infection with viral loads <12 IU/ml. The cobas(®) TaqScreen MPX test, version 2.0, has an advantage over the current Roche blood screening test, the cobas TaqScreen MPX test, for screening donations in countries with a high prevalence of occult HBV infections since the uncertainty associated with identifying samples with very low viremia is removed by the ability of the test to identify the viral target in samples that are reactive with the cobas TaqScreen MPX test, version 2.0. © 2013 International Society of Blood Transfusion.

Microsatellites for Oenothera gayleana and O. hartwegii subsp. filifolia (Onagraceae), and their utility in section Calylophus1

PubMed Central

Lewis, Emily M.; Fant, Jeremie B.; Moore, Michael J.; Hastings, Amy P.; Larson, Erica L.; Agrawal, Anurag A.; Skogen, Krissa A.

2016-01-01

Premise of the study: Eleven nuclear and four plastid microsatellite markers were screened for two gypsum endemic species, Oenothera gayleana and O. hartwegii subsp. filifolia, and tested for cross-amplification in the remaining 11 taxa within Oenothera sect. Calylophus (Onagraceae). Methods and Results: Microsatellite markers were tested in two to three populations spanning the ranges of both O. gayleana and O. hartwegii subsp. filifolia. The nuclear microsatellite loci consisted of both di- and trinucleotide repeats with one to 17 alleles per population. Several loci showed significant deviation from Hardy–Weinberg equilibrium, which may be evidence of chromosomal rings. The plastid microsatellite markers identified one to seven haplotypes per population. The transferability of these markers was confirmed in all 11 taxa within Oenothera sect. Calylophus. Conclusions: The microsatellite loci characterized here are the first developed and tested in Oenothera sect. Calylophus. These markers will be used to assess whether pollinator foraging distance influences population genetic parameters in predictable ways. PMID:26949578

Screening for malnutrition in nursing home residents: comparison of different risk markers and their association to functional impairment.

PubMed

Stange, I; Poeschl, K; Stehle, P; Sieber, C C; Volkert, D

2013-04-01

To identify nursing home residents with malnutrition or at risk of malnutrition by using different markers, determine if the Mini Nutritional Assessment (MNA®) is able to identify all residents at risk according to single risk markers and explore the relation between risk markers and functional impairment. Cross-sectional study. Six German nursing homes. 286 residents (86±7y, 89% female). Screening for malnutrition or its risk included low BMI (≤22 kg/m²), recent weight loss (WL), low food intake (LI) as single risk markers and MNA (<24 points, p.) as composite marker. Prevalence of single nutritional risk markers in different MNA categories was compared by cross-tables. Mental (cognition, mood) and physical function (mobility) were assessed by interviewing nursing staff and association of impaired status to nutritional risk markers determined by Chi² test. 32.9% of residents had a low BMI, 11.9% WL and 21.3% LI. 60.2% were categorized malnourished (18.2%) or at risk of malnutrition (42.0%) by MNA. 64% presented at least one of these nutritional risk markers. Of those classified malnourished by MNA, 96.2% also showed low BMI, WL or LI. In contrast, eleven residents (9.6%) considered well-nourished by MNA presented single risk markers (9 low BMI, 2 WL). Cognitive impairment, depressive symptoms and immobility was present in 59.0%, 20.8% and 25.5%, respectively. Functional impairment, and in particular severe impairment, was to a higher proportion present in residents at nutritional risk independent of the chosen marker (MNA<24 p., low BMI, WL, LI). The high prevalence of nutritional risk highlights the importance of regular screening of nursing home residents. The MNA identified nearly all residents with low BMI, WL and LI. The close association between nutritional risk and functional impairment requires increased awareness for nutritional problems especially in functionally impaired residents, to early initiate nutritional measures and thus, prevent further nutritional and functional deterioration.

Dietary flavonols contribute to false-positive elevation of homovanillic acid, a marker of catecholamine-secreting tumors.

PubMed

Combet, Emilie; Lean, Michael E J; Boyle, James G; Crozier, Alan; Davidson, D Fraser

2011-01-14

Urinary homovanillic acid (HVA) measurement is used routinely as a marker of the first test for the screening of catecholamine-secreting tumors and dopamine metabolism, but generates a large number of false-positive results. With no guidelines for dietary restrictions prior to the test, we hypothesize that consumption of flavonol-rich foods (such as onions, tomatoes, tea) prior to urinary catecholamine screening could be responsible for false-positive urinary HVA in healthy subjects. A randomized, crossover dietary intervention was carried out in healthy subjects (n=17). Volunteers followed either a low or high-flavonol diet, for a duration of 3 days, prior to providing a 24-h urine sample for HVA measurement using a routine, validated liquid chromatography method as well as a gas chromatography-mass spectrometry method. Dietary flavonol intake significantly increased urinary HVA excretion (p < 0.001), with 3 out of 17 volunteers (20%) exceeding the 40 μmol/24 h upper limit of normal for HVA excretion (false-positive result). Dietary flavonols commonly found in foodstuff such as tomatoes, onions, and tea, interfered with the routine urinary HVA screening test and should be avoided in the three-day run-up to the test. Copyright © 2010 Elsevier B.V. All rights reserved.

Significance of CEA and VEGF as Diagnostic Markers of Colorectal Cancer in Lebanese Patients.

PubMed

Dbouk, Hashem A; Tawil, Ayman; Nasr, Fahd; Kandakarjian, Loucine; Abou-Merhi, Raghida

2007-11-08

Carcinoembryonic antigen and vascular endothelial growth factors are among the most important prognostic markers of colorectal cancer. Testing for these markers independently has been of limited value in screening for this tumor. The aim of this study is to determine the importance of simultaneous blood CEA and VEGF level determinations in diagnosis of colorectal cancer. Thirty-six patients diagnosed with colorectal cancer along with eight healthy controls were tested by ELISA for CEA and VEGF levels in serum and plasma, respectively. The positive predictive value of these markers was 95.4% for CEA and 89.5% for VEGF, and for combined CEA and VEGF was also high at 88%. Combined CEA and VEGF blood level assay constitutes a useful panel in detecting patients with colorectal cancer. Positive results allow selection of a subgroup of patients with a high tumor risk; therefore, such tests comprise valuable tumor diagnostic tests to add to current detection methods.

Combined Screening for Early Detection of Pre-Eclampsia

PubMed Central

Park, Hee Jin; Shim, Sung Shin; Cha, Dong Hyun

2015-01-01

Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers. PMID:26247944

Tumor Markers

MedlinePlus

... on its own to screen for cancer. For example, the prostate-specific antigen (PSA) test , which measures the level of PSA in the ... Targeted Cancer Therapies Understanding Cancer ... Institute.” Please note that blog posts that are written by individuals from outside the ...

Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients.

PubMed

Dolman, Jonathan M; Hawkes, Neil D

2005-01-01

Alcohol consumption is often under-reported in patients admitted to general hospitals with acute illness. For alcohol-dependent individuals hospital admission results in an enforced period of abstinence with potential alcohol withdrawal symptoms, and possible life threatening complications. Early detection of alcohol use is therefore beneficial to patients and health services. The purpose of this study was to investigate the performance of the alcohol use disorders identification test (AUDIT) questionnaire in the acute medical setting, and the effect of combining routine biological markers-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and mean corpuscular volume (MCV) on its performance in the early identification of in-patients with alcohol use disorders and at risk of developing symptoms of alcohol withdrawal. Prospective study in consecutive patients admitted to an acute medical admissions ward. All patients were screened using the AUDIT questionnaire and routine blood tests. Patients were then monitored for symptoms of withdrawal using clinical institute withdrawal assessment for alcohol (CIWA-Ar). Of the 874 patients screened using the AUDIT, 98 (11%) screened positive of whom 17 (2% of the 874) experienced clinically significant alcohol withdrawal symptoms, when using serial CIWA-Ar. The AUDIT and serial CIWA-Ar detected all patients who went on to manifest acute withdrawal symptoms. There was no loss of sensitivity at an AUDIT cut-off of 13 or more compared with the lower cut-off of 8 or more. A positive predictive value of 17.3% for an AUDIT score of 8 or more in the detection of withdrawal, increased to 47.1% when found in combination with at least two abnormal biological markers whilst maintaining a sensitivity of 94.1% and specificity of 97.9%. These findings confirm that AUDIT is a useful alcohol screen in general medical settings and that its ability to correctly predict which patients will experience alcohol withdrawal is increased when used in combination with biological markers.

Isolation and characterization of novel microsatellite markers from the sika deer (Cervus nippon) genome.

PubMed

Li, Y M; Bai, C Y; Niu, W P; Yu, H; Yang, R J; Yan, S Q; Zhang, J Y; Zhang, M J; Zhao, Z H

2015-09-28

Microsatellite markers are widely and evenly distributed, and are highly polymorphic. Rapid and convenient detection through automated analysis means that microsatellite markers are widely used in the construction of plant and animal genetic maps, in quantitative trait loci localization, marker-assisted selection, identification of genetic relationships, and genetic diversity and phylogenetic tree construction. However, few microsatellite markers remain to be isolated. We used streptavidin magnetic beads to affinity-capture and construct a (CA)n microsatellite DNA-enriched library from sika deer. We selected sequences containing more than six repeats to design primers. Clear bands were selected, which were amplified using non-specific primers following PCR amplification to screen polymorphisms in a group of 65 unrelated sika deer. The positive clone rate reached 82.9% by constructing the enriched library, and we then selected positive clones for sequencing. There were 395 sequences with CA repeats, and the CA repeat number was 4-105. We selected sequences containing more than six repeats to design primers, of which 297 pairs were designed. We next selected clear bands and used non-specific primers to amplify following PCR amplification. In total, 245 pairs of primers were screened. We then selected 50 pairs of primers to randomly screen for polymorphisms. We detected 47 polymorphic and 3 monomorphic loci in 65 unrelated sika deer. These newly isolated and characterized microsatellite loci can be used to construct genetic maps and for lineage testing in deer. In addition, they can be used for comparative genomics between Cervidae species.

Development and application of a general plasmid reference material for GMO screening.

PubMed

Wu, Yuhua; Li, Jun; Wang, Yulei; Li, Xiaofei; Li, Yunjing; Zhu, Li; Li, Jun; Wu, Gang

The use of analytical controls is essential when performing GMO detection through screening tests. Additionally, the presence of taxon-specific sequences is analyzed mostly for quality control during GMO detection. In this study, 11 commonly used genetic elements involving three promoters (P-35S, P-FMV35S and P-NOS), four marker genes (Bar, NPTII, HPT and Pmi), and four terminators (T-NOS, T-35S, T-g7 and T-e9), together with the reference gene fragments from six major crops of maize, soybean, rapeseed, rice, cotton and wheat, were co-integrated into the same single plasmid to construct a general reference plasmid pBI121-Screening. The suitability test of pBI121-Screening plasmid as reference material indicated that the non-target sequence on the pBI121-Screening plasmid did not affect the PCR amplification efficiencies of screening methods and taxon-specific methods. The sensitivity of screening and taxon-specific assays ranged from 5 to 10 copies of pBI121-Screening plasmid, meeting the sensitivity requirement of GMO detection. The construction of pBI121-Screening solves the lack of a general positive control for screening tests, thereby reducing the workload and cost of preparing a plurality of the positive control. Copyright © 2016 Elsevier B.V. All rights reserved.

EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes

PubMed Central

van Dongen, J J M; Lhermitte, L; Böttcher, S; Almeida, J; van der Velden, V H J; Flores-Montero, J; Rawstron, A; Asnafi, V; Lécrevisse, Q; Lucio, P; Mejstrikova, E; Szczepański, T; Kalina, T; de Tute, R; Brüggemann, M; Sedek, L; Cullen, M; Langerak, A W; Mendonça, A; Macintyre, E; Martin-Ayuso, M; Hrusak, O; Vidriales, M B; Orfao, A

2012-01-01

Most consensus leukemia & lymphoma antibody panels consist of lists of markers based on expert opinions, but they have not been validated. Here we present the validated EuroFlow 8-color antibody panels for immunophenotyping of hematological malignancies. The single-tube screening panels and multi-tube classification panels fit into the EuroFlow diagnostic algorithm with entries defined by clinical and laboratory parameters. The panels were constructed in 2–7 sequential design–evaluation–redesign rounds, using novel Infinicyt software tools for multivariate data analysis. Two groups of markers are combined in each 8-color tube: (i) backbone markers to identify distinct cell populations in a sample, and (ii) markers for characterization of specific cell populations. In multi-tube panels, the backbone markers were optimally placed at the same fluorochrome position in every tube, to provide identical multidimensional localization of the target cell population(s). The characterization markers were positioned according to the diagnostic utility of the combined markers. Each proposed antibody combination was tested against reference databases of normal and malignant cells from healthy subjects and WHO-based disease entities, respectively. The EuroFlow studies resulted in validated and flexible 8-color antibody panels for multidimensional identification and characterization of normal and aberrant cells, optimally suited for immunophenotypic screening and classification of hematological malignancies. PMID:22552007

[Utilisation of salivary markers in nephrology].

PubMed

Podracká, Ľudmila; Celec, Peter; Šebeková, Katarína

2016-01-01

Saliva has a broad diagnostic potential which can be used for detection many pathological conditions including renal dysfunction. In saliva can be measured concentration of urea and creatinine as well as the other uremic markers. Saliva urea nitrogen and creatinine and blood urea and creatinine highly correlated therefore might be used for screening in patients with CKD. Saliva collection is truly non-invasive and is especially suitable for small children and elderly patients. Recently, semiquantitative saliva urea test strip is available. Saliva might become promising dia-gnostic biofluid in nephrological practice.Key words: chronic kidney disease - renal failure - salivary dipstick - salivary markers.

Prenatal screening for fetal aneuploidy in singleton pregnancies.

PubMed

Chitayat, David; Langlois, Sylvie; Douglas Wilson, R

2011-07-01

To develop a Canadian consensus document on maternal screening for fetal aneuploidy (e.g., Down syndrome and trisomy 18) in singleton pregnancies. Pregnancy screening for fetal aneuploidy started in the mid 1960s, using maternal age as the screening test. New developments in maternal serum and ultrasound screening have made it possible to offer all pregnant patients a non-invasive screening test to assess their risk of having a fetus with aneuploidy to determine whether invasive prenatal diagnostic testing is necessary. This document reviews the options available for non-invasive screening and makes recommendations for Canadian patients and health care workers. To offer non-invasive screening for fetal aneuploidy (trisomy 13, 18, 21) to all pregnant women. Invasive prenatal diagnosis would be offered to women who screen above a set risk cut-off level on non-invasive screening or to pregnant women whose personal, obstetrical, or family history places them at increased risk. Currently available non-invasive screening options include maternal age combined with one of the following: (1) first trimester screening (nuchal translucency, maternal age, and maternal serum biochemical markers), (2) second trimester serum screening (maternal age and maternal serum biochemical markers), or (3) 2-step integrated screening, which includes first and second trimester serum screening with or without nuchal translucency (integrated prenatal screen, serum integrated prenatal screening, contingent, and sequential). These options are reviewed, and recommendations are made. Studies published between 1982 and 2009 were retrieved through searches of PubMed or Medline and CINAHL and the Cochrane Library, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. This guideline is intended to reduce the number of prenatal invasive procedures done when maternal age is the only indication. This will have the benefit of reducing the numbers of normal pregnancies lost because of complications of invasive procedures. Any screening test has an inherent false-positive rate, which may result in undue anxiety. It is not possible at this time to undertake a detailed cost-benefit analysis of the implementation of this guideline, since this would require health surveillance and research and health resources not presently available; however, these factors need to be evaluated in a prospective approach by provincial and territorial initiatives. RECOMMENDATIONS 1. All pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies in addition to a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples. (I-A) 2. Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process. (III-A) 3. Maternal age alone is a poor minimum standard for prenatal screening for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available. (II-2A) 4. Invasive prenatal diagnosis for cytogenetic analysis should not be performed without multiple marker screening results except for women who are at increased risk of fetal aneuploidy (a) because of ultrasound findings, (b) because the pregnancy was conceived by in vitro fertilization with intracytoplasmic sperm injection, or (c) because the woman or her partner has a history of a previous child or fetus with a chromosomal abnormality or is a carrier of a chromosome rearrangement that increases the risk of having a fetus with a chromosomal abnormality. (II-2E) 5. At minimum, any prenatal screen offered to Canadian women who present for care in the first trimester should have a detection rate of 75% with no more than a 3% false-positive rate. The performance of the screen should be substantiated by annual audit. (III-B) 6. The minimum standard for women presenting in the second trimester should be a screen that has a detection rate of 75% with no more than a 5% false-positive rate. The performance of the screen should be substantiated by annual audit. (III-B) 7. First trimester nuchal translucency should be interpreted for risk assessment only when measured by sonographers or sonologists trained and accredited for this service and when there is ongoing quality assurance (II-2A), and it should not be offered as a screen without biochemical markers in singleton pregnancies. (I-E) 8. Evaluation of the fetal nasal bone in the first trimester should not be incorporated as a screen unless it is performed by sonographers or sonologists trained and accredited for this service and there is ongoing quality assurance. (II-2E) 9. For women who undertake first trimester screening, second trimester serum alpha fetoprotein screening and/or ultrasound examination is recommended to screen for open neural tube defects. (II-1A) 10. Timely referral and access is critical for women and should be facilitated to ensure women are able to undergo the type of screening test they have chosen as first trimester screening. The first steps of integrated screening (with or without nuchal translucency), contingent, or sequential screening are performed in an early and relatively narrow time window. (II-1A) 11. Ultrasound dating should be performed if menstrual or conception dating is unreliable. For any abnormal serum screen calculated on the basis of menstrual dating, an ultrasound should be done to confirm gestational age. (II-1A) 12. The presence or absence of soft markers or anomalies in the 18- to 20-week ultrasound can be used to modify the a priori risk of aneuploidy established by age or prior screening. (II-2B) 13. Information such as gestational dating, maternal weight, ethnicity, insulin-dependent diabetes mellitus, and use of assisted reproduction technologies should be provided to the laboratory to improve accuracy of testing. (II-2A) 14. Health care providers should be aware of the screening modalities available in their province or territory. (III-B) 15. A reliable system needs to be in place ensuring timely reporting of results. (III-C) 16. Screening programs should be implemented with resources that support audited screening and diagnostic laboratory services, ultrasound, genetic counselling services, patient and health care provider education, and high quality diagnostic testing, as well as resources for administration, annual clinical audit, and data management. In addition, there must be the flexibility and funding to adjust the program to new technology and protocols. (II-3B).

Potential of soluble CD26 as a serum marker for colorectal cancer detection

PubMed Central

Cordero, Oscar J; Imbernon, Monica; Chiara, Loretta De; Martinez-Zorzano, Vicenta S; Ayude, Daniel; de la Cadena, Maria Paez; Rodriguez-Berrocal, F Javier

2011-01-01

Colorectal cancer is characterized by a low survival rate even though the basis for colon cancer development, which involves the evolution of adenomas to carcinoma, is known. Moreover, the mortality rates continue to rise in economically transitioning countries although there is the opportunity to intervene in the natural history of the adenoma–cancer sequence through risk factors, screening, and treatment. Screening in particular accounted for most of the decline in colorectal cancer mortality achieved in the USA during the period 1975-2000. Patients show a better prognosis when the neoplasm is diagnosed early. Among the variety of screening strategies, the methods range from invasive and costly procedures such as colonoscopy to more low-cost and non-invasive tests such as the fecal occult blood test (guaiac and immunochemical). As a non-invasive biological serum marker would be of great benefit because of the performance of the test, several biomarkers, including cytologic assays, DNA and mRNA, and soluble proteins, have been studied. We found that the soluble CD26 (sCD26) concentration is diminished in serum of colorectal cancer patients compared to healthy donors, suggesting the potential utility of a sCD26 immunochemical detection test for early diagnosis. sCD26 originates from plasma membrane CD26 lacking its transmembrane and cytoplasmic domains. Some 90%–95% of sCD26 has been associated with serum dipeptidyl peptidase IV (DPP-IV) activity. DPP-IV, assigned to the CD26 cluster, is a pleiotropic enzyme expressed mainly on epithelial cells and lymphocytes. Our studies intended to validate this test for population screening to detect colorectal cancer and advanced adenomas are reviewed here. PMID:21773075

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting.

PubMed

Chen, Hongda; Zucknick, Manuela; Werner, Simone; Knebel, Phillip; Brenner, Hermann

2015-07-15

Novel noninvasive blood-based screening tests are strongly desirable for early detection of colorectal cancer. We aimed to conduct a head-to-head comparison of the diagnostic performance of 92 plasma-based tumor-associated protein biomarkers for early detection of colorectal cancer in a true screening setting. Among all available 35 carriers of colorectal cancer and a representative sample of 54 men and women free of colorectal neoplasms recruited in a cohort of screening colonoscopy participants in 2005-2012 (N = 5,516), the plasma levels of 92 protein biomarkers were measured. ROC analyses were conducted to evaluate the diagnostic performance. A multimarker algorithm was developed through the Lasso logistic regression model and validated in an independent validation set. The .632+ bootstrap method was used to adjust for the potential overestimation of diagnostic performance. Seventeen protein markers were identified to show statistically significant differences in plasma levels between colorectal cancer cases and controls. The adjusted area under the ROC curves (AUC) of these 17 individual markers ranged from 0.55 to 0.70. An eight-marker classifier was constructed that increased the adjusted AUC to 0.77 [95% confidence interval (CI), 0.59-0.91]. When validating this algorithm in an independent validation set, the AUC was 0.76 (95% CI, 0.65-0.85), and sensitivities at cutoff levels yielding 80% and 90% specificities were 65% (95% CI, 41-80%) and 44% (95% CI, 24-72%), respectively. The identified profile of protein biomarkers could contribute to the development of a powerful multimarker blood-based test for early detection of colorectal cancer. ©2015 American Association for Cancer Research.

Technical standards and guidelines: prenatal screening for Down syndrome that includes first-trimester biochemistry and/or ultrasound measurements.

PubMed

Palomaki, Glenn E; Lee, Jo Ellen S; Canick, Jacob A; McDowell, Geraldine A; Donnenfeld, Alan E

2009-09-01

This statement is intended to augment the current general ACMG Standards and Guidelines for Clinical Genetics Laboratories and to address guidelines specific to first-trimester screening for Down syndrome. The aim is to provide the laboratory the necessary information to ensure accurate and reliable Down syndrome screening results given a screening protocol (e.g., combined first trimester and integrated testing). Information about various test combinations and their expected performance are provided, but other issues such as availability of reagents, patient interest in early test results, access to open neural tube defect screening, and availability of chorionic villus sampling are all contextual factors in deciding which screening protocol(s) will be selected by individual health care providers. Individual laboratories are responsible for meeting the quality assurance standards described by the Clinical Laboratory Improvement Act, the College of American Pathologists, and other regulatory agencies, with respect to appropriate sample documentation, assay validation, general proficiency, and quality control measures. These guidelines address first-trimester screening that includes ultrasound measurement and interpretation of nuchal translucency thickness and protocols that combine markers from both the first and second trimesters. Laboratories can use their professional judgment to make modification or additions.

Colorectal Cancer Screening: Stool DNA and Other Noninvasive Modalities.

PubMed

Bailey, James R; Aggarwal, Ashish; Imperiale, Thomas F

2016-03-01

Colorectal cancer screening dates to the discovery of precancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study.

The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

PubMed

Song, Lele; Jia, Jia; Peng, Xiumei; Xiao, Wenhua; Li, Yuemin

2017-06-08

The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

Developing biochemical and molecular markers for cyanobacterial inoculants.

PubMed

Prasanna, R; Madhan, K; Singh, R N; Chauhan, A K; Nain, L

2010-09-01

Markers for evaluating the establishment of cyanobacteria based on their sensitivity or resistance to antibiotics, saccharide utilization patterns and PCR generated fingerprints were developed. Four selected strains (isolates from rhizosphere soils of diverse agro-ecosystems) have shown potential as diazotrophs and exhibited plant growth promoting abilities. Different responses were obtained on screening against 40 antibiotics, which aided in developing selectable antibiotic markers for each strain. Biochemical profiles generated using standardized chromogenic identification system (including saccharide utilization tests) revealed that 53 % of the saccharides tested were not utilized by any strain, while some strains exhibited unique ability for utilization of saccharides such as melibiose, cellobiose, maltose and glucosamine. PCR based amplification profiles developed using a number of primers based on repeat sequences revealed the utility of 3 primers in providing unique fingerprints for the strains.

MicroRNA markers for forensic body fluid identification obtained from microarray screening and quantitative RT-PCR confirmation

PubMed Central

Zubakov, Dmitry; Boersma, Anton W. M.; Choi, Ying; van Kuijk, Patricia F.; Wiemer, Erik A. C.

2010-01-01

MicroRNAs (miRNAs) are non-protein coding molecules with important regulatory functions; many have tissue-specific expression patterns. Their very small size in principle makes them less prone to degradation processes, unlike messenger RNAs (mRNAs), which were previously proposed as molecular tools for forensic body fluid identification. To identify suitable miRNA markers for forensic body fluid identification, we first screened total RNA samples derived from saliva, semen, vaginal secretion, and venous and menstrual blood for the expression of 718 human miRNAs using a microarray platform. All body fluids could be easily distinguished from each other on the basis of complete array-based miRNA expression profiles. Results from quantitative reverse transcription PCR (RT-PCR; TaqMan) assays for microarray candidate markers confirmed strong over-expression in the targeting body fluid of several miRNAs for venous blood and several others for semen. However, no candidate markers from array experiments for other body fluids such as saliva, vaginal secretion, or menstrual blood could be confirmed by RT-PCR. Time-wise degradation of venous blood and semen stains for at least 1 year under lab conditions did not significantly affect the detection sensitivity of the identified miRNA markers. The detection limit of the TaqMan assays tested for selected venous blood and semen miRNA markers required only subpicogram amounts of total RNA per single RT-PCR test, which is considerably less than usually needed for reliable mRNA RT-PCR detection. We therefore propose the application of several stable miRNA markers for the forensic identification of blood stains and several others for semen stain identification, using commercially available TaqMan assays. Additional work remains necessary in search for suitable miRNA markers for other forensically relevant body fluids. Electronic supplementary material The online version of this article (doi:10.1007/s00414-009-0402-3) contains supplementary material, which is available to authorized users. PMID:20145944

Applying a CAD-generated imaging marker to assess short-term breast cancer risk

NASA Astrophysics Data System (ADS)

Mirniaharikandehei, Seyedehnafiseh; Zarafshani, Ali; Heidari, Morteza; Wang, Yunzhi; Aghaei, Faranak; Zheng, Bin

2018-02-01

Although whether using computer-aided detection (CAD) helps improve radiologists' performance in reading and interpreting mammograms is controversy due to higher false-positive detection rates, objective of this study is to investigate and test a new hypothesis that CAD-generated false-positives, in particular, the bilateral summation of false-positives, is a potential imaging marker associated with short-term breast cancer risk. An image dataset involving negative screening mammograms acquired from 1,044 women was retrospectively assembled. Each case involves 4 images of craniocaudal (CC) and mediolateral oblique (MLO) view of the left and right breasts. In the next subsequent mammography screening, 402 cases were positive for cancer detected and 642 remained negative. A CAD scheme was applied to process all "prior" negative mammograms. Some features from CAD scheme were extracted, which include detection seeds, the total number of false-positive regions, an average of detection scores and the sum of detection scores in CC and MLO view images. Then the features computed from two bilateral images of left and right breasts from either CC or MLO view were combined. In order to predict the likelihood of each testing case being positive in the next subsequent screening, two logistic regression models were trained and tested using a leave-one-case-out based cross-validation method. Data analysis demonstrated the maximum prediction accuracy with an area under a ROC curve of AUC=0.65+/-0.017 and the maximum adjusted odds ratio of 4.49 with a 95% confidence interval of [2.95, 6.83]. The results also illustrated an increasing trend in the adjusted odds ratio and risk prediction scores (p<0.01). Thus, the study showed that CAD-generated false-positives might provide a new quantitative imaging marker to help assess short-term breast cancer risk.

Minimally invasive screening for colitis using attenuated total internal reflectance Fourier transform infrared spectroscopy

PubMed Central

Titus, Jitto; Viennois, Emilie; Merlin, Didier; Perera, A. G. Unil

2016-01-01

This article describes a rapid, simple and cost-effective technique that could lead to a screening method for colitis without the need for biopsies or in vivo measurements. This screening technique includes the testing of serum using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy for the colitis-induced increased presence of mannose. Chronic (Interleukin 10 knockout) and acute (Dextran Sodium Sulphate-induced) models for colitis are tested using the ATR-FTIR technique. Arthritis (Collagen Antibody Induced Arthritis) and metabolic syndrome (Toll like receptor 5 knockout) models are also tested as controls. The marker identified as mannose uniquely screens and distinguishes the colitic from the non-colitic samples and the controls. The reference or the baseline spectrum could be the pooled and averaged spectra of non-colitic samples or the subject's previous sample spectrum. This shows the potential of having individualized route maps of disease status, leading to personalized diagnosis and drug management. PMID:27094092

Preanalytical stability of maternal serum markers hCGβ and PAPP-A.

PubMed

Veyrat, Béatrice; Tosetti, François; Morin, Jean-François; Moineau, Marie-Pierre; Piedimonte, Andrée; Clément, Patrice; Dreux, Sophie; Muller, Françoise

2017-04-01

Down syndrome maternal serum marker screening is based on a risk calculation including the free β - human chorionic gonadotropin (hCGβ) and pregnancy-associated placenta protein type A (PAPP-A). The aim of this study was to define the pre-analytical conditions of stability of these markers both in whole blood at 15-25 ̊C and, after centrifugation, in serum at 4-8 ̊C. 158 patients were included in the study. Two automated workstations were used for assays, Cobas 8000e602, Roche Diagnostics (58 patients tested) and DELFIAXpress, PerkinElmer (100 patients tested). The stability of markers was studied in whole blood (15-25 ̊C) 2, 4, 6 and 8 hours after sampling and in serum stored after centrifugation at 4-8 ̊C at 24, 72 and 120 hours. Variations were defined by (C T - C 2 )/C 2 , C 2 being the marker concentration at 2 hours and C T the concentration at time T. In whole blood kept for 8 hours at 15-25 ̊C, hCGβ increased by a mean 2.4%, whereas the mean increase of PAPP-A was < 1%. In the serum kept for 5 days at 4-8̊C, the mean increase of hCGβ was 4.2%, with no change in PAPP-A. The impact of these variations on risk calculation is low. In conclusion, maternal serum can be store 8 hours at 15-25̊C in whole blood and 5 days at 4-8̊C after centrifugation and serum separation for Down syndrome maternal serum screening.

[Antigens (CEA and CA 19-9) in diagnosis and prognosis colorectal cancer].

PubMed

Grotowski, Maciej

2002-01-01

carcinoembryonic antigen (CEA) was first described more than three decades ago, when its presence was demonstrated in fetal gut tissue and in tumors from gastrointestinal tract. Subsequently, CEA was detected in the circulation of patients and recognized as a serum marker for colorectal cancer. This tumor marker has not been advocated as a screening test for colorectal cancer, however a preoperative CEA serum level is useful for diagnosis and prognosis of recurrence and survival in colorectal cancer patients. The levels of CEA increased with increasing tumor stage. Expression of carbohydrate antigen (CA 19-9) has been described in various malignancies and also in colorectal cancer. This antigen also has not been advocated as a screening test for colorectal cancer. The levels of CA 19-9 increased in advanced stages of colorectal cancer. Despite its lower sensitivity than CEA in early stages of colorectal cancer, the combination of both antigens can provided more information than CEA alone for prognosis of recurrence and survival in those patients.

Screening for the anti-inflammation quality markers of Xiaojin Pills based on HPLC-MS/MS method, COX-2 inhibition test and protein interaction network.

PubMed

Xiong, Xi; He, Ya-Nan; Feng, Bi; Pan, Yuan; Zhang, Hai-Zhu; Ke, Xiu-Mei; Zhang, Yi; Yang, Ming; Han, Li; Zhang, Ding-Kun

2018-05-10

Nowadays, breast disorders seriously affect women's health in an increasing number. In China, Xiaojin Pills are commonly used in the treatment of breast diseases. Doctors have concluded that the combined use of Xiaojin Pills with conventional therapy can significantly improve the efficacy with fewer side effects. However, the prescription of Xiaojin Pills is complicated and their quality control methods cannot completely ensure the quality of Xiaojin Pills. On the basis of its mechanism, our study combined chemical evaluation and biological evaluation to identify the anti-inflammatory markers of Xiaojin Pills. In this manuscript, 13 compounds in Xiaojin Pills were quantified. At the same time, the cyclooxygenase-2 inhibition rates of different Xiaojin Pills were measured and the possible markers were screened by spectrum-effect relationship. Further, anti-inflammatory activities of markers were verified and protein interaction network was analyzed, identifying the components of Protocatechuate, Beta-Boswellic acid and Levistilide A as the anti-inflammatory quality markers of Xiaojin Pills. We hope our studies can provide a scientific theoretical basis for accurately quality control of Xiaojin Pills and reasonable suggestions for pharmaceutical companies and new ideas for the quality control of other medicines.

Cost-effectiveness of magnetic resonance imaging with a new contrast agent for the early diagnosis of Alzheimer's disease.

PubMed

Biasutti, Maria; Dufour, Natacha; Ferroud, Clotilde; Dab, William; Temime, Laura

2012-01-01

Used as contrast agents for brain magnetic resonance imaging (MRI), markers for beta-amyloid deposits might allow early diagnosis of Alzheimer's disease (AD). We evaluated the cost-effectiveness of such a diagnostic test, MRI+CLP (contrastophore-linker-pharmacophore), should it become clinically available. We compared the cost-effectiveness of MRI+CLP to that of standard diagnosis using currently available cognition tests and of standard MRI, and investigated the impact of a hypothetical treatment efficient in early AD. The primary analysis was based on the current French context for 70-year-old patients with Mild Cognitive Impairment (MCI). In alternative "screen and treat" scenarios, we analyzed the consequences of systematic screenings of over-60 individuals (either population-wide or restricted to the ApoE4 genotype population). We used a Markov model of AD progression; model parameters, as well as incurred costs and quality-of-life weights in France were taken from the literature. We performed univariate and probabilistic multivariate sensitivity analyses. The base-case preferred strategy was the standard MRI diagnosis strategy. In the primary analysis however, MRI+CLP could become the preferred strategy under a wide array of scenarios involving lower cost and/or higher sensitivity or specificity. By contrast, in the "screen and treat" analyses, the probability of MRI+CLP becoming the preferred strategy remained lower than 5%. It is thought that anti-beta-amyloid compounds might halt the development of dementia in early stage patients. This study suggests that, even should such treatments become available, systematically screening the over-60 population for AD would only become cost-effective with highly specific tests able to diagnose early stages of the disease. However, offering a new diagnostic test based on beta-amyloid markers to elderly patients with MCI might prove cost-effective.

CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease.

PubMed

Bonadia, Luciana Cardoso; de Lima Marson, Fernando Augusto; Ribeiro, Jose Dirceu; Paschoal, Ilma Aparecida; Pereira, Monica Corso; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia

2014-05-01

There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics. Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I). There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF-related diabetes (p=0.040), chloride concentration in the sweat test (p=0.040) and chronic infection by microorganisms (Staphylococcus aureus - p=0.039; mucoid P. aeruginosa - p=0.001). There is no positive association with the status of other clinical markers and the CFTR genotype groups. For clinical association with pancreatic insufficiency (as clinical marker for digestive symptoms), no association was related. The adults with CF diagnosed by sweat test have specific clinical and genotypic characteristics, being a population that should be studied to cause better future management. Some patients treated as CF disease by clinical symptoms, showed no disease, taking into account the sweat test and complete exon sequencing/MLPA screening. Copyright © 2014. Published by Elsevier B.V.

Evaluation of markers out of the steroid profile for the screening of testosterone misuse. Part II: Intramuscular administration.

PubMed

Kotronoulas, Aristotelis; Gomez-Gómez, Àlex; Fabregat, Andreu; Segura, Jordi; Yang, Sheng; Xing, Yanyi; Moutian, Wu; Marcos, Josep; Joglar, Jesús; Ventura, Rosa; Pozo, Oscar J

2018-05-01

In the fight against doping, the introduction of alternative markers to the steroid profile can be considered as an effective approach to improve the screening capabilities for the detection of testosterone (T) misuse. The aim of this study was to evaluate the potential of several T metabolites (cysteinyl conjugated and glucuronoconjugated resistant to enzymatic hydrolysis) to detect both the transdermal and the intramuscular administration of T. In Part I of the study, we studied the potential of these metabolites for the detection of T transdermal administration. Results revealed that resistant glucuronides can be a suitable complement to the current steroid profile. In this, Part II, dedicated to the intramuscular administration, we studied the potential of cysteinyl conjugated, resistant glucuronoconjugated and 1-cyclopentenoylglycine (1-CPG) for the detection of a single intramuscular injection of T cypionate. Possible differences in the excretion profile of all markers were explored between individuals with low basal (n=6) and medium basal (n=6) values of the testosterone/epitestosterone ratio (T/E). The results showed that all tested markers presented low intra-individual stability in basal conditions. Despite this, all glucuronoconjugated markers and 1-CPG, but not the cysteinyl conjugated markers, provided detection windows that were similar or longer than those obtained by markers currently included in the steroid profile. Based on the results obtained from the 2 parts of this study and from previously reported data, the potential applicability and the limitations of including these markers in the steroid profile are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Detection Rate and Sonographic Signs of Trisomy 21 Fetuses at 14-17 Weeks of Gestation.

PubMed

Bronshtein, Eliezer; Solt, Ido; Bronshtein, Moshe; Gover, Ayala; Wolman, Igal; Blumenfeld, Zeev

2017-01-01

Early prenatal ultrasound is an important part of prenatal screening in Israel. No studies have described the rate of trisomy 21 [T21] identification at 14-17 weeks gestation. To describe the rate of T21 identification by transvaginal sonograms (TVS) at 14-17 weeks gestation. We conducted a historical prospective study. Since 1986, early TVS of 72,000 fetuses at 14-17 weeks gestation have been prospectively recorded together with prenatal screening data at a private ultrasound center (AL-KOL, Haifa). We calculated the fraction of T21 cases by dividing the total number of cases with abnormal sonographic findings by the total number of diagnosed T21 cases. We also examined the percentage of verified T21 cases that had completely normal prenatal screening tests prior to the early prenatal TVS, thus revealing the contribution of this examination to the existing prenatal screening. Fisher's exact test was used to calculate odds ratios for each sonographic marker. Of 137 T21 fetuses, 123 had sonographic markers on early TVS, yielding a prediction capability of at least 89.87%. Of all T21 cases, 14% had completely normal nuchal translucency/first-trimester screening prior to the abnormal 14-17 week TVS findings. Isolated abnormal sonographic findings, which were found to increase the risk for T21, were common atrioventricular septal canal (odds ratio 88.88), duodenal atresia (OR 88.23), nuchal edema (OR 39.14), and hydrocephalus (OR 15.78). Fetal hydronephrosis/pyelectasis was non-significant when isolated (OR 1), and cardiac echogenic focus was associated with a decreased risk (OR 0.13). Early prenatal TVS at 14-17 weeks may identify almost 90% of T21 and adds 14% to the identification rate at the first-trimester screening.

Screening for Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus, and Treponema pallidum by Blood Testing Using a Bio-Flash Technology-Based Algorithm before Gastrointestinal Endoscopy

PubMed Central

Zhen, Chen; QuiuLi, Zhang; YuanQi, An; Casado, Verónica Vocero; Fan, Yuan

2016-01-01

Currently, conventional enzyme immunoassays which use manual gold immunoassays and colloidal tests (GICTs) are used as screening tools to detect Treponema pallidum (syphilis), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and HIV-2 in patients undergoing surgery. The present observational, cross-sectional study compared the sensitivity, specificity, and work flow characteristics of the conventional algorithm with manual GICTs with those of a newly proposed algorithm that uses the automated Bio-Flash technology as a screening tool in patients undergoing gastrointestinal (GI) endoscopy. A total of 956 patients were examined for the presence of serological markers of infection with HIV-1/2, HCV, HBV, and T. pallidum. The proposed algorithm with the Bio-Flash technology was superior for the detection of all markers (100.0% sensitivity and specificity for detection of anti-HIV and anti-HCV antibodies, HBV surface antigen [HBsAg], and T. pallidum) compared with the conventional algorithm based on the manual method (80.0% sensitivity and 98.6% specificity for the detection of anti-HIV, 75.0% sensitivity for the detection of anti-HCV, 94.7% sensitivity for the detection of HBsAg, and 100% specificity for the detection of anti-HCV and HBsAg) in these patients. The automated Bio-Flash technology-based screening algorithm also reduced the operation time by 85.0% (205 min) per day, saving up to 24 h/week. In conclusion, the use of the newly proposed screening algorithm based on the automated Bio-Flash technology can provide an advantage over the use of conventional algorithms based on manual methods for screening for HIV, HBV, HCV, and syphilis before GI endoscopy. PMID:27707942

Screening for Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus, and Treponema pallidum by Blood Testing Using a Bio-Flash Technology-Based Algorithm before Gastrointestinal Endoscopy.

PubMed

Jun, Zhou; Zhen, Chen; QuiuLi, Zhang; YuanQi, An; Casado, Verónica Vocero; Fan, Yuan

2016-12-01

Currently, conventional enzyme immunoassays which use manual gold immunoassays and colloidal tests (GICTs) are used as screening tools to detect Treponema pallidum (syphilis), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and HIV-2 in patients undergoing surgery. The present observational, cross-sectional study compared the sensitivity, specificity, and work flow characteristics of the conventional algorithm with manual GICTs with those of a newly proposed algorithm that uses the automated Bio-Flash technology as a screening tool in patients undergoing gastrointestinal (GI) endoscopy. A total of 956 patients were examined for the presence of serological markers of infection with HIV-1/2, HCV, HBV, and T. pallidum The proposed algorithm with the Bio-Flash technology was superior for the detection of all markers (100.0% sensitivity and specificity for detection of anti-HIV and anti-HCV antibodies, HBV surface antigen [HBsAg], and T. pallidum) compared with the conventional algorithm based on the manual method (80.0% sensitivity and 98.6% specificity for the detection of anti-HIV, 75.0% sensitivity for the detection of anti-HCV, 94.7% sensitivity for the detection of HBsAg, and 100% specificity for the detection of anti-HCV and HBsAg) in these patients. The automated Bio-Flash technology-based screening algorithm also reduced the operation time by 85.0% (205 min) per day, saving up to 24 h/week. In conclusion, the use of the newly proposed screening algorithm based on the automated Bio-Flash technology can provide an advantage over the use of conventional algorithms based on manual methods for screening for HIV, HBV, HCV, and syphilis before GI endoscopy. Copyright © 2016 Jun et al.

Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

PubMed

Romain, A J; Letendre, E; Akrass, Z; Avignon, A; Karelis, A D; Sultan, A; Abdel-Baki, A

2017-04-01

Aim: Prediabetes and type 2 diabetes are highly prevalent among individuals with serious mental illness and increased by antipsychotic medication. Although widely recommended, many obstacles prevent these patients from obtaining a proper screening for dysglycemia. Currently, glycated hemoglobin (HbA1c), fasting glucose, and 2-hour glucose levels from the oral glucose tolerance test are used for screening prediabetes and type 2 diabetes. The objective of this study was to investigate if HbA1c could be used as the only screening test among individuals with serious mental illness. Methods: Cross sectional study comparing the sensitivity of HbA1c, fasting glucose, and 2-h oral glucose tolerance test to detect dysglycemias in serious mental illness participants referred for metabolic complications. Results: A total of 84 participants (43 female; aged: 38.5±12.8 years; BMI: 35.0±6.8 kg/m²) was included. Regarding prediabetes, 44, 44 and 76% were identified by HbA1c, fasting glucose, and 2 h- oral glucose tolerance test respectively and for type 2 diabetes, 60, 53 and 66% were identified by HbA1c, fasting glucose and 2 h-oral glucose tolerance test. The overlap between the 3 markers was low (8% of participants for prediabetes and 26% for Type 2 diabetes). Sensitivity of HbA1c were moderate (range 40-62.5%), while its specificity was excellent (92-93%). Conclusion: The present study indicates a low agreement between HbA1c, fasting glucose and 2-h oral glucose tolerance test. It appears that these markers do not identify the same participants. Thus, HbA1c may not be used alone to detect all glucose abnormalities among individuals with serious mental illness. © Georg Thieme Verlag KG Stuttgart · New York.

Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America.

PubMed

Teixeira, Clarissa; Gomes, Regis; Collin, Nicolas; Reynoso, David; Jochim, Ryan; Oliveira, Fabiano; Seitz, Amy; Elnaiem, Dia-Eldin; Caldas, Arlene; de Souza, Ana Paula; Brodskyn, Cláudia I; de Oliveira, Camila Indiani; Mendonca, Ivete; Costa, Carlos H N; Volf, Petr; Barral, Aldina; Kamhawi, Shaden; Valenzuela, Jesus G

2010-03-23

Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive. We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further tested against additional sand fly species. Recombinant proteins of nine transcripts encoding secreted salivary molecules of Lu. longipalpis were produced, purified, and tested for antigenicity and specificity. Use of recombinant proteins corresponding to immunogenic molecules in Lu. longipalpis saliva identified LJM17 and LJM11 as potential markers of exposure. LJM17 was recognized by human, dog, and fox sera; LJM11 by humans and dogs. Notably, LJM17 and LJM11 were specifically recognized by humans exposed to Lu. longipalpis but not by individuals exposed to Lu. intermedia. Salivary recombinant proteins are of value as markers of vector exposure. In humans, LJM17 and LJM11 emerged as potential markers of specific exposure to Lu. longipalpis, the vector of Leishmania infantum chagasi in Latin America. In dogs, LJM17, LJM11, LJL13, LJL23, and LJL143 emerged as potential markers of sand fly exposure. Testing these recombinant proteins in large scale studies will validate their usefulness as specific markers of Lu. longipalpis exposure in humans and of sand fly exposure in dogs.

Empirical evaluation demonstrated importance of validating biomarkers for early detection of cancer in screening settings to limit the number of false-positive findings.

PubMed

Chen, Hongda; Knebel, Phillip; Brenner, Hermann

2016-07-01

Search for biomarkers for early detection of cancer is a very active area of research, but most studies are done in clinical rather than screening settings. We aimed to empirically evaluate the role of study setting for early detection marker identification and validation. A panel of 92 candidate cancer protein markers was measured in 35 clinically identified colorectal cancer patients and 35 colorectal cancer patients identified at screening colonoscopy. For each case group, we selected 38 controls without colorectal neoplasms at screening colonoscopy. Single-, two- and three-marker combinations discriminating cases and controls were identified in each setting and subsequently validated in the alternative setting. In all scenarios, a higher number of predictive biomarkers were initially detected in the clinical setting, but a substantially lower proportion of identified biomarkers could subsequently be confirmed in the screening setting. Confirmation rates were 50.0%, 84.5%, and 74.2% for one-, two-, and three-marker algorithms identified in the screening setting and were 42.9%, 18.6%, and 25.7% for algorithms identified in the clinical setting. Validation of early detection markers of cancer in a true screening setting is important to limit the number of false-positive findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Using silver and bighead carp cell lines for the identification of a unique metabolite fingerprint from thiram-specific chemical exposure

USGS Publications Warehouse

Putnam, Joel G.; Nelson, Justine; Leis, Eric M; Erickson, Richard A.; Hubert, Terrance D.; Amberg, Jon J.

2017-01-01

Conservation biology often requires the control of invasive species. One method is the development and use of biocides. Identifying new chemicals as part of the biocide registration approval process can require screening millions of compounds. Traditionally, screening new chemicals has been done in vivo using test organisms. Using in vitro (e.g., cell lines) and in silico (e.g., computer models) methods decrease test organism requirements and increase screening speed and efficiency. These methods, however, would be greatly improved by better understanding how individual fish species metabolize selected compounds.We combined cell assays and metabolomics to create a powerful tool to facilitate the identification of new control chemicals. Specifically, we exposed cell lines established from bighead carp and silver carp larvae to thiram (7 concentrations) then completed metabolite profiling to assess the dose-response of the bighead carp and silver carp metabolome to thiram. Forty one of the 700 metabolomic markers identified in bighead carp exhibited a dose-response to thiram exposure compared to silver carp in which 205 of 1590 metabolomic markers exhibited a dose-response. Additionally, we identified 11 statistically significant metabolomic markers based upon volcano plot analysis common between both species. This smaller subset of metabolites formed a thiram-specific metabolomic fingerprint which allowed for the creation of a toxicant specific, rather than a species-specific, metabolomic fingerprint. Metabolomic fingerprints may be used in biocide development and improve our understanding of ecologically significant events, such as mass fish kills.

Controversies in colorectal cancer screening.

PubMed

Pox, Christian P

2014-01-01

Colorectal cancer (CRC) is one of the most common cancers worldwide and a good candidate for screening programmes. However, there is controversy concerning which of the available screening tests should be used. There is general agreement that screening for CRC in the asymptomatic population should begin at the age of 50. Several different screening methods are available which can be separated into those that mainly detect cancers: faecal occult blood tests [guaiac (FOBT) and immunochemical (FIT)], genetic stool tests, blood tests and the M2-pyruvate kinase (M2-PK) test. Methods that detect cancers and polyps are colonoscopy, sigmoidoscopy, CT-colonography (CT-C) and colon capsule endoscopy. The only tests for which a reduction in CRC mortality compared to no screening have been proven in randomized trials are FOBT and sigmoidoscopy. Several trials suggest that FIT are superior to FOBT in terms of detection rates of cancers and advanced adenomas and possibly compliance. There is indirect evidence suggesting efficacy of colonoscopy as a screening test. The role of CT-C is controversial. There is data suggesting a good sensitivity for neoplasia >9 mm with a lower sensitivity for smaller neoplasia. However, radiation exposure is considered a major limitation in some countries. Unresolved questions include the lesion cut-off for referral to colonoscopy and work-up of extracolonic findings. For other methods, like genetic stool testing using newer markers, blood tests, capsule endoscopy and M2-PK, there is currently insufficient data on screening of the asymptomatic population. Key Messages: Colorectal screening is recommended and should be performed in the form of an organized programme. If detection of early-stage cancers is the aim of a screening programme, FIT seem to be superior to FOBT. If detection and removal of adenomas is the aim of a screening programme, endoscopic methods seem to be good alternatives. Sigmoidoscopy is easier to perform but will likely only have an effect on distal cancers. Colonoscopy is more invasive but enables inspection of the whole colon. The role of CT-C, capsule endoscopy, genetic stool tests, blood tests and M2-PK is currently unknown. © 2014 S. Karger AG, Basel.

Effect of a new marker, ADAM12, on Down risk figures in first trimester screening.

PubMed

Valinen, Yrtti; Laitinen, Paivi; Ranta, Jenni; Ignatius, Jaakko; Jarvela, Ilkka; Ryynänen, Markku

2009-07-01

To investigate whether incorporating the measurement of ADAM12 in the risk calculation program LifeCycle, can improve Down screening in the first trimester. In a retrospective case control study, maternal serum ADAM12 concentrations were measured and compared in Down syndrome cases (n = 53) and in controls (n = 226) obtained from first trimester (9-12 weeks) screening samples in Oulu and Kuopio University Hospitals. Median concentration ( microg/l), observed and regressed (weight corrected) MoMs of ADAM12 were calculated. There was a significant difference in ADAM12 levels between Downs and controls during the pregnancy weeks 9 + 0 to 10 + 6, but not thereafter. By adding ADAM12 to the marker set used in the risk calculation program, one screening false negative Down syndrome case occurred in the affected population, which did not alter false positive rate. Adding ADAM12 as a parameter in Down screening did not cause radical changes in the risk value. The test might be useful at 9 and 10 weeks in which it might have the potential to improve the performance of the risk assessment especially for women receiving a result close to the high-risk cut-off. The real influence of ADAM12 remains to be elucidated in larger studies incorporating ADAM12 to the risk calculation program.

Laboratory screening markers in gastroenterology--state of the art.

PubMed

Kocna, Petr; Vanickova, Zdislava; Zima, Tomas

2013-06-01

Screening tests for gastrointestinal diseases acceptable for population with a high sensitivity and high specificity can now be offered by clinical laboratories. This paper summarizes major recent advances in this area of laboratory medicine. Relevant articles published within the last 5 years in the NLM (National Library of Medicine) PubMed - Medline database covering the three gastrointestinal diseases - colorectal cancer, coeliac disease, and atrophic gastritis were included for this overview. In Europe, colorectal cancer (CRCA) is the second most frequent malignant disease. Quantitative immunochemical analysis of the stool for haemoglobin provides the best screening test to date, with both sensitivity and specificity approaching 95%. Even though coeliac disease (CD) affects approximately 1% of the general population, it remains largely unrecognised. Recommended methods for screening currently involve the detection of IgA and IgG antibodies against tissue transglutaminase and deamidated gliadin peptide. Evaluations of screening are now discussed for other diseases of the gastrointestinal tract - such as chronic atrophic gastritis (CAG), and inflammatory bowel disease (IBD). Detection of infection by Helicobacter pylori and stomach-specific plasmatic biomarkers, especially pepsinogen I/II ratio, could help with the prevention of gastric carcinomas. The use of faecal calprotectin as a screening test could substantially reduce the number of invasive methods necessary for the diagnostic work-up of patients with IBD. Screening tests for CRCA and CD have been used worldwide for many years. Screening strategies for gastrointestinal diseases are suggested in the text, based on recent basic science, clinical papers as well as our own experience.

Screening strategies for tubal factor subfertility.

PubMed

den Hartog, J E; Lardenoije, C M J G; Severens, J L; Land, J A; Evers, J L H; Kessels, A G H

2008-08-01

Different screening strategies exist to estimate the risk of tubal factor subfertility, preceding laparoscopy. Three screening strategies, comprising Chlamydia trachomatis IgG antibody testing (CAT), high-sensitivity C-reactive protein (hs-CRP) testing and hysterosalpingography (HSG), were explored using laparoscopy as reference standard and the occurrence of a spontaneous pregnancy as a surrogate marker for the absence of tubal pathology. In this observational study, 642 subfertile women, who underwent tubal testing, participated. Data on serological testing, HSG, laparoscopy and interval conception were collected. Multiple imputations were used to compensate for missing data. Strategy A (HSG) has limited value in estimating the risk of tubal pathology. Strategy B (CAT-->HSG) shows that CAT significantly discerns patients with a high versus low risk of tubal pathology, whereas HSG following CAT has no additional value. Strategy C (CAT-->hs-CRP-->HSG) demonstrates that hs-CRP may be valuable in CAT-positive patients only and HSG has no additional value. CAT is proposed as first screening test for tubal factor subfertility. In CAT-negative women, HSG may be performed because of its high specificity and fertility-enhancing effect. In CAT-positive women, hs-CRP seems promising, whereas HSG has no additional value. The position and timing of laparoscopy deserves critical reappraisal.

[A Method for Selecting Self-Adoptive Chromaticity of the Projected Markers].

PubMed

Zhao, Shou-bo; Zhang, Fu-min; Qu, Xing-hua; Zheng, Shi-wei; Chen, Zhe

2015-04-01

The authors designed a self-adaptive projection system which is composed of color camera, projector and PC. In detail, digital micro-mirror device (DMD) as a spatial light modulator for the projector was introduced in the optical path to modulate the illuminant spectrum based on red, green and blue light emitting diodes (LED). However, the color visibility of active markers is affected by the screen which has unknown reflective spectrum as well. Here active markers are projected spot array. And chromaticity feature of markers is sometimes submerged in similar spectral screen. In order to enhance the color visibility of active markers relative to screen, a method for selecting self-adaptive chromaticity of the projected markers in 3D scanning metrology is described. Color camera with 3 channels limits the accuracy of device characterization. For achieving interconversion of device-independent color space and device-dependent color space, high-dimensional linear model of reflective spectrum was built. Prior training samples provide additional constraints to yield high-dimensional linear model with more than three degrees of freedom. Meanwhile, spectral power distribution of ambient light was estimated. Subsequently, markers' chromaticity in CIE color spaces was selected via maximization principle of Euclidean distance. The setting values of RGB were easily estimated via inverse transform. Finally, we implemented a typical experiment to show the performance of the proposed approach. An 24 Munsell Color Checker was used as projective screen. Color difference in the chromaticity coordinates between the active marker and the color patch was utilized to evaluate the color visibility of active markers relative to the screen. The result comparison between self-adaptive projection system and traditional diode-laser light projector was listed and discussed to highlight advantage of our proposed method.

Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency.

PubMed

Ho, Sirikit; Lukacs, Zoltan; Hoffmann, Georg F; Lindner, Martin; Wetter, Thomas

2007-07-01

In newborn screening with tandem mass spectrometry, multiple intermediary metabolites are quantified in a single analytical run for the diagnosis of fatty-acid oxidation disorders, organic acidurias, and aminoacidurias. Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the markers have been chosen to reflect metabolic pathway deviations. We applied a procedure to extract new markers and diagnostic criteria for newborn screening to the data of newborns with confirmed medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and a control group from the newborn screening program, Heidelberg, Germany. We validated the results with external data of the screening center in Hamburg, Germany. We extracted new markers by performing a systematic search for analyte combinations (features) with high discriminatory performance for MCADD. To select feature thresholds, we applied automated procedures to separate controls and cases on the basis of the feature values. Finally, we built classifiers from these new markers to serve as diagnostic criteria in screening for MCADD. On the basis of chi(2) scores, we identified approximately 800 of >628,000 new analyte combinations with superior discriminatory performance compared with the best published combinations. Classifiers built with the new features achieved diagnostic sensitivities and specificities approaching 100%. Feature construction methods provide ways to disclose information hidden in the set of measured analytes. Other diagnostic tasks based on high-dimensional metabolic data might also profit from this approach.

Towards a systematic nationwide screening strategy for MODY.

PubMed

Shields, Beverley; Colclough, Kevin

2017-04-01

MODY is an early-onset monogenic form of diabetes. Correctly identifying MODY is of considerable importance as diagnosing the specific genetic subtype can inform the optimal treatment, with many patients being able to discontinue unnecessary insulin treatment. Diagnostic molecular genetic testing to confirm MODY is expensive, so screening strategies are required to identify the most appropriate patients for testing. In this issue of Diabetologia, Johansson and colleagues (DOI 10.1007/s00125-016-4167-1 ) describe a nationwide systematic screening approach to identify individuals with MODY in the paediatric age range. They focused testing on patients negative for both GAD and islet antigen 2 (IA-2) islet autoantibodies, thereby ruling out those with markers of type 1 diabetes, the most common form of diabetes in this age group. This commentary discusses the advantages and limitations of the approach, and the caution required when interpreting variants of uncertain pathogenicity identified from testing whole populations rather than targeting only patients with a strong MODY phenotype.

Cell-free DNA noninvasive prenatal screening for aneuploidy versus conventional screening: A systematic review of economic evaluations.

PubMed

Nshimyumukiza, L; Menon, S; Hina, H; Rousseau, F; Reinharz, D

2018-07-01

Although noninvasive prenatal testing (NIPT) for aneuploidies using cell-free fetal DNA in maternal blood has been reported to have a high accuracy, only little evidence about its cost-effectiveness is available. We systematically reviewed and assessed quality of economic evaluation studies published between January 1, 2009 and January 1, 2016 where NIPT was compared to the current screening practices consisting of biochemical markers with or without nuchal translucency (NT) and/or maternal age. We included 16 studies and we found that, at current level of NIPT prices, contingent NIPT provide the best value for money, especially for publicly funded screening programs. NIPT as first-line test was found not cost-effective in the majority of studies. The NIPT unit cost, the risk cut-offs for current screening practice, the screening uptake rates (first- and second-line screening) as well as the costs and uptake rates of invasive diagnostic screening were the most common uncertain variables. The overall quality of included studies was fair. Considering a possible drop in prices and an ongoing NIPT expansion to include other chromosomes abnormalities other than T21, T18, T13 and sex chromosomes aneuploidies, future research are needed to examine the potential cost-effectiveness of implementing NIPT as first-line test. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of new non-invasive tests for colorectal cancer screening: the relevance of information on adenoma detection.

PubMed

Haug, Ulrike; Knudsen, Amy B; Lansdorp-Vogelaar, Iris; Kuntz, Karen M

2015-06-15

Researchers are actively pursuing the development of a new non-invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50-years-old persons to whom CRC screening is offered from age 50-75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29-44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN-COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large-scale) evaluation. © 2014 UICC.

Colorectal cancer: From prevention to personalized medicine

PubMed Central

Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Àlex; Medina-Hayas, Manuel

2014-01-01

Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis. Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is likely that given the quick progression of technology tools in molecular biology, increasingly sensitive and less expensive, these tools will gradually be employed in clinical practice and will likely be developed in mass. PMID:24944469

Colorectal cancer: from prevention to personalized medicine.

PubMed

Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Alex; Medina-Hayas, Manuel

2014-06-14

Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis. Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is likely that given the quick progression of technology tools in molecular biology, increasingly sensitive and less expensive, these tools will gradually be employed in clinical practice and will likely be developed in mass.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

PubMed

Hao, Yibin; Shan, Guoyong; Nan, Kejun

2017-03-01

Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

First and second trimester maternal serum inhibin A levels in twins with pre-eclampsia.

PubMed

Svirsky, Ran; Maymon, Ron; Melcer, Yaakov; Klog, Esther; Cuckle, Howard

2016-11-01

To investigate maternal serum inhibin as a marker of pre-eclampsia (PE) in twins. One hundred forty-three twins and 109 unaffected singleton pregnancies were recruited in the first trimester from the same institution. Blood samples were stored at recruitment and in the second trimester, retrospectively tested for inhibin and values expressed in multiples of the gestation-specific median (MoMs) in singletons, adjusted for maternal weight, as appropriate. The median inhibin level in unaffected twins was 2.04 MoM compared with 1.00 MoM in singletons (P < 0.0001, Wilcoxon Rank Sum Test, one-tailed). Excluding early fetal losses the median in 22 samples from 12 twins with PE was 2.65 MoM compared with 1.99 MoM in 201 samples from 120 unaffected twins (P < 0.02, Wilcoxon Rank Sum Test). This effect was restricted to second trimester samples with medians in cases and controls of 2.86 and 1.91 MoM respectively. Logistic regression of inhibin A together with established PE marker placental growth factor and placental associated plasma protein showed that in the second trimester, it improved screening performance although not reaching statistical significance (P = 0.08). Inhibin A is a potential second trimester marker of PE in twins. It may improve on existing twin screening protocols but more data are required. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Decomposing socio-economic inequality in colorectal cancer screening uptake in England.

PubMed

Solmi, Francesca; Von Wagner, Christian; Kobayashi, Lindsay C; Raine, Rosalind; Wardle, Jane; Morris, Stephen

2015-06-01

Colorectal cancer (CRC) is the second largest cause of cancer death in the UK. Since 2010, CRC screening based on Faecal Occult Blood testing has been offered by the NHS in England biennially to all persons age 60-69 years. Several studies have demonstrated a gradient in uptake using area-level markers of socio-economic status (SES), but few have examined the individual-level contributors to the gradient. We aimed to quantify the extent of SES inequality in CRC screening uptake in England using individual-level data, and to identify individual factors associated with this inequality. We used data from 1833 participants (aged 61-69) in Wave 5 (collected in years 2010/11) of the English Longitudinal Study of Ageing (ELSA) eligible for having been sent at least one CRC screening invitation. Uptake was defined by self-report of ever having been screened as part of the National Screening Programme. We assessed socio-economic inequality using the corrected concentration index of uptake against SES rank, which was derived by regressing a range of SES markers against net non-pension household wealth. Other demographic and health-related variables were included in the analysis. Factors associated with inequality were measured using concentration index decomposition. There was a significant pro-rich gradient in screening uptake (concentration index: 0.16, 95% CI:0.11-0.22), mostly explained within our model by differences in non-pension wealth (38.7%), partner screening status (15.9%), sickness/disability (13.5%), and health literacy (8.5%). Interventions aimed at reducing inequalities in CRC screening uptake should focus on improving acceptability of screening in populations with low levels of education and literacy barriers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence and risk factors of hepatitis B in Spanish prostitutes.

PubMed Central

Requena Caballero, L.; Requena Caballero, C.; Requena Caballero, I.; Sánchez López, M.; Vázquez López, F.; Romero Guerrero, J.; Casado Jiménez, M.

1987-01-01

Eighty prostitutes were tested by solid-phase radioimmunoassay for serum markers of hepatitis B virus (HBV). Of 8 (10%) with hepatitis B surface antigen (HBsAg), 6 (75%) also had hepatitis Be antigen (HBeAg). Antibodies to HBsAg (anti-HBs) and to hepatitis B core antigen (anti-HBc) were found in 52 (65%). Antibodies to HBeAg (anti-HBe) were positive in 32 (40%). Anti-HBc alone was found in 5 (6%) and anti-HBs alone in 2 (2%). Sixty-seven (84%) were positive for at least one HBV marker and 13 (16%) were still susceptible to infection. Hepatitis B markers were more prevalent in prostitutes than in the normal Spanish population. Age, a history of sexually transmitted diseases (STD), drug abuse and promiscuity are factors which were highly related to hepatitis B markers. We concluded that screening prostitutes for the presence of markers and vaccinating those who are negative would be worth while. PMID:3428379

Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

PubMed

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

Pancreatic Reference Set Application: Brian Haab-Van Andel (2012) — EDRN Public Portal

Cancer.gov

New markers are greatly needed for the detection and diagnosis of pancreatic cancer. Patients at high risk for developing pancreatic cancer (for, example because of genetic predisposition or health status) can be screened by endoscopy or a related imaging procedure, but these methods are expensive and burdensome to the patient. Blood-based markers would facilitate regular screening. In addition, patients with known abnormalities of the pancreas (for example, as observed incidentally from an abdominal scan) need to determine whether they have cancer or not. The great majority of patients with pancreatic findings by CT do not have conditions that require treatment, yet nearly all patients undergo invasive and burdensome procedures as a consequence of the CT. Again, a blood-based marker could alleviate this situation and potentially add accuracy to the diagnosis. In preliminary work we showed the potential for highly-accurate discrimination of pancreatic cancer from pancreatitis and healthy control subjects using a panel of protein and glycan markers in the serum. We used an antibody array platform in which we can obtain sensitive, reproducible measurements of protein abundance and glycosylation status in low sample volumes. The detection of the glycosylation status is important for the high accuracy of the test because the glycans attached to the marker proteins are altered in cancer patients. Based on the good performance in these early studies, we now want to validate the performance in rigorously controlled, blinded sample sets. The reference set developed by the EDRN will enable a definitive characterization of our marker performance. In addition, we can make an accurate comparison to other markers that will be applied to the same set and determine whether disparate markers could be used together for added benefit.

Fragile X-related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study.

PubMed

Inaba, Yoshimi; Herlihy, Amy S; Schwartz, Charles E; Skinner, Cindy; Bui, Quang M; Cobb, Joanna; Shi, Elva Z; Francis, David; Arvaj, Alison; Amor, David J; Pope, Kate; Wotton, Tiffany; Cohen, Jonathan; Hewitt, Jacqueline K; Hagerman, Randi J; Metcalfe, Sylvia A; Hopper, John L; Loesch, Danuta Z; Slater, Howard R; Godler, David E

2013-04-01

We show that a novel fragile X-related epigenetic element 2 FMR1 methylation test can be used along with a test for sex-determining region Y (SRY) to provide the option of combined fragile X syndrome and sex chromosome aneuploidy newborn screening. Fragile X-related epigenetic element 2, SRY, and FMR1 CGG repeat analyses were performed on blood and saliva DNA, and in adult and newborn blood spots. The cohort consisted of 159 controls (CGG <40), 187 premutation (CGG 56-170), and 242 full-mutation (CGG ~200-2,000) males and females, 106 sex chromosome aneuploidy individuals, and 151 cytogenetically normal controls. At the 0.435 threshold, fragile X-related epigenetic element 2 analysis in males was robust on both blood DNA and newborn blood spots, with specificity and sensitivity of ~100% for full-mutation genotype. In females, the specificity was 99%, whereas half of full-mutation females were above the 0.435 threshold in both blood DNA and newborn blood spots. Furthermore, at this threshold, the test could not differentiate individuals with Klinefelter syndrome from female controls without using the SRY marker. When combined with SRY analysis, the test was consistent with most results for sex chromosome aneuploidies from karyotyping. Setting specific thresholds for fragile X-related epigenetic element 2 analysis and including the SRY marker provides the option to either include or exclude detection of sex chromosome aneuploidies as part of fragile X syndrome newborn screening.

An integrated approach to uncover quality marker underlying the effects of Alisma orientale on lipid metabolism, using chemical analysis and network pharmacology.

PubMed

Liao, Maoliang; Shang, Haihua; Li, Yazhuo; Li, Tian; Wang, Miao; Zheng, Yanan; Hou, Wenbin; Liu, Changxiao

2018-06-01

Quality control of traditional Chinese medicines is currently a great concern, due to the correlation between the quality control indicators and clinic effect is often questionable. According to the "multi-components and multi-targets" property of TCMs, a new special quality and bioactivity evaluation system is urgently needed. Present study adopted an integrated approach to provide new insights relating to uncover quality marker underlying the effects of Alisma orientale (AO) on lipid metabolism. In this paper, guided by the concept of the quality marker (Q-marker), an integrated strategies "effect-compound-target-fingerprint" was established to discovery and screen the potential quality marker of AO based on network pharmacology and chemical analysis. Firstly, a bioactivity evaluation was performed to screen the main active fractions. Then the chemical compositions were rapidly identified by chemical analysis. Next, networks were constructed to illuminate the interactions between these component and their targets for lipid metabolism, and the potential Q-marker of AO was initially screened. Finally, the activity of the Q-markers was validated in vitro. 50% ethanol extract fraction was found to have the strongest lipid-lowering activity. Then, the network pharmacology was used to clarify the unique relationship between the Q-markers and their integral pharmacological action. Combined with the results obtained, five active ingredients in the 50% ethanol extract fraction were given special considerations to be representative Q-markers: Alisol A, Alisol B, Alisol A 23-acetate, Alisol B 23-acetate and Alisol A 24-acetate, respectively. The chromatographic fingerprints based Q-marker was establishment. The integrated Q-marker screen may offer an alternative quality assessment of herbal medicines. Copyright © 2018. Published by Elsevier GmbH.

Performance of prenatal screening using maternal serum and ultrasound markers for Down syndrome in Chinese women: a systematic review and meta-analysis.

PubMed

Tu, S; Rosenthal, M; Wang, D; Huang, J; Chen, Y

2016-09-01

Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been raised as a result of a recently available noninvasive prenatal test based on cell-free fetal DNA sequencing. To evaluate the screening performance of PSMSUM in detecting DS in Chinese women. An exhaustive literature search of MEDLINE, Embase, the Cochrane Library, ISI Web of Science and China BioMedical Disc. Primary studies, published from January 2004 to November 2014, which examined the screening accuracy of PSMSUM in pregnant Chinese women, compared with a reference standard, either chromosomal verification or inspection of the newborn. Data were extracted as screening positive/negative results for Down and non-Down syndrome pregnancies, allowing estimation of sensitivities and specificities. Risks of bias within and across studies were assessed. Screening accuracy measures were pooled using a bivariate random effects regression model. Seventy-eight studies, involving six categories of PSMSUM, were included. Second-trimester double serum [pooled sensitivity (SEN) = 0.80, pooled specificity (SPE) = 0.95] and triple-serum (pooled SEN = 0.79, pooled SPE = 0.96) screening were the predominant PSMSUM methods. The screening performances of these methods achieved the national standard but varied enormously across studies. First-trimester combined screening (pooled SEN = 0.92, pooled SPE = 0.93) and second-trimester quadruple serum screening (median SEN = 0.86, median SPE = 0.96) performed better, but were rarely used. Second-trimester maternal serum screening has the potential to achieve satisfactory screening performance in middle- and low-income countries. The reported enormous range in screening performance of second-trimester PSMSUM calls for urgent implementation of methods for performance optimization. Meta-analysis results show good accuracy of maternal serum and ultrasound screening for trisomy 21 in Chinese women. © 2016 Royal College of Obstetricians and Gynaecologists.

Pseudomonas screening assay

NASA Technical Reports Server (NTRS)

Margalit, Ruth (Inventor)

1993-01-01

A method for the detection of Pseudomonas bacteria is described where an Azurin-specific antibody is employed for detecting the presence of Azurin in a test sample. The detection of the presence of Azurin in the sample is a conclusive indicator of the presence of the Pseudomonas bacteria since the Azurin protein is a specific marker for this bacterial strain.

Semiconductor nanocrystal-aptamer bioconjugate probes for specific prostate carcinoma cell targeting

NASA Astrophysics Data System (ADS)

Shieh, Felice; Lavery, Laura; Chu, Chitai T.; Richards-Kortum, Rebecca; Ellington, Andrew D.; Korgel, Brian A.

2005-04-01

Cancer of the prostate affects approximately 1 in 11 men. Current early screening for prostate cancer utilizes digital rectal examinations to detect anomalies in the prostate gland and blood test screenings for upregulated levels of prostate specific antigen (PSA). Many of these tests are invasive and can often be inconclusive as PSA levels may be heightened due to benign factors. Prostate specific membrane antigen (PSMA), a well-characterized integral membrane protein, is expressed in virtually all prostate cancers and often correlates with cancer aggressiveness. Therefore, it may be used as an indicator of cancer growth and metastases. PSMA-specific antibodies have been identified and conjugated to fluorescent markers for cancer cell targeting; however, both the antibodies and markers possess significant limitations in their pharmaceutical and diagnostic value. Here we report the use of semiconductor nanocrystals bioconjugated to PSMA-specific aptamer recognition molecules for prostate carcinoma cell targeting. The nanocrystal/aptamer bioconjugates are small biocompatible probes with the potential for color-tunability for multicolor imaging. Ongoing in vitro and in vivo research seeks to introduce these nanoparticle bioconjugates into medical diagnostics.

Periodic health examination, 1996 update: 1. Prenatal screening for and diagnosis of Down syndrome. Canadian Task Force on the Periodic Health Examination.

PubMed

Dick, P T

1996-02-15

To make recommendations to physicians providing prenatal care on (1) whether prenatal screening for and diagnosis of Down syndrome (DS) is advisable and (2) alternative screening and diagnosis manoeuvres. "Triple-marker" screening of maternal serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol; fetal ultrasonographic examination; amniocentesis; and chorionic villus sampling (CVS). Accuracy of detection of DS in fetuses, and risks to the mother, including psychologic distress, and to the fetus from the screening and diagnostic interventions. A MEDLINE search for relevant articles published from Jan. 1, 1966, to Mar. 31, 1994, with the use of MeSH terms "Down syndrome," "prenatal diagnosis," "screening," "prevention," "amniocentesis," "chorionic villus sampling," "ultrasonography," "anxiety," "depression" and "psychological stress" and a manual search of bibliographies, recent issues of key journals and Current Contents. The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. A high value was placed on providing pregnant women with the opportunity to determine whether they are carrying a fetus with DS and to make choices concerning the termination of the pregnancy. The economic issues involved are complex and were not considered. Triple-marker screening identifies an estimated 58% of fetuses with DS, but it has an estimated rate of true-positive results of 0.1% and of false-positive results of 3.7% (given a risk cut-off of one chance in 190 of DS). These rates vary with maternal age and the risk cut-off chosen. Women with a known risk of having a fetus with DS (e.g., those who have had a previous child with DS) may benefit from a reduction in anxiety after confirmation that their fetus does not have DS. Screening allows women at low risk of having a child with DS to detect fetuses with the syndrome, but may cause psychologic distress if there is a false-positive screening test result. Up to 20% of women with positive results of screening tests may decline to undergo a subsequent amniocentesis. Amniocentesis and CVS are very accurate in diagnosing DS in fetuses and have a very low rate of serious complications for the mother. Amniocentesis is associated with a 1.7% rate of fetal loss when it is performed after 16 weeks' gestation, whereas the rate among controls is 0.7% (for a difference of 1%, 95% confidence interval 0.3% to 1.5%). CVS entails a greater risk of fetal loss than amniocentesis (odds ratio 1.32, 95% confidence interval 1.11 to 1.57). There is little evidence from controlled trials of significant associations between amniocentesis or CVS and neonatal morbidity or malformations; however, samples have been too small to show differences in rare outcomes. Results from some case-control studies suggest that CVS increases the risk of transverse limb deficiency. Costs were not considered because they are beyond the scope of this review. There is fair evidence to offer triple-marker screening through a comprehensive program to pregnant women under 35 years of age (grade B recommendation). Women given detailed information about serum-marker screening show more satisfaction with the screening than those not given this information. There is fair evidence to offer amniocentesis or CVS to pregnant women 35 years of age and older and to women with a history of a fetus with DS or of a chromosome 21 anomaly (grade B recommendation). Information on the limitations and advantages of each procedure should be offered. Triple-marker screening may be offered as an alternative to CVS or amniocentesis to pregnant women over 35. Recommendations concerning prenatal diagnosis are similar to those of the US Preventive Services Task Force, the Society of Obstetricians and Gynaecologists of Canada, the Canadian College of Medical Geneticists and the Cochrane Pregnancy and Childbirth Group. No previous specific recommendations concerning triple-maker screening exist. These guidelines were developed and endorsed by the Canadian Task Force on the Periodic Health Examination, which is funded by Health Canada and the National Health Research and Development Program.

Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study.

PubMed

Myers, J E; Kenny, L C; McCowan, L M E; Chan, E H Y; Dekker, G A; Poston, L; Simpson, N A B; North, R A

2013-09-01

To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. Predictive test accuracy study. Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE). Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Preterm pre-eclampsia (delivered before 37(+0)  weeks of gestation). Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement. Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

Identification and validation of sex-linked SCAR markers in dioecious Hippophae rhamnoides L. (Elaeagnaceae).

PubMed

Korekar, Girish; Sharma, Ram Kumar; Kumar, Rahul; Meenu; Bisht, Naveen C; Srivastava, Ravi B; Ahuja, Paramvir Singh; Stobdan, Tsering

2012-05-01

The actinorhizal plant seabuckthorn (Hippophae rhamnoides L., Elaeagnaceae) is a wind pollinated dioecious crop. To distinguish male genotypes from female genotypes early in the vegetative growth phase, we have developed robust PCR-based marker(s). DNA bulk samples from 20 male and 20 female plants each were screened with 60 RAPD primers. Two primers, OPA-04 and OPT-06 consistently amplified female-specific (FS) polymorphic fragments of 1,164 and 868 bp, respectively, that were absent in the male samples. DNA sequence of the two markers did not exhibit significant similarity to previously characterized sequences. A sequence-characterized amplified region marker HrX1 (JQ284019) and HrX2 (JQ284020) designed for the two fragments, continued to amplify the FS allele in 120 female plants but not in 100 male plants tested in the current study. Thus, HrX1 and HrX2 are FS markers that can determine the sex of seabuckthorn plants in an early stage and expedite cultivations for industrial applications.

Prevalence of human immunodeficiency virus type 1 p24 antigen in U.S. blood donors--an assessment of the efficacy of testing in donor screening. The HIV-Antigen Study Group.

PubMed

Alter, H J; Epstein, J S; Swenson, S G; VanRaden, M J; Ward, J W; Kaslow, R A; Menitove, J E; Klein, H G; Sandler, S G; Sayers, M H

1990-11-08

We performed a multicenter study in 1989 to determine whether screening whole-blood donors for human immunodeficiency virus type 1 (HIV-1) p24 antigen would improve transfusion safety by identifying carriers of the virus who are seronegative for HIV-1 antibody. More than 500,000 donations were tested at 13 U.S. blood centers with test kits from two manufacturers. Units found repeatedly reactive were retested in a central laboratory; if the results were positive, they were confirmed by a neutralization assay. A subgroup of units was also tested for HIV-1 by the polymerase chain reaction. Selected donors confirmed or not confirmed as having p24 antigen were contacted for follow-up interviews to identify risk factors and undergo retesting for HIV-1 markers. Positive tests for p24 antigen were confirmed by neutralization in five donors (0.001 percent of all donations tested), all of whom were also positive for HIV-1 antibody and HIV-1 by polymerase chain reaction. Three of the antigen-positive donors had other markers of infectious disease that would have resulted in the exclusion of their blood; two had risk factors for HIV-1 that should have led to self-exclusion. Of 220 blood units with repeatedly reactive p24 antigen whose presence could not be confirmed by neutralization (0.04 percent of the donations studied), none were positive for HIV-1 antibody, HIV-1 by polymerase chain reaction (120 units tested), or virus culture (76 units tested)--attesting to the specificity of confirmatory neutralization. The finding that no donation studied was positive for p24 antigen and negative for HIV-1 antibody suggests that screening donors for p24 antigen with tests of the current level of sensitivity would not add substantially to the safety of the U.S. blood supply.

Noninvasive Tests Do Not Accurately Differentiate Nonalcoholic Steatohepatitis From Simple Steatosis: A Systematic Review and Meta-analysis.

PubMed

Verhaegh, Pauline; Bavalia, Roisin; Winkens, Bjorn; Masclee, Ad; Jonkers, Daisy; Koek, Ger

2018-06-01

Nonalcoholic fatty liver disease is a rapidly increasing health problem. Liver biopsy analysis is the most sensitive test to differentiate between nonalcoholic steatohepatitis (NASH) and simple steatosis (SS), but noninvasive methods are needed. We performed a systematic review and meta-analysis of noninvasive tests for differentiating NASH from SS, focusing on blood markers. We performed a systematic search of the PubMed, Medline and Embase (1990-2016) databases using defined keywords, limited to full-text papers in English and human adults, and identified 2608 articles. Two independent reviewers screened the articles and identified 122 eligible articles that used liver biopsy as reference standard. If at least 2 studies were available, pooled sensitivity (sens p ) and specificity (spec p ) values were determined using the Meta-Analysis Package for R (metafor). In the 122 studies analyzed, 219 different blood markers (107 single markers and 112 scoring systems) were identified to differentiate NASH from simple steatosis, and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. The markers analyzed in the largest proportions of studies were alanine aminotransferase (sens p , 63.5% and spec p , 74.4%) within routine biochemical tests, adiponectin (sensp, 72.0% and spec p , 75.7%) within inflammatory markers, CK18-M30 (sens p , 68.4% and spec p , 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sens p , 69.0% and spec p , 72.7%) within the metabolic markers. Two scoring systems could also be pooled: the NASH test (differentiated NASH from borderline NASH plus simple steatosis with 22.9% sens p and 95.3% spec p ) and the GlycoNASH test (67.1% sens p and 63.8% spec p ). In the meta-analysis, we found no test to differentiate NASH from SS with a high level of pooled sensitivity and specificity (≥80%). However, some blood markers, when included in scoring systems in single studies, identified patients with NASH with ≥80% sensitivity and specificity. Replication studies and more standardized study designs are urgently needed. At present, no marker or scoring system can be recommended for use in clinical practice to differentiate NASH from simple steatosis. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Agronomic Traits and Molecular Marker Identification of Wheat–Aegilops caudata Addition Lines

PubMed Central

Gong, Wenping; Han, Ran; Li, Haosheng; Song, Jianmin; Yan, Hongfei; Li, Genying; Liu, Aifeng; Cao, Xinyou; Guo, Jun; Zhai, Shengnan; Cheng, Dungong; Zhao, Zhendong; Liu, Cheng; Liu, Jianjun

2017-01-01

Aegilops caudata is an important gene source for wheat breeding. Intensive evaluation of its utilization value is an essential first step prior to its application in breeding. In this research, the agronomical and quality traits of Triticum aestivum-Ae. caudata additions B–G (homoeologous groups not identified) were analyzed and evaluated. Disease resistance tests showed that chromosome D of Ae. caudata might possess leaf rust resistance, and chromosome E might carry stem rust and powdery mildew resistance genes. Investigations into agronomical traits suggested that the introduction of the Ae. caudata chromosome in addition line F could reduce plant height. Grain quality tests showed that the introduction of chromosomes E or F into wheat could increase its protein and wet gluten content. Therefore, wheat-Ae. caudata additions D–F are all potentially useful candidates for chromosome engineering activities to create useful wheat-alien chromosome introgressions. A total of 55 EST-based molecular markers were developed and then used to identify the chromosome homoeologous group of each of the Ae. caudata B–G chromosomes. Marker analysis indicated that the Ae. caudata chromosomes in addition lines B to G were structurally altered, therefore, a large population combined with intensive screening pressure should be taken into consideration when inducing and screening for wheat-Ae. caudata compensating translocations. Marker data also indicated that the Ae. caudata chromosomes in addition lines C–F were 5C, 6C, 7C, and 3C, respectively, while the homoeologous group of chromosomes B and G of Ae. caudata are as yet undetermined and need further research. PMID:29075275

Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients: implications for lung cancer screening.

PubMed

Triplette, Matthew; Sigel, Keith M; Morris, Alison; Shahrir, Shahida; Wisnivesky, Juan P; Kong, Chung Y; Diaz, Phillip T; Petraglia, Alycia; Crothers, Kristina

2017-07-31

Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.

A systematic review of first trimester biochemical and molecular predictive tests for preeclampsia.

PubMed

Abdi, Fatemeh; Aghaie, Zohreh; Rahnemaie, Fatemeh Sadat; Alimoradi, Zainab

2018-04-16

Preeclampsia is a multisystem disorder affecting 5%-8% of pregnant women. Considering the ongoing debate over the predicting value of some commercial first trimester tests, the aim of this study was to compare the existing first trimester screening tests for preeclampsia. In this systematic review, relevant articles published during 2000-2017 were extracted from PubMed, Science Direct, Scopus, Cochrane Library, ISI Web of Science, and ProQuest databases. After thorough evaluation of the 412 potentially eligible papers, only 26 papers were selected based on the inclusion criteria. From a total of 412 retrieved studies, 28 papers were found eligible. Most studies had case-control or nested case-control designs. A total of 15164 pregnant women were evaluated in the reviewed studies. Various tests were applied in the first trimester of pregnancy to predict the development of preeclampsia. The most commonly used biomarkers were uterine artery pulsatility index, pregnancy-associated plasma protein A (PAPP-A), adiponectin, human chorionic gonadotropin (hCG) hormone and inhibin-A. Other tests were used in only one or two studies. Based on this review, a combination of markers should be evaluated for the identification of high risk women. Novel methods measuring multiple markers will hopefully facilitate the development of clinically effective screening programs in the future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Large-scale mapping of mutations affecting zebrafish development.

PubMed

Geisler, Robert; Rauch, Gerd-Jörg; Geiger-Rudolph, Silke; Albrecht, Andrea; van Bebber, Frauke; Berger, Andrea; Busch-Nentwich, Elisabeth; Dahm, Ralf; Dekens, Marcus P S; Dooley, Christopher; Elli, Alexandra F; Gehring, Ines; Geiger, Horst; Geisler, Maria; Glaser, Stefanie; Holley, Scott; Huber, Matthias; Kerr, Andy; Kirn, Anette; Knirsch, Martina; Konantz, Martina; Küchler, Axel M; Maderspacher, Florian; Neuhauss, Stephan C; Nicolson, Teresa; Ober, Elke A; Praeg, Elke; Ray, Russell; Rentzsch, Brit; Rick, Jens M; Rief, Eva; Schauerte, Heike E; Schepp, Carsten P; Schönberger, Ulrike; Schonthaler, Helia B; Seiler, Christoph; Sidi, Samuel; Söllner, Christian; Wehner, Anja; Weiler, Christian; Nüsslein-Volhard, Christiane

2007-01-09

Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations.

Dysferlin quantification in monocytes for rapid screening for dysferlinopathies.

PubMed

Sánchez-Chapul, Laura; Ángel-Muñoz, Miguel Del; Ruano-Calderón, Luis; Luna-Angulo, Alexandra; Coral-Vázquez, Ramón; Hernández-Hernández, Óscar; Magaña, Jonathan J; León-Hernández, Saúl R; Escobar-Cedillo, Rosa E; Vargas, Steven

2016-12-01

In this study, we determined normal levels of dysferlin expression in CD14 + monocytes by flow cytometry (FC) as a screening tool for dysferlinopathies. Monocytes from 183 healthy individuals and 29 patients were immunolabeled, run on an FACScalibur flow cytometer, and analyzed by FlowJo software. The relative quantity of dysferlin was expressed as mean fluorescence intensity (MFI). Performance of this diagnostic test was assessed by calculating likelihood ratios at different MFI cut-off points, which allowed definition of 4 disease classification groups in a simplified algorithm. The MFI value may differentiate patients with dysferlinopathy from healthy individuals; it may be a useful marker for screening purposes. Muscle Nerve 54: 1064-1071, 2016. © 2016 Wiley Periodicals, Inc.

Breast Reference Set Application: Chris Li-FHCRC (2015) — EDRN Public Portal

Cancer.gov

We propose to evaluate nine candidate biomarkers for ER+ breast cancer in samples from the EDRN Breast Cancer Reference Set. These biomarkers have been preliminarily validated in preclinical samples. The intended clinical applications of these markers are to: 1. Inform timing of a subsequent mammogram in women with a negative screening mammogram; 2. Inform continuation of mammographic screening among women 75-79 years; 3. Prioritize women who should be screened with mammography in areas with limited resources. Testing the reference samples would further expedite addressing these intended clinical applications by providing further validation data to support requests for samples from other sources for further Phase 3 evaluation (e.g., WHI, PLCO, and samples collected at the time of mammographic screening from the University of Toronto and UCSF).

First trimester contingent testing with either nuchal translucency or cell-free DNA. Cost efficiency and the role of ultrasound dating.

PubMed

Conner, Peter; Gustafsson, Sven; Kublickas, Marius

2015-04-01

To evaluate the performance and cost efficacy of different first-trimester contingent screening strategies based on an initial analysis of biochemical markers. Retrospective study. Swedish National Quality Register for prenatal diagnosis. 35,780 women with singleton pregnancies. Serum values from first trimester biochemistry were re-analyzed in a contingent approach. For risks between 1:40 and 1:1000, risk estimates from nuchal translucency measurements were added and outcomes were compared using either a final cut-off risk of 1:200 to proceed with invasive testing or offering non-invasive prenatal testing. In a subgroup of 12,836 women with regular menstrual cycles the same analyses were performed using data on the last menstrual period for determining gestational age. The costs of detecting one case of aneuploidy were compared. Comparison of screening strategies. The detection rate was the same (87%) in the contingent group as in complete combined screening, with only 41% requiring a nuchal translucency scan. As an alternative, offering non-invasive prenatal testing to the intermediate risk group would result in a detection rate of 98%, but the cost to detect one case of trisomy 21 would be 83% higher than the cost associated with traditional combined screening. First trimester examination using a contingent approach will achieve similar results compared with full combined screening. Non-invasive prenatal testing will not be cost-effective when a high proportion of pregnancies need further testing. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Multiplex Polymerase Chain Reaction for Identification of Shigellae and Four Shigella Species Using Novel Genetic Markers Screened by Comparative Genomics.

PubMed

Kim, Hyun-Joong; Ryu, Ji-Oh; Song, Ji-Yeon; Kim, Hae-Yeong

2017-07-01

In the detection of Shigella species using molecular biological methods, previously known genetic markers for Shigella species were not sufficient to discriminate between Shigella species and diarrheagenic Escherichia coli. The purposes of this study were to screen for genetic markers of the Shigella genus and four Shigella species through comparative genomics and develop a multiplex polymerase chain reaction (PCR) for the detection of shigellae and Shigella species. A total of seven genomic DNA sequences from Shigella species were subjected to comparative genomics for the screening of genetic markers of shigellae and each Shigella species. The primer sets were designed from the screened genetic markers and evaluated using PCR with genomic DNAs from Shigella and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, was developed from the evaluated primer sets, and its performance was demonstrated with specifically amplified results from each Shigella species. This Shigella multiplex PCR is the first to be reported with novel genetic markers developed through comparative genomics and may be a useful tool for the accurate detection of the Shigella genus and species from closely related bacteria in clinical microbiology and food safety.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer and optimal selection of traditional Chinese medicine target.

PubMed

Tian, Tongde; Chen, Chuanliang; Yang, Feng; Tang, Jingwen; Pei, Junwen; Shi, Bian; Zhang, Ning; Zhang, Jianhua

2017-03-01

The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. KEGG analysis was employed to establish apoptotic regulatory network model based on screened genetic markers, and optimization was conducted on TCM targets. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, P53, APC, DCC and PTEN, among which DCC has the highest diagnostic efficiency. Apoptotic regulatory network was built by KEGG analysis. Currently, it was reported that TCM has regulatory function on gene locus in apoptotic regulatory network. The apoptotic regulatory model of colorectal cancer established in this study provides theoretical evidence for early diagnosis and TCM targeted therapy of colorectal cancer in clinic.

A resource of large-scale molecular markers for monitoring Agropyron cristatum chromatin introgression in wheat background based on transcriptome sequences.

PubMed

Zhang, Jinpeng; Liu, Weihua; Lu, Yuqing; Liu, Qunxing; Yang, Xinming; Li, Xiuquan; Li, Lihui

2017-09-20

Agropyron cristatum is a wild grass of the tribe Triticeae and serves as a gene donor for wheat improvement. However, very few markers can be used to monitor A. cristatum chromatin introgressions in wheat. Here, we reported a resource of large-scale molecular markers for tracking alien introgressions in wheat based on transcriptome sequences. By aligning A. cristatum unigenes with the Chinese Spring reference genome sequences, we designed 9602 A. cristatum expressed sequence tag-sequence-tagged site (EST-STS) markers for PCR amplification and experimental screening. As a result, 6063 polymorphic EST-STS markers were specific for the A. cristatum P genome in the single-receipt wheat background. A total of 4956 randomly selected polymorphic EST-STS markers were further tested in eight wheat variety backgrounds, and 3070 markers displaying stable and polymorphic amplification were validated. These markers covered more than 98% of the A. cristatum genome, and the marker distribution density was approximately 1.28 cM. An application case of all EST-STS markers was validated on the A. cristatum 6 P chromosome. These markers were successfully applied in the tracking of alien A. cristatum chromatin. Altogether, this study provided a universal method of large-scale molecular marker development to monitor wild relative chromatin in wheat.

Cost-Effectiveness of Magnetic Resonance Imaging with a New Contrast Agent for the Early Diagnosis of Alzheimer's Disease

PubMed Central

Biasutti, Maria; Dufour, Natacha; Ferroud, Clotilde; Dab, William; Temime, Laura

2012-01-01

Background Used as contrast agents for brain magnetic resonance imaging (MRI), markers for beta-amyloid deposits might allow early diagnosis of Alzheimer's disease (AD). We evaluated the cost-effectiveness of such a diagnostic test, MRI+CLP (contrastophore-linker-pharmacophore), should it become clinically available. Methodology/Principal Findings We compared the cost-effectiveness of MRI+CLP to that of standard diagnosis using currently available cognition tests and of standard MRI, and investigated the impact of a hypothetical treatment efficient in early AD. The primary analysis was based on the current French context for 70-year-old patients with Mild Cognitive Impairment (MCI). In alternative “screen and treat” scenarios, we analyzed the consequences of systematic screenings of over-60 individuals (either population-wide or restricted to the ApoE4 genotype population). We used a Markov model of AD progression; model parameters, as well as incurred costs and quality-of-life weights in France were taken from the literature. We performed univariate and probabilistic multivariate sensitivity analyses. The base-case preferred strategy was the standard MRI diagnosis strategy. In the primary analysis however, MRI+CLP could become the preferred strategy under a wide array of scenarios involving lower cost and/or higher sensitivity or specificity. By contrast, in the “screen and treat” analyses, the probability of MRI+CLP becoming the preferred strategy remained lower than 5%. Conclusions/Significance It is thought that anti-beta-amyloid compounds might halt the development of dementia in early stage patients. This study suggests that, even should such treatments become available, systematically screening the over-60 population for AD would only become cost-effective with highly specific tests able to diagnose early stages of the disease. However, offering a new diagnostic test based on beta-amyloid markers to elderly patients with MCI might prove cost-effective. PMID:22532859

[Comparative study of protein markers in serum and bronchoalveolar lavage fluid from patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry].

PubMed

Zhou, Ji-hong; Liu, Guang-nan; Huang, Si-ming; Zhong, Xiao-ning; Su, Hong; Zhou, Yi

2011-04-01

To detect the protein markers in serum and bronchoalveolar lavage fluid (BALF) of the patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technology, and to explore if they can be used as markers for the diagnosis of lung cancer. SELDI-TOF-MS technology and protein chips weak cation exchange (WCX-2 chip) were used to detect the protein mass spectrum in serum and BALF of 35 patients with lung cancer and 18 cases of benign pulmonary diseases. The different protein markers were analyzed by Biomarker Pattern Software and the initial diagnosis models were set up. The diagnosis models were verified further by blind screen to confirm the efficacy of diagnosis. Five protein peaks in the sera of the patients with lung cancer were significantly higher (P < 0.05). The protein peak with a mass/charge ratio (M/Z) of 5639 was selected to establish the classification tree model. The sensitivity of diagnosis was 80% (28/35) and the specificity was 78% (14/18). The results verified by blind screen showed a sensitivity of 85% (17/20), a specificity of 90% (9/10), a crude accuracy (CA) of 87% (26/30) and Youden's index (γ) of 0.7. Eight protein peaks in the BALF of the patients with lung cancer were significantly higher (P < 0.05). The different protein peaks with M/Z of 7976 and 11 809 respectively were selected to establish the classification tree model. The sensitivity of diagnosis was 86% (30/35) and the specificity was 72% (13/18). The results verified by blind screen showed a sensitivity of 90% (18/20), a specificity of 90% (9/10), a CA of 90% (27/30) and γ of 0.8. There was a complementary role in combination of differential proteins in serum and BALF and the sensitivity, specificity and accuracy of diagnosis for lung cancer were 100% by parallel test. The SELDI-TOF-MS technology can screen out the differential protein markers in serum and BALF of the patients with lung cancer, which show high sensitivity and specificity as tumor markers. The differential proteins in the BALF may be more promising for clinical application.

Maternal biochemical serum screening for Down syndrome in pregnancy with human immunodeficiency virus infection.

PubMed

Le Meaux, Jean-Patrick; Tsatsaris, Vassilis; Schmitz, Thomas; Fulla, Yvonne; Launay, Odile; Goffinet, François; Azria, Elie

2008-08-01

To estimate the influence of human immunodeficiency virus (HIV) infection and antiretroviral therapy on maternal serum markers levels and the false-positive rate with biochemical maternal serum screening for Down syndrome. We performed a 1:1 matched case-control study comparing 132 HIV-infected women with single pregnancy to controls selected among non-HIV-infected women matched on geographical origin and fetal sex. Of HIV-infected women, 47.7% were receiving antiretroviral therapy. Groups did not differ in multiples of the median (MoM) levels of total human chorionic gonadotrophin. The MoM alpha fetoprotein level did not differ between total HIV-infected women and control women but was significantly lower for untreated HIV-positive women compared with control women (0.91 compared with 1.03 MoM, P<.01) and compared with treated HIV-positive women (0.91 compared with 1.18 MoM, P<.01). The false-positive rate of biochemical screening did not differ between groups. Untreated HIV infection is associated with lower maternal serum alpha fetoprotein levels. Nevertheless, the false-positive rate of double-marker second-trimester Down syndrome serum screening did not appear to be affected in our sample of HIV-infected women, whether women were receiving antiretroviral therapy at the time of the test or not.

76 FR 40736 - NIH State-of-the-Science Conference on the Role of Active Surveillance in the Management of Men...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... blood test that measures prostate-specific antigen (PSA), a tumor marker. More than half of cancers detected with PSA screening are localized (confined to the prostate), not aggressive at diagnosis, and... which PSA levels are closely monitored, prostate biopsies may be repeated, and eventual treatment is...

A study on software-based sensing technology for multiple object control in AR video.

PubMed

Jung, Sungmo; Song, Jae-Gu; Hwang, Dae-Joon; Ahn, Jae Young; Kim, Seoksoo

2010-01-01

Researches on Augmented Reality (AR) have recently received attention. With these, the Machine-to-Machine (M2M) market has started to be active and there are numerous efforts to apply this to real life in all sectors of society. To date, the M2M market has applied the existing marker-based AR technology in entertainment, business and other industries. With the existing marker-based AR technology, a designated object can only be loaded on the screen from one marker and a marker has to be added to load on the screen the same object again. This situation creates a problem where the relevant marker'should be extracted and printed in screen so that loading of the multiple objects is enabled. However, since the distance between markers will not be measured in the process of detecting and copying markers, the markers can be overlapped and thus the objects would not be augmented. To solve this problem, a circle having the longest radius needs to be created from a focal point of a marker to be copied, so that no object is copied within the confines of the circle. In this paper, software-based sensing technology for multiple object detection and loading using PPHT has been developed and overlapping marker control according to multiple object control has been studied using the Bresenham and Mean Shift algorithms.

Obstetrical complications associated with abnormal maternal serum markers analytes.

PubMed

Gagnon, Alain; Wilson, R Douglas

2008-10-01

To review the obstetrical outcomes associated with abnormally elevated or decreased level of one or more of the most frequently measured maternal serum marker analytes used in screening for aneuploidy. To provide guidance to facilitate the management of pregnancies that have abnormal levels of one of more markers and to assess the usefulness of these markers as a screening test. Perinatal outcomes associated with abnormal levels of maternal serum markers analytes are compared with the outcomes of pregnancies with normal levels of the same analytes or the general population. The Cochrane Library and Medline were searched for English-language articles published from 1966 to February 2007, relating to maternal serum markers and perinatal outcomes. Search terms included PAPP-A (pregnancy associated plasma protein A), AFP (alphafetoprotein), hCG (human chorionic gonadotropin), estriol, unconjugated estriol, inhibin, inhibin-A, maternal serum screen, triple marker screen, quadruple screen, integrated prenatal screen, first trimester screen, and combined prenatal screen. All study types were reviewed. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Key individual studies on which the recommendations are based are referenced. Supporting data for each recommendation are summarized with evaluative comments and references. The evidence was evaluated using the guidelines developed by the Canadian Task Force on Preventive Health Care. The evidence collected was reviewed by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada. The benefit expected from this guideline is to facilitate early detection of potential adverse pregnancy outcomes when risks are identified at the time of a maternal serum screen. It will help further stratification of risk and provide options for pregnancy management to minimize the impact of pregnancy complications. The potential harms resulting from such practice are associated with the so called false positive (i.e., uncomplicated pregnancies labelled at increased risk for adverse perinatal outcomes), the potential stress associated with such a label, and the investigations performed for surveillance in this situation. No cost-benefit analysis is available to assess costs and savings associated with this guideline. SUMMARY STATEMENTS: 1. An unexplained level of a maternal serum marker analyte is defined as an abnormal level after confirmation of gestational age by ultrasound and exclusion of maternal, fetal, or placental causes for the abnormal level. (III) 2. Abnormally elevated levels of serum markers are associated with adverse pregnancy outcomes in twin pregnancies, after correction for the number of fetuses. Spontaneous or planned mutifetal reductions may result in abnormal elevations of serum markers. (II-2) RECOMMENDATIONS: 1. In the first trimester, an unexplained low PAPP-A (< 0.4 MoM) and/or a low hCG (< 0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) In the second trimester, an unexplained elevation of maternal serum AFP (> 2.5 MoM), hCG (> 3.0 MoM), and/or inhibin-A (> or =2.0 MoM) or a decreased level of maternal serum AFP (< 0.25 MoM) and/or unconjugated estriol (< 0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) 2. Pregnant woman with an unexplained elevated PAPP-A or hCG in the first trimester and an unexplained low hCG or inhibin-A and an unexplained elevated unconjugated estriol in the second trimester should receive normal antenatal care, as this pattern of analytes is not associated with adverse perinatal outcomes. (II-2A) 3. The combination of second or third trimester placenta previa and an unexplained elevated maternal serum AFP should increase the index of suspicion for placenta accreta, increta, or percreta. (II-2B) An assessment (ultrasound, MRI) of the placental-uterine interface should be performed. Abnormal invasion should be strongly suspected, and the planning of delivery location and technique should be done accordingly. (III-C) 4. A prenatal consultation with the medical genetics department is recommended for low unconjugated estriol levels (<0.3 MoM), as this analyte pattern can be associated with genetic conditions. (II-2B) 5. The clinical management protocol for identification of potential adverse obstetrical outcomes should be guided by one or more abnormal maternal serum marker analyte value rather than the false positive screening results for the trisomy 21 and/or the trisomy 18 screen. (II-2B) 6. Pregnant woman who are undergoing renal dialysis or who have had a renal transplant should be offered maternal serum screening, but interpretation of the result is difficult as the level of serum hCG is not reliable. (II-2A) 7. Abnormal maternal uterine artery Doppler in association with elevated maternal serum AFP, hCG, or inhibin-A or decreased PAPP-A identifies a group of women at greater risk of IUGR and gestational hypertension with proteinuria. Uterine artery Doppler measurements may be used in the evaluation of an unexplained abnormal level of either of these markers. (II-2B) 8. Further research is recommended to identify the best protocol for pregnancy management and surveillance in women identified at increased risk of adverse pregnancy outcomes based on an abnormality of a maternal serum screening analyte. (III-A) 9. In the absence of evidence supporting any specific surveillance protocol, an obstetrician should be consulted in order to establish a fetal surveillance plan specific to the increased obstetrical risks (maternal and fetal) identified. This plan may include enhanced patient education on signs and symptoms of the most common complications, increased frequency of antenatal visits, increased ultrasound (fetal growth, amniotic fluid levels), and fetal surveillance (biophysical profile, arterial and venous Doppler), and cervical length assessment. (III-A) 10. Limited information suggests that, in women with elevated hCG in the second trimester and/or abnormal uterine artery Doppler (at 22-24 weeks), low-dose aspirin (60-81 mg daily) is associated with higher birthweight and lower incidence of gestational hypertension with proteinuria. This therapy may be used in women who are at risk. (II-2B) 11. Further studies are recommended in order to assess the benefits of low-dose aspirin, low molecular weight heparin, or other therapeutic options in pregnancies determined to be at increased risk on the basis of an abnormal maternal serum screening analyte. (III-A) 12. Multiple maternal serum markers screening should not be used at present as a population-based screening method for adverse pregnancy outcomes (such as preeclampsia, placental abruption, and stillbirth) outside an established research protocol, as sensitivity is low, false positive rates are high, and no management protocol has been shown to clearly improve outcomes. (II-2D) When maternal serum screening is performed for the usual clinical indication (fetal aneuploidy and/or neural tube defect), abnormal analyte results can be utilized for the identification of pregnancies at risk and to direct their clinical management. (II-2B) Further studies are recommended to determine the optimal screening method for poor maternal and/or perinatal outcomes. (III-A).

St2-80: a new FISH marker for St genome and genome analysis in Triticeae.

PubMed

Wang, Long; Shi, Qinghua; Su, Handong; Wang, Yi; Sha, Lina; Fan, Xing; Kang, Houyang; Zhang, Haiqin; Zhou, Yonghong

2017-07-01

The St genome is one of the most fundamental genomes in Triticeae. Repetitive sequences are widely used to distinguish different genomes or species. The primary objectives of this study were to (i) screen a new sequence that could easily distinguish the chromosome of the St genome from those of other genomes by fluorescence in situ hybridization (FISH) and (ii) investigate the genome constitution of some species that remain uncertain and controversial. We used degenerated oligonucleotide primer PCR (Dop-PCR), Dot-blot, and FISH to screen for a new marker of the St genome and to test the efficiency of this marker in the detection of the St chromosome at different ploidy levels. Signals produced by a new FISH marker (denoted St 2 -80) were present on the entire arm of chromosomes of the St genome, except in the centromeric region. On the contrary, St 2 -80 signals were present in the terminal region of chromosomes of the E, H, P, and Y genomes. No signal was detected in the A and B genomes, and only weak signals were detected in the terminal region of chromosomes of the D genome. St 2 -80 signals were obvious and stable in chromosomes of different genomes, whether diploid or polyploid. Therefore, St 2 -80 is a potential and useful FISH marker that can be used to distinguish the St genome from those of other genomes in Triticeae.

Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.

PubMed

Nankivell, Brian J; Renthawa, Jasveen; Jeoffreys, Neisha; Kable, Kathy; O'Connell, Philip J; Chapman, Jeremy R; Wong, Germaine; Sharma, Raghwa N

2015-08-01

Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction. We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients. The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results. Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.

High throughput and miniaturised systems for biodegradability assessments.

PubMed

Cregut, Mickael; Jouanneau, Sulivan; Brillet, François; Durand, Marie-José; Sweetlove, Cyril; Chenèble, Jean-Charles; L'Haridon, Jacques; Thouand, Gérald

2014-01-01

The society demands safer products with a better ecological profile. Regulatory criteria have been developed to prevent risks for human health and the environment, for example, within the framework of the European regulation REACH (Regulation (EC) No 1907, 2006). This has driven industry to consider the development of high throughput screening methodologies for assessing chemical biodegradability. These new screening methodologies must be scalable for miniaturisation, reproducible and as reliable as existing procedures for enhanced biodegradability assessment. Here, we evaluate two alternative systems that can be scaled for high throughput screening and conveniently miniaturised to limit costs in comparison with traditional testing. These systems are based on two dyes as follows: an invasive fluorescent dyes that serves as a cellular activity marker (a resazurin-like dye reagent) and a noninvasive fluorescent oxygen optosensor dye (an optical sensor). The advantages and limitations of these platforms for biodegradability assessment are presented. Our results confirm the feasibility of these systems for evaluating and screening chemicals for ready biodegradability. The optosensor is a miniaturised version of a component already used in traditional ready biodegradability testing, whereas the resazurin dye offers an interesting new screening mechanism for chemical concentrations greater than 10 mg/l that are not amenable to traditional closed bottle tests. The use of these approaches allows generalisation of high throughput screening methodologies to meet the need of developing new compounds with a favourable ecological profile and also assessment for regulatory purpose.

Cross-parent reliability in rating ASD markers in infants.

PubMed

Ben-Sasson, Ayelet; Amit-Ben-Simhon, Hemda; Meyer, Sonya

2015-06-01

To investigate the congruence and discrepancies between mother and father reports of early autism spectrum disorders (ASD) markers. Mothers (n = 80) and fathers (n = 78) of 12-month-old infants (55% boys) completed the first year inventory (FYI), an ASD norm-referenced screening questionnaire. Mothers also completed the Infant Toddler Social Emotional Assessment (ITSEA). There were significant and moderate intra-class correlations between mother and father reports for most FYI factors. Fathers' median FYI social-communication domain score was almost twice that of mothers. Mann-Whitney tests indicated that fathers rated their child significantly higher than mothers on the four FYI social-communication factors and on the sensory processing factor. Linear weighted kappa analyses indicated poor agreement on gaze-related and reactivity FYI items. FYI social-communication and sensory-regulatory factors showed significant correlations with corresponding ITSEA scores. Social-communication markers pose a greater challenge for consistent report across parents than sensory-regulatory markers.

Can one blood draw replace transrectal ultrasonography-estimated prostate volume to predict prostate cancer risk?

PubMed

Carlsson, Sigrid V; Peltola, Mari T; Sjoberg, Daniel; Schröder, Fritz H; Hugosson, Jonas; Pettersson, Kim; Scardino, Peter T; Vickers, Andrew J; Lilja, Hans; Roobol, Monique J

2013-09-01

To explore whether a panel of kallikrein markers in blood: total, free and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2, could be used as a non-invasive alternative for predicting prostate cancer on biopsy in a screening setting. The study cohort comprised previously unscreened men who underwent sextant biopsy owing to elevated PSA (≥3 ng/mL) in two different centres of the European Randomized Study of Screening for Prostate Cancer, Rotterdam (n = 2914) and Göteborg (n = 740). A statistical model, based on kallikrein markers, was compared with one based on established clinical factors for the prediction of biopsy outcome. The clinical tests were found to be no better than blood markers, with an area under the curve in favour of the blood measurements of 0.766 vs. 0.763 in Rotterdam and 0.809 vs. 0.774 in Göteborg. Adding digital rectal examination (DRE) or DRE plus transrectal ultrasonography (TRUS) volume to the markers improved discrimination, although the increases were small. Results were similar for predicting high-grade cancer. There was a strong correlation between the blood measurements and TRUS-estimated prostate volume (Spearman's correlation 0.60 in Rotterdam and 0.57 in Göteborg). In previously unscreened men, each with indication for biopsy, a statistical model based on kallikrein levels was similar to a clinical model in predicting prostate cancer in a screening setting, outside the day-to-day clinical practice. Whether a clinical approach can be replaced by laboratory analyses or used in combination with decision models (nomograms) is a clinical judgment that may vary from clinician to clinician depending on how they weigh the different advantages and disadvantages (harms, costs, time, invasiveness) of both approaches. © 2013 BJU International.

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China.

PubMed

Yu, Fang Fang; Ping, Zhi Guang; Yao, Chong; Wang, Zhi Wen; Wang, Fu Qi; Guo, Xiong

2017-02-01

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Extension and refinement of the predictive value of different classes of markers in ADNI: Four year follow-up data

PubMed Central

Gomar, Jesus J; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

2014-01-01

Background This study examined the predictive value of different classes of markers in the progression from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) over an extended 4 year follow-up in ADNI. Methods MCI patients assessed on clinical, cognitive, MRI, PET-FDG, and CSF markers at baseline, and followed on a yearly basis for four years to ascertain progression to AD. Logistic regression models were fitted in clusters including demographics, APOE genotype, cognitive markers, and biomarkers (morphometric, PET-FDG, CSF Abeta and tau). Results The predictive model at four years revealed that two cognitive measures, an episodic memory measure and a clock drawing screening test, were the best predictors of conversion (AUC= 0.78). Conclusions This model of prediction is consistent to the previous model at two years, thus highlighting the importance of cognitive measures in progression from MCI to AD. Cognitive markers were more robust predictors than biomarkers. PMID:24613706

Multiplex-Ready Technology for mid-throughput genotyping of molecular markers.

PubMed

Bonneau, Julien; Hayden, Matthew

2014-01-01

Screening molecular markers across large populations in breeding programs is generally time consuming and expensive. The Multiplex-Ready Technology (MRT) (Hayden et al., BMC genomics 9:80, 2008) was created to optimize polymorphism screening and genotyping using standardized PCR reaction conditions. The flexibility of this method maximizes the number of markers (up to 24 markers SSR or SNP, ideally small PCR product <500 bp and highly polymorphic) by using fluorescent dye (VIC, FAM, NED, and PET) and a semiautomated DNA fragment analyzer (ABI3730) capillary electrophoresis for large numbers of DNA samples (96 or 384 samples).

A Study on Software-based Sensing Technology for Multiple Object Control in AR Video

PubMed Central

Jung, Sungmo; Song, Jae-gu; Hwang, Dae-Joon; Ahn, Jae Young; Kim, Seoksoo

2010-01-01

Researches on Augmented Reality (AR) have recently received attention. With these, the Machine-to-Machine (M2M) market has started to be active and there are numerous efforts to apply this to real life in all sectors of society. To date, the M2M market has applied the existing marker-based AR technology in entertainment, business and other industries. With the existing marker-based AR technology, a designated object can only be loaded on the screen from one marker and a marker has to be added to load on the screen the same object again. This situation creates a problem where the relevant marker’should be extracted and printed in screen so that loading of the multiple objects is enabled. However, since the distance between markers will not be measured in the process of detecting and copying markers, the markers can be overlapped and thus the objects would not be augmented. To solve this problem, a circle having the longest radius needs to be created from a focal point of a marker to be copied, so that no object is copied within the confines of the circle. In this paper, software-based sensing technology for multiple object detection and loading using PPHT has been developed and overlapping marker control according to multiple object control has been studied using the Bresenham and Mean Shift algorithms. PMID:22163444

High-Content, High-Throughput Screening for the Identification of Cytotoxic Compounds Based on Cell Morphology and Cell Proliferation Markers

PubMed Central

Martin, Heather L.; Adams, Matthew; Higgins, Julie; Bond, Jacquelyn; Morrison, Ewan E.; Bell, Sandra M.; Warriner, Stuart; Nelson, Adam; Tomlinson, Darren C.

2014-01-01

Toxicity is a major cause of failure in drug discovery and development, and whilst robust toxicological testing occurs, efficiency could be improved if compounds with cytotoxic characteristics were identified during primary compound screening. The use of high-content imaging in primary screening is becoming more widespread, and by utilising phenotypic approaches it should be possible to incorporate cytotoxicity counter-screens into primary screens. Here we present a novel phenotypic assay that can be used as a counter-screen to identify compounds with adverse cellular effects. This assay has been developed using U2OS cells, the PerkinElmer Operetta high-content/high-throughput imaging system and Columbus image analysis software. In Columbus, algorithms were devised to identify changes in nuclear morphology, cell shape and proliferation using DAPI, TOTO-3 and phosphohistone H3 staining, respectively. The algorithms were developed and tested on cells treated with doxorubicin, taxol and nocodazole. The assay was then used to screen a novel, chemical library, rich in natural product-like molecules of over 300 compounds, 13.6% of which were identified as having adverse cellular effects. This assay provides a relatively cheap and rapid approach for identifying compounds with adverse cellular effects during screening assays, potentially reducing compound rejection due to toxicity in subsequent in vitro and in vivo assays. PMID:24505478

Evaluation of the Microsoft Kinect for screening ACL injury.

PubMed

Stone, Erik E; Butler, Michael; McRuer, Aaron; Gray, Aaron; Marks, Jeffrey; Skubic, Marjorie

2013-01-01

A study was conducted to evaluate the use of the skeletal model generated by the Microsoft Kinect SDK in capturing four biomechanical measures during the Drop Vertical Jump test. These measures, which include: knee valgus motion from initial contact to peak flexion, frontal plane knee angle at initial contact, frontal plane knee angle at peak flexion, and knee-to-ankle separation ratio at peak flexion, have proven to be useful in screening for future knee anterior cruciate ligament (ACL) injuries among female athletes. A marker-based Vicon motion capture system was used for ground truth. Results indicate that the Kinect skeletal model likely has acceptable accuracy for use as part of a screening tool to identify elevated risk for ACL injury.

[Hyperechogenic fetal bowel as a marker of fetal cystic fibrosis].

PubMed

Sukupová, M; Dhaifalah, I; Adamík, Z; Havalová, J

2015-01-01

Hyperechogenic bowel (HB) occurs in 0.1 to 1.8% of normal pregnancies. In most cases it has no consequence for the foetus, but can be associated with cystic fibrosis (CF), chromosomal defects, genetic syndromes, viral infections, gastrointestinal pathology, missed gravidity, IUGR and preterm labour. Assessment the risk of the foetus having CF or other abnormalities when HB was detected during ultrasound screening in the second trimester of pregnancy in our centre. Retrospective study. Department of Obstetrics and Gynecology, Centre of Fetal Medicine and Genetics, KNTB a.s. Zlín. Retrospective analysis of 149 cases of HB between 17 to 22 weeks of pregnancy detected from January 2008 to April 2012. HB was evaluated according to its degree of echogenicity (Slotnik/Abuhamed classification), presence or absence of other ultrasound markers and the result of first trimester combined screening result. When stage II or III HB and/or borderline risk in first trimester screening, and presence of other ultrasound markers was detected, amniocentesis (AMC) was performed to investigate the karyotype, mutations in the CFTR gene and presence of viral infections (cytomegalovirus and parvovirus B19). If stage I or II HB and/or negative I. trimester screening and no other ultrasound markers, viral infections and mutations in the CFTR gene were investigated form maternal blood. If positive, paternal blood sampling testing for mutation in the CFTR gene was performed. If a mutation was detected in both parents, AMC was performed. Mutations of the CFTR gene was investigated with a commercial panel of 33 to 50 most common mutations. Postnatally the outcome of neonatal screening for CF(IRT) and any newborns with congenital malformations were ascertained. HB was seen in 149 foetuses, AMC was performed in 94 (63%), and blood sampling in 55 (37%). Two mutations in the CFTR gene associated with a severe form of CF (deltaF508/3849 KBC +10 T) were found in one foetus from the AMC group with stage III HB. The parents decided to terminate the pregnancy. The incidence of HB in our group was 0.7%. In 4 foetuses (2.7%) with stage II HB heterozygous deltaF508 mutation was found, in the rest no mutations were detected. Parents of heterozygous carriers underwent genetic consultation. Postnatal CF screening (IRT level from a heel prick sample) was negative; therefore no further molecular genetic analysis was performed. Infection was detected in three foetuses; one case was managed with intrauterine transfusion and in the other two cases parents decided for termination. Four cases (2.7%) were terminated because of severe congenital anomalies. Minor congenital abnormalities were detected in seven (4.7%) cases. Intrauterine death was detected in three (2%) pregnancies. Based on our results, HB can be considered as a significant marker for the risk of CF, especially in HB stages II and III. It also demonstrates the importance of this marker for the risk of other foetal abnormalities.

The Non-Word Repetition Task as a Clinical Marker of Specific Language Impairment in Spanish-Speaking Children

ERIC Educational Resources Information Center

Girbau, Dolors

2016-01-01

Forty native Spanish-speaking children (age 8;0-10;3), 20 with Specific Language Impairment (SLI) and 20 with Typical Language Development (TLD), received a battery of psycholinguistic tests, IQ, hearing screenings, and the Spanish Non-word Repetition Task (NRT). The children's repetition of 20 non-words was scored. The percentage of correct…

Utility of Helicobacter spp. associated GFD markers for detecting avian fecal pollution in natural waters of two continents.

PubMed

Ahmed, W; Harwood, V J; Nguyen, K; Young, S; Hamilton, K; Toze, S

2016-01-01

Avian fecal droppings may negatively impact environmental water quality due to the presence of high concentrations of fecal indicator bacteria (FIB) and zoonotic pathogens. This study was aimed at evaluating the performance characteristics and utility of a Helicobacter spp. associated GFD marker by screening 265 fecal and wastewater samples from a range of avian and non-avian host groups from two continents (Brisbane, Australia and Florida, USA). The host-prevalence and -specificity of this marker among fecal and wastewater samples tested from Brisbane were 0.58 and 0.94 (maximum value of 1.00). These values for the Florida fecal samples were 0.30 (host-prevalence) and 1.00 (host-specificity). The concentrations of the GFD markers in avian and non-avian fecal nucleic acid samples were measured at a test concentration of 10 ng of nucleic acid at Brisbane and Florida laboratories using the quantitative PCR (qPCR) assay. The mean concentrations of the GFD marker in avian fecal nucleic acid samples (5.2 × 10(3) gene copies) were two orders of magnitude higher than non-avian fecal nucleic acid samples (8.6 × 10(1) gene copies). The utility of this marker was evaluated by testing water samples from the Brisbane River, Brisbane and a freshwater creek in Florida. Among the 18 water samples tested from the Brisbane River, 83% (n = 18) were positive for the GFD marker, and the concentrations ranged from 6.0 × 10(1)-3.2 × 10(2) gene copies per 100 mL water. In all, 92% (n = 25) water samples from the freshwater creek in Florida were also positive for the GFD marker with concentrations ranging from 2.8 × 10(1)-1.3 × 10(4) gene copies per 100 mL water. Based on the results, it can be concluded that the GFD marker is highly specific to avian host groups, and could be used as a reliable marker to detect the presence and amount of avian fecal pollution in environmental waters. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Development of DArT-based PCR markers for selecting drought-tolerant spring barley.

PubMed

Fiust, Anna; Rapacz, Marcin; Wójcik-Jagła, Magdalena; Tyrka, Mirosław

2015-08-01

The tolerance of spring barley (Hordeum vulgare L.) cultivars to spring drought is an important agronomic trait affecting crop yield and quality in Poland. Therefore, breeders require new molecular markers to select plants with lower spring drought susceptibility. With the advent of genomic selection technology, simple molecular tools may still be applicable to screen material for markers of the most important traits and in-depth genome scanning. In previous studies, diversity arrays technology (DArT)-based genetic maps were constructed for F2 populations of Polish fodder and malt barley elite breeding lines, and 15 and 18 quantitative trait loci (QTLs) related to spring drought tolerance were identified, respectively. In this paper, we show the results of a conversion of 30 DArT markers corresponding to 11 QTLs into simple sequence repeat (SSR) and sequence tagged site (STS) markers. Twenty-two polymorphic markers were obtained, including 13 DArT-based SSRs. Additionally, 31 SSR markers, located in close proximity to the DArT markers, were selected from the GrainGenes database and tested. Further analyses of 24 advanced breeding lines with different drought tolerances confirmed that five out of the 30 converted markers, as well as three out of the 31 additional SSR markers, were effective in marker-assisted selection for drought tolerance. The possible function of clones related to these markers in drought tolerance is discussed.

A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.

PubMed

Liu, Fan; Arias-Vásquez, Alejandro; Sleegers, Kristel; Aulchenko, Yurii S; Kayser, Manfred; Sanchez-Juan, Pascual; Feng, Bing-Jian; Bertoli-Avella, Aida M; van Swieten, John; Axenovich, Tatiana I; Heutink, Peter; van Broeckhoven, Christine; Oostra, Ben A; van Duijn, Cornelia M

2007-07-01

Alzheimer disease (AD) is the most common cause of dementia. We conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that is conducted in a recently isolated population from the southwestern area of The Netherlands. All patients and their 170 closely related relatives were genotyped using 402 microsatellite markers. Extensive genealogy information was collected, which resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees, to reduce the computational burden of linkage analysis. Simulations aiming to evaluate the effect of pedigree splitting on false-positive probabilities showed that a LOD score of 3.64 corresponds to 5% genomewide type I error. Multipoint analysis revealed four significant and one suggestive linkage peaks. The strongest evidence of linkage was found for chromosome 1q21 (heterogeneity LOD [HLOD]=5.20 at marker D1S498). Approximately 30 cM upstream of this locus, we found another peak at 1q25 (HLOD=4.0 at marker D1S218). These two loci are in a previously established linkage region. We also confirmed the AD locus at 10q22-24 (HLOD=4.15 at marker D10S185). There was significant evidence of linkage of AD to chromosome 3q22-24 (HLOD=4.44 at marker D3S1569). For chromosome 11q24-25, there was suggestive evidence of linkage (HLOD=3.29 at marker D11S1320). We next tested for association between cognitive function and 4,173 single-nucleotide polymorphisms in the linked regions in an independent sample consisting of 197 individuals from the GRIP region. After adjusting for multiple testing, we were able to detect significant associations for cognitive function in four of five AD-linked regions, including the new region on chromosome 3q22-24 and regions 1q25, 10q22-24, and 11q25. With use of cognitive function as an endophenotype of AD, our study indicates the that the RGSL2, RALGPS2, and C1orf49 genes are the potential disease-causing genes at 1q25. Our analysis of chromosome 10q22-24 points to the HTR7, MPHOSPH1, and CYP2C cluster. This is the first genomewide screen that showed significant linkage to chromosome 3q23 markers. For this region, our analysis identified the NMNAT3 and CLSTN2 genes. Our findings confirm linkage to chromosome 11q25. We were unable to confirm SORL1; instead, our analysis points to the OPCML and HNT genes.

Analysis of the discriminative methods for diagnosis of benign and malignant solitary pulmonary nodules based on serum markers.

PubMed

Wang, Wanping; Liu, Mingyue; Wang, Jing; Tian, Rui; Dong, Junqiang; Liu, Qi; Zhao, Xianping; Wang, Yuanfang

2014-01-01

Screening indexes of tumor serum markers for benign and malignant solitary pulmonary nodules (SPNs) were analyzed to find the optimum method for diagnosis. Enzyme-linked immunosorbent assays, an automatic immune analyzer and radioimmunoassay methods were used to examine the levels of 8 serum markers in 164 SPN patients, and the sensitivity for differential diagnosis of malignant or benign SPN was compared for detection using a single plasma marker or a combination of markers. The results for serological indicators that closely relate to benign and malignant SPNs were screened using the Fisher discriminant analysis and a non-conditional logistic regression analysis method, respectively. The results were then verified by the k-means clustering analysis method. The sensitivity when using a combination of serum markers to detect SPN was higher than that using a single marker. By Fisher discriminant analysis, cytokeratin 19 fragments (CYFRA21-1), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and breast cancer antigen (CA153), which relate to the benign and malignant SPNs, were screened. Through non-conditional logistic regression analysis, CYFRA21-1, SCC and CA153 were obtained. Using the k-means clustering analysis, the cophenetic correlation coefficient (0.940) obtained by the Fisher discriminant analysis was higher than that obtained with logistic regression analysis (0.875). This study indicated that the Fisher discriminant analysis functioned better in screening out serum markers to recognize the benign and malignant SPN. The combined detection of CYFRA21-1, CA125, SCC and CA153 is an effective way to distinguish benign and malignant SPN, and will find an important clinical application in the early diagnosis of SPN. © 2014 S. Karger GmbH, Freiburg.

[Impact of current approaches to laboratory screening of donated blood and its components on hepatitis B virus infection in patients with blood system diseases].

PubMed

Ignatova, E N; Tupoleva, T A; Ovchinnikova, E N; Romanova, T Yu; Yaroslavtseva, N G; Filatov, F P; Troitskaya, V V; Kuzmina, L A; Parovichnikova, E N; Gaponova, T V; Savchenko, V G

To evaluate the detection rate of markers for hepatitis B virus (HBV) in the blood samples taken from patients with blood system diseases, by applying the current approaches to examining donated blood and its components for markers of viral infections. The investigation included blood samples from patients with blood system diseases (n=364) and donors (n=5,011). The results of laboratory screening of donated blood samples (n=13,081) were retrospectively analyzed. Commercial kits of reagents were used for immunochemical assay and polymerase chain reaction. Patients with blood system diseases were recorded to have markers of active HBV infection in 12.6% of cases, anti-HBc in 31.3%, and anti-HBs in 37.6%. A retrospective analysis of the results of screening donated blood samples showed the presence of markers for active HBV infection in 0.28% of cases. A prospective examination of blood donors revealed markers of HBV infection in 4.83% of cases, including those of active forms in 0.54% and anti-HBc in 4.79%. The markers of active HBV infection in donors were only anti-HBc IgM in 0.42% of cases. The blood samples from donors with an anti-HBs titer of >200 mIU/ml contained anti-HBc IgM in 10.5%. In the last 5-7 years, the detection rate of markers of HBV infection in the blood samples of patients with blood system diseases have remained at a high level. Screening for decreed markers fails to identify people with inapparent infections among the donors. Even high anti-HBs concentrations in the donated blood may be a risk for HBV transmission by transfusion to a recipient.

EDRN Breast and Ovary Cancer CVC, Study 4: Phase 3 Validation of Ovarian Cancer Serum Markers in Preclinical WHI Samples — EDRN Public Portal

Cancer.gov

The WHI offers an opportunity to evaluate ovarian cancer markers and screening decision rules developed and validated in EDRN CVC Studies 2 and 3 in women who were not being screened. It is particularly well suited to validation of risk markers, since many serum samples were drawn well before clinical diagnosis of cancer in the WHI cohorts. A strategy is needed to identify from among the general population of women over the age of 50 those at high-risk for a diagnosis of ovarian/fallopian tube cancer so that they can be referred for appropriate surveillance, imaging or surgical consult. Tools to identify high-risk women will be investigated including serum markers CA125, HE4, MSLN, and MMP7 and epidemiologic risk factors. We will optimize decision rules using stored serum samples from the WHI OS and conduct a simulated prospective validation using stored serum samples from the WHI CT. Decision rules to select women for ovarian cancer screening will be investigated as well as decision rules for use in ovarian cancer screening.

Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis

PubMed Central

Thariani, Rahber; Henry, Norah Lynn; Ramsey, Scott D; Blough, David K; Barlow, Bill; Gralow, Julie R; Veenstra, David L

2014-01-01

Background Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. Aim To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II–III breast cancer survivors. Materials & methods We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3–6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. Results The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30–60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. Conclusion Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation. PMID:24236631

Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma.

PubMed

Anderson, Bradley W; Suh, Yun-Suhk; Choi, Boram; Lee, Hyuk-Joon; Yab, Tracy C; Taylor, William; Dukek, Brian A; Berger, Calise K; Cao, Xiaoming; Foote, Patrick H; Devens, Mary E; Boardman, Lisa A; Kisiel, John B; Mahoney, Douglas W; Slettedahl, Seth W; Allawi, Hatim T; Lidgard, Graham P; Smyrk, Thomas C; Yang, Han-Kwang; Ahlquist, David A

2018-05-29

Gastric adenocarcinoma (GAC) is the third most common cause of cancer mortality worldwide. Accurate and affordable non-invasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDMs) for GAC, validate their discrimination for GAC in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from GAC cases and normal controls. Following discovery by unbiased whole methylome sequencing, candidate MDMs were validated by blinded methylation-specific PCR in archival case-control tissues from U.S. and South Korean patients. Top MDMs were then assayed by an analytically sensitive method (quantitative real-time allele-specific target and signal amplification) in a blinded pilot study on archival plasma from GAC cases and normal controls. Whole methylome discovery yielded novel and highly discriminant candidate MDMs. In tissue, a panel of candidate MDMs detected GAC in 92-100% of U.S. and S. Korean cohorts at 100% specificity. Levels of most MDMs increased progressively from normal mucosa through metaplasia, adenoma, and GAC with variation in points of greatest marker acquisition. In plasma, a 3 marker panel ( ELMO1 , ZNF569 , C13orf18) detected 86% (95% CI 71-95%) of GACs at 95% specificity. Novel MDMs appear to accurately discriminate GAC from normal controls in both tissue and plasma. The point of aberrant methylation during oncogenesis varies by MDM, which may have relevance to marker selection in clinical applications. Further exploration of these MDMs for GAC screening and surveillance is warranted. Copyright ©2018, American Association for Cancer Research.

The electro-mechanical window in anaesthetized guinea pigs: a new marker in screening for Torsade de Pointes risk

PubMed Central

Guns, P-J; Johnson, DM; Van Op den bosch, J; Weltens, E; Lissens, J

2012-01-01

BACKGROUND AND PURPOSE QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A negative electro-mechanical (E-M) window has recently been proposed as an alternative risk marker for TdP in a canine LQT1 model. Here, we evaluated the E-M window in anaesthetized guinea pigs as a screening marker for TdP in humans. EXPERIMENTAL APPROACH The effects of various reference drugs and changes in body temperature on the E-M window were assessed in instrumented guinea pigs. The E-M window was defined as the delay between the duration of the electrical (QT interval) and mechanical (QLVPend) systole. KEY RESULTS Drugs with known TdP liability (quinidine, haloperidol, domperidone, terfenadine, thioridazine and dofetilide), but not those with no TdP risk in humans (salbutamol and diltiazem) consistently decreased the E-M window. Interestingly, drugs with known clinical QT prolongation, but with low risk for TdP (amiodarone, moxifloxacin and ciprofloxacin) did not decrease the E-M window. Furthermore, the E-M window was minimally affected by changes in heart rate or body temperature. CONCLUSIONS AND IMPLICATIONS A decreased E-M window was consistently observed with drugs already known to have high TdP risk, but not with drugs with low or no TdP risk. These results suggest that the E-M window in anaesthetized guinea pigs is a risk marker for TdP in humans. PMID:22122450

PLCO Ovarian Phase III Validation Study — EDRN Public Portal

Cancer.gov

Our preliminary data indicate that the performance of CA 125 as a screening test for ovarian cancer can be improved upon by additional biomarkers. With completion of one additional validation step, we will be ready to test the performance of a consensus marker panel in a phase III validation study. Given the original aims of the PLCO trial, we believe that the PLCO represents an ideal longitudinal cohort offering specimens for phase III validation of ovarian cancer biomarkers.

Gender disparities in screening for congenital hypothyroidism using thyroxine as a primary screen.

PubMed

DeMartino, Lenore; McMahon, Rebecca; Caggana, Michele; Tavakoli, Norma Parvin

2018-06-26

Newborn screening for congenital hypothyroidism (CH) is based on testing for the markers thyroxine (T4) and/or thyroid stimulating hormone (TSH). Diagnosis of CH is complicated because many factors affect the levels of these hormones including infant birth weight, prematurity, and age at specimen collection. We investigated whether the sex of the newborn affected the levels of T4 and TSH and consequently the outcome of newborn screening. In New York State, the Newborn Screening program initially tests all infants for T4 and any baby with a result in the lowest 10% is triaged for TSH screening. We analyzed data from 2008 to 2016 to determine mean and median T4 and TSH values and how these results correlate with the sex of infants who are reported as borderline, referred and confirmed with CH. T4 and TSH concentrations in dried blood spots were measured using commercially available fluoroimmunoassays. From 2008 to 2016, of the 2.4 million specimens tested for thyroxine, 51.5% were from male and 48.5% were from female infants. Male infants constituted 60% of specimens triaged for TSH testing, 64.9% of repeat requests and 59.6% of referrals, but only 49% of confirmed CH cases. The mean and median T4 values were lower (a difference of approximately 0.8-1.1 μg/dL each year), and the median TSH values were higher in male compared to female infants. Natural differences in thyroid hormone levels in male and female infants leads to male infants being disproportionately represented in the false positive category.

Newborn screening of metabolic disorders: recent progress and future developments.

PubMed

Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

2008-01-01

Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation.

Evaluation of Bovine Feces-Associated Microbial Source Tracking Markers and Their Correlations with Fecal Indicators and Zoonotic Pathogens in a Brisbane, Australia, Reservoir

PubMed Central

Sritharan, T.; Palmer, A.; Sidhu, J. P. S.; Toze, S.

2013-01-01

This study was aimed at evaluating the host specificity and host sensitivity of two bovine feces-associated bacterial (BacCow-UCD and cowM3) and one viral [bovine adenovirus (B-AVs)] microbial source tracking (MST) markers by screening 130 fecal and wastewater samples from 10 target and nontarget host groups in southeast Queensland, Australia. In addition, 36 water samples were collected from a reservoir and tested for the occurrence of all three bovine feces-associated markers along with fecal indicator bacteria (FIB), Campylobacter spp., Escherichia coli O157, and Salmonella spp. The overall host specificity values of the BacCow-UCD, cowM3, and B-AVs markers to differentiate between bovine and other nontarget host groups were 0.66, 0.88, and 1.00, respectively (maximum value of 1.00). The overall host sensitivity values of these markers, however, in composite bovine wastewater and individual bovine fecal DNA samples were 0.93, 0.90, and 0.60, respectively (maximum value of 1.00). Among the 36 water samples tested, 56%, 22%, and 6% samples were PCR positive for the BacCow-UCD, cowM3, and B-AVs markers, respectively. Among the 36 samples tested, 50% and 14% samples were PCR positive for the Campylobacter 16S rRNA and E. coli O157 rfbE genes, respectively. Based on the results, we recommend that multiple bovine feces-associated markers be used if possible for bovine fecal pollution tracking. Nonetheless, the presence of the multiple bovine feces-associated markers along with the presence of potential zoonotic pathogens indicates bovine fecal pollution in the reservoir water samples. Further research is required to understand the decay rates of these markers in relation to FIB and zoonotic pathogens. PMID:23417003

Prevalence of markers for HIV, hepatitis B and hepatitis C infection in UK military recruits.

PubMed

Brown, A E; Ross, D A; Simpson, A J H; Erskine, R S; Murphy, G; Parry, J V; Gill, O N

2011-08-01

An unlinked anonymous survey was conducted to measure the prevalence of selected markers for HIV, hepatitis B and C infection in recruits to the UK Armed Forces to inform future screening and hepatitis B vaccination policies. During 2007, nearly 14 000 left-over samples taken from new recruits for blood typing were collected, unlinked from identifiers and anonymously tested for HIV, hepatitis C and current and past cleared hepatitis B infection. Overall, serological evidence of HIV and hepatitis C was found in 0·06% and 0·06% of recruits, respectively. Evidence of past cleared and current hepatitis B infection was found in 3·63% and 0·37% of recruits, respectively. Overall, prevalence rates were broadly consistent with UK population estimates of infection. However, HIV and hepatitis B prevalence was higher in recruits of African origin than in those from the UK (P<0·0001). Screening for these infections is an option that could be considered for those entering Services from high-prevalence countries.

Uterine Artery Doppler in Screening for Preeclampsia and Fetal Growth Restriction.

PubMed

Pedroso, Marianna Amaral; Palmer, Kirsten Rebecca; Hodges, Ryan James; Costa, Fabricio da Silva; Rolnik, Daniel Lorber

2018-05-01

 To perform a comprehensive review of the current evidence on the role of uterine artery Doppler, isolated or in combination with other markers, in screening for preeclampsia (PE) and fetal growth restriction (FGR) in the general population. The review included recently published large cohort studies and randomized trials.  A search of the literature was conducted using Medline, PubMed, MeSH and ScienceDirect. Combinations of the search terms "preeclampsia," "screening," "prediction," "Doppler," "Doppler velocimetry," "fetal growth restriction," "small for gestational age" and "uterine artery" were used. Articles in English (excluding reviews) reporting the use of uterine artery Doppler in screening for PE and FGR were included.  Thirty articles were included. As a single predictor, uterine artery Doppler detects less than 50% of the cases of PE and no more than 40% of the pregnancies affected by FGR. Logistic regression-based models that allow calculation of individual risk based on the combination of multiple markers, in turn, is able to detect ∼ 75% of the cases of preterm PE and 55% of the pregnancies resulting in small for gestational age infants.  The use of uterine artery Doppler as a single predictive test for PE and FGR has poor accuracy. However, its combined use in predictive models is promising, being more accurate in detecting preterm PE than FGR. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Influence of gravidity and foetal gender on the value of screening variables in the first trimester of pregnancy.

PubMed

Illescas, Tamara; Fernández, Cristina; Ortega, Dolores; de la Puente, Miriam; Coronado, Pluvio; Montalvo, Joaquín

2013-03-01

Combined screening for chromosome abnormalities in the first trimester of pregnancy is based on maternal age, nuchal translucency (NT) and biochemical markers (PAPP-A and free β-hCG). We sought to assess the value of the variables used in the combined screening strategy taking into account maternal gravidity and foetal gender. Between July 1999 and December 2009, a total of 21,193 singleton pregnancies were screened for aneuploidy in the first trimester, in the Hospital Clínico San Carlos (Madrid, Spain). In the original database foetal gender data were available in 4370 euploid cases, and there were 2343 women with at least two consecutive pregnancies. We conducted a retrospective assessment of ultrasound and biochemical markers taking into account foetal gender and maternal gravidity, and evaluated the effect on the performance of screening, in terms of detection rates and false positive rates. Information on pregnancy outcome was obtained from the hospital's intranet medical records or by contacting the patient by telephone postpartum. Karyotype was ascertained by amniocentesis or chorionic villus sampling, and euploid status was assumed in newborns with normal phenotype. Student's t-tests (paired or unpaired as appropriate) were applied to the data, and the Bland-Altmann method was applied in evaluating individual differences in markers between successive gestations. PAPP-A decreased significantly between the first and the second pregnancy (p<0.01). PAPP-A and free β-hCG values were significantly higher (p=0.04 and p<0.01 respectively) and NT was lower (p=0.02) in pregnancies with a female foetus. Correlations between the biochemical variables in relation to gravidity and foetal gender can introduce a bias in the calculated risk of chromosome abnormalities. Differences in NT measurements with respect to foetal gender do not seem to be of clinical importance. NT is independent of gravidity so routine use of NT compensates for the influence of these maternal-foetal variables on the values of biochemical parameters. Hence, the bias in overall combined screening is small. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

PubMed

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-04-14

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

PubMed Central

Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-01-01

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma. PMID:24744577

Safety of blood supply in the Caribbean countries: role of screening blood donors for markers of hepatitis B and C viruses.

PubMed

Cruz, Jose R; Pérez-Rosales, Maria Dolores; Zicker, Fabio; Schmunis, Gabriel A

2005-12-01

Blood transfusions carry risks of untoward reactions, including the transmission of infections, such as hepatitis B and C. Proper blood donor recruitment and selection, and adequate laboratory screening for infectious markers diminish the risk of transfusion-transmitted infections. To estimate the potential risk of acquiring transfusion-transmitted infections by hepatitis B or hepatitis C in 24 Caribbean countries during the period of 1996 to 2003. Official national reports for 1996, 2000-2003 of the yearly number of blood donors, screening coverage, and prevalence of serological markers for infectious diseases were used to estimate the risk of patients receiving an HBV- or HCV-positive unit of blood, and of developing an infection after receiving a positive unit. Estimates of number of infections transmitted through transfusion and number of infections prevented by screening of blood were also obtained. During the period analyzed, HBV screening coverage among blood donors was 100% in all countries with the exception of Grenada (0% in 1996) and Saint Lucia (99.5% in 2002). For HCV, only 10 countries reported universal screening in 1996, while 15 did in 2003. The number of countries that did not screen any units for HCV decreased from 11 in 1996 to five in 2003. In general, high prevalence rates of HBV (10-75 per 1000 donors) and HCV (7-19.3 per 1000 donors) markers were found in the majority of countries. We estimated that 235 infections by HCV (1:12471 donations) and two infections by HBV (1:1465373) were transmitted through transfusion because of lack of screening. On the other hand, screening of blood for transfusion prevented 21 005 HCV and 22 100 HBV infections. Blood donor recruitment and coverage of screening for transfusion-transmitted infections, especially HCV, must be improved in the Caribbean countries.

Recognition of Naegleriae ameba surface protein epitopes by anti-human CD45 antibodies.

PubMed

Ravine, Terrence J; Polski, Jacek M; Jenkins, James

2010-04-01

Phagocytosis is a highly conserved mechanism exhibited by both free-living amebas and mammalian blood cells. Similarities demonstrated by either cell type during engulfment of the same bacterial species may imply analogous surface proteins involved in receptor-mediated endocytosis. The increased availability of anti-human leukocyte antibodies or clusters of differentiation (CD) markers used in conjunction with flow cytometric (FCM) and/or immunohistochemical (IHC) analysis provides investigators with a relatively easy method to screen different cell populations for comparable plasma membrane proteins. In this study, we incubated Naegleria and Acanthamoeba amebas with several directly conjugated anti-human leukocyte monoclonal antibodies (mAb) for similarly recognized amebic epitopes. CD marker selection was based upon a recognized role of each mAb in phagocyte activation and/or uptake of bacteria. These included CD14, CD45, and CD206. In FCM, only one CD45 antibody demonstrated strong reactivity with both Naegleria fowleri and Naegleria gruberi that was not expressed in similarly tested Acanthamoeba species. Additional testing of N. gruberi by IHC demonstrated reactivity to a different CD45 antibody. Our results suggest a possible utility of using anti-human leukocyte antibodies to screen amebic cells for similarly expressed protein epitopes. In doing so, several important items must be considered when selecting potential mAbs for testing to increase the probability of a positive result.

Tumour marker measurements in the diagnosis and monitoring of breast cancer.

PubMed

Cheung, K L; Graves, C R; Robertson, J F

2000-04-01

Elevation of established blood tumour markers correlates with the stage of breast cancer. The major role of current blood markers is therefore in the diagnosis and monitoring of metastatic disease. A combination of markers is better than a single marker with the most widely adopted combination being CEA and one MUC1 mucin, commonly detected as either CA15.3 or CA27.29. Tumour marker measurement is now used as a complementary test in the diagnosis of symptomatic metastases. In the monitoring of therapeutic response to both endocrine and cytotoxic therapies in advanced disease, biochemical assessment using blood markers not only correlates with conventional UICC criteria but has a lot of advantages which make it a potentially superior way of assessment. In this regard, CA15.3, CEA and ESR are the best validated combination. Studies are ongoing to evaluate the use of sequential blood tumour marker measurements in the follow-up of patients after treatment for their primary breast cancer, in terms of both early detection and early therapeutic intervention. Further randomized studies are also required to ascertain that marker-directed therapy is superior to the current practice for metastatic disease. In line with clinical studies, intensive laboratory work is being carried out to optimize the use of blood markers in advanced disease as well as to exploit their use in screening and diagnosis of early primary breast cancer.

Surveillance and monitoring in breast cancer survivors: maximizing benefit and minimizing harm.

PubMed

Jochelson, Maxine; Hayes, Daniel F; Ganz, Patricia A

2013-01-01

Although the incidence of breast cancer has increased, breast cancer mortality has decreased, likely as a result of both breast cancer screening and improved treatment. There are well over two million breast cancer survivors in the United States for whom appropriate surveillance continues to be a subject of controversy. The guidelines from the American Society of Clinical Oncology (ASCO) and the American College of Physicians are clear: only performance of yearly screening mammography is supported by evidence. Although advanced imaging technologies and sophisticated circulating tumor biomarker studies are exquisitely sensitive for the detection of recurrent breast cancer, there is no proof that earlier detection of metastases will improve outcome. A lack of specificity may lead to more tests and patient anxiety. Many breast cancer survivors are not followed by oncologists, and their doctors may not be familiar with these recommendations. Oncologists also disregard the data. A plethora of both blood tests and nonmammographic imaging tests are frequently performed in asymptomatic women. The blood tests, marker studies, and advanced imaging techniques are expensive and, with limited health care funds, may prevent funding for more appropriate aspects of patient care. Abnormal marker studies lead to additional imaging procedures. Repeated CT scans and radionuclide imaging may induce a second cancer because of the radiation dose, and invasive procedures performed as a result of these examinations also add risk to patients without clear benefits. Improved adherence to the current guidelines can cut costs, reduce risks, and improve patient quality of life without adversely affecting outcome.

Screening for prodromal Parkinson's disease in the general community: a sleep-based approach.

PubMed

Postuma, Ronald B; Pelletier, Amelie; Berg, Daniela; Gagnon, Jean-Francois; Escudier, Frédérique; Montplaisir, Jacques

2016-05-01

Neuroprotective therapy for Parkinson's disease (PD) is most likely to be effective if provided in its prodromal stages. However, identifying prodromal PD is difficult because PD is relatively uncommon, and most markers are nonspecific. Rapid eye movement (REM) sleep behavior disorder (RBD) is by far the strongest clinical marker of prodromal PD, but most patients do not seek out medical attention. Developing an efficient way of diagnosing RBD from the general community may be the most practical method to detect prodromal PD. We developed a screening strategy that began with a newspaper advertisement containing a single-question screen for RBD. All screen-positive subjects underwent an interview based on the Innsbruck RBD inventory aimed to optimize the positive predictive value. Those who passed both screens underwent confirmatory polysomnography. The proportion of screened RBD patients who met the International Parkinson and Movement Disorder Society (MDS) criteria for prodromal PD was assessed. A broad array of clinical markers of neurodegeneration was compared between newspaper-screened RBD patients and 130 RBD patients clinically referred to the sleep center. Of 111 RBD-screen-positive participants, 40 (36%) passed the secondary screen, and 29 underwent full polysomnography. Of these 29 patients, 19 were ultimately proven to have RBD (PPV = 66%), 12 (63%) of whom met the criteria for prodromal PD. Compared to patients referred to the sleep center, newspaper-screened patients had similar age, sex, olfaction, autonomic function, and color vision. However, motor and cognitive assessments were slightly better in newspaper-screened patients. A multistep screening approach using RBD screening questionnaires and telephone follow-up can efficiently identify prodromal PD in the general community. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of novel microsatellite markers for Holothurian scabra (Holothuriidae), Apostichopus japonicas (Stichopodidae) and cross-species testing in other sea cucumbers

NASA Astrophysics Data System (ADS)

Shangguan, Jingbo; Li, Zhongbao

2017-06-01

Thirty-five new microsatellite loci from the sea cucumbers Holothurian scabra (Jaeger, 1833) and Apostichopus japonicas (Selenka, 1867) were screened and characterized using the method of magnetic bead enrichment. Of the twenty-four polymorphic loci tested, eighteen were consistent with Hardy-Weinberg equilibrium after a modified false discovery rate (B-Y FDR) correction, whereas six showed statistically significant deviations (CHS2 and CHS11: P <0.014790; FCS1, FCS6, FCS8 and FCS14: P <0.015377). Furthermore, four species of plesiomorphous and related sea cucumbers (Holothurian scabra, Holothuria leucospilota, Stichopus horrens and Apostichopus japonicas) were tested for mutual cross-amplification using a total of ninety microsatellite loci. Although transferability and universality of all loci were generally low, the results of the cross-species study showed that the markers can be applied to identify individuals to species according to the presence or absence of specific microsatellite alleles. The microsatellite markers reported here will contribute to the study of genetic diversity, assisted breeding, and population conservation in sea cucumbers, as well as allow for the identification of individuals to closely related species.

Development of novel microsatellite markers for Holothurian scabra (Holothuriidae), Apostichopus japonicas (Stichopodidae) and cross-species testing in other sea cucumbers

NASA Astrophysics Data System (ADS)

Shangguan, Jingbo; Li, Zhongbao

2018-03-01

Thirty-five new microsatellite loci from the sea cucumbers Holothurian scabra (Jaeger, 1833) and Apostichopus japonicas (Selenka, 1867) were screened and characterized using the method of magnetic bead enrichment. Of the twenty-four polymorphic loci tested, eighteen were consistent with Hardy-Weinberg equilibrium after a modified false discovery rate (B-Y FDR) correction, whereas six showed statistically significant deviations (CHS2 and CHS11: P<0.014 790; FCS1, FCS6, FCS8 and FCS14: P<0.015 377). Furthermore, four species of plesiomorphous and related sea cucumbers ( Holothurian scabra, Holothuria leucospilota, Stichopus horrens and Apostichopus japonicas) were tested for mutual cross-amplification using a total of ninety microsatellite loci. Although transferability and universality of all loci were generally low, the results of the cross-species study showed that the markers can be applied to identify individuals to species according to the presence or absence of specific microsatellite alleles. The microsatellite markers reported here will contribute to the study of genetic diversity, assisted breeding, and population conservation in sea cucumbers, as well as allow for the identification of individuals to closely related species.

Heterogeneity of heat-resistant proteases from milk Pseudomonas species.

PubMed

Marchand, Sophie; Vandriesche, Gonzalez; Coorevits, An; Coudijzer, Katleen; De Jonghe, Valerie; Dewettinck, Koen; De Vos, Paul; Devreese, Bart; Heyndrickx, Marc; De Block, Jan

2009-07-31

Pseudomonas fragi, Pseudomonas lundensis and members of the Pseudomonas fluorescens group may spoil Ultra High Temperature (UHT) treated milk and dairy products, due to the production of heat-stable proteases in the cold chain of raw milk. Since the aprX gene codes for a heat-resistant protease in P. fluorescens, the presence of this gene has also been investigated in other members of the genus. For this purpose an aprX-screening PCR test has been developed. Twenty-nine representatives of important milk Pseudomonas species and thirty-five reference strains were screened. In 42 out of 55 investigated Pseudomonas strains, the aprX gene was detected, which proves the potential of the aprX-PCR test as a screening tool for potentially proteolytic Pseudomonas strains in milk samples. An extensive study of the obtained aprX-sequences on the DNA and the amino acid level, however, revealed a large heterogeneity within the investigated milk isolates. Although this heterogeneity sets limitations to a general detection method for all proteolytic Pseudomonas strains in milk, it offers a great potential for the development of a multiplex PCR screening test targeting individual aprX-genes. Furthermore, our data illustrated the potential use of the aprX gene as a taxonomic marker, which may help in resolving the current taxonomic deadlock in the P. fluorescens group.

Down syndrome screening in assisted conception twins: an iatrogenic medical challenge.

PubMed

Ben-Ami, Ido; Maymon, Ron; Svirsky, Ran; Cuckle, Howard; Jauniaux, Eric

2013-11-01

The objective of this study was to provide a critical analysis of the impact of assisted conception on prenatal screening for Down syndrome (DS) in twin pregnancies and the value of various screening modalities for early detection of anomalies. The literature was searched using PubMed and the Cochrane Library focusing on prenatal screening and antenatal care of assisted-conception twin pregnancies. Serum screening alone is of limited value in detecting aneuploid twins, because the unaffected cotwin can "mask" the abnormal serum results of an affected one. In addition, this test can designate the pregnancy as at high risk but not identify the affected fetus. Nuchal translucency (NT) screening is the best available modality and a highly effective screening method for twin pregnancies. Among twins, NT alone has a 69% DS detection rate, first-trimester combined NT and serum biochemistry has a 72% DS detection rate, and an integrated screen will have an 80% DS detection rate at a 5% FPR. The data in the literature concerning the effect of assisted conception on maternal serum screening markers in twin pregnancies are scarce. Down syndrome screening in assisted-conception twins presents clinical and technical challenges. Therefore, assisted-conception twins need close monitoring from conception to delivery, by a practitioner familiar with the available screening modalities and their relative accuracy.

Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California

ERIC Educational Resources Information Center

Windham, Gayle C.; Lyall, Kristen; Anderson, Meredith; Kharrazi, Martin

2016-01-01

We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD…

OS090. Performance of candidate clinical and biochemical markers in screening early in pregnancy to detect women at high risk to develop preeclampsia.

PubMed

Forest, J-C; Massé, J; Bujold, E; Rousseau, F; Charland, M; Thériault, S; Lafond, J; Giguère, Y

2012-07-01

The advent of early preventive measures, such as low-dose aspirin targeting women at high risk of preeclampsia (PE), emphasizes the need for better detection. Despite the emergence of promising biochemical markers linked to the pathophysiological processes, systematic reviews have shown that, until now, no single tests fulfill the criteria set by WHO for biomarkers to screen for a disease. However, recent literature reveals that by combining various clinical, biophysical and biochemical markers into multivariate algorithms, one can envisage to estimate the risk of PE with a performance that would reach clinical utility and cost-effectiveness, but this remains to be demonstrated in various environments and health care settings. To investigate, in a prospective study, the clinical utility of candidate biomarkers and clinical data to detect, early in pregnancy, women at risk to develop PE and to propose a multivariate prediction algorithm combining clinical parameters to biochemical markers. 7929 pregnant women prospectively recruited at the first prenatal visit, provided blood samples, clinical and sociodemographic information. 214 pregnant women developed hypertensive disorders of pregnancy (HDP) of which 88 had PE (1.2%), including 44 with severe PE (0.6%). A nested case-control study was performed including for each case of HDP two normal pregnancies matched for maternal age, gestational age at recruitment, ethnicity, parity, and smoking status. Based on the literature we selected the most promising markers in a multivariate logistic regression model: mean arterial pressure (MAP), BMI, placental growth factor (PlGF), soluble Flt-1, inhibin A and PAPP-A. Biomarker results measured between 10-18 weeks gestation were expressed as multiples of the median. Medians were determined for each gestational week. When combined with MAP at the time of blood sampling and BMI at the beginning of pregnancy, the four biochemical markers discriminate normal pregnancies from those with HDP. At a 5% false positive rate, 37% of the affected pregnancies would have been detected. However, considering the prevalence of HDP in our population, the positive predictive value would have been only 15%. If all the predicted positive women would have been proposed a preventive intervention, only one out 6.7 women could have potentially benefited. In the case of severe PE, performance was not improved, sensitivity was the same, but the positive predictive value decreased to 3% (lower prevalence of severe PE). In our low-risk Caucasian population, neither individual candidate markers nor multivariate risk algorithm using an a priori combination of selected markers reached a performance justifying implementation. This also emphasizes the necessity to take into consideration characteristics of the population and environment influencing prevalence before promoting wide implementation of such screening strategies. In a perspective of personalized medicine, it appears more than ever mandatory to tailor recommendations for HDP screening according not only to individual but also to population characteristics. Copyright © 2012. Published by Elsevier B.V.

Development of novel microsatellite markers for the Northern Goshawk (Accipiter gentilis) and their utility in cross-species amplification

USGS Publications Warehouse

Haughey, Christy; Sage, George K.; Degange, Gabriel; Sonsthagen, Sarah A.; Talbot, Sandra L.

2016-01-01

The Northern Goshawk (Accipiter gentilis) is a large forest raptor with a Holarctic distribution and, in some portions of its range, a species of conservation concern. To augment previously reported genetic markers, 13 novel polymorphic microsatellite markers were developed to establish individual identification and familial relationships, to assess levels of genetic diversity, and to identify diagnostic markers. Of the 22 loci tested, 13 were polymorphic, seven were monomorphic, and two failed to amplify. This suite of microsatellite loci yielded a combined probability of parental exclusion of 98%; a single individual sampled from a North American population can be reliably identified using a combination of seven of the 13 polymorphic loci. Cross-species screening in Cooper's Hawks (A. cooperii) and Sharp-shinned Hawks (A. striatus) of the 20 loci that successfully amplified in Northern Goshawks identified 13 loci as polymorphic in each species. Six of these loci (Age1303, Age1308, Age1309, Age1312, and Age1314) appeared to be useful in distinguishing between Accipiter species. These markers will be useful to researchers investigating populations of North American accipiters.

Screening white spot syndrome virus (WSSV)-resistant molecular markers from Fenneropenaeus chinensis

NASA Astrophysics Data System (ADS)

Wu, Yingying; Meng, Xianhong; Kong, Jie; Luan, Sheng; Luo, Kun; Wang, Qingyin; Zheng, Yongyun

2017-02-01

White spot syndrome virus (WSSV)-resistant molecular markers were screened from the selectively bred new variety `Huanghai No. 2' of Fenneropenaeus chinensis using unlabeled-probe high-resolution melting (HRM) technique. After the artificial infection with WSSV, the first 96 dead shrimps and the last 96 surviving shrimps were collected, representing WSSV-susceptible and -resistant populations, respectively. The genotypes at well-developed 39 single nucleotide polymorphisms (SNPs) loci were obtained. As revealed in the Chi-square test, 3 SNPs, genotype A/A of contig C364-89AT, genotype A/A of C2635-527CA and genotype C/T of contig C12355-592CT, were positively correlated with disease-resistance traits. Other 2 SNPs, genotype G/G of contig C283-145AG and genotype C/C of contig C12355-592CT, were negatively correlated. Moreover, analysis with BlastX program for disease-resistant SNPs indicated that 3 contigs, Contig283, Contig364 and Contig12355, matched to the functional genes of effector caspase of Penaeus monodon, peptide transporter family 1-like protein, and 40S ribosomal protein S2 of Perca flavescens with high sequence similarity. The results will be helpful to provide theoretical and technical supports for molecular marker-assisted selective breeding of F. chinensis.

[Construction and Function Verification of a Novel Shuttle Vector Containing a Marker Gene Self-deletion System].

PubMed

Li, Lili; Wang, Zhan; Zhou, Yubai; Zhang, Fang; Shen, Sisi; Li, Zelin; Zeng, Yi

2015-09-01

For rapid and accurate screening of recombinant modified vaccinia virus Ankara (rMVA) that satisfied the quality standards of clinical trials, a novel shuttle vector that can delete the marker gene automatically during virus propagation was construted: pZL-EGFP. To construct the pZL-EGFP, the original shuttle vector pSC11 was modified by replacing the LacZ marker gene with enhanced green fluorescent protein (EGFP) and then inserting homologous sequences of TKL into the flank regions of EGFP. Baby hamster kidney (BHK)-21 cells were cotransfected with pZL-EGFP and MVA, and underwent ten passages and one plaque screening to obtain the EGFP-free rMVA carrying the exogenous gene. Resulting rMVA was tested by polymerase chain reaction and western blotting to verify pZL-EGFP function. A novel shuttle vector pZL-EGFP containing an EGFP marker gene which could be deleted automatically was constructed. This gene deletion had no effect on the activities of rMVA, and the exogenous gene could be expressed stably. These results suggest that rMVA can be packaged efficiently by homologous recombination between pZL-EGFP and MVA in BHK-21 cells, and that the carried EGFP gene can be removed automatically by intramolecular homologous recombination during virus passage. Meanwhile, the gene deletion had no influence on the activities of rMVA and the expression of exogenous target gene. This study lays a solid foundation for the future research.

Screening mosaic F1 females for mutations affecting zebrafish heart induction and patterning.

PubMed

Alexander, J; Stainier, D Y; Yelon, D

1998-01-01

The genetic pathways underlying the induction and anterior-posterior patterning of the heart are poorly understood. The recent emergence of the zebrafish model system now allows a classical genetic approach to such challenging problems in vertebrate development. Two large-scale screens for mutations affecting zebrafish embryonic development have recently been completed; among the hundreds of mutations identified were several that affect specific aspects of cardiac morphogenesis, differentiation, and function. However, very few mutations affecting induction and/or anterior-posterior patterning of the heart were identified. We hypothesize that a directed approach utilizing molecular markers to examine these particular steps of heart development will uncover additional such mutations. To test this hypothesis, we are conducting two parallel screens for mutations that affect either the induction or the anterior-posterior patterning of the zebrafish heart. As an indicator of cardiac induction, we examine expression of nkx2.5, the earliest known marker of precardiac mesoderm; to assess anterior-posterior patterning, we distinguish ventricle from atrium with antibodies that recognize different myosin heavy chain isoforms. In order to expedite the examination of a large number of mutations, we are screening the haploid progeny of mosaic F1 females. In these ongoing screens, we have identified four mutations that affect nkx2.5 expression as well as 21 that disrupt either ventricular or atrial development and thus far have recovered several of these mutations, demonstrating the value of our approach. Future analysis of these and other cardiac mutations will provide further insight into the processes of induction and anterior-posterior patterning of the heart.

Pain as a confounding factor in postnatal depression screening.

PubMed

Jardri, Renaud; Maron, Michel; Delion, Pierre; Thomas, Pierre

2010-12-01

Postnatal depression (PND) is one of the most serious complications following delivery in developed countries today. Thus, early screening strategies by first-line healthcare workers are of primary importance. Pain following childbirth has been proposed as a possible risk-marker for later depressive disorder. We tested this assumption and explored the possible link between pain and overestimation of PND risk in routine clinical screenings. We assessed 320 women between the third and fifth day after delivery as well as at 8 weeks post-partum (PP). Midwives were asked to evaluate the risk of later PND upon discharge from the maternity unit; additionally, pain measurements were obtained using the Visual Analogic Scale (VAS) over the same time period. A stepwise logistic regression analysis was performed to identify the risk markers linked to a positive depressive disorder diagnosis (according to the MINI-DSM-IV) at 8 weeks PP. Multivariate risk analysis showed no statistical link between physical pain shortly after childbirth and subsequent PND diagnosis at 8 weeks PP. However, VAS measurements for pain were significantly higher for women that the midwives estimated to be at risk for PND (|Z| = 2.78, p = 0.005), suggesting the routine clinical screening for PND is susceptible for false-positives. Psychiatrists should encourage midwives to have an empathetic approach, to increase the detection as well as treatment of mental and physical suffering in early postpartum. At the same time, adequate education programmes for early PND screening should be proposed to non-psychiatric staffs to demonstrate that women at risk of PND often show minimal physical symptoms.

Survey of South African fruit juices using a fast screening HILIC-MS method.

PubMed

Stander, Marietjie A; Kühn, Wernich; Hiten, Nicholas F

2013-01-01

Adulteration of fruit juices--by the addition of sugar or other less expensive fruit juices as well as preservatives, artificial sweeteners and colours--was tested for by using a developed screening method. The method employs hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) using electrospray ionisation in the negative mode and ultraviolet light detection. Different fruit juices can be differentiated by the content of marker compounds like sorbitol, certain phenolic molecules and their saccharide profile. This method was used to test 46 fruit juice samples from the retail market as well as 12 control samples. The study focused on the main types of fruit juices consumed on the South African market including apple, orange, grape and blends of these juices with other fruits like mango, pear and guava. Overall, the 46 samples tested mostly agreed with label claims. One grape juice sample was adulterated, probably with apple juice. Natamycin above the legal limits was found in two samples. In addition, two samples contained natamycin and one sample benzoate without it being indicated on the label. The method is well suited as a quick screening method for fruit juice adulteration and if used routinely would reduce fruit juice adulteration without the cost of the current array of tests needed for authenticity testing.

Using lessons from breast, cervical, and colorectal cancer screening to inform the development of lung cancer screening programs.

PubMed

Armstrong, Katrina; Kim, Jane J; Halm, Ethan A; Ballard, Rachel M; Schnall, Mitchell D

2016-05-01

Multiple advisory groups now recommend that high-risk smokers be screened for lung cancer by low-dose computed tomography. Given that the development of lung cancer screening programs will face many of the same issues that have challenged other cancer screening programs, the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium was used to identify lessons learned from the implementation of breast, cervical, and colorectal cancer screening that should inform the introduction of lung cancer screening. These lessons include the importance of developing systems for identifying and recruiting eligible individuals in primary care, ensuring that screening centers are qualified and performance is monitored, creating clear communication standards for reporting screening results to referring physicians and patients, ensuring follow-up is available for individuals with abnormal test results, avoiding overscreening, remembering primary prevention, and leveraging advances in cancer genetics and immunology. Overall, this experience emphasizes that effective cancer screening is a multistep activity that requires robust strategies to initiate, report, follow up, and track each step as well as a dynamic and ongoing oversight process to revise current screening practices as new evidence regarding screening is created, new screening technologies are developed, new biological markers are identified, and new approaches to health care delivery are disseminated. Cancer 2016;122:1338-1342. © 2016 American Cancer Society. © 2016 American Cancer Society.

Comparison of candidate vCJD in vitro diagnostic assays using identical sample sets.

PubMed

Cooper, J K; Ladhani, K; Minor, P

2012-02-01

With four transfusion related transmissions of variant Creutzfeldt-Jakob Disease (vCJD), three of which developed clinical disease and the other died of other causes but was positive for markers of infection, there is an increased urgency to identify and implement a test for blood donor screening. With limited amounts of blood samples from vCJD cases available test evaluation is challenging. Alternative approaches are therefore needed. Control and vCJD tissues homogenates, where levels of markers of infectivity are known, were sequentially diluted in pooled human plasma. Identical sets of samples were provided blind to research groups developing diagnostic tests for vCJD; identical sample sets allows for direct comparisons of sensitivity to be made. Control and vCJD tissue homogenates were sequentially diluted in pooled human plasma (detergent solvent treated or cryo-depleted) supplied by commercial fractionators. Dilutions of vCJD tissues were within and beyond the limits of detection previously determined by the conformation-dependent immunoassay (Cooper et al.: Vox Sang 2007;92:302-310; Bellon et al.: J Gen Virol 2003;84: 1921-1925). A number of methods were used for the analysis of the blinded panels; with background signal from the normal prion protein (PrP) being removed by digestion with proteinase, epitope protection or selective capture of PrP(tse). Assay sensitivities were directly compared using identical sample sets. This approach identified several transmissible spongiform encephalopathies (TSE) diagnostic tests, based on different principles, high in analytical sensitivity that reproducibly detected markers of vCJD infectivity in tissue homogenates. The approach outlined has successfully compared in vitro diagnostics assays for their sensitivity and reproducibility and is a first step toward the evaluation of an assay suitable for blood donor screening/diagnosis of vCJD. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

Addressing the challenges of chronic viral infections and addiction in prisons: the PRODEPIST study.

PubMed

Jacomet, Christine; Guyot-Lénat, Angeline; Bonny, Corinne; Henquell, Cécile; Rude, Morgane; Dydymski, Sylviane; Lesturgeon, Jean-Alexandre; Lambert, Céline; Pereira, Bruno; Schmidt, Jeannot

2016-02-01

In 2010 only 30.9%, of the Puy-de-Dome prison detainees were screened for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV). Our goal was then to promote these assesments, as well as to identify addictive behaviour using FAGERSTROM, Cannabis Abuse Screening Test and CAGE tests, diagnose fibrosis by means of Fibrometer or Fibroscan in hepatic virus carriers and heavy drinkers, and perform HBV vaccinations. This prospective study of adult detainees in the prisons of Puy-de-Dome, France, took place from June 2012 to December 2013. Of the 702 incarcerated individuals, 396(56.4%) were screened and 357(50.9%) enrolled. HIV prevalence was 0.3%, HCV 4.7% and HBV 0.6%. While 234/294(79.6%) smokers and 115/145(79.3%) cannabis users were screened for dependence, excessive alcohol consumption was tested for in 91/179(50.8%) cases. Fibrosis was screened for in 75/80(93.7%) individuals selected with 16.0% presenting with moderate to severe fibrosis, 4/9(44.4%) HCV carriers and 8/65(12.3%) excessive alcohol consumers. HBV vaccination was given to 81/149(54.4%) individuals with no serological markers. A total of nine HIV tests were conducted at the 57 discharge consultations, involving 215 detainees being released, all of which were negative. The promotion of these evaluations proved beneficial, although viral screening could be achieved for only approaching half of the detainees, as could alcohol consumption assessment and HBV vaccination for those concerned. Fibrosis screening revealed lesions in HCV carriers yet also in heavy drinkers, who are typically less likely to be assessed. Consultations and HIV screening on release were found to be rarely possible. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

The effect of fetal gender on second-trimester maternal serum inhibin-A concentration.

PubMed

Lam, Y H; Tang, M H

2001-08-01

Second-trimester serum inhibin-A is increasingly used as a fourth marker in addition to the triple test to screen for Down syndrome. We investigated whether fetal gender had an effect on serum inhibin-A concentration. A retrospective analysis was done on 316 normal pregnancies and 48 Down syndrome pregnancies in which maternal serum inhibin-A assays were performed between 15 and 20 weeks of gestation and in which the fetal sex was known. The median inhibin-A MoM (95% CI) for normal pregnancies in the presence of a male fetus was 0.93 (range 0.88-1.03). This was significantly lower than that in the presence of a female fetus (median MoM=1.04). The gender difference was not observed in the Down syndrome pregnancies. The increased inhibin-A concentration would lead to a 2.3-fold higher false-positive rate in the presence of a female fetus (10.6% vs. 4.6%; p<0.05, Chi-square test). Because of the small number of cases studied, the results need to be substantiated by a larger series. If the gender effect is confirmed, adjustment for fetal sex may be necessary when inhibin-A is used as a screening marker. Copyright 2001 John Wiley & Sons, Ltd.

Elastic-net regularization approaches for genome-wide association studies of rheumatoid arthritis.

PubMed

Cho, Seoae; Kim, Haseong; Oh, Sohee; Kim, Kyunga; Park, Taesung

2009-12-15

The current trend in genome-wide association studies is to identify regions where the true disease-causing genes may lie by evaluating thousands of single-nucleotide polymorphisms (SNPs) across the whole genome. However, many challenges exist in detecting disease-causing genes among the thousands of SNPs. Examples include multicollinearity and multiple testing issues, especially when a large number of correlated SNPs are simultaneously tested. Multicollinearity can often occur when predictor variables in a multiple regression model are highly correlated, and can cause imprecise estimation of association. In this study, we propose a simple stepwise procedure that identifies disease-causing SNPs simultaneously by employing elastic-net regularization, a variable selection method that allows one to address multicollinearity. At Step 1, the single-marker association analysis was conducted to screen SNPs. At Step 2, the multiple-marker association was scanned based on the elastic-net regularization. The proposed approach was applied to the rheumatoid arthritis (RA) case-control data set of Genetic Analysis Workshop 16. While the selected SNPs at the screening step are located mostly on chromosome 6, the elastic-net approach identified putative RA-related SNPs on other chromosomes in an increased proportion. For some of those putative RA-related SNPs, we identified the interactions with sex, a well known factor affecting RA susceptibility.

First-trimester maternal serum human chorionic gonadotrophin as a marker for fetal chromosomal disorders. The Dutch Working Party on Prenatal Diagnosis.

PubMed

Van Lith, J M

1992-06-01

The Dutch Working Party on Prenatal Diagnosis has initiated a study on the possibilities of first-trimester screening for fetal chromosomal disorders. We report on maternal serum human chorionic gonadotrophin (MS-hCG) measurements in 1348 pregnancies with a chromosomally normal fetus and 53 pregnancies with a chromosomally abnormal fetus. The median MS-hCG concentration in 24 pregnancies with Down's syndrome was 1.19 multiples of the normal median (MoM). The MS-hCG distributions in normal and Down's syndrome pregnancies did not differ significantly (t-test: t = 1.945, p greater than 0.05). We also found no difference between normal pregnancies and pregnancies with other chromosomal disorders (six cases of trisomy 18, MoM = 0.80; four cases of sex chromosome abnormality, MoM = 1.01; 17 cases of chromosomal mosaicism in chorionic villi, MoM = 1.11). Selecting an upper limit at the 90th centile could detect 25 per cent of pregnancies with Down's syndrome. We conclude that, in the first trimester, MS-hCG as a screening factor for Down's syndrome is of minor value. However, MS-hCG could be a useful factor in a first-trimester screening programme based on a combination of markers.

Immunomagnetic Nano-Screening Chip for Circulating Tumor Cells Detection in Blood

NASA Astrophysics Data System (ADS)

Horton, A. P.; Lane, N.; Tam, J.; Sokolov, K.; Garner, H. R.; Uhr, J. W.; Zhang, X. J.

2010-03-01

We present a novel method towards diagnose cancer at an early stage via a blood test. Early diagnosis is high on the future agenda of oncologists because of significant evidence that it will result in a higher cure rate. Capture of circulating tumor cells (CTCs) which are known to escape from carcinomas at an early stage offers such an opportunity. We design, fabricate and optimize the nanomagnetic-screening chip that captures the CTCs in microfluid, and further integrate the nano-chip with the new multispectral imaging system so that it can quantify different tumor markers and automate the entire instrument. Specifically, hybrid plasmonic (Fe2O3-core Au shell) nanoparticles, conjugated a collection of antibodies especially chosen to target breast cancer CTCs, with high magnetic susceptibility will be used for effective immunomagnetic CTC isolation. Greatly increased sensitivity over previous attempts is demonstrated by decreasing the length scale for interactions between the magnetic-nanoparticle-tagged CTCs and the isolative magnetic field, while increasing the effective cross-sectional area over which this interaction takes place. The screening chip is integrated with a novel hyperspectral microscopic imaging (HMI) platform capable of recording the entire emission spectra in a single pass evaluation. The combined system will precisely quantify up to 10 tumor markers on CTCs.

RAPD markers linked to eastern filbert blight resistance in Corylus avellana

Treesearch

S.A. Mehlenbacher; R.N. Brown; J.W. Davis; H. Chen; N.V. Bassil; D.C. Smith; Thomas L. Kubisiak

2004-01-01

A total of 1,110 decamer primers were screened for RAPD markers linked to a dominant allele in hazelnut (Corylus avellana) that confers resistance to eastern filbert blight caused by Anisogramma anomnala. Twenty RAPD markers linked in coupling, and five markers linked in repulsion, were found. A seedling population was used to...

Triglyceride-based screening tests fail to recognize cardiometabolic disease in African immigrant and African-American men.

PubMed

Yu, Sophia S K; Ramsey, Natalie L M; Castillo, Darleen C; Ricks, Madia; Sumner, Anne E

2013-02-01

The prevalence of cardiometabolic disease in Africa now rivals that of Western nations. Therefore, screening programs that lead to effective prevention of cardiometabolic disease in Africans is imperative. Most screening tests for cardiometabolic disease use triglyceride (TG) levels as a criterion. However, the failure rate of TG-based screening tests in African Americans is high. In Africans, the efficacy of TG-based screening tests is unknown. Our goal was to determine the association between hypertriglyceridemia (TG ≥150 mg/dL) and cardiometabolic disease in African and African-American men. This was a cross-sectional study of 155 men (80 African immigrants, 75 African Americans) [age, 35±9 years, mean±standard deviation (SD), body mass index (BMI) 28.5±5.2 kg/m(2)] who self-identified as healthy. Lipid profiles were performed. Glucose tolerance and insulin resistance was determined by oral glucose tolerance tests (OGTT) and the insulin sensitivity index (S(I)), respectively. Cardiometabolic disease was defined by four possible subtypes--prediabetes, diabetes, insulin resistance, or metabolic triad [hyperinsulinemia, hyperapolipoprotein B, small low-density lipoprotein (LDL) particles]. TG levels were higher in men with cardiometabolic disease than without (88±43 versus 61±26 mg/dL, P<0.01). However, <10% of men with cardiometabolic disease had TG ≥150 mg/dL. Even within each cardiometabolic disease subtype, the prevalence of TG ≥150 mg/dL was <10%. Furthermore, TG levels in the 5% of men identified by OGTT as diabetic were ≤100 mg/dL (mean 71±24, range 45-100 mg/dL). Hypertriglyceridemia is a poor marker of cardiometabolic disease in men of African descent. Therefore TG-based screening tests fail to identify both African immigrants and African-American men with cardiometabolic disease. As a consequence, the opportunity for early intervention and prevention is lost.

Molecular-Directed Treatment of Differentiated Thyroid Cancer: Advances in Diagnosis and Treatment.

PubMed

Yip, Linwah; Sosa, Julie Ann

2016-07-01

Thyroid cancer incidence is increasing, and when fine-needle aspiration biopsy results are cytologically indeterminate, the diagnosis is often still established only after thyroidectomy. Molecular marker testing may be helpful in guiding patient-oriented and tailored management of thyroid nodules and thyroid cancer. To summarize available data on the use of molecular testing to improve the diagnosis and prognostication of thyroid cancer. A MEDLINE review was conducted using the primary search terms molecular, thyroid cancer, thyroid nodule, and gene expression classifier in search strings. Articles were restricted to those published between January 1, 2010, and June 1, 2015, inclusive of adult humans, and reported in the English language only. Of 867 titles screened, 67 articles were further identified for review of the full text. The 2 most studied molecular marker testing techniques for indeterminate thyroid nodules include gene expression classifier analysis and evaluation for somatic mutations or rearrangements that are commonly found in thyroid cancer (7-gene panel). Nodules with benign results on gene expression classifier analysis can be associated with less than a 5% risk of cancer and may be observed, while nodules with positive results on the 7-gene panel may have a higher risk of cancer (80%-100%) and definitive surgery can be recommended. However, cancer prevalence and geographic variations in histologic subtypes may affect accuracy and clinical applicability of both tests. Molecular marker tests such as ThyroSeq version 2.1 are more comprehensive, but they need further validation. Preoperative risk stratification using molecular markers also may be used to better define the optimal extent of thyroidectomy for patients with thyroid cancer. Molecular markers potentially can augment the diagnostic specificity of fine-needle aspiration biopsy to better differentiate cytologically indeterminate nodules that can be safely observed from cytologically indeterminate nodules that may be associated with differentiated thyroid cancer. Long-term follow-up data are still needed; in the end, patient preference regarding the relative risks and benefits of molecular testing is at the crux of decision making.

Improving population health or the population itself? Health technology assessment and our genetic future.

PubMed

Bassett, Ken; Lee, Patricia M; Green, Carolyn J; Mitchell, Lisa; Kazanjian, Arminée

2004-01-01

The province of British Columbia (BC), Canada is developing its first population-wide prenatal genetic screening program, known as triple-marker screening (TMS). TMS, initiated with a simple blood test, is most commonly used to screen for fetuses with the chromosomal abnormality known as Down syndrome or neural tube disorders. Women testing TMS-positive are offered diagnostic amniocentesis and, if the diagnosis is confirmed, selective second-trimester abortion. The project described in this study was initiated to address the broad range of issues arising from this testing technology and provides an example of the new type of health technology assessment (HTA) contribution emerging (and likely to become increasing necessary) in health policy development. With the advent of prenatal genetic screening programs, would-be parents gain the promise of identifying target conditions and, hence, the option of selective abortion of affected fetuses. There is considerable awareness that these developments pose challenges in every dimension (ethical, political, economic, and clinical) of the health-care environment. In the effort to construct an appropriate prenatal screening policy, therefore, administrators have understandably sought guidance from within the field of HTA. The report authors concluded that, within the restricted path open to it, the role of government is relatively clear. It has the responsibility to maintain equal access to prenatal testing, as to any other health service. It should also require maintenance of medical standards and evaluation of program performance. At the same time, policy-makers need actively to support those individuals born with disabilities and their families.

Validation of a rapid lateral flow test for the simultaneous determination of β-lactam drugs and flunixin in raw milk.

PubMed

Douglas, David; Banaszewski, Katie; Juskelis, Rima; Al-Taher, Fadwa; Chen, Yang; Cappozzo, Jack; McRobbie, Lindsay; Salter, Robert S

2012-07-01

β-Lactam antibiotics are the most commonly used drugs on dairy farms. β-Lactam residues in milk are kept out of the human milk supply with good agricultural practices and mandatory truck screening performed by the dairy industry under Appendix N of the Pasteurized Milk Ordinance. Flunixin, a nonsteroidal and anti-inflammatory drug, appears in dairy cattle tissue residues with a frequency similar to the occurrence of penicillin G. This creates concern that flunixin residues could be in milk and would go undetected under current milk screening programs. A single test that combines mandatory β-lactam screening with voluntary flunixin screening is an economical approach for monitoring and controlling for potential flunixin or 5-hydroxyflunixin, the primary flunixin metabolite marker in milk. The objective of this study was to validate a β-lactam and flunixin rapid lateral flow test (LFT) and compare the results obtained with a liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of flunixin and 5-hydroxyflunixin in raw milk with a limit of detection of , 1 ppb, equivalent to 1 ng/ml. Using the LFT, three combined manufactured lots of test strips detected penicillin G at 2.0 ppb, ampicillin at 6.8 ppb, amoxicillin at 5.9 ppb, cephapirin at 13.4 ppb, ceftiofur (total metabolites) at 63 ppb, and 5-hydroxyflunixin at 1.9 ppb at least 90% of the time with 95% confidence. The LFT also detected incurred flunixin milk samples that were analyzed with the LC-MS/MS and diluted to tolerance in raw milk. The detection levels for the LFT are lower than the U.S. safe levels or tolerances and qualify the test to be used in compliance with U.S. milk screening programs.

CFTR DeltaF508 mutation detection from dried blood samples in the first trimester of pregnancy: a possible routine prenatal screening strategy for cystic fibrosis?

PubMed

Konialis, Christopher P; Hagnefelt, Birgitta; Kazamia, Constantina; Karapanou, Sophia; Pangalos, Constantinos

2007-01-01

The implementation and evaluation of a proposed wide-scale prenatal screening strategy, based on DNA isolated from dried blood spots in the first trimester of pregnancy, for the early detection of pregnancies at risk for cystic fibrosis (CF). The screening was performed in conjunction with routine biochemical marker screening for Down's syndrome risk in the first trimester of pregnancy. DNA was isolated from 1,233 dried blood spots and analyzed for the presence of the CF transmembrane regulator DeltaF508 mutation. Women carriers were offered and accepted the option for additional full testing of their partners in order to assess the risk for the fetus. All 1,233 samples were successfully analyzed, identifying 23 DeltaF508 carriers, corresponding to a DeltaF508 carrier rate of approximately 1/55 (1.8%). All partners of the women carriers were further tested without revealing any need for further prenatal testing in this group. This study reveals the relatively high frequency of the DeltaF508 CF mutation in the Greek population. More importantly, we demonstrate that the proposed prenatal screening strategy, based on the ease and cost-effectiveness of the analysis for the detection of a single common mutation, can be considered as a feasible and practical approach for wide-scale prenatal screening for CF, following the sequential model. It is applied early on in pregnancy, allowing for the timely management of families at risk for the corresponding genetic disorders. Finally, it can easily be extended to include screening for other common genetic disorders in specific population groups.

First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

PubMed

Cowans, Nicholas J; Spencer, Kevin

2007-03-01

PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (<1.5 kg), low birthweight (<2.5 kg), large birthweight (>4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and development by breaking down IGF binding proteins and causing the release of free IGF for uptake into cells to promote growth. In those cases that eventually result in poor fetal growth, levels of PAPP-A and ADAM12 at 11-14 weeks are significantly lower than normal-in this instance, lowered PAPP-A and ADAM12 would result in less free IGF being available for cell uptake and growth stimulation. Further studies may elucidate if screening using such modalities can lead to new potential treatments for poorly growing fetuses. Copyright (c) 2007 John Wiley & Sons, Ltd.

Development of novel polymorphic microsatellite markers for the silver fox (Vulpes vulpes).

PubMed

Yan, S Q; Bai, C Y; Qi, S M; Li, Y M; Li, W J; Sun, J H

2015-06-01

The silver fox (Vulpes vulpes), a coat color variant of the red fox, is one of the most important fur-bearing animals. To date, development of microsatellite loci for the silver fox has been limited and mainly based on cross-amplification by using canine SSR primers. In this study, 28 polymorphic microsatellite markers were isolated and identified for silver fox through the construction and screening of an (AC)n-enriched library. The number of alleles per locus ranged from 2 to 8 based on 48 individuals tested. The expected and observed hetero- zygosity and polymorphism information content per locus ranged from 0.2544 to 0.859, 0.2083 to 0.7917, and 0.2181 to 0.821, respectively. The polymorphic markers presented in this study may be useful for future analysis of the genetic diversity and population structure of farmed silver fox and wild red fox.

Improving Detection of HIV-Associated Cognitive Impairment: Comparison of the International HIV Dementia Scale and a Brief Screening Battery.

PubMed

de Almeida, Sérgio Monteiro; Kamat, Rujvi; Cherner, Mariana; Umlauf, Anya; Ribeiro, Clea E; de Pereira, Ana Paula; Franklin, Donald; Heaton, Robert K; Ellis, Ronald J

2017-03-01

The International HIV Dementia Scale (IHDS) was developed to screen for HIV-associated dementia, but it has been used more generally for HIV-associated neurocognitive disorder (HAND). This study sought to examine the accuracy of the IHDS in a cohort of Brazilian HIV-infected individuals and compare its performance to an alternative screening battery for detecting HAND. A total of 108 participants (including 60 HIV-infected persons) completed the IHDS and a gold standard neuropsychological (NP) battery of 17 tests. As alternative screening method, all possible 3-test combinations from the NP battery were examined and a superiority index (a marker of specificity and sensitivity) was calculated. Sensitivity and specificity to HAND using the standard IHDS cutpoint of 10 were 36% and 75%, respectively. The best balance between sensitivity and specificity was accomplished with a modified cutpoint of 11.5, which yielded sensitivity of 72% and specificity of 58%. The top two most sensitive test combinations, compared with the gold standard NP battery, were Trail Making Test A, Wechsler Adult Intelligence Scale III Digit Symbol and Hopkins Verbal Learning Test-Revised Total Recall (sensitivity 91%, specificity 96%), and Digit Symbol, Brief Visuospatial Memory Test-Revised Total Recall and Grooved Pegboard Test-dominant hand (sensitivity 94%, specificity 91%). Both test combinations can be administered in less than 10 minutes and were more accurate than the IHDS in classifying HIV+ participants as NP impaired or unimpaired. These data suggest that demographically corrected T-scores from commonly used NP measures with modest time and material demands can improve identification of patients with HAND who may benefit from a more extensive NP examination.

Early detection of Alzheimer disease: methods, markers, and misgivings.

PubMed

Green, R C; Clarke, V C; Thompson, N J; Woodard, J L; Letz, R

1997-01-01

There is at present no reliable predictive test for most forms of Alzheimer disease (AD). Although some information about future risk for disease is available in theory through ApoE genotyping, it is of limited accuracy and utility. Once neuroprotective treatments are available for AD, reliable early detection will become a key component of the treatment strategy. We recently conducted a pilot survey eliciting attitudes and beliefs toward an unspecified and hypothetical predictive test for AD. The survey was completed by a convenience sample of 176 individuals, aged 22-77, which was 75% female, 30% African-American, and of which 33% had a family member with AD. The survey revealed that 69% of this sample would elect to obtain predictive testing for AD if the test were 100% accurate. Individuals were more likely to desire predictive testing if they had an a priori belief that they would develop AD (p = 0.0001), had a lower educational level (p = 0.003), were worried that they would develop AD (p = 0.02), had a self-defined history of depression (p = 0.04), and had a family member with AD (p = 0.04). However, the desire for predictive testing was not significantly associated with age, gender, ethnicity, or income. The desire to obtain predictive testing for AD decreased as the assumed accuracy of the hypothetical test decreased. A better short-term strategy for early detection of AD may be computer-based neuropsychological screening of at-risk (older aged) individuals to identify very early cognitive impairment. Individuals identified in this manner could be referred for diagnostic evaluation and early cases of AD could be identified and treated. A new self-administered, touch-screen, computer-based, neuropsychological screening instrument called Neurobehavioral Evaluation System-3 is described, which may facilitate this type of screening.

Selection and validation of enzymatic activities as functional markers in wood biotechnology and fungal ecology.

PubMed

Mathieu, Yann; Gelhaye, Eric; Dumarçay, Stéphane; Gérardin, Philippe; Harvengt, Luc; Buée, Marc

2013-02-15

The dead wood and forest soils are sources of diversity and under-explored fungal strains with biotechnological potential, which require to be studied. Numerous enzymatic tests have been proposed to investigate the functional potential of the soil microbial communities or to test the functional abilities of fungal strains. Nevertheless, the diversity of these functional markers and their relevance in environmental studies or biotechnological screening does still have not been demonstrated. In this work, we assessed ten different extracellular enzymatic activities involved in the wood decaying process including β-etherase that specifically cleaves the β-aryl ether linkages in the lignin polymer. For this purpose, a collection of 26 fungal strains, distributed within three ecological groups (white, brown and soft rot fungi), has been used. Among the ten potential functional markers, the combinatorial use of only six of them allowed separation between the group of white and soft rot fungi from the brown rot fungi. Moreover, our results suggest that extracellular β-etherase is a rare and dispensable activity among the wood decay fungi. Finally, we propose that this set of markers could be useful for the analysis of fungal communities in functional and environmental studies, and for the selection of strains with biotechnological interests. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of a molecular test of Paget's disease of bone.

PubMed

Guay-Bélanger, Sabrina; Simonyan, David; Bureau, Alexandre; Gagnon, Edith; Albert, Caroline; Morissette, Jean; Siris, Ethel S; Orcel, Philippe; Brown, Jacques P; Michou, Laëtitia

2016-03-01

Depending on populations, 15 to 40% of patients have a familial form of Paget's disease of bone (PDB), which is transmitted in an autosomal-dominant mode of inheritance with incomplete penetrance. To date, only SQSTM1 gene mutations have been linked to the disease. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in patient non-carriers of SQSTM1 mutations, but they have minor size effects. The current clinical practice guidelines still recommend to measure total serum alkaline phosphatase (sALP) for PDB screening. However, genetic or bone biomarkers alone may lack sensitivity to detect PDB. Thus, the objective of this study was to develop a molecular test of PDB, combining genetic and bone biomarkers, in order to detect PDB, which is frequently asymptomatic. We genotyped 35 SNPs previously associated with PDB in 305 patients, and 292 healthy controls. In addition, serum levels of 14 bone biomarkers were assayed in 51 patients and 151 healthy controls. Bivariate and multivariate logistic regression models with adjustment for age and sex were fitted to search for a combination of SNPs and/or bone biomarkers that could best detect PDB in patient non-carriers of SQSTM1 mutations. First, a combination of five genetic markers gave rise to the highest area under the ROC curve (AUC) with 95% confidence interval [95% CI] of 0.731 [0.688; 0.773], which allowed us to detect 81.5% of patients with PDB. Second, a combination of two bone biomarkers had an AUC of 0.822 [0.726; 0.918], and was present in 81.5% of patients with PDB. Then, the combination of the five genetic markers and the two bone biomarkers increased the AUC up to 0.892 [0.833; 0.951], and detected 88.5% of patients with PDB. These results suggested that an algorithm integrating first a screen for SQSTM1 gene mutations, followed by either a genetic markers combination or a combined genetic and biochemical markers test in patients non-carrier of any SQSTM1 mutation, may detect the PDB phenotype better than biomarkers already available in the clinical practice. Copyright © 2016 Amgen Inc. Published by Elsevier Inc. All rights reserved.

Computerized visuo-spatial memory test as a supplementary screening test for dementia.

PubMed

Maki, Yohko; Yoshida, Hiroshi; Yamaguchi, Haruyasu

2010-06-01

To prepare for a super-aging society, effective dementia screening tests are required. The most salient deficit appearing from the early stages of dementia/Alzheimer's disease (AD) is a deterioration in memory. The Hasegawa Dementia Scale-revised (HDS-R) and the Mini-Mental State Examination (MMSE) are widely used in Japan to screen for dementia. Both place an emphasis on memory function, but neither examines visuo-spatial memory (VSM) function, even though VSM deficits are a sensitive marker for the detection of conversion to dementia. Furthermore, brief tests of VSM that are appropriate for screening have not been standardized. Thus, in the present study, we devised a brief, computer-aided short-term VSM test. Sixty-six aged people were evaluated. Using the Clinical Dementia Rating (CDR), it was found that 29 could be considered normal controls (NC; CDR 0), 10 had mild cognitive impairment (MCI; CDR 0.5), 15 had mild dementia (CDR 1), and 12 had moderate to severe dementia (CDR 2-3). The VSM test estimated how many locations each subject could memorize. Several numbered circles were shown on a monitor and subjects were required to memorize the location of these circles sequentially. After the numbers on the circles on the screen had disappeared, the subjects were required to indicate the circles in ascending order. A touch panel screen was used for this test to make it easier. The HDS-R was applied to subjects with MCI and dementia. The mean (+/-SD) VSM score in subjects with MCI (5.70 +/- 0.96) was significantly lower than that in NC subjects (6.69 +/- 0.82), but significantly higher than that in subjects classified as CDR 1 (4.67 +/- 0.87). There was no significant difference in VSM scores between subjects classified as CDR 1 and CDR 2-3 (3.80 +/- 0.80). There was a moderate significant correlation between VSM and HDS-R scores. In the present study, the VSM test detected differences in VSM function among NC subjects and subjects with MCI and mild dementia. The software program for the VSM test is distributed for free so that it can be widely used.

A strategy for screening and identifying mycotoxins in herbal medicine using ultra-performance liquid chromatography with tandem quadrupole time-of-flight mass spectrometry.

PubMed

Fang, Lian-xiang; Xiong, Ai-zhen; Wang, Rui; Ji, Shen; Yang, Li; Wang, Zheng-tao

2013-09-01

The objective of this study was to develop an effective strategy for screening and identifying mycotoxins in herbal medicine (HM). Here, Imperatae Rhizoma, a commonly used Chinese herb, was selected as a model HM. A crude drug contaminated with fungi was analyzed by comparing with uncontaminated ones. Ultra-performance LC coupled to tandem quadrupole TOF-MS (UPLC-Q-TOF-MS) with collision energy function was applied to analyze different samples from Imperatae Rhizoma. Then, MarkerLynx(TM) software was employed to screen the excess components in analytes, compared with control samples, and those selected markers were likely to be the metabolites of fungi. Furthermore, each of the accurate masses of the markers obtained from MarkerLynx(TM) was then searched in a mycotoxins/fungal metabolites database established in advance. The molecular formulas with relative mass error between the measured and theoretical mass within 5 ppm were chosen and then applied to MassFragment(TM) analysis for further confirmation of their structures. With the use of this approach, five mycotoxins that have never been reported in HM were identified in contaminated Imperatae Rhizoma. The results demonstrate the potential of UPLC-Q-TOF-MS coupled with the MarkerLynx(TM) software and MassFragment(TM) tool as an efficient and convenient method to screen and identify mycotoxins in herbal materials and aid in the quality control of HM. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Circulating Markers of Vascular Injury and Angiogenesis in ANCA-Associated Vasculitis

PubMed Central

Monach, Paul A; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Cuthbertson, David; Krischer, Jeffrey; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Ikle, David; Kallenberg, Cees GM; Langford, Carol A; Mueller, Mark; Seo, Philip; St.Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Gu, Yi-Zhong; Snyder, Ronald D; Merkel, Peter A

2011-01-01

Objective To identify biomarkers that distinguish between active ANCA-associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV. 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Serum levels of E-selectin, ICAM-3, MMP1, MMP3, MMP9, P-selectin, thrombomodulin, and VEGF were measured at study screening (time of active disease) and at month 6. ESR and CRP levels had been measured at the time of the clinical visit. The primary outcome was the difference in marker level between screening and month 6 among patients in remission (BVAS/WG score of 0) at month 6. Results All subjects had severe active vasculitis (mean BVAS/WG score 8.6 +/− 3.2 SD) at screening. Among the 123 subjects clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP3 levels were also higher among the 23 subjects with active disease at month 6 than among the 123 subjects in remission. MMP3 levels correlated weakly with ESR and CRP. Conclusion Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers. PMID:21953143

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Etiologic and Early Marker Studies (EEMS), 2016 Winter Review Cycle Has New Website | Division of Cancer Prevention

Cancer.gov

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Etiologic and Early Marker Studies (EEMS) has a new application process for specimen requests. Researchers planning to submit a grant application in response to the Funding Opportunity Announcement PAR-15-297 must use a new website to submit applications. |

Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro

PubMed Central

Chhor, Vibol; Le Charpentier, Tifenn; Lebon, Sophie; Oré, Marie-Virgine; Celador, Idoia Lara; Josserand, Julien; Degos, Vincent; Jacotot, Etienne; Hagberg, Henrik; Sävman, Karin; Mallard, Carina; Gressens, Pierre; Fleiss, Bobbi

2013-01-01

Microglia mediate multiple facets of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype is an appealing neurotherapeutic strategy but a comprehensive study of classical and more novel microglial phenotypic markers in vitro is lacking. The aim of this study was to outline the temporal expression of a battery of phenotype markers from polarised microglia to generate an in vitro tool for screening the immunomodulatory potential of novel compounds. We characterised expression of thirty-one macrophage/microglial phenotype markers in primary microglia over time (4, 12, 36, and 72 h), using RT-qPCR or multiplex protein assay. Firstly, we selected Interleukin-4 (IL-4) and lipopolysaccharide (LPS) as the strongest M1–M2 polarising stimuli, from six stimuli tested. At each time point, markers useful to identify that microglia were M1 included iNOS, Cox-2 and IL-6 and a loss of M2a markers. Markers useful for quantifying M2b-immunomodulatory microglia included, increased IL-1RA and SOCS3 and for M2a-repair and regeneration, included increased arginase-1, and a loss of the M1 and M2b markers were discriminatory. Additional markers were regulated at fewer time points, but are still likely important to monitor when assessing the immunomodulatory potential of novel therapies. Further, to facilitate identification of how novel immunomodulatory treatments alter the functional affects of microglia, we characterised how the soluble products from polarised microglia affected the type and rate of neuronal death; M1/2b induced increasing and M2a-induced decreasing neuronal loss. We also assessed any effects of prior activation state, to provide a way to identify how a novel compound may alter phenotype depending on the stage of injury/insult progression. We identified generally that a prior M1/2b reduced the ability of microglia to switch to M2a. Altogether, we have characterised a profile of phenotype markers and a mechanism of assessing functional outcome that we can use as a reference guide for first-line screening of novel immunomodulatory therapies in vitro in the search for viable neuroprotectants. PMID:23454862

T25 repeat in the 3' untranslated region of the CASP2 gene: a sensitive and specific marker for microsatellite instability in colorectal cancer.

PubMed

Findeisen, Peter; Kloor, Matthias; Merx, Sabine; Sutter, Christian; Woerner, Stefan M; Dostmann, Nicole; Benner, Axel; Dondog, Bolormaa; Pawlita, Michael; Dippold, Wolfgang; Wagner, Rudolf; Gebert, Johannes; von Knebel Doeberitz, Magnus

2005-09-15

DNA mismatch repair deficiency is observed in about 10% to 15% of all colorectal carcinomas and in up to 90% of hereditary nonpolyposis colorectal cancer (HNPCC) patients. Tumors with mismatch repair defects acquire mutations in short repetitive DNA sequences, a phenomenon termed high-level microsatellite instability (MSI-H). The diagnosis of MSI-H in colon cancer is of increasing relevance, because MSI-H is an independent prognostic factor in colorectal cancer, seems to influence the efficacy of adjuvant chemotherapy, and is the most important molecular screening tool to identify HNPCC patients. To make MSI typing feasible for the routine pathology laboratory, highly reproducible and cost effective laboratory tests are required. Here, we describe a novel T25 mononucleotide marker in the 3'untranslated region of the CASP2 gene (CAT25) that displayed a quasimonomorphic repeat pattern in normal tissue of 200 unrelated individuals of Caucasian origin. In addition, CAT25 was monomorphic also in all tested donors of African and Asian origin (n = 102 and n = 79, respectively) and thus differs from the most commonly used markers BAT25 and BAT26. Without the analysis of corresponding normal tissue, CAT25 correctly detected 56 of 57 colorectal cancer specimens classified as MSI-H by using the standard National Cancer Institute/International Collaborative Group-HNPCC marker panel. Combined with the standard markers BAT25 and BAT26 in a multiplex PCR, all MSI-H colorectal cancer samples were typed correctly. No false-positive results were obtained in 60 non-MSI-H control colorectal cancer specimens. These data suggest that CAT25 should be included into novel marker panels for microsatellite testing thus allowing for a significant reduction of the complexity and costs of MSI typing. Moreover, CAT25 represents a highly promising marker for early detection of colorectal cancer in HNPCC germ line mutation carriers.

A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.

PubMed

Barber, T J; Moyle, G; Hill, A; Jagjit Singh, G; Scourfield, A; Yapa, H M; Waters, L; Asboe, D; Boffito, M; Nelson, M

2016-05-01

Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 μmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

PubMed

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

2016-02-07

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

Colon cancer screening: which non-invasive filter tests?

PubMed

Pox, Christian

2011-01-01

The following non-invasive stool tests for colorectal cancer (CRC) screening exist: guaiac or immunochemical fecal occult blood testing (FOBT), genetic stool tests and the M2-PK. Currently the most widely used tests are guaiac-based (gFOBT). Several randomized controlled trials have shown that gFOBT are able to achieve a reduction in CRC-related mortality. This reduction is achieved by detecting asymptomatic cancers at an early stage with a better prognosis. However, gFOBT have a low sensitivity for colorectal adenomas and are thus unlikely to be able to reduce the incidence of CRC. Furthermore, gFOBT are not specific for human blood and can be influenced by external factors. Immunochemical tests (iFOBT) only detect human blood in the stool. In two recent randomized studies from the Netherlands comparing guaiac and immunochemical tests in the asymptomatic population, iFOBT were found to detect more cancers than gFOBT. Furthermore, iFOBT were able to detect more advanced adenomas thus having the potential to be able to reduce the incidence of CRC as well as CRC-related mortality. In the recently released European CRC screening guidelines, iFOBT are considered the screening test of choice. Several questions remain however. It is currently unknown what the optimal cut-off value for an iFOBT to be considered positive should be and what the number of stool samples is that are required. Genetic stool tests detect mutations in stool that can be found in CRC. The original test testing for 21 genetic changes was found to be superior to gFOBT for the detection of cancers. However, the sensitivity was moderate (51.6%) and the sensitivity for advanced adenomas was low. In the meantime the test has been modified improving DNA extraction and reducing the number of mutations tested for as well as including a methylation marker. The efficacy of the modified test in the screening population is unknown. M2-PK is an isomer of the enzyme pyruvate kinase that is involved in glycolysis. Studies have found a good sensitivity for cancers, a low sensitivity for advanced adenomas with a specificity of around 80%. Further studies in the screening population are required. Copyright © 2011 S. Karger AG, Basel.

Peptide Transduction-Based Therapies for Prostate Cancer

DTIC Science & Technology

2004-06-01

using an M13 peptide phage display library. Initial screening of the library for transduction of tumors in vivo has identified peptides able to...marker conjugates may have to be tested. (Months 6-12, Year 1) Progress: These experiments have been initiated. Task 4. An M13 peptide phage display ... phage 12 amino acid control peptide display library (New England Biolabs, Beverly, MA ) was used. Briefly, One nude mouse bearing a human tumor line

Genome-wide survey and analysis of microsatellites in giant panda (Ailuropoda melanoleuca), with a focus on the applications of a novel microsatellite marker system.

PubMed

Huang, Jie; Li, Yu-Zhi; Du, Lian-Ming; Yang, Bo; Shen, Fu-Jun; Zhang, He-Min; Zhang, Zhi-He; Zhang, Xiu-Yue; Yue, Bi-Song

2015-02-07

The giant panda (Ailuropoda melanoleuca) is a critically endangered species endemic to China. Microsatellites have been preferred as the most popular molecular markers and proven effective in estimating population size, paternity test, genetic diversity for the critically endangered species. The availability of the giant panda complete genome sequences provided the opportunity to carry out genome-wide scans for all types of microsatellites markers, which now opens the way for the analysis and development of microsatellites in giant panda. By screening the whole genome sequence of giant panda in silico mining, we identified microsatellites in the genome of giant panda and analyzed their frequency and distribution in different genomic regions. Based on our search criteria, a repertoire of 855,058 SSRs was detected, with mono-nucleotides being the most abundant. SSRs were found in all genomic regions and were more abundant in non-coding regions than coding regions. A total of 160 primer pairs were designed to screen for polymorphic microsatellites using the selected tetranucleotide microsatellite sequences. The 51 novel polymorphic tetranucleotide microsatellite loci were discovered based on genotyping blood DNA from 22 captive giant pandas in this study. Finally, a total of 15 markers, which showed good polymorphism, stability, and repetition in faecal samples, were used to establish the novel microsatellite marker system for giant panda. Meanwhile, a genotyping database for Chengdu captive giant pandas (n = 57) were set up using this standardized system. What's more, a universal individual identification method was established and the genetic diversity were analysed in this study as the applications of this marker system. The microsatellite abundance and diversity were characterized in giant panda genomes. A total of 154,677 tetranucleotide microsatellites were identified and 15 of them were discovered as the polymorphic and stable loci. The individual identification method and the genetic diversity analysis method in this study provided adequate material for the future study of giant panda.

Screening and confirmation of microRNA markers for forensic body fluid identification.

PubMed

Wang, Zheng; Zhang, Ji; Luo, Haibo; Ye, Yi; Yan, Jing; Hou, Yiping

2013-01-01

MicroRNAs (miRNAs, ∼22 nucleotides) are small, non-protein coding RNAs that regulate gene expression at the post-transcriptional level. MiRNAs can express in a tissue-specific manner, and have been introduced to forensic body fluid identification. In this study, we employed the qPCR-array (TaqMan(®) Array Human MicroRNA Cards) to screen the body fluid-specific miRNAs. Seven candidate miRNAs were identified as potentially body fluid-specific and could be used as forensically relevant body fluid markers: miR16 and miR486 for venous blood, miR888 and miR891a for semen, miR214 for menstrual blood, miR124a for vaginal secretions, and miR138-2 for saliva. The candidate miRNA markers were then validated via hydrolysis probes quantitative real-time polymerase chain reaction (TaqMan-qPCR). In addition, BestKeeper software was used to validate the expression stability of four genes, RNU44, RNU48, U6 and U6b, regularly used as reference genes (RGs) for studies involving forensic body fluids. The current study suggests that U6 could be used as a proper RG of miRNAs in forensic body fluid identification. The relative expression ratios (R) of miR486, miR888, miR214, miR16 and miR891a can differentiate the target body fluid from other body fluids that were tested in this study. The detection limit of TaqMan-qPCR of the five confirmed miRNA markers was 10pg of total RNA. The effect of time-wise degradation of blood stains and semen stains for 1 month under normal laboratory conditions was tested and did not significantly affect the detection results. Herein, this study proposes five body fluid-specific miRNAs for the forensic identification of venous blood, semen, and menstrual blood, of which miR486, miR888, and miR214 may be used as new markers for body fluid identification. Additional work remains necessary in search for suitable miRNA markers and stable RGs for forensic body fluid identification. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Screening with HbA1c identifies only one in two individuals with diagnosis of prediabetes at oral glucose tolerance test: findings in a real-world Caucasian population.

PubMed

Chilelli, Nino Cristiano; Cosma, Chiara; Ragazzi, Eugenio; Burlina, Silvia; Zaninotto, Martina; Plebani, Mario; Lapolla, Annunziata

2014-10-01

Discordance between HbA1c and OGTT in screening pre-diabetes may occur because of lack of laboratory standardization, distinct underlying pathophysiological processes or different ethnicity. We evaluated HbA1c efficacy for screening OGTT-defined IFG and IGT conditions in a large Caucasian population using the newly revised IFCC protocol. A total of 501 consecutive subjects were screened for pre-diabetic conditions with OGTT with 75 g of glucose. Testing for HbA1c, lipid profile and fasting insulin levels was also performed. For detecting differences between continuous variables, ANOVA followed by Tukey's honestly significant difference (HSD) post hoc test was used. Logistic regression and ROC curve analysis were also performed for assessing HbA1c screening efficacy. ROC curve analysis showed that optimal HbA1c cut-off for detecting IFG was 5.6 % (sensitivity of 78 % and specificity of 63 %), while for IGT, the optimal cut-off was 5.9 % (sensitivity of 46 % and specificity of 84 %), with AUCs < 0.8. Screening with HbA1c identified 53.4 % of the 193 patients with IFG and/or IGT diagnosed at OGTT. As regards surrogate markers of insulin resistance, we observed a trend towards higher values of HOMA-IR and lower QUICKI values in subjects with IFG than in those with IGT. Patients with pre-diabetes at both tests had similar values of HOMA and QUICKI, compared with those with altered OGTT only. IFCC-aligned HbA1c assay proved scarcely effective in detecting IFG and/or IGT in a large Caucasian population, identifying only half of the patients with abnormal OGTT. Moreover, adding HbA1c screening to OGTT may be of little benefit in identifying subjects with a worse metabolic profile.

Screening for osteoporosis in the adult U.S. population: ACPM position statement on preventive practice.

PubMed

Lim, Lionel S; Hoeksema, Laura J; Sherin, Kevin

2009-04-01

Osteoporosis is a common and costly disease that is associated with high morbidity and mortality. There is a lack of direct evidence supporting the benefits of bone mineral density (BMD) screening on osteoporosis outcomes. However, there is indirect evidence to support screening for osteoporosis given the availability of medications with good antifracture efficacy. This paper addresses the position of the American College of Preventive Medicine (ACPM) on osteoporosis screening. The medical literature was reviewed for studies examining the benefits and harms of osteoporosis screening. An overview is also provided of available modalities for osteoporosis screening, risk-assessment tools, cost effectiveness, benefits and harms of screening, rationale for the study, and recommendations from leading health organizations and ACPM. A review was done of English language articles published prior to September 2008 that were retrieved via search on PubMed, from references from pertinent review or landmark articles, and from websites of leading health organizations. There were no randomized controlled trials (RCTs) of osteoporosis screening on fracture outcomes. However, there was one observational study that demonstrated reduced fracture incidence among recipients of BMD testing. Dual energy x-ray absorptiometry is currently one of the most widely accepted and utilized methods for assessing BMD. Other potential tests for detecting osteoporosis include quantitative ultrasound, quantitative computer tomography, and biochemical markers of bone turnover. Testing via BMD is a cost-effective method for detecting osteoporosis in both men and women. Osteoporosis risk-assessment tools such as the WHO fracture-risk algorithm are useful supplements to BMD assessments as they provide estimates of absolute fracture risks. They can also be used with or without BMD testing to assist healthcare providers and patients in making decisions regarding osteoporosis treatments. All adult patients aged >or=50 years should be evaluated for risk factors for osteoporosis. Screening with BMD testing for osteoporosis is recommended in women aged >or=65 years and in men aged >or=70 years. Younger postmenopausal women and men aged 50-69 years should undergo screening if they have at least one major or two minor risk factors for osteoporosis. It is also recommended that clinicians consider using an osteoporosis risk-assessment tool to evaluate absolute fracture risk to determine appropriate osteoporosis therapies.

Node-pore sensing enables label-free surface-marker profiling of single cells.

PubMed

Balakrishnan, Karthik R; Whang, Jeremy C; Hwang, Richard; Hack, James H; Godley, Lucy A; Sohn, Lydia L

2015-03-03

Flow cytometry is a ubiquitous, multiparametric method for characterizing cellular populations. However, this method can grow increasingly complex with the number of proteins that need to be screened simultaneously: spectral emission overlap of fluorophores and the subsequent need for compensation, lengthy sample preparation, and multiple control tests that need to be performed separately must all be considered. These factors lead to increased costs, and consequently, flow cytometry is performed in core facilities with a dedicated technician operating the instrument. Here, we describe a low-cost, label-free microfluidic method that can determine the phenotypic profiles of single cells. Our method employs Node-Pore Sensing to measure the transit times of cells as they interact with a series of different antibodies, each corresponding to a specific cell-surface antigen, that have been functionalized in a single microfluidic channel. We demonstrate the capabilities of our method not only by screening two acute promyelocytic leukemia human cells lines (NB4 and AP-1060) for myeloid antigens, CD13, CD14, CD15, and CD33, simultaneously, but also by distinguishing a mixture of cells of similar size—AP-1060 and NALM-1—based on surface markers CD13 and HLA-DR. Furthermore, we show that our method can screen complex subpopulations in clinical samples: we successfully identified the blast population in primary human bone marrow samples from patients with acute myeloid leukemia and screened these cells for CD13, CD34, and HLA-DR. We show that our label-free method is an affordable, highly sensitive, and user-friendly technology that has the potential to transform cellular screening at the benchside.

A single mini-barcode test to screen for Australian mammalian predators from environmental samples

PubMed Central

MacDonald, Anna J; Sarre, Stephen D

2017-01-01

Abstract Identification of species from trace samples is now possible through the comparison of diagnostic DNA fragments against reference DNA sequence databases. DNA detection of animals from non-invasive samples, such as predator faeces (scats) that contain traces of DNA from their species of origin, has proved to be a valuable tool for the management of elusive wildlife. However, application of this approach can be limited by the availability of appropriate genetic markers. Scat DNA is often degraded, meaning that longer DNA sequences, including standard DNA barcoding markers, are difficult to recover. Instead, targeted short diagnostic markers are required to serve as diagnostic mini-barcodes. The mitochondrial genome is a useful source of such trace DNA markers because it provides good resolution at the species level and occurs in high copy numbers per cell. We developed a mini-barcode based on a short (178 bp) fragment of the conserved 12S ribosomal ribonucleic acid mitochondrial gene sequence, with the goal of discriminating amongst the scats of large mammalian predators of Australia. We tested the sensitivity and specificity of our primers and can accurately detect and discriminate amongst quolls, cats, dogs, foxes, and devils from trace DNA samples. Our approach provides a cost-effective, time-efficient, and non-invasive tool that enables identification of all 8 medium-large mammal predators in Australia, including native and introduced species, using a single test. With modification, this approach is likely to be of broad applicability elsewhere. PMID:28810700

A Narrow Quantitative Trait Locus in C. elegans Coordinately Affects Longevity, Thermotolerance, and Resistance to Paraquat

PubMed Central

Vertino, Anthony; Ayyadevara, Srinivas; Thaden, John J.; Reis, Robert J. Shmookler

2011-01-01

By linkage mapping of quantitative trait loci, we previously identified at least 11 natural genetic variants that significantly modulate Caenorhabditis elegans life-span (LS), many of which would have eluded discovery by knock-down or mutation screens. A region on chromosome IV between markers stP13 and stP35 had striking effects on longevity in three inter-strain crosses (each P < 10−9). In order to define the limits of that interval, we have now constructed two independent lines by marker-based selection during 20 backcross generations, isolating the stP13–stP35 interval from strain Bergerac-BO in a CL2a background. These congenic lines differed significantly from CL2a in LS, assayed in two environments (each P < 0.001). We then screened for exchange of flanking markers to isolate recombinants that partition this region, because fine-mapping the boundaries for overlapping heteroallelic spans can greatly narrow the implicated interval. Recombinants carrying the CL2a allele at stP35 were consistently long-lived compared to those retaining the Bergerac-BO allele (P < 0.001), and more resistant to temperature elevation and paraquat (each ∼1.7-fold, P < 0.0001), but gained little protection from ultraviolet or peroxide stresses. Two rounds of recombinant screening, followed by fine-mapping of break-points and survival testing, narrowed the interval to 0.18 Mb (13.35–13.53 Mb) containing 26 putative genes and six small-nuclear RNAs – a manageable number of targets for functional assessment. PMID:22303358

A Multiplex Immunoassay Using the Guthrie Specimen to Detect T-Cell Deficiencies Including Severe Combined Immunodeficiency Disease

PubMed Central

Janik, David K.; Lindau-Shepard, Barbara; Comeau, Anne Marie; Pass, Kenneth A.

2011-01-01

BACKGROUND Severe combined immunodeficiency (SCID) fulfills many of the requirements for addition to a newborn screening panel. Two newborn screening SCID pilot studies are now underway using the T-cell receptor excision circle (TREC) assay, a molecular technique. Here we describe an immunoassay with CD3 as a marker for T cells and CD45 as a marker for total leukocytes that can be used with the Guthrie specimen. METHODS The multiplexing capabilities of the Luminex platform were used. Antibody pairs were used to capture and detect CD3 and CD45 from a single 3-mm punch of the Guthrie specimen. The assay for each bio-marker was developed separately in identical buffers and then combined to create a multiplex assay. RESULTS Using calibrators made from known amounts of leukocytes, a detection limit of 0.25 × 106 cells/mL for CD3 and 0.125 × 106 cells/mL for CD45 was obtained. Affinity tests showed no cross-reactivity between the antibodies to CD3 and CD45. The multiplex assay was validated against 8 coded specimens of known clinical status and linked to results from the TREC assay that had identified them. All were correctly identified by the CD345 assay. CONCLUSIONS The performance parameters of the CD345 assay met the performance characteristics generally accepted for immunoassays. Our assay classifications of positive specimens concur with previous TREC results. This CD345 assay warrants evaluation as a viable alternative or complement to the TREC assay as a primary screening tool for detecting T-cell immunodeficiencies, including SCID, in Guthrie specimens. PMID:20660143

A novel electrochemical immunosensor based on PG for early screening of depression markers-heat shock protein 70.

PubMed

Sun, Bolu; Cai, Jinying; Li, Wuyan; Gou, Xiaodan; Gou, Yuqiang; Li, Dai; Hu, Fangdi

2018-07-15

In this study, a novel electrochemical immunosensor for early screening of depression markers-heat shock protein 70 (HSP70) was successfully developed based on the porous graphene (PG) with huge specific surface area and excellent structure. Benefiting from the strong adsorption and good bioactivity of PG which was initially prepared via a simple pyrolysis process, a variety of heat shock protein70 (HSP70) can be firmly loaded on the PG to construct the basic electrode (HSP70/PG/GCE)，which was characterized by the cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), respectively. Due to the HSP70 fixed on the surface of basic electrode and the HSP70 in the samples can competitively combine with the horseradish peroxidase labeled human HSP 70 antibody (HRP-Strept-Biotin-Ab). As a result, it presented a negative correlation between the concentration of HSP70 in samples and the detection signal of the proposed electrochemical immunosensor (HRP-Strept-Biotin-Ab-HSP70/PG/GCE) in the test liquid. The application of PG with excellent electrical conductivity in construction of immunosensor remarkably improved the sensitivity of the immunosensor for detection of HSP70. The proposed immunosensor demonstrated a wide linear range of 0.0448 ~ 100 ng/mL with a low detection limit of 0.02 ng/mL at 3σ. Moreover, the proposed immunosensor could be applied for the sensitive and efficient detection of HSP70 in real samples with good precision, acceptable stability, reproducibility and satisfactory results. Therefore, the HSP70 immunosensor provides a novel and convenient method for early clinical screening of depression markers-heat shock protein 70. Copyright © 2018 Elsevier B.V. All rights reserved.

Gestational Diabetes Mellitus: Post-partum Risk and Follow Up.

PubMed

Poola-Kella, Silpa; Steinman, Rachel A; Mesmar, Bayan; Malek, Rana

2018-01-31

Women with gestational diabetes mellitus (GDM) are at an increased risk for developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. In this review, we will discuss postpartum cardiovascular and diabetes risk in women with a history of GDM and different ways to improve postpartum screening. This review involves a comprehensive literature review on gestational diabetes and postpartum risk for cardiovascular disease and diabetes mellitus as well as post-partum screening methods. Cardiovascular risk post-partum is potentiated by increased inflammatory markers leading to worsening atherosclerosis and cardiovascular events downstream. Decreased insulin sensitivity and β cell compensation, recurrent GDM, maternal factors such as pre and post-partum weight gain and lactation may contribute to T2DM risk. Postpartum glucose testing is essential in screening women as hyperglycemia in pregnancy has long term effects on both cardiovascular disease and diabetes risk on the mother. Long and short term improvement to post-partum glucose testing is essential to decreasing cardiometabolic and diabetes risk in women with gestational diabetes mellitus. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

SNP detection in Na/K ATP-ase gene α1 subunit of bisexual and parthenogenetic Artemia strains by RFLP screening.

PubMed

Manaffar, R; Zare, S; Agh, N; Abdolahzadeh, N; Soltanian, S; Sorgeloos, P; Bossier, P; Van Stappen, G

2011-01-01

In order to find a marker for differentiating between a bisexual and a parthenogenetic Artemia strain, Exon-7 of the Na/K ATPase α(1) subunit gene was screened by RFLP technique. The results revealed a constant synonymous SNP (single nucleotide polymorphism) in digestion by the Tru1I enzyme that was consistent with these two types of Artemia. This SNP was identified as an accurate molecular marker for discrimination between bisexual and parthenogenetic Artemia. According to the Nei's genetic distance (1973), the lowest genetic distance was found between individuals from Artemia urmiana Günther 1890 and parthenogenetic populations, making the described marker the first marker to easily distinguish between these two cooccurring species. © 2010 Blackwell Publishing Ltd.

Clinical potential of proteomics in the diagnosis of ovarian cancer.

PubMed

Ardekani, Ali M; Liotta, Lance A; Petricoin, Emanuel F

2002-07-01

The need for specific and sensitive markers of ovarian cancer is critical. Finding a sensitive and specific test for its detection has an important public health impact. Currently, there are no effective screening options available for patients with ovarian cancer. CA-125, the most widely used biomarker for ovarian cancer, does not have a high positive predictive value and it is only effective when used in combination with other diagnostic tests. However, pathologic changes taking place within the ovary may be reflected in biomarker patterns in the serum. Combination of mass spectra generated by new proteomic technologies, such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) and artificial-intelligence-based informatic algorithms, have been used to discover a small set of key protein values and discriminate normal from ovarian cancer patients. Serum proteomic pattern analysis might be applied ultimately in medical screening clinics, as a supplement to the diagnostic work-up and evaluation.

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PubMed

Trentham-Dietz, Amy; Ergun, Mehmet Ali; Alagoz, Oguzhan; Stout, Natasha K; Gangnon, Ronald E; Hampton, John M; Dittus, Kim; James, Ted A; Vacek, Pamela M; Herschorn, Sally D; Burnside, Elizabeth S; Tosteson, Anna N A; Weaver, Donald L; Sprague, Brian L

2018-02-01

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Applying a new computer-aided detection scheme generated imaging marker to predict short-term breast cancer risk

NASA Astrophysics Data System (ADS)

Mirniaharikandehei, Seyedehnafiseh; Hollingsworth, Alan B.; Patel, Bhavika; Heidari, Morteza; Liu, Hong; Zheng, Bin

2018-05-01

This study aims to investigate the feasibility of identifying a new quantitative imaging marker based on false-positives generated by a computer-aided detection (CAD) scheme to help predict short-term breast cancer risk. An image dataset including four view mammograms acquired from 1044 women was retrospectively assembled. All mammograms were originally interpreted as negative by radiologists. In the next subsequent mammography screening, 402 women were diagnosed with breast cancer and 642 remained negative. An existing CAD scheme was applied ‘as is’ to process each image. From CAD-generated results, four detection features including the total number of (1) initial detection seeds and (2) the final detected false-positive regions, (3) average and (4) sum of detection scores, were computed from each image. Then, by combining the features computed from two bilateral images of left and right breasts from either craniocaudal or mediolateral oblique view, two logistic regression models were trained and tested using a leave-one-case-out cross-validation method to predict the likelihood of each testing case being positive in the next subsequent screening. The new prediction model yielded the maximum prediction accuracy with an area under a ROC curve of AUC  =  0.65  ±  0.017 and the maximum adjusted odds ratio of 4.49 with a 95% confidence interval of (2.95, 6.83). The results also showed an increasing trend in the adjusted odds ratio and risk prediction scores (p  <  0.01). Thus, this study demonstrated that CAD-generated false-positives might include valuable information, which needs to be further explored for identifying and/or developing more effective imaging markers for predicting short-term breast cancer risk.

Development and application of microsatellites in candidate genes related to wood properties in the Chinese white poplar (Populus tomentosa Carr.).

PubMed

Du, Qingzhang; Gong, Chenrui; Pan, Wei; Zhang, Deqiang

2013-02-01

Gene-derived simple sequence repeats (genic SSRs), also known as functional markers, are often preferred over random genomic markers because they represent variation in gene coding and/or regulatory regions. We characterized 544 genic SSR loci derived from 138 candidate genes involved in wood formation, distributed throughout the genome of Populus tomentosa, a key ecological and cultivated wood production species. Of these SSRs, three-quarters were located in the promoter or intron regions, and dinucleotide (59.7%) and trinucleotide repeat motifs (26.5%) predominated. By screening 15 wild P. tomentosa ecotypes, we identified 188 polymorphic genic SSRs with 861 alleles, 2-7 alleles for each marker. Transferability analysis of 30 random genic SSRs, testing whether these SSRs work in 26 genotypes of five genus Populus sections (outgroup, Salix matsudana), showed that 72% of the SSRs could be amplified in Turanga and 100% could be amplified in Leuce. Based on genotyping of these 26 genotypes, a neighbour-joining analysis showed the expected six phylogenetic groupings. In silico analysis of SSR variation in 220 sequences that are homologous between P. tomentosa and Populus trichocarpa suggested that genic SSR variations between relatives were predominantly affected by repeat motif variations or flanking sequence mutations. Inheritance tests and single-marker associations demonstrated the power of genic SSRs in family-based linkage mapping and candidate gene-based association studies, as well as marker-assisted selection and comparative genomic studies of P. tomentosa and related species.

Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity.

PubMed

Kostenko, L; Kjer-Nielsen, L; Nicholson, I; Hudson, F; Lucas, A; Foley, B; Chen, K; Lynch, K; Nguyen, J; Wu, A H B; Tait, B D; Holdsworth, R; Mallal, S; Rossjohn, J; Bharadwaj, M; McCluskey, J

2011-07-01

HLA-B57 and HLA-B58 are major histocompatibility class (MHC)-I allotypes that are potentially predictive of important clinical immune phenotypes. HLA-B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA-B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA-B57 and HLA-B58 that provides an inexpensive and sensitive screen for these MHC-I allotypes. The usefulness of HLA-B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity in a cohort of patients enrolled in the PREDICT-1 trial. Our data show that patients who test negative by mAb screening comprise 90%-95% of all individuals in most human populations and require no further human leukocyte antigen (HLA) typing. Patients who test positive by mAb screening should proceed to high-resolution typing to ascertain the presence of HLA-B*5701 or HLA-B*5801. Hence, mAb screening provides a low-cost alternative to high-resolution typing of all patients and lends itself to point-of-care diagnostics and rapid ascertainment of low-risk patients who can begin immediate therapy with abacavir, flucloxacillin or allopurinol. © 2011 John Wiley & Sons A/S.

A review of designer anabolic steroids in equine sports.

PubMed

Waller, Christopher C; McLeod, Malcolm D

2017-09-01

In recent years, the potential for anabolic steroid abuse in equine sports has increased due to the growing availability of designer steroids. These compounds are readily accessible online in 'dietary' or 'nutritional' supplements and contain steroidal compounds which have never been tested or approved as veterinary agents. They typically have unusual structures or substitution and as a result may pass undetected through current anti-doping screening protocols, making them a significant concern for the integrity of the industry. Despite considerable focus in human sports, until recently there has been limited investigation into these compounds in equine systems. To effectively respond to the threat of designer steroids, a detailed understanding of their metabolism is needed to identify markers and metabolites arising from their misuse. A summary of the literature detailing the metabolism of these compounds in equine systems is presented with an aim to identify metabolites suitable for incorporation into screening protocols by anti-doping laboratories. The future of equine anti-doping research is likely to be guided by the incorporation of alternate testing matrices into routine screening, the improvement of in vitro technologies that can mimic in vivo equine metabolism, and the improvement of instrumentation or analytical methods that allow for the development of untargeted screening, and metabolomics approaches for use in anti-doping screening protocols. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Screening of (-SEA) α-thalassaemia using an immunochromatographic strip assay for the ζ-globin chain in a population with a high prevalence and heterogeneity of haemoglobinopathies.

PubMed

Jomoui, Wittaya; Fucharoen, Goonnapa; Sanchaisuriya, Kanokwan; Fucharoen, Supan

2017-01-01

The presence of the ζ-globin chain is a good marker of (-- SEA ) α 0 -thalassaemia. We evaluated an immunochromatographic (IC) strip assay for ζ-globin in screening for (-- SEA ) α 0 -thalassaemia in a population with a high prevalence and heterogeneity of haemoglobinopathies. The study was carried out on 300 screen positive blood samples of Thai individuals. The IC strip assay for the ζ-globin chain was performed on all samples. The results were interpreted with thalassaemia genotyping using standard haemoglobin and DNA analyses. Several thalassaemia genotypes were noted. Among the 300 subjects investigated, 79 had a positive IC strip assay for ζ-globin and (-- SEA ) α 0 -thalassaemia was identified in 40 of them. No (-- SEA ) α 0 -thalassaemia was detected in the remaining 39 samples with a positive IC strip test result or in the 221 samples with a negative IC strip test result. Further DNA analysis identified α + -thalassaemia in 25 of the 39 (-- SEA ) α 0 -thalassaemia negative samples. Using this IC strip assay in combination with a conventional screening protocol for (-- SEA ) α 0 -thalassaemia could provide sensitivity and specificity of 100% and 90.4%, respectively. IC strip assay for ζ-globin is simple, rapid and does not require sophisticated equipment. Use of this test in addition to the existing screening protocol could detect potential (-- SEA ) α 0 -thalassaemia leading to a significant reduction in the workload of DNA analysis. This could be used in areas where haemoglobinopathies are prevalent and heterogeneous but molecular testing is not available. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Salivary diagnostics and its impact in dentistry, research, education, and the professional community.

PubMed

Slavkin, H C; Fox, C H; Meyer, D M

2011-10-01

Oral fluid-based (salivary) tests have the potential to create practical, point-of-care clinical instruments that are convenient, practical, and comfortable to use in dentistry and medicine. Currently, there are no simple, accurate, and inexpensive sampling, screening, or detection methods to support definitive diagnostic platforms across dental and medical disciplines. Though the benefits from advancing screening and detection technologies seem eminent, analytical, chemical, molecular, genetic, and protein markers are still under development. Clinical applications in patient care must be validated independently to ensure that they are clinically accurate, reliable, precise, and uniformly consistent for screening and detecting specific diseases or conditions. As technology designed to improve patient care through risk assessment, prevention, and disease management is transferred into clinical practice, dentistry may need to reassess its role in general health care. © International & American Associations for Dental Research

HPLC-MS/MS investigation of biochemical markers for the disclosure of erythropoietin abuse in sports

NASA Astrophysics Data System (ADS)

Appolonova, S. A.; Dikunets, M. A.; Rodchenkov, G. M.

2009-04-01

The polypeptide hormone erythropoietin (EPO), which is a forbidden doping drug, was determined by high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). The hypothesis about the influence of EPO on the asymmetric dimethylarginine (ADMA)-dimethylargininedime-thylaminohydrolase (DDAH)-NO-synthase system was verified. Changes in this system can serve as indirect biochemical markers of the presence of the forbidden EPO drug in the organism. In the test group, the concentrations of biochemical markers varied from 10 to 40 μg/ml for ADMA and symmetrical DMA (SDMA) and from 0.5 to 10 μg/ml for arginine and citrulline. A single intravenous administration of r-HuEPO (Epocrin, 2000 ME/day) for two volunteers reliably increased ADMA, SDMA, arginine, and citrulline concentrations to 40-270 μg/ml, 40-240μg/ml, 10-60 μg/ml, and 12-140 μg/ml, respectively, with respect to the reference values. The simultaneous increase in arginine, methylarginines, and citrulline contents could be an indirect marker of EPO abuse. The method is recommended for fast screening analysis.

Improving detection of HIV-associated cognitive impairment: Comparison of the International HIV Dementia Scale and a Brief Screening Battery

PubMed Central

de Almeida, Sergio Monteiro; Kamat, Rujvi; Cherner, Mariana; Umlauf, Anya; Ribeiro, Clea Elisa; de Pereira, Ana Paula; Franklin, Donald; Heaton, Robert K.; Ellis, Ronald J.

2016-01-01

Objectives The International HIV Dementia Scale (IHDS) was developed to screen for HIV-associated dementia (HAD), but it has been used more generally for HIV-associated neurocognitive disorder (HAND). This study sought to examine the accuracy of the IHDS in a cohort of Brazilian HIV-infected individuals and compare its performance to an alternative screening battery for detecting HAND. Methods 108 participants (including 60 HIV-infected persons), completed the IHDS and a gold standard neuropsychological (NP) battery of 17 tests. As alternative screening method, all possible three-test combinations from the NP battery were examined and a superiority index (a marker of specificity and sensitivity) was calculated. Results Sensitivity and specificity to HAND using the standard IHDS cutpoint of 10 were 36% and 75% respectively. The best balance between sensitivity and specificity was accomplished with a modified cutpoint of 11.5, which yielded sensitivity of 72% and specificity of 58%. The top two most sensitive test combinations, compared to the gold standard NP battery, were Trail Making Test A, WAIS-III Digit Symbol (DS) and HVLT-R Total Recall (sensitivity 91%, specificity 96%), and DS, BVMT-R Total Recall and Grooved Pegboard Test-Dominant Hand (sensitivity 94%, specificity 91%). Conclusions Both test combinations can be administered in under 10 minutes and were more accurate than the IHDS in classifying HIV+ participants as NP impaired or unimpaired. These data suggest that demographically corrected T-scores from commonly used NP measures with modest time and material demands can improve identification of patients with HAND who may benefit from a more extensive NP examination. PMID:27828876

Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases

PubMed Central

Mercado, Monica Vázquez-Del; Chan, Edward K. L.

2010-01-01

Autoantibody tests have been used extensively in diagnosis and follow-up of patients in rheumatology clinics. Immunofluorescent antinuclear antibody test using HEp-2 cells is still considered the gold standard for screening of autoantibodies, and most of specific autoantibodies are currently tested by ELISA as a next step. Among the many autoantibody specificities described, some have been established as clinically useful diagnostic markers and are included in the classification criteria of diseases. Despite a long history of routine tests and attempts to standardize such assays, there are still limitations and problems that clinicians need to be aware of. Clinicians should be able to use autoantibody tests more efficiently and effectively with a basic knowledge on the significance of and potential problems in autoantibody tests. PMID:19277826

Predicting gestational age using neonatal metabolic markers

PubMed Central

Ryckman, Kelli K.; Berberich, Stanton L.; Dagle, John M.

2016-01-01

Background Accurate gestational age estimation is extremely important for clinical care decisions of the newborn as well as for perinatal health research. Although prenatal ultrasound dating is one of the most accurate methods for estimating gestational age, it is not feasible in all settings. Identifying novel and accurate methods for gestational age estimation at birth is important, particularly for surveillance of preterm birth rates in areas without routine ultrasound dating. Objective We hypothesized that metabolic and endocrine markers captured by routine newborn screening could improve gestational age estimation in the absence of prenatal ultrasound technology. Study Design This is a retrospective analysis of 230,013 newborn metabolic screening records collected by the Iowa Newborn Screening Program between 2004 and 2009. The data were randomly split into a model-building dataset (n = 153,342) and a model-testing dataset (n = 76,671). We performed multiple linear regression modeling with gestational age, in weeks, as the outcome measure. We examined 44 metabolites, including biomarkers of amino acid and fatty acid metabolism, thyroid-stimulating hormone, and 17-hydroxyprogesterone. The coefficient of determination (R2) and the root-mean-square error were used to evaluate models in the model-building dataset that were then tested in the model-testing dataset. Results The newborn metabolic regression model consisted of 88 parameters, including the intercept, 37 metabolite measures, 29 squared metabolite measures, and 21 cubed metabolite measures. This model explained 52.8% of the variation in gestational age in the model-testing dataset. Gestational age was predicted within 1 week for 78% of the individuals and within 2 weeks of gestation for 95% of the individuals. This model yielded an area under the curve of 0.899 (95% confidence interval 0.895−0.903) in differentiating those born preterm (<37 weeks) from those born term (≥37 weeks). In the subset of infants born small-for-gestational age, the average difference between gestational ages predicted by the newborn metabolic model and the recorded gestational age was 1.5 weeks. In contrast, the average difference between gestational ages predicted by the model including only newborn weight and the recorded gestational age was 1.9 weeks. The estimated prevalence of preterm birth <37 weeks’ gestation in the subset of infants that were small for gestational age was 18.79% when the model including only newborn weight was used, over twice that of the actual prevalence of 9.20%. The newborn metabolic model underestimated the preterm birth prevalence at 6.94% but was closer to the prevalence based on the recorded gestational age than the model including only newborn weight. Conclusions The newborn metabolic profile, as derived from routine newborn screening markers, is an accurate method for estimating gestational age. In small-for-gestational age neonates, the newborn metabolic model predicts gestational age to a better degree than newborn weight alone. Newborn metabolic screening is a potentially effective method for population surveillance of preterm birth in the absence of prenatal ultrasound measurements or newborn weight. PMID:26645954

Predicting gestational age using neonatal metabolic markers.

PubMed

Ryckman, Kelli K; Berberich, Stanton L; Dagle, John M

2016-04-01

Accurate gestational age estimation is extremely important for clinical care decisions of the newborn as well as for perinatal health research. Although prenatal ultrasound dating is one of the most accurate methods for estimating gestational age, it is not feasible in all settings. Identifying novel and accurate methods for gestational age estimation at birth is important, particularly for surveillance of preterm birth rates in areas without routine ultrasound dating. We hypothesized that metabolic and endocrine markers captured by routine newborn screening could improve gestational age estimation in the absence of prenatal ultrasound technology. This is a retrospective analysis of 230,013 newborn metabolic screening records collected by the Iowa Newborn Screening Program between 2004 and 2009. The data were randomly split into a model-building dataset (n = 153,342) and a model-testing dataset (n = 76,671). We performed multiple linear regression modeling with gestational age, in weeks, as the outcome measure. We examined 44 metabolites, including biomarkers of amino acid and fatty acid metabolism, thyroid-stimulating hormone, and 17-hydroxyprogesterone. The coefficient of determination (R(2)) and the root-mean-square error were used to evaluate models in the model-building dataset that were then tested in the model-testing dataset. The newborn metabolic regression model consisted of 88 parameters, including the intercept, 37 metabolite measures, 29 squared metabolite measures, and 21 cubed metabolite measures. This model explained 52.8% of the variation in gestational age in the model-testing dataset. Gestational age was predicted within 1 week for 78% of the individuals and within 2 weeks of gestation for 95% of the individuals. This model yielded an area under the curve of 0.899 (95% confidence interval 0.895-0.903) in differentiating those born preterm (<37 weeks) from those born term (≥37 weeks). In the subset of infants born small-for-gestational age, the average difference between gestational ages predicted by the newborn metabolic model and the recorded gestational age was 1.5 weeks. In contrast, the average difference between gestational ages predicted by the model including only newborn weight and the recorded gestational age was 1.9 weeks. The estimated prevalence of preterm birth <37 weeks' gestation in the subset of infants that were small for gestational age was 18.79% when the model including only newborn weight was used, over twice that of the actual prevalence of 9.20%. The newborn metabolic model underestimated the preterm birth prevalence at 6.94% but was closer to the prevalence based on the recorded gestational age than the model including only newborn weight. The newborn metabolic profile, as derived from routine newborn screening markers, is an accurate method for estimating gestational age. In small-for-gestational age neonates, the newborn metabolic model predicts gestational age to a better degree than newborn weight alone. Newborn metabolic screening is a potentially effective method for population surveillance of preterm birth in the absence of prenatal ultrasound measurements or newborn weight. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Screening of IR50 x Rathu Heenati F7 RILs and identification of SSR markers linked to brown planthopper (Nilaparvata lugens Stål) resistance in rice (Oryza sativa L.).

PubMed

Kumari, Sanju; M Sheba, Jennifer; Marappan, Maheshwaran; Ponnuswamy, Shanmugasunderam; Seetharaman, Suresh; Pothi, Nagarajan; Subbarayalu, Mohankumar; Muthurajan, Raveendran; Natesan, Senthil

2010-09-01

Brown planthopper (Nilaparvata lugens Stål) is one of the major insect pests of rice. A Sri Lankan indica rice cultivar Rathu Heenati was found to be resistant to all biotypes of the brown planthopper. In the present study, a total of 268 F(7) RILs of IR50 and Rathu Heenati were phenotyped for their level of resistance against BPH by the standard seedbox screening test (SSST) in the greenhouse. A total of 53 SSR primers mapped on the chromosome 3 were used to screen the polymorphism between the parents IR50 and Rathu Heenati, out of which eleven were found to be polymorphic between IR50 and Rathu Heenati. The eleven primers that have shown polymorphism between the IR50 and Rathu Heenati parents were genotyped in a set of five resistant RILs and five susceptible RILs along with the parents for co-segregation analysis. Among the eleven primers, two primers namely RM3180 (18.22 Mb) and RM2453 (20.19 Mb) showed complete co-segregation with resistance. The identification of SSR markers linked with BPH resistant could be used for the maker assisted selection (MAS) program in rice breeding and to map the resistant genes on rice chromosomes for further gene cloning.

Screening bioactive quality control markers of QiShenYiQi dripping pills based on the relationship between the ultra-high performance liquid chromatography fingerprint and vascular protective activity.

PubMed

Zhuo, Limeng; Peng, Jingjing; Zhao, Yunli; Li, Dongxiang; Xie, Xiuman; Tong, Ling; Yu, Zhiguo

2017-10-01

Traditional Chinese medicine consists of complex phytochemical constituents. Selecting appropriate analytical markers of traditional Chinese medicine is a critical step in quality control. Currently, the combination of fingerprinting and efficacy evaluation is considered as a useful method for screening active ingredients in complex mixtures. This study was designed to develop an orthogonal partial least squares model for screening bioactive quality control markers of QishenYiqi dripping pills based on the fingerprint-efficacy relationship. First, the chemical fingerprints of 49 batches of QishenYiqi dripping pill samples were established by ultra-high performance liquid chromatography coupled with a photodiode array detector. Second, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was exploited to systematically investigate the 36 copossessing fingerprint components in QishenYiqi dripping pills. The vascular protective activity of QishenYiqi dripping pills was determined by using a cell counting kit-8 assay. Finally, fingerprint-efficacy relationship was established by orthogonal partial least squares model. The results indicated that ten components exhibited strong correlation with vascular protective activity, and these were preliminarily screened as quality control markers. The present study provided a novel idea for the study of the pharmacodynamic material basis and quality evaluation of QishenYiqi dripping pills. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards a Modular, Robust, and Portable Sensing Platform for Biological and Point of Care Diagnostics

DTIC Science & Technology

2013-07-01

drugs at potentially very low concentrations in a variety of complex media such as saliva, blood, urine , and other bodily fluids. These handheld...flow assays, such as pregnancy tests, disease and drug abuse screens, and blood protein markers, exhibit widespread use. Recent parallel advances...gadgets have the potential to lower the cost of diagnosis and save immense amounts of time by removing the need to collect, preserve, and ship samples

Analytical validation of a novel multiplex test for detection of advanced adenoma and colorectal cancer in symptomatic patients.

PubMed

Dillon, Roslyn; Croner, Lisa J; Bucci, John; Kairs, Stefanie N; You, Jia; Beasley, Sharon; Blimline, Mark; Carino, Rochele B; Chan, Vicky C; Cuevas, Danissa; Diggs, Jeff; Jennings, Megan; Levy, Jacob; Mina, Ginger; Yee, Alvin; Wilcox, Bruce

2018-05-30

Early detection of colorectal cancer (CRC) is key to reducing associated mortality. Despite the importance of early detection, approximately 40% of individuals in the United States between the ages of 50-75 have never been screened for CRC. The low compliance with colonoscopy and fecal-based screening may be addressed with a non-invasive alternative such as a blood-based test. We describe here the analytical validation of a multiplexed blood-based assay that measures the plasma concentrations of 15 proteins to assess advanced adenoma (AA) and CRC risk in symptomatic patients. The test was developed on an electrochemiluminescent immunoassay platform employing four multi-marker panels, to be implemented in the clinic as a laboratory developed test (LDT). Under the Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologists (CAP) regulations, a United States-based clinical laboratory utilizing an LDT must establish performance characteristics relating to analytical validity prior to releasing patient test results. This report describes a series of studies demonstrating the precision, accuracy, analytical sensitivity, and analytical specificity for each of the 15 assays, as required by CLIA/CAP. In addition, the report describes studies characterizing each of the assays' dynamic range, parallelism, tolerance to common interfering substances, spike recovery, and stability to sample freeze-thaw cycles. Upon completion of the analytical characterization, a clinical accuracy study was performed to evaluate concordance of AA and CRC classifier model calls using the analytical method intended for use in the clinic. Of 434 symptomatic patient samples tested, the percent agreement with original CRC and AA calls was 87% and 92% respectively. All studies followed CLSI guidelines and met the regulatory requirements for implementation of a new LDT. The results provide the analytical evidence to support the implementation of the novel multi-marker test as a clinical test for evaluating CRC and AA risk in symptomatic individuals. Copyright © 2018 Elsevier B.V. All rights reserved.

Is the relationship between sedentary behaviour and cardiometabolic health in adolescents independent of dietary intake? A systematic review.

PubMed

Fletcher, E; Leech, R; McNaughton, S A; Dunstan, D W; Lacy, K E; Salmon, J

2015-09-01

Screen time, but not overall sedentary behaviour, is consistently related to cardiometabolic health in adolescents. Because of the associations screen time has with dietary intake, diet may be an important factor in the screen time and health relationship; however, evidence has not previously been synthesized. Thus, the aim of this systematic review was to explore whether the associations between various sedentary behaviours and cardiometabolic risk markers are independent of dietary intake in adolescents. Online databases and personal libraries were searched for peer-reviewed original research articles published in English before March 2014. Included studies assessed associations between sedentary behaviour and cardiometabolic markers in 12- to 18-year-olds and adjusted for dietary intake. Twenty-five studies met the inclusion criteria. From the 21 studies examining sedentary behaviour and adiposity, the majority found significant positive associations between television viewing, screen time and self-reported overall sedentary behaviour with markers of adiposity, independent of dietary intake. No significant associations between screen time with blood pressure and cholesterol were reported. Sedentary behaviour appears to be associated with adiposity in adolescents, irrespective of dietary intake. However, the variability of dietary variables between studies suggests further work is needed to understand the role of dietary intake when examining these associations in youth. © 2015 World Obesity.

Rv1458c: a new diagnostic marker for identification of Mycobacterium tuberculosis complex in a novel duplex PCR assay.

PubMed

Shrivastava, Kamal; Garima, Kushal; Narang, Anshika; Bhattacharyya, Kausik; Vishnoi, Ekta; Singh, Roshan Kumar; Chaudhry, Anil; Prasad, Rajendra; Bose, Mridula; Varma-Basil, Mandira

2017-03-01

We explored the efficiency of Rv1458c, the gene encoding a putative ABC drug transporter specific for the Mycobacterium tuberculosis complex (MTBC), as a diagnostic marker. A 190 bp region of Rv1458c and a 300 bp region of hsp65 were targeted in a novel duplex PCR assay and the results were compared with those for PCR restriction analysis(PRA) using the restriction enzymes NruI and BamHI. Species identification of a subset of the isolates (n=50) was confirmed by sequencing. Clinical isolates of M. tuberculosis (n=426) obtained from clinically suspected patients of pulmonary tuberculosis and mycobacterial (n=13) and non-mycobacterial (n=8) reference strains were included in the study. The duplex PCR assay correctly identified 320/426 isolates as MTBC and 106/426 isolates as non-tuberculous mycobacteria(NTM). The test was 100 % specific and sensitive when compared with NruI/BamHI PCR restriction analysis and highlighted the use of Rv1458c as a diagnostic marker for MTBC. The duplex PCR assay could be developed for use as a screening test to identify MTBC in clinical specimens in peripheral laboratories with limited resources.

Genetic Testing in Pancreatic Ductal Adenocarcinoma: Implications for Prevention and Treatment.

PubMed

Peters, Mary Linton B; Tseng, Jennifer F; Miksad, Rebecca A

2016-07-01

This article reviews the progress to date and future directions for investigation of germline and somatic genetic testing to inform pancreatic adenocarcinoma (PDAC) treatment, screening, and prevention strategies. We searched PubMed to identify recent articles regarding genetic testing in pancreatic cancer, including both germline and somatic testing, and recent genome-wide association studies. References were specifically hand searched as relevant. Guidelines for testing and screening high-risk individuals were included. We searched clinicaltrials.gov to review the current landscape of active clinical trials. Approximately 10% of PDACs are associated with an identified germline mutation. Although germline mutations may inform treatment options and identify high-risk individuals for screening in other cancers, the data on PDAC are only now emerging. For example, poly adenosine diphosphate ribose polymerase (PARP) inhibitors are under investigation for BRCA-associated PDAC. Somatic mutations have also been identified in PDAC. However, current data are limited regarding treatment for potential PDAC somatic driver mutations. Although erlotinib is used in PDAC, its use is not targeted based on a tumor marker. Many tyrosine kinase inhibitors targeted toward potential driver mutations and critical pathways are in development, including BRAF/MEK, ALK, and CDK4/6. A consensus on screening strategies for individuals at high risk for PDAC is still evolving because of the relatively low prevalence of the disease, the relative invasiveness of endoscopic procedures often used as part of screening, and the lack of a clear survival benefit. Pancreatic cancer has been slower to move toward genomic testing, partially because of a lower prevalence of mutations and partially because of a limited effect of results on treatment choices outside a clinical trial. This is an area of active investigation, and we anticipate that there will be both preventive and therapeutic implications of driver mutations in the coming decade. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma.

PubMed

Reznik, Robert; Hendifar, Andrew E; Tuli, Richard

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided.

Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma

PubMed Central

Reznik, Robert; Hendifar, Andrew E.; Tuli, Richard

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided. PMID:24624093

Hyalella IQ Toxicity Test{trademark} as a predictor of whole sediment toxicity with diversely contaminated sediments

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

Douglas, W.S.; Hayes, K.R.

1994-12-31

The IQ TOXICITY TEST{trademark} is a toxicity screening test that evaluates the organism`s galactosidase enzyme system functionality as a predictor of acute toxicity. Organisms are exposed to a potentially toxic solution for approximately one hour. Following the exposure, the organisms are exposed to a slurry of a galactoside sugar tagged with a fluorescent marker (methylumbelliferyl galactoside) for 15--20 minutes. A black light can then be used to examine whether the hemolymph of the organism contains free umbelliferone, which brightly fluoresces. The organisms are then scored as ``on`` or ``off`` with respect to free umbelliferone. This endpoint can then be usedmore » to calculate an EC50, which is comparable to a whole effluent, pure compound, or sediment toxicity test. Slightly different methodologies are used for different toxicity test organisms. The objective of this presentation is to discuss the use of the IQ{trademark} methodology with porewater extract exposures of the amphipod Hyalella azteca as a predictor of results of whole sediment toxicity tests. The results of over thirty 10 and 28-day whole sediment toxicity tests and the concurrent Hyalella azteca 10 TOXICITY TESTS{trademark} are compared and discussed. The use of screening tests as a reduced cost method for initial site assessment will be discussed.« less

Novel autoantibody markers for early and seronegative rheumatoid arthritis.

PubMed

Somers, Klaartje; Geusens, Piet; Elewaut, Dirk; De Keyser, Filip; Rummens, Jean-Luc; Coenen, Marieke; Blom, Marlies; Stinissen, Piet; Somers, Veerle

2011-02-01

Approximately one-third of rheumatoid arthritis (RA) patients are seronegative for the 2 serological RA markers, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACCP). Moreover, the sensitivities of both markers are lower in the diagnostically important early disease phase. The aim of this study was to identify additional autoantibody markers for early RA and for RF-negative, ACCP-negative (seronegative) RA. We screened an RA synovium cDNA phage display library with autoantibodies in plasma from 10 early (symptoms of maximum 1 year) and 10 seronegative (RF-negative, ACCP-negative) RA patients with validation in 72 additional RA patients and 121 controls (38 healthy controls, 43 patients with other inflammatory rheumatic diseases, 20 osteoarthritis patients and 20 subjects with mechanical joint complaints). Fourteen novel autoantibodies were identified that showed a 54% sensitivity and 90% specificity for RA. For 11 of these autoantibodies, an exclusive presence was demonstrated in RA patients (100% specificity, 37% sensitivity) as compared to controls. All early RA patients were positive for at least one of the identified autoantibodies and antibody-positivity was associated with a shorter disease duration (P = 0.0087). 52% of RA patients who initially tested negative for RF and ACCP, tested positive for at least one of the 14 novel autoantibodies, resulting in a 19% increase in sensitivity compared to current serological testing. Moreover, 5 identified autoantibodies were detected more frequently in seronegative RA patients, indicating that these autoantibodies constitute novel candidate markers for this RA subtype. We demonstrated that the targets of 3 of these 5 autoantibodies had an increased expression in RA synovial tissue compared to control synovial tissue, pointing towards a biological rationale for these auto antibody targets in RA. In conclusion, we identified novel candidate autoantibody markers for RA that can be detected in early and seronegative RA patients indicating the potential added value for RA diagnostics. Copyright © 2010 Elsevier Ltd. All rights reserved.

Diagnostic value of cystatin C for diagnosis of early renal damages in type 2 diabetic mellitus patients: The first experience in Iran

PubMed Central

Javanmardi, Mitra; Azadi, Namam-Ali; Amini, Sabrieh; Abdi, Mohammad

2015-01-01

Background: Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus. Now-a-days, cystatin C (CysC) is introduced as a new marker for diagnosis of renal damages; however, use of this marker in clinical laboratories is still controversial. The present study was aimed to evaluate the diagnostic value of serum CysC for early detection or monitoring treatment of kidney damages in the Kurdish people with type 2 diabetes mellitus. Materials and Methods: Glomerular filtration rate (GFR) was estimated by Modification of Diet in Renal Disease formula. Serum CysC and urine microalbumin were also measured in 126 diabetic and healthy subjects. Blood glycated hemoglobin (Hb) also measured in all healthy and diabetic patients. Two independent samples t-test, Mann-Whitney U-test, one-way ANOVA, and Kruskal-Wallis test, as well as Pearson/Spearman correlation coefficient statistical tests were used as appropriate. Results: Serum CysC was higher (1312.41 ng/ml) in diabetic patients with GFR <60 ml/min than other subjects (993.25 ng/ml) (patients with normal kidney function and healthy subjects). A borderline significant correlation between CysC and estimating GFR (rs = −0.16, P = 0.05) but highly significant with microalbumin (rs = 0.22, P = 0.014) was observed. Serum CysC sensitivity, negative and positive predictive values were 100 and 4%. Conclusion: CysC cover variation of GFR and urine microalbumin, but it cannot be used as a surrogating marker of glycated Hb. According to our results, it seems that serum CysC is a useful marker for screening of DN; but it cannot be used for monitoring of treatment in diabetic patients. PMID:26600832

Diagnostic value of screening tests in subgroups of women with recurrent pregnancy loss.

PubMed

Guzel, Ali Irfan; Erkılınç, Selçuk; Özer, Irfan; Celik, Yusuf; Yılmaz, Nafiye; Doğanay, Melike

2015-03-01

To evaluate the diagnostic value of screening laboratory tests in women who had recurrent pregnancy loss (RPL). A total of 252 women with RPL managed in our tertiary referral research and education hospital were included in the study. Risk factors recorded involved age, gravidity, parity, number of prior live births, number of pregnancy losses, and thrombophlia tests. The cases were divided into three different groups and each group was analyzed separately. There was no statistically significant difference between the first and second groups in terms of clinical and laboratory parameters (p > 0.05). In the third group, there was a statistically significant difference among cases in terms of parity, gravidity, number of pregnancy losses, serum AT III levels, APCR, and age of the women. According to the logistic regression model, odds ratios (95% CI) were 6.116 (3.797-9.852), 5.665 (2.657-12.079), 4.763 (3.099-7.321), 4.729 (3.080-7.260), 2.820 (1.836-4.333), and 1.911 (1.232-2.965), respectively. We do not recommend the screening of all women with RPL, but in women with high parity and those who had prior live birth pregnancies, increased AT III, and APCR may be diagnostic markers for subsequent pregnancy loss.

The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results.

PubMed

Mahon, Jeffrey L; Sosenko, Jay M; Rafkin-Mervis, Lisa; Krause-Steinrauf, Heidi; Lachin, John M; Thompson, Clinton; Bingley, Polly J; Bonifacio, Ezio; Palmer, Jerry P; Eisenbarth, George S; Wolfsdorf, Joseph; Skyler, Jay S

2009-04-01

TrialNet's goal to test preventions for type 1 diabetes has created an opportunity to gain new insights into the natural history of pre-type 1 diabetes. The TrialNet Natural History Study (NHS) will assess the predictive value of existing and novel risk markers for type 1 diabetes and will find subjects for prevention trials. The NHS is a three-phase, prospective cohort study. In phase 1 (screening), pancreatic autoantibodies (glutamic acid decarboxylase, insulin, ICA-512, and islet cell antibodies) are measured. Phase 2 (baseline risk assessment) includes oral glucose tolerance tests (OGTTs) in antibody-positive subjects and estimation of 5-yr diabetes risks according to the OGTT and number of confirmed positive antibody tests. Phase 3 (follow-up risk assessments) requires OGTTs every 6 months. In phases 2 and 3, samples are collected for future tests of T-lymphocyte function, autoantibody isotypes, RNA gene expression, and proteomics. The primary outcome is diabetes onset. Of 12 636 relatives screened between March 2004 and December 2006, 605 (4.8%) were positive for at least one biochemical antibody. Of these, 322 were confirmed antibody positive and completed phase 2, of whom 296 subjects were given preliminary 5-yr diabetes risks of <25% (n = 132), > or =25% (n = 36), and > or =50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, > or =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =50%). The NHS is identifying potential prevention trial subjects and is assembling a large cohort that will provide new natural history information about pre-type 1 diabetes. Follow-up to diabetes will help establish the biological significance and clinical value of novel type 1 diabetes risk markers.

Enabling multiplexed testing of pooled donor cells through whole-genome sequencing.

PubMed

Chan, Yingleong; Chan, Ying Kai; Goodman, Daniel B; Guo, Xiaoge; Chavez, Alejandro; Lim, Elaine T; Church, George M

2018-04-19

We describe a method that enables the multiplex screening of a pool of many different donor cell lines. Our method accurately predicts each donor proportion from the pool without requiring the use of unique DNA barcodes as markers of donor identity. Instead, we take advantage of common single nucleotide polymorphisms, whole-genome sequencing, and an algorithm to calculate the proportions from the sequencing data. By testing using simulated and real data, we showed that our method robustly predicts the individual proportions from a mixed-pool of numerous donors, thus enabling the multiplexed testing of diverse donor cells en masse.More information is available at https://pgpresearch.med.harvard.edu/poolseq/.

Expression of surface markers on the human monocytic leukaemia cell line, THP-1, as indicators for the sensitizing potential of chemicals.

PubMed

An, Susun; Kim, Seoyoung; Huh, Yong; Lee, Tae Ryong; Kim, Han-Kon; Park, Kui-Lea; Eun, Hee Chul

2009-04-01

Evaluation of skin sensitization potential is an important part of the safety assessment of cosmetic ingredients and topical drugs. Recently, evaluation of changes in surface marker expression induced in dendritic cells (DC) or DC surrogate cell lines following exposure to chemicals represents one approach for in vitro test methods. The study aimed to test the change of expression patterns of surface markers on THP-1 cells by chemicals as a predictive in vitro method for contact sensitization. We investigated the expression of CD54, CD86, CD83, CD80, and CD40 after a 1-day exposure to sensitizers (1-chloro-2,4-dinitrobenzene; 2,4-dinitrofluorobenzene; benzocaine; 5-chloro-2-methyl-4-isothiazolin-3-one; hexyl cinnamic aldehyde; eugenol; nickel sulfate hexahydrate; potassium dichromate; cobalt sulfate; 2-mercaptobenzothiazole; and ammonium tetrachloroplatinate) and non-sensitizers (sodium lauryl sulfate, benzalkonium chloride, lactic acid, salicylic acid, isopropanol, and dimethyl sulphoxide). The test concentrations were 0.1x, 0.5x, and 1x of the 50% inhibitory concentration, and the relative fluorescence intensity was used as an expression indicator. By evaluating the expression patterns of CD54, CD86, and CD40, we could classify the chemicals as sensitizers or non-sensitizers, but CD80 and CD83 showed non-specific patterns of expression. These data suggest that the THP-1 cells are good model for screening contact sensitizers and CD40 could be a useful marker complementary to CD54 and CD86.

Screening interspecific hybrids of Populus (P. ciliata x maximowiczii) using AFLP markers.

PubMed

Chauhan, N; Negi, M S; Sabharwal, V; Khurana, D K; Lakshmikumaran, M

2004-03-01

Hybrids of Populus ciliata x maximowiczii are very vigorous and outperform both the parents in growth performance and yield. Genetic evaluation of 24 of these interspecific hybrids along with the two mother trees ( Populus ciliata), and five male-parent ( Populus maximowiczii) genotypes was carried out using the AFLP marker assay. Eight AFLP primer combinations detected 428 markers, of which 280 (66%) were polymorphic. Genetic relationships within the samples were evaluated by generating the similarity matrix based on Jaccard's coefficient. The phenetic dendrograms, as well as the PCO plots, separated the hybrids and the two parent species into three distinct clusters. The hybrids grouped closer to the P. ciliata (female parent) cluster as compared to the P. maximowiczii (male parent) cluster. The hybrid cluster contained internal groupings, which correlated to some extent with growth performance. The four best performing hybrids (42m1, 65m1, 23m2, Cm2-5-20/91) formed a distinct sub-cluster. Data from a single primer combination was sufficient for distinguishing the hybrids from the parents and assigning paternity. The hybrids showed 22 markers that were absent in P. ciliata but were monomorphically present in all the hybrids, suggesting outcrossing and common paternity. Further, these 22 markers were found in all the P. maximowiczii genotypes confirming it as the male parent. These male-specific markers can be converted to SCAR markers and used for rapid screening of the P.ciliata x maximowiczii hybrids. The primer combination E-AAC x M-CAA was identified as most suitable for ascertaining true hybridity. AFLP proves to be a useful tool for screening of P. ciliata x maximowiczii hybrids at the early stages of development.

Microsatellite DNA markers detects 95% of chromosome 22q11 deletions

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

Bonnet, D.; Cormier-Daire, V.; Munnich, A.

Cono-truncal cardiac malformations account for some 50% of congenital heart defects in newborn infants. Recently, hemizygosity for chromosome 22q11.2 was reported in patients with the DiGeorge/Velo-cardio-facial syndromes (DGS/VCFS) and causally related disorders. We have explored the potential use of microsatellite DNA markers for rapid detection of 22q11 deletions in 19 newborn infants referred for cono-truncal heart malformations with associated DGS/VCFS anomalies. A failure of parental inheritance was documented in 84.2% of cases (16/19). PCR-based genotyping using microsatellite DNA markers located within the commonly deleted region allowed us either to confirm or reject a 22q11 microdeletion in 94.3% of cases (18/19)more » within 24 hours. This test is now currently performed in the infants referred to us for a cono-truncal heart malformation as a first intention screening for 22q11 microdeletion. 10 refs., 1 fig., 1 tab.« less

Allelism analysis of BrRfp locus in different restorer lines and map-based cloning of a fertility restorer gene, BrRfp1, for pol CMS in Chinese cabbage (Brassica rapa L.).

PubMed

Zhang, Huamin; Wu, Junqing; Dai, Zihui; Qin, Meiling; Hao, Lingyu; Ren, Yanjing; Li, Qingfei; Zhang, Lugang

2017-03-01

In Chinese cabbage, there are two Rf loci for pol CMS and one of them was mapped to a 12.6-kb region containing a potential candidate gene encoding PPR protein. In Chinese cabbage (Brassica rapa), polima cytoplasmic male sterility (pol CMS) is an important CMS type and is widely used for hybrid breeding. By extensive test crossing in Chinese cabbage, four restorer lines (92s105, 01s325, 00s109, and 88s148) for pol CMS were screened. By analyzing the allelism of the four restorer lines, it was found that 92s105, 01s325, and 00s109 had the same "restorers of fertility" (Rf) locus (designated as BrRfp1), but 88s148 had a different Rf locus (designated as BrRfp2). For fine mapping the BrRfp1 locus of 92s105, a BC 1 F 1 population with 487 individuals and a BC 1 F 2 population with 2485 individuals were successively constructed. Using simple sequence repeat (SSR) markers developed from Brassica rapa reference genome and InDel markers derived from whole-genome resequencing data of 94c9 and 92s105, BrRfp1 was mapped to a 12.6-kb region containing a potential candidate gene encoding pentatricopeptide repeat-containing protein. Based on the nucleotide polymorphisms of the candidate gene sequence between the restoring and nonrestoring alleles, a co-segregating marker SC718 was developed, which would be helpful for hybrid breeding by marker-assisted screening and for detecting new restorer lines.

Novel biotechnology approaches in colorectal cancer diagnosis and therapy.

PubMed

Kavousipour, Soudabeh; Khademi, Fathemeh; Zamani, Mozhdeh; Vakili, Bahareh; Mokarram, Pooneh

2017-06-01

With ever-increasing molecular information about colorectal cancer (CRC), there is an expectation to detect more sensitive and specific molecular markers for new advanced diagnostic methods that can surpass the limitations of current screening tests. Moreover, enhanced molecular pathology knowledge about cancer has led to the development of targeted therapies, designed to interfere with specific aberrant biological pathways in cancer. Furthermore, biotechnology has opened a new window in CRC diagnosis and treatment by introducing different application of antibodies, antibody fragments, non-Ig scaffold proteins, and aptamers in targeted therapy and drug delivery. This review summarizes the molecular diagnostic and therapeutic approaches in CRC with a focus on genetic and epigenetic alterations, protein and metabolite markers as well as targeted therapy and drug delivery by Ig-scaffold proteins, non-Ig scaffold proteins, nanobodies, and aptamers.

A pilot study on screening blood donors with individual-donation nucleic acid testing in China

PubMed Central

Dong, Jie; Wu, Yaling; Zhu, Hong; Li, Gan; Lv, Mengen; Wu, Daxiao; Li, Xiaotao; Zhu, Faming; Lv, Hangjun

2014-01-01

Background Nucleic acid amplification testing (NAT) is not yet obligatory in China for blood donor screening and the risk of enzyme immunoassay (EIA)-negative, NAT-reactive donations in Chinese blood donors has rarely been reported. The aim of this study was to screen a population of Chinese blood donors using a triplex individual-donation (ID)-NAT assay and assess the safety benefits of implementing NAT. Materials and methods Between 1st August, 2010 and 31st December, 2011 all donations at a Chinese blood centre were screened individually using the Procleix® Ultrio® assay, a multiplex NAT assay for the detection of hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human immunodeficiency virus-1 (HIV-1) RNA. All donations were also screened for HBsAg, anti-HIV and anti-HCV using two different EIA for each marker. Samples with discordant results between NAT and EIA were further tested with an alternative NAT assay (Cobas® TaqMan®). Potential yield cases (serologically negative/NAT-reactive donors) were further evaluated when possible. Results During the study period a total of 178,447 donations were screened by NAT and EIA, among which 169 HBV NAT yield cases (0.095%) were detected. No N AT yield cases were found for HIV-1 or HCV. For the HBV NAT yield cases, follow-up results showed that 11 (6.51%) were probable or confirmed HBV window period infections, 5 (2.96%) were chronic HBV carriers and 153 (90.53%) were probable or confirmed occult HBV infections. There was a statistically significant difference between the NAT-positive rates for first-time vs repeat donations (0.472% vs 0.146%, respectively; P<0.001). Discussion Our data demonstrate that the potential HBV yield rate was 1:1,056 for blood donations in the Zhejiang province of China. Implementation of NAT will provide a significant increment in safety relative to serological screening alone. PMID:24333061

Can We Predict Technical Aptitude?: A Systematic Review.

PubMed

Louridas, Marisa; Szasz, Peter; de Montbrun, Sandra; Harris, Kenneth A; Grantcharov, Teodor P

2016-04-01

To identify background characteristics and cognitive tests that may predict surgical trainees' future technical performance, and therefore be used to supplement existing surgical residency selection criteria. Assessment of technical skills is not commonly incorporated as part of the selection process for surgical trainees in North America. Emerging evidence, however, suggests that not all trainees are capable of reaching technical competence. Therefore, incorporating technical aptitude into selection processes may prove useful. A systematic search was carried out of the MEDLINE, PsycINFO, and Embase online databases to identify all studies that assessed associations between surrogate markers of innate technical abilities in surgical trainees, and whether these abilities correlate with technical performance. The quality of each study was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation system. A total of 8035 records were identified. After screening by title, abstract, and full text, 52 studies were included. Very few surrogate markers were found to predict technical performance. Significant associations with technical performance were seen for 1 of 23 participant-reported surrogate markers, 2 of 25 visual spatial tests, and 2 of 19 dexterity tests. The assessment of trainee Basic Performance Resources predicted technical performance in 62% and 75% of participants. To date, no single test has been shown to reliably predict the technical performance of surgical trainees. Strategies that rely on assessing multiple innate abilities, their interaction, and their relationship with technical skill may ultimately be more likely to serve as reliable predictors of future surgical performance.

Novel SSR Markers from BAC-End Sequences, DArT Arrays and a Comprehensive Genetic Map with 1,291 Marker Loci for Chickpea (Cicer arietinum L.)

PubMed Central

Nayak, Spurthi N.; Varghese, Nicy; Shah, Trushar M.; Penmetsa, R. Varma; Thirunavukkarasu, Nepolean; Gudipati, Srivani; Gaur, Pooran M.; Kulwal, Pawan L.; Upadhyaya, Hari D.; KaviKishor, Polavarapu B.; Winter, Peter; Kahl, Günter; Town, Christopher D.; Kilian, Andrzej; Cook, Douglas R.; Varshney, Rajeev K.

2011-01-01

Chickpea (Cicer arietinum L.) is the third most important cool season food legume, cultivated in arid and semi-arid regions of the world. The goal of this study was to develop novel molecular markers such as microsatellite or simple sequence repeat (SSR) markers from bacterial artificial chromosome (BAC)-end sequences (BESs) and diversity arrays technology (DArT) markers, and to construct a high-density genetic map based on recombinant inbred line (RIL) population ICC 4958 (C. arietinum)×PI 489777 (C. reticulatum). A BAC-library comprising 55,680 clones was constructed and 46,270 BESs were generated. Mining of these BESs provided 6,845 SSRs, and primer pairs were designed for 1,344 SSRs. In parallel, DArT arrays with ca. 15,000 clones were developed, and 5,397 clones were found polymorphic among 94 genotypes tested. Screening of newly developed BES-SSR markers and DArT arrays on the parental genotypes of the RIL mapping population showed polymorphism with 253 BES-SSR markers and 675 DArT markers. Segregation data obtained for these polymorphic markers and 494 markers data compiled from published reports or collaborators were used for constructing the genetic map. As a result, a comprehensive genetic map comprising 1,291 markers on eight linkage groups (LGs) spanning a total of 845.56 cM distance was developed (http://cmap.icrisat.ac.in/cmap/sm/cp/thudi/). The number of markers per linkage group ranged from 68 (LG 8) to 218 (LG 3) with an average inter-marker distance of 0.65 cM. While the developed resource of molecular markers will be useful for genetic diversity, genetic mapping and molecular breeding applications, the comprehensive genetic map with integrated BES-SSR markers will facilitate its anchoring to the physical map (under construction) to accelerate map-based cloning of genes in chickpea and comparative genome evolution studies in legumes. PMID:22102885

Higher Expression of miR-182 in Cytology Specimens of High-Grade Urothelial Cell Carcinoma: A Potential Diagnostic Marker.

PubMed

Wei, Shuanzeng; Bing, Zhanyong; Yao, Yuan; Master, Stephen R; Gupta, Prabodh

2015-01-01

MicroRNAs (miRs) are short noncoding RNA molecules that posttranscriptionally modulate protein expression. There are distinct miR alterations characterizing urothelial cell carcinoma (UCC) of the urinary bladder. In this study, we investigate the possibility of using miR as a noninvasive marker in the screening of UCC. The total RNA was extracted from 75 cytology specimens including bladder or renal washings and voided urines. Cases comprise UCC (21 high grade and 6 low grade), 25 normal controls and 23 cases with a history of UCC but negative at the time of testing (negative with a positive history). The expressions of miR-96, miR-182, miR-183, miR-200c, miR-21, miR-141 and miR-30b were determined using quantitative TaqMan real-time PCR. This study shows that the level of miR-182 is higher in cytology specimens from high-grade UCC patients as compared to normal controls. Measuring miR-182 may provide a potential alternative or adjunct approach for screening high-grade UCC. © 2015 S. Karger AG, Basel.

Resolving kangaroo phylogeny and overcoming retrotransposon ascertainment bias.

PubMed

Dodt, William G; Gallus, Susanne; Phillips, Matthew J; Nilsson, Maria A

2017-12-01

Reconstructing phylogeny from retrotransposon insertions is often limited by access to only a single reference genome, whereby support for clades that do not include the reference taxon cannot be directly observed. Here we have developed a new statistical framework that accounts for this ascertainment bias, allowing us to employ phylogenetically powerful retrotransposon markers to explore the radiation of the largest living marsupials, the kangaroos and wallabies of the genera Macropus and Wallabia. An exhaustive in silico screening of the tammar wallaby (Macropus eugenii) reference genome followed by experimental screening revealed 29 phylogenetically informative retrotransposon markers belonging to a family of endogenous retroviruses. We identified robust support for the enigmatic swamp wallaby (Wallabia bicolor) falling within a paraphyletic genus, Macropus. Our statistical approach provides a means to test for incomplete lineage sorting and introgression/hybridization in the presence of the ascertainment bias. Using retrotransposons as "molecular fossils", we reveal one of the most complex patterns of hemiplasy yet identified, during the rapid diversification of kangaroos and wallabies. Ancestral state reconstruction incorporating the new retrotransposon phylogenetic information reveals multiple independent ecological shifts among kangaroos into more open habitats, coinciding with the Pliocene onset of increased aridification in Australia from ~3.6 million years ago.

Values of molecular markers in the differential diagnosis of thyroid abnormalities.

PubMed

Tennakoon, T M P B; Rushdhi, M; Ranasinghe, A D C U; Dassanayake, R S

2017-06-01

Thyroid cancer (TC), follicular adenoma (FA) and Hashimoto's thyroiditis (HT) are three of the most frequently reported abnormalities that affect the thyroid gland. A frequent co-occurrence along with similar histopathological features is observed between TC and FA as well as between TC and HT. The conventional diagnostic methods such as histochemical analysis present complications in differential diagnosis when these abnormalities occur simultaneously. Hence, the authors recognize novel methods based on screening genetic defects of thyroid abnormalities as viable diagnostic and prognostic methods that could complement the conventional methods. We have extensively reviewed the existing literature on TC, FA and HT and also on three genes, namely braf, nras and ret/ptc, that could be used to differentially diagnose the three abnormalities. Emphasis was also given to the screening methods available to detect the said molecular markers. It can be conferred from the analysis of the available data that the utilization of braf, nras and ret/ptc as markers for the therapeutic evaluation of FA and HT is debatable. However, molecular screening for braf, nras and ret/ptc mutations proves to be a conclusive method that could be employed to differentially diagnose TC from HT and FA in the instance of a suspected co-occurrence. Thyroid cancer patients can be highly benefited from the screening for the said genetic markers, especially the braf gene due to its diagnostic value as well as due to the availability of personalized medicine targeted specifically for braf mutants.

Association mapping of iron deficiency chlorosis loci in soybean (Glycine max L. Merr.) advanced breeding lines.

PubMed

Wang, Ju; McClean, Phillip E; Lee, Rian; Goos, R Jay; Helms, Ted

2008-04-01

Association mapping is an alternative to mapping in a biparental population. A key to successful association mapping is to avoid spurious associations by controlling for population structure. Confirming the marker/trait association in an independent population is necessary for the implementation of the marker in other genetic studies. Two independent soybean populations consisting of advanced breeding lines representing the diversity within maturity groups 00, 0, and I were screened in multi-site, replicated field trials to discover molecular markers associated with iron deficiency chlorosis (IDC), a major yield-limiting factor in soybean. Lines with extreme phenotypes were initially screened to identify simple sequence repeat (SSR) markers putatively associated with the IDC. Marker data collected from all lines were used to control for population structure and kinship relationships. Single factor analysis of variance (SFA) and mixed linear model (MLM) analyses were used to discover marker/trait associations. The MLM analyses, which include population structure, kinship or both factors, reduced the number of markers significantly associated with IDC by 50% compared with SFA. With the MLM approach, three markers were found to be associated with IDC in the first population. Two of these markers, Satt114 and Satt239, were also found to be associated with IDC in the second confirmation population. For both populations, those lines with the tolerance allele at both these two marker loci had significantly lower IDC scores than lines with one or no tolerant alleles.

Serum markers for prostate cancer: a rational approach to the literature.

PubMed

Steuber, Thomas; O'Brien, Matthew Frank; Lilja, Hans

2008-07-01

Due to its universal applicability for early detection and prediction of cancer stage and disease recurrence, widespread implementation of serum-based prostate-specific antigen (PSA) measurements has a significant influence on current treatment strategies for men with prostate cancer (PCa). However, over-detection and the resultant over-treatment of indolent cancers have been strongly implicated to occur. Using current recommended guidelines, the PSA test suffers from both limited sensitivity and specificity to enable efficacious population-based cancer detection. Therefore, novel biomarkers are much needed to complement PSA by enhancing its diagnostic and prognostic performance. The present literature on serum markers for PCa was reviewed. PSA derivatives, molecular PSA isoforms, and novel molecular targets in blood were summarized and weighted against their potential to improve decision-making of men with PCa. Current evidence suggests that no single analyte is likely to achieve the desired level of diagnostic and prognostic accuracy for PCa. However, the combination of biomarkers with clinical and demographic data, for example, using established standard nomograms, has produced progress toward the goal of both optimal screening and risk assessment. Furthermore, potential candidate molecular markers for PCa can be derived from high-throughput technologies. Current studies demonstrate that understanding dynamic PSA changes over time may offer diagnostic and prognostic information. Bridging the gap between basic science and clinical practice represents the main goal in the near future to enable physicians to tailor risk-adjusted screening and treatment strategies for current patients with PCa.

[Linkage analysis of a family with familial hypertriglyceridemia].

PubMed

Tang, Xin; Lin, Ying; Liu, Bing; Ma, Shi; Yang, Yang; Yang, Zheng-lin

2009-10-01

To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen.

PubMed

Woodruff, Samantha A; Sontag, Marci K; Accurso, Frank J; Sokol, Ronald J; Narkewicz, Michael R

2017-01-01

Prevalence and risks for elevated liver enzymes have not been studied systematically in children with CF identified by newborn screen. 298 CF children identified by newborn screen since 1982. AST, ALT and GGT tested at annual visits. Percent of children with 1 or ≥2 values of elevated AST, ALT and GGT determined. Relationship of liver enzymes to clinical factors or subsequent liver disease was analyzed RESULTS: At least one abnormal value for AST (63%), ALT (93%) and ALT ≥1.5× ULN (52%) occurred by 21years of age. Liver enzyme elevations were not correlated with CFTR mutation, meconium ileus or ethnicity. AST and GGT ≥1.5× ULN were associated with later advanced liver disease HR (CI) 6.53 (2.02-21.1) and 4.03 (1.15-13.45), respectively. Elevated liver enzymes are common during childhood in CF patients identified by newborn screen. Elevated AST and GGT may be markers for risk of advanced liver disease. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Nuchal translucency and first trimester risk assessment: a systematic review.

PubMed

Sheppard, Celeste; Platt, Lawrence D

2007-06-01

First-trimester risk assessment for fetal aneuploidy using nuchal translucency (NT) measurement is rapidly gaining popularity in the United States. In combination with maternal serum markers in the first trimester, the screening performance is exceptionally good, with detection rates of more than 80% at a screen positive rate of 5%. Recently, the method has been validated for screening for Down syndrome and other aneuploidies in multicenter trials in the United States and elsewhere. Compliance with established criteria for measurement of the NT is essential to achieve uniform reliability and high screening test sensitivity. There is an international consensus about the importance of specific training in the NT examination, conformity to standards of NT measurement, and regular audit for quality assurance. In the United States, the Nuchal Translucency Quality Review program has been developed to administer credentialing and quality review for registered practitioners. The Nuchal Translucency Quality Review credentials signify the proficiency of the sonographer or sonologist in NT measurement and participation in a regular quality assurance audit. We encourage accreditation of clinical sites offering first-trimester risk assessment to ensure the highest quality care.

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis.

PubMed

Vordenbäumen, Stefan; Lueking, Angelika; Budde, Petra; Zucht, Hans-Dieter; Goehler, Heike; Brinks, Ralph; Fischer-Betz, Rebecca; Richter, Jutta; Bleck, Ellen; Detert, Jacqueline; Langer, Hans-Eckhard; Sörgel, Anne; Burmester, Gerd-Rüdiger; Schulz-Knappe, Peter; Schneider, Matthias

2016-10-12

The aim was to identify novel diagnostic autoantibody candidates for rheumatoid arthritis (RA) by comprehensive screening for autoreactivity. We incubated 5892 recombinant proteins coupled to fluorescent beads, with patients' sera for the detection of IgG-autoantibodies in three independent patient cohorts: A (n = 72 patients with established RA); B/B- (n = 116 patients with early RA (B) and n = 51 CCP-negative patients with early RA from B (B-)); and C (n = 184 patients with early seronegative RA), in comparison to matched healthy controls. Intersects of significantly increased autoantibodies as determined by the Mann-Whitney test were sought. Screening of 5892 antigens in RA cohorts A and B, or the seronegative cohorts B- and C revealed intersects of 23 and 13 significantly increased autoantibodies, respectively. Reactivity to three antigens was increased in all cohorts tested: N-acetylglucosamine-1-phosphate transferase, gamma subunit (GNPTG), heterogeneous nuclear ribonucleoprotein A1-like 2 (HNRNPA1), and insulin-like growth factor binding protein 2 (IGFBP2). Comprehensive sequential screening for autoantibodies reveals novel candidates for diagnostic markers in both seropositive and seronegative RA and suggests new fields of research into the pathogenesis of RA.

The double-antigen ELISA concept for early detection of Erns -specific classical swine fever virus antibodies and application as an accompanying test for differentiation of infected from marker vaccinated animals.

PubMed

Meyer, D; Fritsche, S; Luo, Y; Engemann, C; Blome, S; Beyerbach, M; Chang, C-Y; Qiu, H-J; Becher, P; Postel, A

2017-12-01

Emergency vaccination with live marker vaccines represents a promising control strategy for future classical swine fever (CSF) outbreaks, and the first live marker vaccine is available in Europe. Successful implementation is dependent on a reliable accompanying diagnostic assay that allows differentiation of infected from vaccinated animals (DIVA). As induction of a protective immune response relies on virus-neutralizing antibodies against E2 protein of CSF virus (CSFV), the most promising DIVA strategy is based on detection of E rns -specific antibodies in infected swine. The aim of this study was to develop and to evaluate a novel E rns -specific prototype ELISA (pigtype CSFV E rns Ab), which may be used for CSF diagnosis including application as an accompanying discriminatory test for CSFV marker vaccines. The concept of a double-antigen ELISA was shown to be a solid strategy to detect E rns -specific antibodies against CSFV isolates of different genotypes (sensitivity: 93.5%; specificity: 99.7%). Furthermore, detection of early seroconversion is advantageous compared with a frequently used CSFV E2 antibody ELISA. Clear differences in reactivity between sera taken from infected animals and animals vaccinated with various marker vaccines were observed. In combination with the marker vaccine CP7_E2alf, the novel ELISA represents a sensitivity of 90.2% and a specificity of 93.8%. However, cross-reactivity with antibodies against ruminant pestiviruses was observed. Interestingly, the majority of samples tested false-positive in other E rns -based antibody ELISAs were identified correctly by the novel prototype E rns ELISA and vice versa. In conclusion, the pigtype CSFV E rns Ab ELISA can contribute to an improvement in routine CSFV antibody screening, particularly for analysis of sera taken at an early time point after infection and is applicable as a DIVA assay. An additional E rns antibody assay is recommended for identification of false-positive results in a pig herd immunized with the licensed CP7_E2alf marker vaccine. © 2017 Blackwell Verlag GmbH.

Weak cation exchange magnetic beads coupled with matrix-assisted laser desorption ionization-time of flight-mass spectrometry in screening serum protein markers in osteopenia.

PubMed

He, Wei-Tao; Liang, Bo-Cheng; Shi, Zhen-Yu; Li, Xu-Yun; Li, Chun-Wen; Shi, Xiao-Lin

2016-01-01

The present study aimed at investigating the weak cation magnetic separation technology and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) in screening serum protein markers of osteopenia from ten postmenopausal women and ten postmenopausal women without osteopenia as control group, to find a new method for screening biomarkers and establishing a diagnostic model for primary type I osteoporosis. Serum samples were collected from postmenopausal women with osteopenia and postmenopausal women with normal bone mass. Proteins were extracted from serum samples by weak cation exchange magnetic beads technology, and mass spectra acquisition was done by MALDI-TOF-MS. The visualization and comparison of data sets, statistical peak evaluation, model recognition, and discovery of biomarker candidates were handled by the proteinchip data analysis system software(ZJU-PDAS). The diagnostic models were established using genetic arithmetic based support vector machine (SVM). The SVM result with the highest Youden Index was selected as the model. Combinatorial Peaks having the highest accuracy in distinguishing different samples were selected as potential biomarker. From the two group serum samples, a total of 133 differential features were selected. Ten features with significant intensity differences were screened. In the pair-wise comparisons, processing of MALDI-TOF spectra resulted in the identification of ten differential features between postmenopausal women with osteopenia and postmenopausal women with normal bone mass. The difference of features by Youden index showed that the highest features had a mass to charge ratio of 1699 and 3038 Da. A diagnosis model was established with these two peaks as the candidate marker, and the specificity of the model is 100 %, the sensitivity was 90 % by leave-one-out cross validation test. The two groups of specimens in SVM results on the scatter plot could be clearly distinguished. The peak with m/z 3038 in the SVM model was suggested as Secretin by TagIdent tool. To provide further validation, the secretin levels in serum were analyzed using enzyme-linked immunosorbent assays that is a competitive inhibition enzyme immunoassay technique for the in vitro quantitative measurement of secretin in human serum.

Screening for abnormal vaginal microflora by self-assessed vaginal pH does not enable detection of sexually transmitted infections in Ugandan women.

PubMed

Donders, Gilbert G G; Donders, Francesca; Bellen, Gert; Depuydt, Christophe; Eggermont, Natalie; Michiels, Thirsa; Lule, John; Byamughisa, Jacobat

2016-06-01

Is self-assessed vaginal pH measurement to detect abnormal vaginal bacterial microflora (AVF) an adequate prescreening method for detection of genital sexually transmitted infections (STIs)? A total of 360 Ugandan women tested themselves with a gloved finger and a pH color strip. PCR for bacterial vaginosis (BV)-associated bacteria was tested by PCR for Mycoplasma hominis, Ureaplasma urealyticum, and/or Atopobium vaginae, while the STIs were diagnosed by positive PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and/or Trichomonas vaginalis. A strong correlation was found between self-assessed pH values and BV-associated bacteria (P<0.0001), but not with STIs, not as single infections, nor in general. Self-measured vaginal pH correlated well with markers of high-risk microflora types such as BV or aerobic vaginitis, but not with STIs. Hence, in a screening program addressing AVF in low-resource countries, extra specific tests are required to exclude STIs. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparing the cost-effectiveness of four novel risk markers for screening asymptomatic individuals to prevent cardiovascular disease (CVD) in the US population.

PubMed

van Kempen, Bob J H; Ferket, Bart S; Steyerberg, Ewout W; Max, Wendy; Myriam Hunink, M G; Fleischmann, Kirsten E

2016-01-15

High sensitivity CRP (hsCRP), coronary artery calcification on CT (CT calcium), carotid artery intima media thickness on ultrasound (cIMT) and ankle-brachial index (ABI) improve prediction of cardiovascular disease (CVD) risk, but the benefit of screening with these novel risk markers in the U.S. population is unclear. A microsimulation model evaluating lifelong cost-effectiveness for individuals aged 40-85 at intermediate risk of CVD, using 2003-2004 NHANES-III (N=3736), Framingham Heart Study, U.S. Vital Statistics, meta-analyses of independent predictive effects of the four novel risk markers and treatment effects was constructed. Using both an intention-to-treat (assumes adherence <100% and incorporates disutility from taking daily medications) and an as-treated (100% adherence and no disutility) analysis, quality adjusted life years (QALYs), lifetime costs (2014 US $), and incremental cost-effectiveness ratios (ICER in $/QALY gained) of screening with hsCRP, CT coronary calcium, cIMT and ABI were established compared with current practice, full adherence to current guidelines, and ubiquitous statin therapy. In the intention-to-treat analysis in men, screening with CT calcium was cost effective ($32,900/QALY) compared with current practice. In women, screening with hsCRP was cost effective ($32,467/QALY). In the as-treated analysis, statin therapy was both more effective and less costly than all other strategies for both men and women. When a substantial disutility from taking daily medication is assumed, screening men with CT coronary calcium is likely to be cost-effective whereas screening with hsCRP has value in women. The individual perceived disutility for taking daily medication should play a key role in the decision. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening.

PubMed

Tong, Zhi-Bin; Hogberg, Helena; Kuo, David; Sakamuru, Srilatha; Xia, Menghang; Smirnova, Lena; Hartung, Thomas; Gerhold, David

2017-02-01

More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

PubMed

Diez-Perez, A; Naylor, K E; Abrahamsen, B; Agnusdei, D; Brandi, M L; Cooper, C; Dennison, E; Eriksen, E F; Gold, D T; Guañabens, N; Hadji, P; Hiligsmann, M; Horne, R; Josse, R; Kanis, J A; Obermayer-Pietsch, B; Prieto-Alhambra, D; Reginster, J-Y; Rizzoli, R; Silverman, S; Zillikens, M C; Eastell, R

2017-03-01

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

A reporter system for replication-competent gammaretroviruses: the inGluc-MLV-DERSE assay

PubMed Central

Aloia, Amanda L.; Duffy, Lisa; Pak, Vladimir; Lee, KyeongEun; Sanchez-Martinez, Silvia; Derse, David; Heidecker, Gisela; Cornetta, Kenneth; Rein, Alan

2012-01-01

While novel retroviral vectors for use in gene-therapy products are reducing the potential for formation of replication-competent retrovirus (RCR), it remains crucial to screen products for RCR for both research and clinical purposes. For clinical grade gammaretrovirus-based vectors, RCR screening is achieved by an extended S+L− or marker rescue assay, while standard methods for replication-competent lentivirus detection are still in development. In this report, we describe a rapid and sensitive method for replication-competent gammaretrovirus detection. We used this assay to detect three members of the gammaretrovirus family and compared the sensitivity of our assay with well-established methods for retrovirus detection, including the extended S+L− assay. Results presented here demonstrate that this assay should be useful for gene-therapy product testing. PMID:22402321

Antenatal diagnosis of Down syndrome: how good is state of the art.

PubMed

Mittal, Riju; Varghese, Raji Mathew; Puliyel, Jacob M

2009-01-01

A newborn with Down syndrome can be expected once in a thousand deliveries. Amniocentesis for karyotyping of foetal cells or detection of foetal cell in the maternal circulation ie, fluorescent in-situ hybridisation (FISH) and karyotyping, are definitive methods of making the diagnosis antenatally. The cost of doing this routinely in all pregnancies is prohibitive. This has led to dependence on screening tests, to select women more likely to be carrying a Down foetus, to offer karyotyping in a more cost efficient manner. Unfortunately, these screening criteria, namely maternal age, biochemical markers and ultrasound pointers, are rather insensitive and miss a large number of cases of Down syndrome. At the same time they are very non-specific, picking up a large number of false positive cases, resulting in undue anxiety and unnecessary alarm in a large number of mothers. Till a non-invasive, definitive test, like FISH can be routinely used in all pregnancies at affordable costs, accurate antenatal diagnosis on a community basis will be a hit and miss affair.

Intelligent Noninvasive Diagnosis of Aneuploidy: Raw Values and Highly Imbalanced Dataset.

PubMed

Neocleous, Andreas C; Nicolaides, Kypros H; Schizas, Christos N

2017-09-01

The objective of this paper is to introduce a noninvasive diagnosis procedure for aneuploidy and to minimize the social and financial cost of prenatal diagnosis tests that are performed for fetal aneuploidies in an early stage of pregnancy. We propose a method by using artificial neural networks trained with data from singleton pregnancy cases, while undergoing first trimester screening. Three different datasets 1 with a total of 122 362 euploid and 967 aneuploid cases were used in this study. The data for each case contained markers collected from the mother and the fetus. This study, unlike previous studies published by the authors for a similar problem differs in three basic principles: 1) the training of the artificial neural networks is done by using the markers' values in their raw form (unprocessed), 2) a balanced training dataset is created and used by selecting only a representative number of euploids for the training phase, and 3) emphasis is given to the financials and suggest hierarchy and necessity of the available tests. The proposed artificial neural networks models were optimized in the sense of reaching a minimum false positive rate and at the same time securing a 100% detection rate for Trisomy 21. These systems correctly identify other aneuploidies (Trisomies 13&18, Turner, and Triploid syndromes) at a detection rate greater than 80%. In conclusion, we demonstrate that artificial neural network systems can contribute in providing noninvasive, effective early screening for fetal aneuploidies with results that compare favorably to other existing methods.

Screening for chronic kidney disease of uncertain aetiology in Sri Lanka: usability of surrogate biomarkers over dipstick proteinuria.

PubMed

Ratnayake, Samantha; Badurdeen, Zeid; Nanayakkara, Nishantha; Abeysekara, Tilak; Ratnatunga, Neelakanthi; Kumarasiri, Ranjith

2017-06-19

The use of dipstick proteinuria to screen Chronic Kidney Disease of uncertain aetiology (CKDu) in Sri Lanka is a recently debated matter of dispute. The aim of this study was to assess the suitability of biomarkers: serum creatinine, cystatin C and urine albumin to creatinine ratio (ACR) for screening CKDu in Sri Lanka. Forty-four male CKDu patients and 49 healthy males from a CKDu-endemic region were selected. Meanwhile, 25 healthy males from a non-endemic region were selected as an absolute control. The diagnostic accuracy of each marker was compared using the above three study groups. In receiver operating characteristics (ROC) plots for creatinine, cystatin C and ACR, values of area under the curve (AUC) were 0.926, 0.920 and 0.737 respectively when CKDu was compared to non-endemic control. When CKDu was compared to endemic control, AUCs of above three analytes were distinctly lower as 0.718, 0.808 and 0.678 respectively. Cystatin C exhibited the highest sensitivity for CKDu when analyzed against both control groups where respective sensitivities were 0.75 against endemic control and 0.89 against non-endemic control. ROC-optimal cutoff limits of creatinine, cystatin C and ACR in CKDu vs non-endemic control were 89.0 μmol/L, 1.01 mg/L and 6.06 mg/g-Cr respectively, whereas in CKDu vs endemic control the respective values were 111.5 μmol/L, 1.22 mg/L and 12.66 mg/g-Cr. Amongst the three biomarkers evaluated in this study, our data suggest that Cystatin C is the most accurate functional marker in detecting CKDu in endemic regions, yet the high cost hinders its usability on general population. Creatinine is favorable over dipstick proteinuria owing to its apparent accuracy and cost efficiency, while having the ability to complement the kidney damage marker (ACR) in screening. ACR may not be favorable as a standalone screening marker in place of dipstick proteinuria due to its significant decline in sensitivity against the CKDu-endemic population. However, creatinine and ACR in a complementary manner could overcome current shortcomings of dipstick proteinuria and such a dual marker tool could be commodious in screening CKDu-type tubulointerstital diseases. Furthermore, use of ACR may also increase the ability to clinically discriminate CKDu from other glomerular nephropathies.

A Rational Approach for Discovering and Validating Cancer Markers in Very Small Samples Using Mass Spectrometry and ELISA Microarrays

DOE PAGES

Zangar, Richard C.; Varnum, Susan M.; Covington, Chandice Y.; ...

2004-01-01

Identifying useful markers of cancer can be problematic due to limited amounts of sample. Some samples such as nipple aspirate fluid (NAF) or early-stage tumors are inherently small. Other samples such as serum are collected in larger volumes but archives of these samples are very valuable and only small amounts of each sample may be available for a single study. Also, given the diverse nature of cancer and the inherent variability in individual protein levels, it seems likely that the best approach to screen for cancer will be to determine the profile of a battery of proteins. As a result,more » a major challenge in identifying protein markers of disease is the ability to screen many proteins using very small amounts of sample. In this review, we outline some technological advances in proteomics that greatly advance this capability. Specifically, we propose a strategy for identifying markers of breast cancer in NAF that utilizes mass spectrometry (MS) to simultaneously screen hundreds or thousands of proteins in each sample. The best potential markers identified by the MS analysis can then be extensively characterized using an ELISA microarray assay. Because the microarray analysis is quantitative and large numbers of samples can be efficiently analyzed, this approach offers the ability to rapidly assess a battery of selected proteins in a manner that is directly relevant to traditional clinical assays.« less

Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

PubMed

Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-02-01

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of stillbirth, including fetal growth restriction. The development of "omic" technologies presents a huge opportunity to identify novel biomarkers for fetal growth restriction. The hope is that when such markers are measured alongside ultrasonic fetal biometry, the combination would have strong predictive power for fetal growth restriction and its related complications. However, a series of important methodological considerations in assessing the diagnostic effectiveness of new tests will have to be addressed. The challenge thereafter will be to identify novel disease-modifying interventions, which are the essential partner to an effective screening test to achieve clinically effective population-based screening. Copyright © 2017 Elsevier Inc. All rights reserved.

Associations Between Religion-Related Factors and Cervical Cancer Screening Among Muslims in Greater Chicago

PubMed Central

Padela, Aasim I.; Peek, Monica; Johnson-Agbakwu, Crista E.; Hosseinian, Zahra; Curlin, Farr

2015-01-01

Objective This study aimed to assess rates of Papanicolaou (Pap) testing and associations between religion-related factors and these rates among a racially and ethnically diverse sample of American Muslim women. Materials and Methods A community-based participatory research design was used in partnering with the Council of Islamic Organizations of Greater Chicago to recruit Muslim women attending mosque and community events. These participants self-administered surveys incorporating measures of fatalism, religiosity, perceived discrimination, Islamic modesty, and a marker of Pap test use. Results A total of 254 survey respondents were collected with nearly equal numbers of Arabs, South Asians, and African American respondents. Of these respondents, 84% had obtained a Pap test in their lifetime, with individuals who interpret disease as a manifestation of God’s punishment having a lower odds of having had Pap testing after controlling for sociodemographic factors (odds ratio [OR] = 0.87, 95% CI = 0.77–1.0). In multivariate models, living in the United States for more than 20 years (OR = 4.7, 95% CI = 1.4–16) and having a primary care physician (OR = 7.7, 95% CI = 2.5–23.4) were positive predictors of having had a Pap test. Ethnicity, fatalistic beliefs, perceived discrimination, and modesty levels were not significantly associated with Pap testing rates. Conclusions To our knowledge, this is the first study to assess Pap testing behaviors among a diverse sample of American Muslim women and to observe that negative religious coping (e.g., viewing health problems as a punishment from God) is associated with a lower odds of obtaining a Pap test. The relationship between religious coping and cancer screening behaviors deserves further study so that religious values can be appropriately addressed through cancer screening programs. PMID:24914883

Diagnostic test pepsinogen I and combination with tumor marker CEA in gastric cancer

NASA Astrophysics Data System (ADS)

Sembiring, J.; Sarumpaet, K.; Ganie, R. A.

2018-03-01

Gastric cancer (GC) is the fifth leading cause of cancer and the third leading cause of cancer-related mortality globally. Human pepsinogens (HP) are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and GC. HP are biochemically and immunochemically classified into two groups: pepsinogen I (PG I) and PG II. Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in normal mucosal cells but increased amounts are associated with adenocarcinoma, especially colorectal cancer. CEA in combination with other tumour markers can be used in pre-operative staging and thereby assist in the planning of the type of surgery required and future management options. The purpose of this study was to diagnose test PG I and combination with tumor marker CEA in 32 patients suspected with GC. There was a significant difference in levels of CEA between GC group with non-GC with a value p <0.001. PGI sensitivity was 70.58% and specificity 93.3%. The sensitivity of PGI and CEA combination of 94.1% and specificity 80%. The area of AUC obtained was 92.7% at 95% confidence interval (82.7-100%). This AUC value indicated that the value of diagnostic accuracy of the PGI and CEA combinations of 92.7%.

DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

PubMed

Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

2014-09-01

Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In Silico and In Vitro Anticancer Activity of Isolated Novel Marker Compound from Chemically Modified Bioactive Fraction from Curcuma longa (NCCL).

PubMed

Naqvi, Arshi; Malasoni, Richa; Gupta, Swati; Srivastava, Akansha; Pandey, Rishi R; Dwivedi, Anil Kumar

2017-10-01

Turmeric ( Curcuma longa ) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). NCCL was prepared from HM. The chemical structure of the marker compound isolated from NCCL was determined from 1D/2D nuclear magnetic resonance, mass spectroscopy, and Fourier transform infrared. The compound so isolated was subjected to in silico and in vitro screenings to test its inhibitory effect on estrogen receptors. Molecular docking studies revealed that the binding poses of the compound I was energetically favorable. Among NCCL and compound I taken for in vitro studies, NCCL had exhibited good anti-cancer activity over compound I against MCF-7, MDA-MB-231, DU-145, and PC-3 cells. This is the first study about the synthesis of a chemically modified bioactive fraction which used a standardized extract since the preparation of the HM. It may be concluded that NCCL fraction having residual components induce more cell death than compound I alone. Thus, NCCL may be used as a potent therapeutic drug. In the present paper, a standardized hexane soluble fraction of Curcuma longa (HM) was chemically modified to give a novel bioactive fraction (NCCL). A novel marker compound was isolated from NCCL and was characerized using various spectral techniques. The compound so isolated was investigated for in-silico screenings. NCCL and isolated compound was subjected to in-vitro anti-cancer screenings against MCF 7, MDA MB 231 (breast adenocarcinoma) and DU 145 and PC 3 cell lines (androgen independent human prostate cancer cells). The virtual screenings reveals that isolated compound has shown favourable drug like properties. NCCL fraction having residual components induces more cell death in these four cancer cell lines than isolated compound alone. Abbreviations used: HM: Herbal Medicament; NCCL: Chemically modified HM; FT-IR: Fourier transform-infrared spectroscopy; NMR: Nuclear magnetic resonance spectroscopy; MS: Mass spectroscopy; HPLC: High-performance liquid chromatography; ER: Estrogen receptor; MTT: 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; MIC: Minimum inhibitory concentration; TAM: Tamoxifen KBr: Potassium bromide; DMSO: Dimethyl sulfoxide; ACN: Acetonitrile; PDB: Protein Data Bank; PDA: Photodiode array detector.

Discrimination and identification of Q-markers based on 'Spider-web' mode for quality control of traditional Chinese medicine.

PubMed

Jiang, Zhenzuo; Yang, Jing; Wang, Yuefei

2017-12-28

The safety and effectiveness of traditional Chinese medicine (TCM) in clinical practice is directly related to the quality of TCM. And, the quality control of TCM is a pivotal issue to the quality of TCM, but also an obstacle impeding the modernization of TCM. The purpose of this work is to compile and develop a strategy based on discrimination and identification of quality markers (Q-markers) for quality control of TCM. Mainly established by seven variables derived from four dimensions including content, stability, pharmacokinetics and pharmacology, the 'Spider-web' mode was undertaken to assess the Q-marker property of candidate compounds originated from TCM by taking regression area (A) and coefficient variation (CV) of the tested compounds into account. The importance index (ImI), ImI = A × 1/CV, was suggested to focus Q-markers. The compounds with larger regression area (A) and less coefficient variation (CV) are preferentially adopted as Q-markers, which should possess the satisfactory properties of content, stability, pharmacokinetics and pharmacological activity. To the contrary, the compounds are excluded on the grounds of the unsatisfactory Q-markers' property, less regression area (A) and larger coefficient variation (CV), which cannot represent the quality of TCM. The 'Spider-web' mode can filter out the redundant constituents and focus on the key indexes of quality control - Q-markers. The screened Q-markers possess the optimal integrated properties of content, stability, pharmacokinetics and pharmacology among the numerous and complicated ingredients of TCM, which can comprehensively characterize inherent quality of TCM. In summary, the novel strategy established in this work provides a valuable perspective for the quality control of TCM. Copyright © 2017 Elsevier GmbH. All rights reserved.

DNA markers in molecular diagnostics for hepatocellular carcinoma

PubMed Central

Su, Ying-Hsiu; Lin, Selena Y; Song, Wei; Jain, Surbhi

2015-01-01

Hepatocellular carcinoma (HCC) is the one of the leading causes of cancer mortality in the world, mainly due to the difficulty of early detection and limited therapeutic options. The implementation of HCC surveillance programs in well-defined, high-risk populations were only able to detect about 40–50% of HCC at curative stages (Barcelona Clinic Liver Cancer stages 0 & 1) due to the low sensitivities of the current screening methods. The advance of sequencing technologies has identified numerous modifications as potential candidate DNA markers for diagnosis/surveillance. Here we aim to provide an overview of the DNA alterations that result in activation of cancer pathways known to potentially drive HCC carcinogenesis and to summarize performance characteristics of each DNA marker in the periphery (blood or urine) for HCC screening. PMID:25098554

Biochemical markers assisted screening of Fusarium wilt resistant Musa paradisiaca (L.) cv. puttabale micropropagated clones.

PubMed

Venkatesh; Krishna, V; Kumar, K Girish; Pradeepa, K; Kumar, S R Santosh; Kumar, R Shashi

2013-07-01

An efficient protocol was standardized for screening of panama wilt resistant Musa paradisiaca cv. Puttabale clones, an endemic cultivar of Karnataka, India. The synergistic effect of 6-benzyleaminopurine (2 to 6 mg/L) and thidiazuron (0.1 to 0.5 mg/L) on MS medium provoked multiple shoot induction from the excised meristem. An average of 30.10 +/- 5.95 shoots was produced per propagule at 4 mg/L 6-benzyleaminopurine and 0.3 mg/L thidiazuron concentrations. Elongation of shoots observed on 5 mg/L BAP augmented medium with a mean length of 8.38 +/- 0.30 shoots per propagule. For screening of disease resistant clones, multiple shoot buds were mutated with 0.4% ethyl-methane-sulfonate and cultured on MS medium supplemented with Fusarium oxysporum f. sp. cubense (FOC) culture filtrate (5-15%). Two month old co-cultivated secondary hardened plants were used for screening of disease resistance against FOC by the determination of biochemical markers such as total phenol, phenylalanine ammonia lyase, oxidative enzymes like peroxidase, polyphenol oxidase, catalase and PR-proteins like chitinase, beta-1-3 glucanase activities. The mutated clones of M. paradisiaca cv. Puttabale cultured on FOC culture filtrate showed significant increase in the levels of biochemical markers as an indicative of acquiring disease resistant characteristics to FOC wilt.

Detection and genetic distance of resistant populations of Pseudosuccinea columella (Mollusca: Lymnaeidae) to Fasciola hepatica (Trematoda: Digenea) using RAPD markers.

PubMed

Calienes, Aymé Fernandez; Fraga, Jorge; Pointier, Jean-Pierre; Yong, Mary; Sanchez, Jorge; Coustau, Christine; Gutiérrez, Alfredo; Théron, André

2004-09-01

Twelve natural populations of Pseudosuccinea columella snails, sampled in the western and central regions of Cuba, were analyzed using the RAPD-PCR technique to screen for resistance to Fasciola hepatica. Ten OPA primers previously shown to produce marker bands for resistance and susceptibility were tested. A new population of P. columella (El Azufre, Pinar del Río) exhibited the amplification patterns of resistant snails, and its resistant status was confirmed after experimental exposure to miracidia. No genetic variability was detected across or within the susceptible isolates. Similarly, the novel resistant isolate displayed an RAPD profile identical to the profile of two other isolates previously identified as resistant to F. hepatica. However, clear differences in RAPD banding patterns and genetic distance were observed between resistant and susceptible isolates.

Novel microsatellite loci for Agave parryi and cross-amplification in Agave palmeri (Agavaceae).

PubMed

Lindsay, Denise L; Edwards, Christine E; Jung, Michael G; Bailey, Pamela; Lance, Richard F

2012-07-01

To examine the foraging behavior of nectarivorous bats in southeastern Arizona, we developed microsatellite primers in Agave parryi. These markers were also tested for cross-amplification and applicability to assess patterns of genetic diversity and structure in A. palmeri. Utilizing DNA sequence data from 454 shotgun sequencing, we identified seven novel polymorphic microsatellite loci in A. parryi and screened them for cross-amplification in A. palmeri. These markers were characterized in two populations of 30 individuals each for each species. In A. parryi, all primers were polymorphic and amplified between three and 12 alleles per population. In A. palmeri, all primers amplified, six were polymorphic, and allelic diversity ranged from one to 16 alleles per population. Our results demonstrate the applicability of these microsatellite primers for population genetics studies in both A. parryi and A. palmeri.

Early detection of glaucoma by means of a novel 3D computer‐automated visual field test

PubMed Central

Nazemi, Paul P; Fink, Wolfgang; Sadun, Alfredo A; Francis, Brian; Minckler, Donald

2007-01-01

Purpose A recently devised 3D computer‐automated threshold Amsler grid test was used to identify early and distinctive defects in people with suspected glaucoma. Further, the location, shape and depth of these field defects were characterised. Finally, the visual fields were compared with those obtained by standard automated perimetry. Patients and methods Glaucoma suspects were defined as those having elevated intraocular pressure (>21 mm Hg) or cup‐to‐disc ratio of >0.5. 33 patients and 66 eyes with risk factors for glaucoma were examined. 15 patients and 23 eyes with no risk factors were tested as controls. The recently developed 3D computer‐automated threshold Amsler grid test was used. The test exhibits a grid on a computer screen at a preselected greyscale and angular resolution, and allows patients to trace those areas on the grid that are missing in their visual field using a touch screen. The 5‐minute test required that the patients repeatedly outline scotomas on a touch screen with varied displays of contrast while maintaining their gaze on a central fixation marker. A 3D depiction of the visual field defects was then obtained that was further characterised by the location, shape and depth of the scotomas. The exam was repeated three times per eye. The results were compared to Humphrey visual field tests (ie, achromatic standard or SITA standard 30‐2 or 24‐2). Results In this pilot study 79% of the eyes tested in the glaucoma‐suspect group repeatedly demonstrated visual field loss with the 3D perimetry. The 3D depictions of visual field loss associated with these risk factors were all characteristic of or compatible with glaucoma. 71% of the eyes demonstrated arcuate defects or a nasal step. Constricted visual fields were shown in 29% of the eyes. No visual field changes were detected in the control group. Conclusions The 3D computer‐automated threshold Amsler grid test may demonstrate visual field abnormalities characteristic of glaucoma in glaucoma suspects with normal achromatic Humphrey visual field testing. This test may be used as a screening tool for the early detection of glaucoma. PMID:17504855

Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics.

PubMed

Sin, Mandy L Y; Mach, Kathleen E; Sinha, Rahul; Wu, Fan; Trivedi, Dharati R; Altobelli, Emanuela; Jensen, Kristin C; Sahoo, Debashis; Lu, Ying; Liao, Joseph C

2017-07-15

Purpose: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. Experimental Design: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients ( n = 13) and controls ( n = 10). Eight bladder cancer specific and 3 reference genes identified by RNA-seq were quantitated by qPCR in a training cohort of 102 urine samples. A diagnostic model based on the training cohort was constructed using multiple logistic regression. The model was further validated in an independent cohort of 101 urines. Results: A total of 418 genes were found to be differentially expressed between bladder cancer and controls. Validation of a subset of these genes was used to construct an equation for computing a probability of bladder cancer score (P BC ) based on expression of three markers ( ROBO1, WNT5A , and CDC42BPB ). Setting P BC = 0.45 as the cutoff for a positive test, urine testing using the three-marker panel had overall 88% sensitivity and 92% specificity in the training cohort. The accuracy of the three-marker panel in the independent validation cohort yielded an AUC of 0.87 and overall 83% sensitivity and 89% specificity. Conclusions: Urine-based molecular diagnostics using this three-marker signature could provide a valuable adjunct to cystoscopy and may lead to a reduction of unnecessary procedures for bladder cancer diagnosis. Clin Cancer Res; 23(14); 3700-10. ©2017 AACR . ©2017 American Association for Cancer Research.

Phase II Validation of a New Panel of Biomarkers for Early Detection of Ovarian Cancer — EDRN Public Portal

Cancer.gov

While all cancer patients could potentially benefit from earlier detection and prevention, the development of new screening technologies and chemoprevention for epithelial ovarian cancer (EOC) is unique in this regard. EOC is characterized by few early symptoms, presentation at an advanced stage, and poor survival. Presently there is no commercially available test that is diagnostic for either early or advanced stage epithelial ovarian cancer. The most commonly used marker, CA125, identifies a group of cell surface glycoproteins, which have uncertain biological behavior and very limited clinical utility for the detection of early stage disease. In recent years, several approaches have been used in order to develop a test for early detection, including the analysis of serum samples by SELDI-TOF and MALDI-TOF to find proteins or protein fragments of unknown identity that detect the presence/absence of cancer. Unfortunately, at the present time, none of these techniques have been shown to be adequate. Therefore, the development of a test that can detect early stages of the disease could dramatically improve treatment success and long-term survival. We have developed a new blood test based on a different approach: 1) we used known proteins related to cancer biology, 2) we characterized these proteins with several different screening steps using samples obtained from both healthy and cancer patient populations, and 3) validated the results with different techniques. Using split point analysis with four markers, 96 out of 100 EOC patients (96%) were correctly diagnosed with ovarian cancer (including 23 of 24 patients with Stage I/II EOC). In the healthy group, 6 out of 106 individuals were diagnosed incorrectly (5.6%). Working in collaboration with the Early Detection Network (EDRN/NCI/NIH), we performed Phase I discovery study confirming the potential application of this test for early detection of ovarian cancer (Preliminary results). The main objective of this pr

Targeted Provision of Oral Iron: The Evolution of a Practical Screening Option123

PubMed Central

Crowley, Caitlin R.; Solomons, Noel W.; Schümann, Klaus

2012-01-01

Universal oral iron supplementation, undertaken according to 1998 WHO guidelines, produced adverse consequences among some children in malaria-endemic areas. Prompted by the Pemba trial, which revealed excessive hospitalizations and deaths, WHO advised that iron supplementation in such regions be accompanied by previous screening for iron deficiency. This agenda, however, poses issues of cost, benefit, acceptability, technical feasibility, and reliability of such screening. The cost of equipment and personnel is balanced against savings from iron supplements spared and treatment for morbidity averted. Costs aside, the most efficacious acceptable screening approach for avoiding hospitalization and deaths must be fielded. Screening before supplementation can be used to assess hematological, iron, and possible inflammatory status to differentiate the source of decreased hemoglobin concentration. Iron deficiency has often been inferred from hematological status markers. The need for extraction of blood, albeit capillary in origin, and high assay costs limit the use of validated methods in screening. Noninvasive methods, i.e., not requiring the extraction of blood, provide the most acceptable and potentially least expensive approach for determining hematological or iron status. Although a noninvasive technique for iron and inflammatory status would be the ideal, it is unattained. Field-friendly, skin-probe hemoglobin devices, derived from instruments for clinical settings, are being developed and tested for eventual rollout in malarial areas. Given a firm grounding for the theoretical requirements needed to advance the screening agenda, evaluation and monitoring of the performance of screening devices can proceed hand in hand. PMID:22797993

A plant-based chemical genomics screen for the identification of flowering inducers.

PubMed

Fiers, Martijn; Hoogenboom, Jorin; Brunazzi, Alice; Wennekes, Tom; Angenent, Gerco C; Immink, Richard G H

2017-01-01

Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to influence this process. We aimed to discover novel compounds that are able to induce flowering in the model plant Arabidopsis. For this purpose we developed a plant-based screening platform that can be used in a chemical genomics study. Here we describe the set-up of the screening platform and various issues and pitfalls that need to be addressed in order to perform a chemical genomics screening on Arabidopsis plantlets. We describe the choice for a molecular marker, in combination with a sensitive reporter that's active in plants and is sufficiently sensitive for detection. In this particular screen, the firefly Luciferase marker was used, fused to the regulatory sequences of the floral meristem identity gene APETALA1 (AP1) , which is an early marker for flowering. Using this screening platform almost 9000 compounds were screened, in triplicate, in 96-well plates at a concentration of 25 µM. One of the identified potential flowering inducing compounds was studied in more detail and named Flowering1 (F1). F1 turned out to be an analogue of the plant hormone Salicylic acid (SA) and appeared to be more potent than SA in the induction of flowering. The effect could be confirmed by watering Arabidopsis plants with SA or F1, in which F1 gave a significant reduction in time to flowering in comparison to SA treatment or the control. In this study a chemical genomics screening platform was developed to discover compounds that can induce flowering in Arabidopsis. This platform was used successfully, to identify a compound that can speed-up flowering in Arabidopsis.

The serological screening of deceased tissue donors within the English Blood Service for infectious agents--a review of current outcomes and a more effective strategy for the future.

PubMed

Kitchen, A D; Gillan, H L

2010-04-01

The overall effectiveness of the NHSBT screening programme for infectious agents in deceased tissue donors is examined and evaluated in terms of current outcomes and how to improve upon these outcomes. The screening results and any subsequent confirmatory results from a total of 1659 samples from NHSBT deceased donors referred to NTMRL for screening for infectious agents were included in the analysis. Overall 1566/1659 (94.4%) of the samples were screen negative. A total of 93 were repeat reactive on screening for one or more of the mandatory markers screened for, of which only 12 (13%) were subsequently confirmed to be positive on confirmatory testing. The majority of the repeat reactive samples were demonstrating non-specific reactivity with the screening assays in use. Overall, the NHSBT screening programme for infectious agents in deceased tissue donors is very effective with a relatively low overall loss of donors because of non-specific reactivity. However, unnecessary loss of tissue products is not acceptable, and although this programme compares favourably with the outcomes of other such programmes, the confirmatory results obtained demonstrate both the need and the potential for improving the outcomes. This is particularly important as one donor may donate more than one product, and can be achieved very easily with a change to the screening algorithm followed, using the confirmatory data obtained to support and validate this change. CONTENTS SUMMARY: Critical analysis of the NHSBT screening programme for infectious agents in deceased tissue donors and a strategy involving the design and use of a different screening algorithm to improve these outcomes.

SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells.

PubMed

Dubois, Nicole C; Craft, April M; Sharma, Parveen; Elliott, David A; Stanley, Edouard G; Elefanty, Andrew G; Gramolini, Anthony; Keller, Gordon

2011-10-23

To identify cell-surface markers specific to human cardiomyocytes, we screened cardiovascular cell populations derived from human embryonic stem cells (hESCs) against a panel of 370 known CD antibodies. This screen identified the signal-regulatory protein alpha (SIRPA) as a marker expressed specifically on cardiomyocytes derived from hESCs and human induced pluripotent stem cells (hiPSCs), and PECAM, THY1, PDGFRB and ITGA1 as markers of the nonmyocyte population. Cell sorting with an antibody against SIRPA allowed for the enrichment of cardiac precursors and cardiomyocytes from hESC/hiPSC differentiation cultures, yielding populations of up to 98% cardiac troponin T-positive cells. When plated in culture, SIRPA-positive cells were contracting and could be maintained over extended periods of time. These findings provide a simple method for isolating populations of cardiomyocytes from human pluripotent stem cell cultures, and thereby establish a readily adaptable technology for generating large numbers of enriched cardiomyocytes for therapeutic applications.

Validation of Recombinant Salivary Protein PpSP32 as a Suitable Marker of Human Exposure to Phlebotomus papatasi, the Vector of Leishmania major in Tunisia

PubMed Central

Bettaieb, Jihene; Abdeladhim, Maha; Hadj Kacem, Saoussen; Abdelkader, Rania; Gritli, Sami; Chemkhi, Jomaa; Aslan, Hamide; Kamhawi, Shaden; Ben Salah, Afif; Louzir, Hechmi; Valenzuela, Jesus G.; Ben Ahmed, Melika

2015-01-01

Background During a blood meal, female sand flies, vectors of Leishmania parasites, inject saliva into the host skin. Sand fly saliva is composed of a large variety of components that exert different pharmacological activities facilitating the acquisition of blood by the insect. Importantly, proteins present in saliva are able to elicit the production of specific anti-saliva antibodies, which can be used as markers for exposure to vector bites. Serological tests using total sand fly salivary gland extracts are challenging due to the difficulty of obtaining reproducible salivary gland preparations. Previously, we demonstrated that PpSP32 is the immunodominant salivary antigen in humans exposed to Phlebotomus papatasi bites and established that humans exposed to P. perniciosus bites do not recognize it. Methodology/Principal Findings Herein, we have validated, in a large cohort of 522 individuals, the use of the Phlebotomus papatasi recombinant salivary protein PpSP32 (rPpSP32) as an alternative method for testing exposure to the bite of this sand fly. We also demonstrated that screening for total anti-rPpSP32 IgG antibodies is sufficient, being comparable in efficacy to the screening for IgG2, IgG4 and IgE antibodies against rPpSP32. Additionally, sera obtained from dogs immunized with saliva of P. perniciosus, a sympatric and widely distributed sand fly in Tunisia, did not recognize rPpSP32 demonstrating its suitability as a marker of exposure to P. papatasi saliva. Conclusions/Significance Our data indicate that rPpSP32 constitutes a useful epidemiological tool to monitor the spatial distribution of P. papatasi in a particular region, to direct control measures against zoonotic cutaneous leishmaniasis, to assess the efficiency of vector control interventions and perhaps to assess the risk of contracting the disease. PMID:26368935

Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy.

PubMed

Burlina, Alberto B; Polo, Giulia; Salviati, Leonardo; Duro, Giovanni; Zizzo, Carmela; Dardis, Andrea; Bembi, Bruno; Cazzorla, Chiara; Rubert, Laura; Zordan, Roberta; Desnick, Robert J; Burlina, Alessandro P

2018-03-01

Lysosomal storage diseases (LSDs) are inborn errors of metabolism resulting from 50 different inherited disorders. The increasing availability of treatments and the importance of early intervention have stimulated newborn screening (NBS) to diagnose LSDs and permit early intervention to prevent irreversible impairment or severe disability. We present our experience screening newborns in North East Italy to identify neonates with Mucopolysaccharidosis type I (MPS I) and Pompe, Fabry, and Gaucher diseases. Activities of acid β-glucocerebrosidase (ABG; Gaucher), acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), and acid α-L-iduronidase (IDUA; MPS-I) in dried blood spots (DBS) from all newborns during a 17-month period were determined by multiplexed tandem mass spectrometry (MS/MS) using the NeoLSD ® assay system. Enzymatic activity cutoff values were determined from 3500 anonymous newborn DBS. In the screening study, samples were retested if the value was below cutoff and a second spot was requested, with referral for confirmatory testing and medical evaluation if a low value was obtained. From September 2015 to January 2017, 44,411 newborns were screened for the four LSDs. We recalled 40 neonates (0.09%) for collection of a second DBS. Low activity was confirmed in 20, who had confirmatory testing. Ten of 20 had pathogenic mutations: two Pompe, two Gaucher, five Fabry, and one MPS-I. The incidences of Pompe and Gaucher diseases were similar (1/22,205), with Fabry disease the most frequent (1/8882) and MPS-I the rarest (1/44411). The combined incidence of the four disorders was 1/4411 births. Simultaneously determining multiple enzyme activities by MS/MS, with a focus on specific biochemical markers, successfully detected newborns with LSDs. The high incidence of these disorders supports this screening program.

Levels and Types of Alcohol Biomarkers in DUI and Clinic Samples for Estimating Workplace Alcohol Problemsa

PubMed Central

Marques, Paul R

2013-01-01

Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways – a workplace for many – provides an example for work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this report, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average 8 months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (DUI). Drivers in alcohol interlock programs log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher program entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This report summarizes selected biomarkers’ potential for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cutoff levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID:22311827

Current issues in diagnostic breast pathology.

PubMed

Walker, Rosemary A; Hanby, Andy; Pinder, Sarah E; Thomas, Jeremy; Ellis, Ian O

2012-09-01

On behalf of the NHS Breast Screening Programme Pathology Coordinating Group we present recommendations for terminology and diagnostic criteria for a number of key areas of practice in breast pathology where terminology can be confusing and where accurate communication will ensure appropriate clinical management. These recommendations cover columnar cell lesions and the spectrum of changes that can be seen in these epithelial proliferations, lobular neoplasia, micrometastases and isolated tumour cells in axillary lymph nodes, the use of basal/myoepithelial markers in diagnostic practice and oestrogen receptor testing in ductal carcinoma in situ.

Microsatellite markers for the endangered Roanoke logperch, Percina rex (Percidae) and their potential utility for other darter species

USGS Publications Warehouse

Dutton, D.J.; Roberts, J.H.; Angermeier, P.L.; Hallerman, E.M.

2008-01-01

The Roanoke logperch (Percina rex Jordan and Evermann), an endangered fish, occurs in only six watersheds in the Roanoke and Chowan river drainages of Virginia, USA. The species' population genetic structure is poorly known. We developed 16 microsatellite markers that were reliably scorable and polymorphic P. rex. Markers were also screened in seven other darter species of the genus Percina. Most markers exhibited successful amplification and polymorphism in several species. These markers may therefore prove useful for population genetic studies in other darters, a diverse but highly imperiled group. ?? 2008 The Authors.

Between pregnancy biological variability of first trimester markers of Down syndrome and the implications for screening in subsequent pregnancies: an issue revisited.

PubMed

Spencer, Kevin

2002-10-01

To assess the level of correlation of first trimester biochemical and biophysical markers of Down syndrome between different pregnancies in the same individual. To assess the impact that between pregnancy biological variability has on the likelihood that women who are at increased risk in a first pregnancy being also at increased risk in a subsequent pregnancy. During a three period women attending the OSCAR clinic at Harold Wood Hospital have had the opportunity to have first trimester screening for Down syndrome and other aneuploidies using the maternal serum biochemical markers free beta-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A) in conjunction with fetal nuchal translucency (NT) thickness and maternal age. Of the 111,105 women undergoing such screening, the computer records were examined for women who had more than one pregnancy. The results from 1002 women with two normal singleton pregnancies were available for analysis. Marker correlations (as MoM) were established between the pregnancies and the proportion of women likely to be at increased risk in each pregnancy estimated, as was the likelihood of women being at increased risk in both pregnancies. For fetal NT there was no correlation between NT MoM in the first and second pregnancy (r = 0.0959, p > 0.10). For maternal serum free beta-hCG MoM a significant correlation was found (r = 0.3976, p < 0.001), as was also found for PAPP-A MoM (r = 0.4371, p < 0.001). The implication for such between pregnancy marker association is that women who have an increased risk of Down syndrome in one pregnancy are two or three times more likely to repeat this event in their next pregnancy. This information may be useful in counselling women when undergoing first trimester screening in a subsequent pregnancy. Copyright 2002 John Wiley & Sons, Ltd.

Visualization of nanoconstructions with DNA-Aptamers for targeted molecules binding on the surface of screen-printed electrodes

NASA Astrophysics Data System (ADS)

Lapin, Ivan N.; Shabalina, Anastasiia V.; Svetlichyi, Valery A.; Kolovskaya, Olga S.

2018-04-01

Nanoconstructions of gold nanoparticles (NPs) obtained via pulsed laser ablation in liquid with DNA-aptamer specific to protein tumor marker were visualized on the surface of screen-printed electrode using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). AuNPs/aptamer nanoconstuctions distribution on the solid surface was studied. More uniform coverage of the carbon electrode surface with the nanoconstuctions was showed in comparison with DNA-aptamer alone on the golden electrode surface. Targeted binding of the tumor marker molecules with the AuNPs/DNA-aptamer nanoconstuctions was approved.

Remarkable variation in the informativeness of RFLP markers linked to hemophilia B locus in Indian population groups: implication in the strategy for carrier detection.

PubMed

Mukherjee, S; Saha, A; Kumar P, Senthil; Chandak, G R; Majumder, P P; Ray, K

2006-01-01

Hemophilia B, an X-linked recessive bleeding disorder, is caused by heterogeneous mutations in the factor IX (F9) gene. Hence, carriers of the disease are usually detected by F9 gene linked RFLP analysis. We aimed to test a set of RFLP markers (DdeI, XmnI, MnlI, TaqI & HhaI), used worldwide for carrier detection, to estimate its heterozygosity in different population groups of India, and identify additional single nucleotide polymorphisms (SNPs) if necessary. A total of 8 population groups encompassing different regions of India, consisting of 107 unrelated normal females without any history of hemophilia B in the family and 13 unrelated obligate carriers were recruited in the study. Regions of F9 gene were amplified by PCR from genomic DNA of the donors followed by restriction enzyme digestion and/or sequencing as appropriate. Combined informativeness for the markers varied between 52-86% among normal females belonging to different geographical locations of India. Haplotype analysis revealed that the most prevalent haplotype lacked the restriction sites for all five RFLP markers. Screening regions of F9 gene that harbor 10 SNPs reported in dbSNP yielded only two SNPs, which increased the overall informativeness in each population group and heterozygosity in the obligate carriers for the disease from 38% to 69%. Our data show that heterozygosity of commonly used RFLP markers is remarkably variable across different regions of India. Thus prudent selection of the markers based on specific population groups including usage of additional markers is recommended for efficient carrier detection.

EDRN Breast and Ovary Cancer CVC, Study 2: Phase 3 retrospective validation of ovarian cancer early detection markers in serial preclinical samples from the PLCO trial — EDRN Public Portal

Cancer.gov

Over 70% of women with ovarian/fallopian tube cancer (OC) are diagnosed with advanced stage disease which has a 5-year relative survival rate of 30%. Five-year survival is 90% when disease is confined to the ovaries, but overall survival is poor because only 25% of cases are found early. Screening for ovarian cancer using tools with high sensitivity is potentially cost-effective, but because OC is so rare, very high specificity is needed to achieve an acceptable PPV. We have conducted preliminary work both in clinical and in preclinical (CARET) samples. We have identified candidate markers, developed assays for novel markers including HE4 and MSLN, and evaluated their diagnostic performance. We evaluated the markers’ contribution to a diagnostic panel in a standard set in order to identify the best of the candidates and developed methods for combining markers to define a decision rule for a marker panel. We found that our PEB rule yields comparable performance to the Single Threshold (ST) rule 2 years earlier, using the same two markers. The PEB makes an even larger contribution with the 4-marker panel. The 4-marker panel with the PEB rule represents a substantial improvement over any of the other decision rules as a first-line screen to select women for imaging. Our goal in the proposed work is to estimate the improvement in performance possible in the PLCO serial samples.

Evaluating markers for the early detection of cancer: overview of study designs and methods.

PubMed

Baker, Stuart G; Kramer, Barnett S; McIntosh, Martin; Patterson, Blossom H; Shyr, Yu; Skates, Steven

2006-01-01

The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention.

Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

PubMed Central

Simonic, I; Gericke, G S; Ott, J; Weber, J L

1998-01-01

Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q. PMID:9718333

Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

PubMed

Simonic, I; Gericke, G S; Ott, J; Weber, J L

1998-09-01

Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q.

Efficient Generation of Marker-Free Transgenic Rice Plants Using an Improved Transposon-Mediated Transgene Reintegration Strategy1

PubMed Central

Gao, Xiaoqing; Zhou, Jie; Li, Jun; Zou, Xiaowei; Zhao, Jianhua; Li, Qingliang; Xia, Ran; Yang, Ruifang; Wang, Dekai; Zuo, Zhaoxue; Tu, Jumin; Tao, Yuezhi; Chen, Xiaoyun; Xie, Qi; Zhu, Zengrong

2015-01-01

Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize (Zea mays) Activator/Dissociation (Ds) transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest was linked to green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent protein-aided counterselection against T-DNA was used together with polymerase chain reaction (PCR)-based positive selection for the gene of interest to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) δ-endotoxin gene into the Ds elements and transformed transposon vectors into rice (Oryza sativa) cultivars via Agrobacterium tumefaciens. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis. Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops. PMID:25371551

A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads.

PubMed

Jones, M P; Chey, W D; Singh, S; Gong, H; Shringarpure, R; Hoe, N; Chuang, E; Talley, N J

2014-02-01

The development of a reliable biomarker for irritable bowel syndrome (IBS) remains one of the major aims of research in functional gastrointestinal disorders (FGIDs) and is complicated by the absence of a perfect reference standard. Previous efforts based on genetic and immune markers have showed promise, but have not been robust. To evaluate an extensive panel of gene expression and serology markers combined with psychological measures in differentiating IBS from health and between subtypes of IBS. Of subjects eligible for analysis (N = 244), 168 met criteria for IBS (60 IBS-C, 57 IBS-D and 51 mixed), while 76 were free of any FGID. A total of 34 markers were selected based on pathways implicated in pathophysiology of IBS or whole human genome screening. Psychological measures were recorded that covered anxiety, depression and somatisation. Models differentiating disease and health were based on unconditional logistic regression and performance assessed through area under the receiver-operator characteristic curve (AUC), sensitivity and specificity. The performance of a combination of 34 markers was good in differentiating IBS from health (AUC = 0.81) and was improved considerably with the addition of four psychological markers (combined AUC = 0.93). Of the 34 markers considered, discrimination was derived largely from a small subset. Good discrimination was also obtained between IBS subtypes with the best being observed for IBS-C vs. IBS-D (AUC = 0.92); however, psychological variables provided almost no incremental discrimination subtypes over biological markers (combined AUC = 0.94). A combination of gene expression and serological markers in combination with psychological measures shows exciting progress towards a diagnostic test for IBS compared with healthy subjects, and to discriminate IBS-C from IBS-D. © 2014 John Wiley & Sons Ltd.

Efficient generation of marker-free transgenic rice plants using an improved transposon-mediated transgene reintegration strategy.

PubMed

Gao, Xiaoqing; Zhou, Jie; Li, Jun; Zou, Xiaowei; Zhao, Jianhua; Li, Qingliang; Xia, Ran; Yang, Ruifang; Wang, Dekai; Zuo, Zhaoxue; Tu, Jumin; Tao, Yuezhi; Chen, Xiaoyun; Xie, Qi; Zhu, Zengrong; Qu, Shaohong

2015-01-01

Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize (Zea mays) Activator/Dissociation (Ds) transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest was linked to green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent protein-aided counterselection against T-DNA was used together with polymerase chain reaction (PCR)-based positive selection for the gene of interest to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) δ-endotoxin gene into the Ds elements and transformed transposon vectors into rice (Oryza sativa) cultivars via Agrobacterium tumefaciens. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis. Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops. © 2015 American Society of Plant Biologists. All Rights Reserved.

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

PubMed Central

Terry, Kathryn L.; Schock, Helena; Fortner, Renée T.; Hüsing, Anika; Fichorova, Raina N.; Yamamoto, Hidemi S.; Vitonis, Allison F.; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Onland-Moret, N. Charlotte; Peeters, Petra H.; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J.; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J.; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C.; Gunter, Marc J.; Merritt, Melissa A.; Riboli, Elio; Cramer, Daniel W.; Kaaks, Rudolf

2016-01-01

Purpose About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases. PMID:27060155

Genome skimming identifies polymorphism in tern populations and species

PubMed Central

2012-01-01

Background Terns (Charadriiformes: Sterninae) are a lineage of cosmopolitan shorebirds with a disputed evolutionary history that comprises several species of conservation concern. As a non-model system in genetics, previous study has left most of the nuclear genome unexplored, and population-level studies are limited to only 15% of the world's species of terns and noddies. Screening of polymorphic nuclear sequence markers is needed to enhance genetic resolution because of supposed low mitochondrial mutation rate, documentation of nuclear insertion of hypervariable mitochondrial regions, and limited success of microsatellite enrichment in terns. Here, we investigated the phylogenetic and population genetic utility for terns and relatives of a variety of nuclear markers previously developed for other birds and spanning the nuclear genome. Markers displaying a variety of mutation rates from both the nuclear and mitochondrial genome were tested and prioritized according to optimal cross-species amplification and extent of genetic polymorphism between (1) the main tern clades and (2) individual Royal Terns (Thalasseus maxima) breeding on the US East Coast. Results Results from this genome skimming effort yielded four new nuclear sequence-based markers for tern phylogenetics and 11 intra-specific polymorphic markers. Further, comparison between the two genomes indicated a phylogenetic conflict at the base of terns, involving the inclusion (mitochondrial) or exclusion (nuclear) of the Angel Tern (Gygis alba). Although limited mitochondrial variation was confirmed, both nuclear markers and a short tandem repeat in the mitochondrial control region indicated the presence of considerable genetic variation in Royal Terns at a regional scale. Conclusions These data document the value of intronic markers to the study of terns and allies. We expect that these and additional markers attained through next-generation sequencing methods will accurately map the genetic origin and species history of this group of birds. PMID:22333071

A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort.

PubMed

Terry, Kathryn L; Schock, Helena; Fortner, Renée T; Hüsing, Anika; Fichorova, Raina N; Yamamoto, Hidemi S; Vitonis, Allison F; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Peeters, Petra H; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C; Gunter, Marc J; Merritt, Melissa A; Riboli, Elio; Cramer, Daniel W; Kaaks, Rudolf

2016-09-15

About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664-75. ©2016 AACRSee related commentary by Skates, p. 4542. ©2016 American Association for Cancer Research.

Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

PubMed

Yaron, Y; Cherry, M; Kramer, R L; O'Brien, J E; Hallak, M; Johnson, M P; Evans, M I

1999-10-01

We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.

Portable guided-mode resonance biosensor platform for point-of-care testing

NASA Astrophysics Data System (ADS)

Sung, Gun Yong; Kim, Wan-Joong; Ko, Hyunsung; Kim, Bong K.; Kim, Kyung-Hyun; Huh, Chul; Hong, Jongcheol

2012-10-01

It represents a viable solution for the realization of a portable biosensor platform that could screen/diagnose acute myocardial infarction by measuring cardiac marker concentrations such as cardiac troponin I (cTnI), creatine kinase MB (CK-MB), and myoglobin (MYO) for application to u-health monitoring system. The portable biosensor platform introduced in this presentation has a more compact structure and a much higher measuring resolution than a conventional spectrometer system. Portable guided-mode resonance (GMR) biosensor platform was composed of a biosensor chip stage, an optical pick-up module, and a data display panel. Disposable plastic GMR biosensor chips with nano-grating patterns were fabricated by injection-molding. Whole blood filtration and label-free immunoassay were performed on these single chips, automatically. Optical pick-up module was fabricated by using the miniaturized bulk optics and the interconnecting optical fibers and a tunable VCSEL (vertical cavity surface emitting laser). The reflectance spectrum from the GMR biosensor was measured by the optical pick-up module. Cardiac markers in human serum with concentrations less than 0.1ng/mL were analyzed using a GMR biosensor. Analysis time was 30min, which is short enough to meet clinical requirements. Our results show that the GMR biosensor will be very useful in developing lowcost portable biosensors that can screen for cardiac diseases.

Functional expression and pharmaceutical efficacy of cardiac-specific ion channels in human embryonic stem cell-derived cardiomyocytes.

PubMed

Kim, Han Sol; Yoon, Jung Won; Li, Hongliang; Jeong, Geun Ok; Park, Jin Ju; Shin, Sung Eun; Jang, Il Ho; Kim, Jae Ho; Park, Won Sun

2017-10-23

Cardiomyocytes differentiated from human pluripotent stem cells provide promising tools for screening of cardiotoxic drugs. For evaluation of human pluripotent stem cell-derived cardiomyocytes for cardiotoxicity test, in the present study, human embryonic stem cells (hESCs) were differentiated to cardiomyocytes, followed by metabolic selection to enrich the differentiated cardiomyocytes. The highly purified hESC-derived cardiomyocytes (hESC-CMs) expressed several cardiomyocyte-specific markers including cTnT, MLC2a, and α-SA, but not pluripotency markers, such as OCT4 and NANOG. Patch clamp technique and RT-PCR revealed the expression of cardiomyocyte-specific Na + , Ca 2+ , and K + channels and cardiac action potential in hESC-CMs. To explore the potential use of hESC-CMs as functional cardiomyocytes for drug discovery and cardiotoxicity screening, we examined the effects of bisindolylmaleimide (BIM) (I), which inhibits native cardiac Ca 2+ channels, on the Ca 2+ channel activity of hESC-CMs. We observed a similar response for the BIM (I)-induced modulation of Ca 2+ channels between hESC-CMs and native cardiomyocytes through L-type Ca 2+ channel current. These results suggest that hESC-CMs can be useful for evaluation of pharmaceutical efficacy and safety of novel drug candidate in cardiac research.

Recent developments and new applications of tandem mass spectrometry in newborn screening.

PubMed

Rinaldo, Piero; Tortorelli, Silvia; Matern, Dietrich

2004-08-01

To summarize recent developments in the field of newborn screening related to the use of tandem mass spectrometry as an analytic platform. Novel inborn errors of metabolism with informative amino acid and/or acylcarnitine profiles have been characterized, increasing the complexity of the differential diagnosis of abnormal results. In addition, methods have been developed for the analysis in dried blood spots of steroids and lysosomal enzymes. Previously unrecognized genotype/phenotype correlations have been found among cohorts of patients whose conditions were diagnosed by screening rather than clinically. Several government entities and professional organizations have issued position statements on newborn screening, and worldwide outcome studies continue to underscore the clinical and financial benefits of expanded newborn screening. Although it is done inconsistently, newborn screening in the United States is undergoing a rapid expansion driven by the introduction of tandem mass spectrometry in at least 34 state programs. This technology is also used to detect disease markers beyond acylcarnitines and amino acids, as both primary and second-tier tests. In addition to analytic improvements, there is a trend toward the development of joint programs not limited to contiguous geographic areas, often based upon public-private partnerships. This review will summarize several new developments in the field that have occurred since early 2003 and will mention others likely to occur in the near future.

Relating Stool Microbial Metabolite Levels, Inflammatory Markers and Dietary Behaviors to Screening Colonoscopy Findings in a Racially/Ethnically Diverse Patient Population.

PubMed

Bridges, Kristina M; Diaz, Francisco J; Wang, Zhiwen; Ahmed, Ishfaq; Sullivan, Debra K; Umar, Shahid; Buckles, Daniel C; Greiner, K Allen; Hester, Christina M

2018-02-26

Colorectal cancer (CRC) is the third leading cause of cancer death for both men and women in the United States, yet it is treatable and preventable. African Americans have higher incidence of CRC than other racial/ethnic groups, however, it is unclear whether this disparity is primarily due to environmental or biological factors. Short chain fatty acids (SCFAs) are metabolites produced by bacteria in the colon and are known to be inversely related to CRC progression. The aim of this study is to investigate how stool SCFA levels, markers of inflammation in stool and dietary intake relate to colonoscopy findings in a diverse patient population. Stool samples from forty-eight participants were analyzed for SCFA levels and inflammatory markers (lysozyme, secretory IgA, lactoferrin). Additionally, participants completed the National Cancer Institute's Diet History Questionnaire II (DHQ II) to report dietary intake over the past year. Subsequently, the majority of participants underwent screening colonoscopy. Our results showed that African Americans had higher total levels of SCFAs in stool than other racial/ethnic groups, significantly lower intake of non-starchy vegetables and similar inflammatory marker expression and colonoscopy outcomes, compared to others. This work is an initial exploration into the biological and clinical factors that may ultimately inform personalized screening approaches and clinical decision-making to improve colorectal cancer disparities for African Americans.

Relating Stool Microbial Metabolite Levels, Inflammatory Markers and Dietary Behaviors to Screening Colonoscopy Findings in a Racially/Ethnically Diverse Patient Population

PubMed Central

Bridges, Kristina M.; Diaz, Francisco J.; Wang, Zhiwen; Ahmed, Ishfaq; Sullivan, Debra K.; Umar, Shahid; Buckles, Daniel C.; Greiner, K. Allen; Hester, Christina M.

2018-01-01

Colorectal cancer (CRC) is the third leading cause of cancer death for both men and women in the United States, yet it is treatable and preventable. African Americans have higher incidence of CRC than other racial/ethnic groups, however, it is unclear whether this disparity is primarily due to environmental or biological factors. Short chain fatty acids (SCFAs) are metabolites produced by bacteria in the colon and are known to be inversely related to CRC progression. The aim of this study is to investigate how stool SCFA levels, markers of inflammation in stool and dietary intake relate to colonoscopy findings in a diverse patient population. Stool samples from forty-eight participants were analyzed for SCFA levels and inflammatory markers (lysozyme, secretory IgA, lactoferrin). Additionally, participants completed the National Cancer Institute’s Diet History Questionnaire II (DHQ II) to report dietary intake over the past year. Subsequently, the majority of participants underwent screening colonoscopy. Our results showed that African Americans had higher total levels of SCFAs in stool than other racial/ethnic groups, significantly lower intake of non-starchy vegetables and similar inflammatory marker expression and colonoscopy outcomes, compared to others. This work is an initial exploration into the biological and clinical factors that may ultimately inform personalized screening approaches and clinical decision-making to improve colorectal cancer disparities for African Americans. PMID:29495356

First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome.

PubMed

Shiefa, S; Amargandhi, M; Bhupendra, J; Moulali, S; Kristine, T

2013-01-01

The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two biochemical markers i.e. serum free β-human chorionic gonadotrophin (free β-hCG) and pregnancy associated plasma protein A (PAPP-A), maternal age and fetal nuchal translucency (NT) thickness at 11 + 0-13 + 6 weeks of gestation. A beneficial consequence of screening is the early diagnosis or trisomies 21, 18 and 13. At 11 + 0-13 + 6 weeks, the relative prevalence of trisomies 18 and 13 to trisomy 21 are found to be one to three and one to seven, respectively. All three trisomies are associated with increased maternal age, increased fetal NT and decreased PAPP-A, but in trisomy 21 serum free β-hCG is increased whereas in trisomies 18 and 13 free β-hCG is decreased.

Results of a diabetic retinopathy screening. Risk markers analysis.

PubMed

Ancochea, G; Martín Sánchez, M D

2016-01-01

To identify risk markers for retinopathy in patients from our geographic area, and to compare them with those published in other studies. To design a screening interval strategy, taking into account these results, and compare it with intervals suggested in published studies. Cross-sectional observational study on 383 diabetic patients with no previous retinopathy diagnosis, who were screened for diabetic retinopathy. An analysis was made on the possible association between patient factors and presence of retinopathy. A greater probability for finding retinopathy in diabetic patients was associated to insulin treatment in our study, with a statistical significance level of 95%. In patients with less than 10year onset of their diabetes, only mild retinopathy without macular oedema was found. Insulin treatment and time of onset of diabetes should be taken into account when designing efficient screening strategies for diabetic retinopathy. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

A randomized trial to evaluate the use of text messaging, letter and telephone call reminders to improve return of blood donors with reactive serologic tests

PubMed Central

Porto-Ferreira, Francisco Augusto; de Almeida-Neto, Cesar; Murphy, Edward L.; de Camargo Montebello, Sandra; Nogueira, Fátima Aparecida Hangai; Koga da Silva, Edina Mariko; MacFarland, William; Custer, Brian

2016-01-01

Introduction Low return rates for notification and counseling among donors with reactive serologic screening tests have been reported worldwide. A randomized trial to test the effectiveness of text message, letter or telephone call reminders to improve return among non-responding first-time blood donors with reactive serologic tests was conducted. Methods Donors with serologically reactive screening test results who had a cell phone and resided in the metropolitan telephone area code of São Paulo in the period from August 2013 through July 2014 were eligible. A consecutive sample of first-time donors with reactive screening tests who had not responded to a standard letter requesting the donor return to the blood center were randomly assigned to receive a text, a new letter or a telephone call requesting return for notification and counseling. Return rates were measured over the subsequent 30 days. Results Return following a phone call reminder was better than a text message (39.8% vs. 28.4%; OR=1.66; 95%CI 1.05–2.64) but not better than a letter (39.8% vs. 34.4%; OR=1.32; 95%CI 0.83–2.12). Older age was a predictor of higher rate of return with each year increase in age associated with a 2% increase in the odds of return (OR=1.02; 95%CI 1.01–1.04). Conclusion In non-responding serologic reactive donors, telephone call led to a higher return rate than text message. The results of this study suggest that use of text messages, while attractive for its simplicity, will not lead to increased donor notification success following serologically reactive marker results from blood donation in Brazil. PMID:27774609

Multiplexed Analysis of Serum Breast and Ovarian Cancer Markers by Means of Suspension Bead-quantum Dot Microarrays

NASA Astrophysics Data System (ADS)

Brazhnik, Kristina; Sokolova, Zinaida; Baryshnikova, Maria; Bilan, Regina; Nabiev, Igor; Sukhanova, Alyona

Multiplexed analysis of cancer markers is crucial for early tumor diagnosis and screening. We have designed lab-on-a-bead microarray for quantitative detection of three breast cancer markers in human serum. Quantum dots were used as bead-bound fluorescent tags for identifying each marker by means of flow cytometry. Antigen-specific beads reliably detected CA 15-3, CEA, and CA 125 in serum samples, providing clear discrimination between the samples with respect to the antigen levels. The novel microarray is advantageous over the routine single-analyte ones due to the simultaneous detection of various markers. Therefore the developed microarray is a promising tool for serum tumor marker profiling.

Intergrated Systems Biology Approach for Ovarian Cancer Biomarker Discovery — EDRN Public Portal

Cancer.gov

The overall objective is to validate serum protein markers for early diagnosis of ovarian cancer with the ultimate goal being to develop a multiparametric panel consisting of 2-4 novel markers with 10 known markers for phase 3 analysis. In phase 1, we will screen for markers able to pass a threshold of 98% specificity and 30% sensitivity in a cohort of 300 women. Markers that pass phase 1 validation will be investigated in a phase 2 PRoBE cohort with a 98% specificity and 70% sensitivity cut-off. Finally, markers that pass phase 2 validation will be evaluated in EDRN CVC laboratory specimens with a cut-off of > 98% specificity and 90% sensitivity.

EST-SSR marker revealed effective over biochemical and morphological scepticism towards identification of specific turmeric (Curcuma longa L.) cultivars.

PubMed

Sahoo, Ambika; Jena, Sudipta; Kar, Basudeba; Sahoo, Suprava; Ray, Asit; Singh, Subhashree; Joshi, Raj Kumar; Acharya, Laxmikanta; Nayak, Sanghamitra

2017-05-01

Turmeric (Curcuma longa L., family Zingiberaceae) is one of the most economically important plants for its use in food, medicine, and cosmetic industries. Cultivar identification is a major constraint in turmeric, owing to high degree of morphological similarity that in turn, affects its commercialization. The present study addresses this constraint, using EST-SSR marker based, molecular identification of 8 elite cultivars and 88 accessions in turmeric. Fifty EST-SSR primers were screened against eight cultivars of turmeric (Suroma, Roma, Lakadong, Megha, Alleppey Supreme, Kedaram, Pratibha, and Suvarna); out of which 11 primers showed polymorphic banding pattern. The polymorphic information content (PIC) of these primers ranged from 0.13 to 0.48. However, only three SSR loci (CSSR 14, CSSR 15, and CSSR 18) gave reproducible unique banding pattern clearly distinguishing the cultivars 'Lakadong' and 'Suvarna' from other cultivars tested. These three unique SSR markers also proved to be effective in identification of 'Lakadong' cultivars when analysed with 88 accessions of turmeric collected from different agro-climatic regions. Furthermore, two identified cultivars (Lakadong and Suvarna) could also be precisely differentiated when analysed and based on phylogenetic tree, with other 94 genotypes of turmeric. The novel SSR markers can be used for identification and authentication of two commercially important turmeric cultivars 'Lakadong' and 'Suvarna'.

Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective

PubMed Central

2011-01-01

Background A screening programme for pregnant women has been in place since the 1950s in the Netherlands. In 2004 universal HIV screening according to opting out was implemented. Here, we describe the evaluation of the effectiveness of antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus (HBV) and syphilis in preventing mother-to-child transmission, by using various data sources. Methods The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. Results Each year, around 185,000 pregnant women were screened for HIV, HBV and syphilis. Refusal rates for the screening tests were low, and were highest (0.2%) for HIV. The estimated annual prevalence of HIV among pregnant women was 0.05%. Prior to the introduction of screening, 5-10 children were born with HIV annually After the introduction of screening in 2004, only 4 children were born with HIV (an average of 1 per year). Two of these mothers had become pregnant prior to 2004; the third mother was HIV negative at screening and probably became infected after screening; the fourth mother's background was unknown. Congenital syphilis was diagnosed in fewer than 5 newborns annually and 5 children were infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually as a result of screening. Conclusions The screening programme was effective in detecting HIV, HBV and syphilis in pregnant women and in preventing transmission to the child. Since the introduction of the HIV screening the number of children born with HIV has fallen dramatically. Previous publication [Translation from: 'Prenatale screening op hiv, hepatitis B en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine ' (NTVG, in Dutch)] PMID:21718466

Microsatellite markers for the endangered Roanoke logperch, Percina rex (Percidae) and their potential utility for other darter species.

PubMed

Dutton, Daniel J; Roberts, James H; Angermeier, Paul L; Hallerman, Eric M

2008-07-01

The Roanoke logperch (Percina rex Jordan and Evermann), an endangered fish, occurs in only six watersheds in the Roanoke and Chowan river drainages of Virginia, USA. The species' population genetic structure is poorly known. We developed 16 microsatellite markers that were reliably scorable and polymorphic P. rex. Markers were also screened in seven other darter species of the genus Percina. Most markers exhibited successful amplification and polymorphism in several species. These markers may therefore prove useful for population genetic studies in other darters, a diverse but highly imperiled group. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.

High prevalence of HIV p24 antigen among HIV antibody negative prospective blood donors in Ile-Ife, Nigeria.

PubMed

Japhet, Margaret Oluwatoyin; Adewumi, Moses Olubusuyi; Adesina, Olufisayo Adeyemi; Donbraye, Emmanuel

2016-01-01

Blood transfusion service centers in Nigeria screen donated blood for markers of HIV infection using antibody- (Ab) based rapid test and in some centers, positives are re-tested using Ab-based ELISA. Paucity of data exists on p24 antigen prevalence among HIV Ab-negative donors in Nigeria. This study aims at detecting HIV p24 antigen among prospective blood donors in Osun State, Nigeria. Prospective blood donors negative for HIV antibodies using Determine test kit were re-tested using BIORAD GENSCREEN Ultra Ag-Ab ELISA kit, a fourth-generation ELISA kit that detects HIV antibodies/p24 antigen. Of the 169 HIV Ab-negative prospective donors, 10 (5.9%) were positive for HIV p24 antigen and 70% (7/10) of them were in the age range 18-30 years. Results of this study show that blood transfusion is still one of the major routes of HIV transmission in Nigeria and a higher proportion is among youth. Inclusion of p24 antigen testing into the blood donor screening will help reduce transfusion associated HIV in Nigeria if Nucleic Acid Testing (NAT) of all blood donor samples is not affordable; also, HIV enlightenment programs tailored toward youth may help reduce this rate among donors since more young people donate blood in low/middle-income countries than in high-income countries.

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map.

PubMed

N'Diaye, Amidou; Haile, Jemanesh K; Cory, Aron T; Clarke, Fran R; Clarke, John M; Knox, Ron E; Pozniak, Curtis J

2017-01-01

Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype-based analysis over single marker analysis to detect loci associated with colour traits in durum wheat.

Monitoring of 30 marker candidates in early Parkinson disease as progression markers.

PubMed

Mollenhauer, Brit; Zimmermann, Johannes; Sixel-Döring, Friederike; Focke, Niels K; Wicke, Tamara; Ebentheuer, Jens; Schaumburg, Martina; Lang, Elisabeth; Trautmann, Ellen; Zetterberg, Henrik; Taylor, Peggy; Friede, Tim; Trenkwalder, Claudia

2016-07-12

This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09-0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06-0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24-0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25-0.64), and RBD by PSG (d 0.37; CI 0.19-0.55) as well as VBM units of cortical gray matter (d -0.2; CI -0.3 to -0.09) and hippocampus (d -0.15; CI -0.27 to -0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d -0.19; CI -0.36 to -0.02) and 2 depression scales (Beck Depression Inventory d -0.18; CI -0.36 to 0; Montgomery-Åsberg Depression Rating Scale d -0.26; CI -0.47 to -0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression. © 2016 American Academy of Neurology.

A novel organotypic 3D sweat gland model with physiological functionality

PubMed Central

Grüdl, Sabine; Banowski, Bernhard; Giesen, Melanie; Sättler, Andrea; Proksch, Peter; Welss, Thomas; Förster, Thomas

2017-01-01

Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers. To resemble the in vivo situation as close as possible, we applied the hanging drop cultivation technology regaining most of the markers when cultured in its natural spherical environment. To compare the organotypic 3D sweat gland model versus human sweat glands in vivo, we compared markers relevant for the eccrine sweat gland using transcriptomic and proteomic analysis. Comparing the marker profile, a high in vitro-in vivo correlation was shown. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), muscarinic acetylcholine receptor M3 (CHRM3), Na+-K+-Cl- cotransporter 1 (NKCC1), calcium-activated chloride channel anoctamin-1 (ANO1/TMEM16A), and aquaporin-5 (AQP5) are found at significant expression levels in the 3D model. Moreover, cholinergic stimulation with acetylcholine or pilocarpine leads to calcium influx monitored in a calcium flux assay. Cholinergic stimulation cannot be achieved with the sweat gland cell line NCL-SG3 used as a sweat gland model system. Our results show clear benefits of the organotypic 3D sweat gland model versus 2D cultures in terms of the expression of essential eccrine sweat gland key regulators and in the physiological response to stimulation. Taken together, this novel organotypic 3D sweat gland model shows a good in vitro-in vivo correlation and is an appropriate alternative for screening of potential bioactives regulating the sweat mechanism. PMID:28796813

Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study.

PubMed

Bancroft, Elizabeth K; Page, Elizabeth C; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S; Mitchell, Gillian; Drew, Kate; Mæhle, Lovise; Axcrona, Karol; Evans, D Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J; Buys, Saundra; Conner, Tom; Ausems, Margreet G; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R; Maia, Sofia; Foulkes, William D; Taherian, Nassim; Ruijs, Marielle; Helderman-van den Enden, Apollonia T; Izatt, Louise; Davidson, Rosemarie; Adank, Muriel A; Walker, Lisa; Schmutzler, Rita; Tucker, Kathy; Kirk, Judy; Hodgson, Shirley; Harris, Marion; Douglas, Fiona; Lindeman, Geoffrey J; Zgajnar, Janez; Tischkowitz, Marc; Clowes, Virginia E; Susman, Rachel; Ramón y Cajal, Teresa; Patcher, Nicholas; Gadea, Neus; Spigelman, Allan; van Os, Theo; Liljegren, Annelie; Side, Lucy; Brewer, Carole; Brady, Angela F; Donaldson, Alan; Stefansdottir, Vigdis; Friedman, Eitan; Chen-Shtoyerman, Rakefet; Amor, David J; Copakova, Lucia; Barwell, Julian; Giri, Veda N; Murthy, Vedang; Nicolai, Nicola; Teo, Soo-Hwang; Greenhalgh, Lynn; Strom, Sara; Henderson, Alex; McGrath, John; Gallagher, David; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Dearnaley, David; Costello, Philandra; Eyfjord, Jorunn; Rothwell, Jeanette; Falconer, Alison; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Kote-Jarai, Zsofia; Lubinski, Jan; Axcrona, Ulrika; Melia, Jane; McKinley, Joanne; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Wilson, Penny; Killick, Emma; Moss, Sue; Eeles, Rosalind A

2014-09-01

Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. To report the first year's screening results for all men at enrollment in the study. We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy. PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment. Copyright © 2014 European Association of Urology. All rights reserved.

Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program.

PubMed

Lim, J S; Tan, E S; John, C M; Poh, S; Yeo, S J; Ang, J S M; Adakalaisamy, P; Rozalli, R A; Hart, C; Tan, E T H; Ranieri, E; Rajadurai, V S; Cleary, M A; Goh, D L M

2014-01-01

IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore. Copyright © 2014 Elsevier Inc. All rights reserved.

The Vertical Drop Jump Is a Poor Screening Test for ACL Injuries in Female Elite Soccer and Handball Players: A Prospective Cohort Study of 710 Athletes.

PubMed

Krosshaug, Tron; Steffen, Kathrin; Kristianslund, Eirik; Nilstad, Agnethe; Mok, Kam-Ming; Myklebust, Grethe; Andersen, Thor Einar; Holme, Ingar; Engebretsen, Lars; Bahr, Roald

2016-04-01

The evidence linking knee kinematics and kinetics during a vertical drop jump (VDJ) to anterior cruciate ligament (ACL) injury risk is restricted to a single small sample. Still, the VDJ test continues to be advocated for clinical screening purposes. To test whether 5 selected kinematic and kinetic variables were associated with future ACL injuries in a large cohort of Norwegian female elite soccer and handball players. Furthermore, we wanted to assess whether the VDJ test can be recommended as a screening test to identify players with increased risk. Cohort study; Level of evidence, 2. Elite female soccer and handball players participated in preseason screening tests from 2007 through 2014. The tests included marker-based 3-dimensional motion analysis of a drop-jump landing. We followed a predefined statistical protocol in which we included the following candidate risk factors in 5 separate logistic regression analyses, with new ACL injury as the outcome: (1) knee valgus angle at initial contact, (2) peak knee abduction moment, (3) peak knee flexion angle, (4) peak vertical ground-reaction force, and (5) medial knee displacement. A total of 782 players were tested (age, 21 ± 4 years; height, 170 ± 7 cm; body mass, 67 ± 8 kg), of which 710 were included in the analyses. We registered 42 new noncontact ACL injuries, including 12 in previously ACL-injured players. Previous ACL injury (relative risk, 3.8; 95% CI, 2.1-7.1) and medial knee displacement (odds ratio, 1.40; 95% CI, 1.12-1.74 per 1-SD change) were associated with increased risk for injury. However, among the 643 players without previous injury, we found no association with medial knee displacement. A receiver operating characteristic curve analysis of medial knee displacement showed an area under the curve of 0.6, indicating a poor-to-failed combined sensitivity and specificity of the test, even when including previously injured players. Of the 5 risk factors considered, medial knee displacement was the only factor associated with increased risk for ACL. However, receiver operating characteristic curve analysis indicated a poor combined sensitivity and specificity when medial knee displacement was used as a screening test for predicting ACL injury. For players with no previous injury, none of the VDJ variables were associated with increased injury risk. VDJ tests cannot predict ACL injuries in female elite soccer and handball players. © 2016 The Author(s).

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

Belinsky, Steven A; Palmisano, William A

A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection ofmore » lung and other cancers.« less

Homozygosity mapping in albinism patients using a novel panel of 13 STR markers inside the nonsyndromic OCA genes: introducing 5 novel mutations.

PubMed

Khordadpoor-Deilamani, Faravareh; Akbari, Mohammad Taghi; Karimipoor, Morteza; Javadi, Gholam Reza

2016-05-01

Albinism is a heterogeneous genetic disorder of melanin synthesis that results in hypopigmented hair, skin and eyes. It is associated with decreased visual acuity, nystagmus, strabismus and photophobia. Six genes are known to be involved in nonsyndromic oculocutaneous albinism (OCA). In this study, we aimed to find the disease causing mutations in albinism patients using homozygosity mapping. Twenty three unrelated patients with nonsyndromic OCA or autosomal recessive ocular albinism were recruited in this study. All of the patients' parents had consanguineous marriage and all were screened for TYR mutations previously. At first, we performed homozygosity mapping using fluorescently labeled primers to amplify a novel panel of 13 STR markers inside the OCA genes and then the screened loci in each family were studied using PCR and cycle sequencing methods. We found five mutations including three mutations in OCA2, one mutation in SLC45A2 and one mutation in C10ORF11 genes, all of which were novel. In cases where the disease causing mutations are identical by descent due to a common ancestor, these STR markers can enable us to screen for the responsible genes.

Collaborative Review: Risk-Based Prostate Cancer Screening

PubMed Central

Zhu, Xiaoye; Albertsen, Peter C.; Andriole, Gerald L.; Roobol, Monique J.; Schröder, Fritz H.; Vickers, Andrew J.

2016-01-01

Context Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification with regard to PCa risk and aggressiveness is necessary to identify those men who are at risk and may actually benefit from early detection. Objective This review critically examines the current evidence regarding risk-based PCa screening. Evidence acquisition A search of the literature was performed using the Medline database. Further studies were selected based on manual searches of reference lists and review articles. Evidence synthesis Prostate-specific antigen (PSA) has been shown to be the single most significant predictive factor for identifying men at increased risk of developing PCa. Especially in men with no additional risk factors, PSA alone provides an appropriate marker up to 30 yr into the future. After assessment of an early PSA test, the screening frequency may be determined based on individualized risk. A limited list of additional factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been identified to modify risk and are important for consideration in routine practice. In men with a known PSA, risk calculators may hold the promise of identifying those who are at increased risk of having PCa and are therefore candidates for biopsy. Conclusions PSA testing may serve as the foundation for a more risk-based assessment. However, the decision to undergo early PSA testing should be a shared one between the patient and his physician based on information balancing its advantages and disadvantages. PMID:22134009

Assessment of a self-deferral form for screening blood donors, Chiang Mai University Hospital, Thailand.

PubMed

Thaikruea, Lakkana; Nantachit, Niwes; Leetrakool, Nipapan; Fongsatitkul, Ladda; Sompan, Prakai; Heaton, Andrew; Nelson, Kenrad E

2008-09-01

A self-deferral form has been used to screen Chiang Mai University Hospital blood donors and was improved in 2005. It has never been evaluated. The study aimed to assess the self-deferral form procedures in detecting infected donors. Sera from 5,083 donors, who passed the self-deferral screening form, were tested with the routine immuno-assays (serology) for HIV 1 and 2 antibodies, P24 antigen, HCV antibodies, HBV surface antigen, and syphilis. Antibody negative sera were also tested individually with the the Procleix Ultrio Assay for HIV-1 DNA, HCV RNA, and HBV DNA. The donors who had discrepant results between serology and NAT were evaluated with additional tests, including a more sensitive Alternative Nucleic Acid Test, AntiBcore IgM, AntiBcore IgG, HBsAg and Anti HBs. Among 5,083 donors, 331 (6.5%) had at least one positive marker. In multiple logistic regression analysis, the statistically significant factors (adjusted odds ratio and 95% CI) for infection were age 30 years or below [1.45 (1.03, 2.03)], male gender [2.73 (1.64, 4.56)], primary school or lower education [1.56 (1.09, 2.23)], first-time donation [1.82 (1.25, 2.67)], and frequent donation [0.80 (0.70, 0.92)]. The safest donors were females, older than 30 years, with an education more than primary school, and frequent donation. Because of missing responses to some sensitive questions, there remains a need for further improvement of the self-deferral form.

Measuring molecular biomarkers in epidemiologic studies: laboratory techniques and biospecimen considerations.

PubMed

Erickson, Heidi S

2012-09-28

The future of personalized medicine depends on the ability to efficiently and rapidly elucidate a reliable set of disease-specific molecular biomarkers. High-throughput molecular biomarker analysis methods have been developed to identify disease risk, diagnostic, prognostic, and therapeutic targets in human clinical samples. Currently, high throughput screening allows us to analyze thousands of markers from one sample or one marker from thousands of samples and will eventually allow us to analyze thousands of markers from thousands of samples. Unfortunately, the inherent nature of current high throughput methodologies, clinical specimens, and cost of analysis is often prohibitive for extensive high throughput biomarker analysis. This review summarizes the current state of high throughput biomarker screening of clinical specimens applicable to genetic epidemiology and longitudinal population-based studies with a focus on considerations related to biospecimens, laboratory techniques, and sample pooling. Copyright © 2012 John Wiley & Sons, Ltd.

Receipt of Cancer Screening Is a Predictor of Life Expectancy.

PubMed

Goodwin, James S; Sheffield, Kristin; Li, Shuang; Tan, Alai

2016-11-01

Obtaining cancer screening on patients with limited life expectancy has been proposed as a measure for low quality care for primary care physicians (PCPs). However, administrative data may underestimate life expectancy in patients who undergo screening. To determine the association between receipt of screening mammography or PSA and overall survival. Retrospective cohort study from 1/1/1999 to 12/31/2012. Receipt of screening was assessed for 2001-2002 and survival from 1/1/2003 to 12/31/2012. Life expectancy was estimated as of 1/1/03 using a validated algorithm, and was compared to actual survival for men and women, stratified by receipt of cancer screening. A 5 % sample of Medicare beneficiaries aged 69-90 years as of 1/1/2003 (n = 906,723). Receipt of screening mammography in 2001-2002 for women, or a screening PSA test in 2002 for men. Survival from 1/1/2003 through 12/31/2012. Subjects were stratified by life expectancy based on age and comorbidity. Within each stratum, the subjects with prior cancer screening had actual median survivals higher than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men. In a Cox model, non-receipt of screening in women had an impact on survival (HR = 1.52; 95 % CI = 1.51, 1.54) similar in magnitude to a diagnosis of complicated diabetes or heart failure, and was comparable to uncomplicated diabetes or liver disease in men (HR = 1.23; 1.22, 1.25). Receipt of cancer screening is a powerful marker of health status that is not captured by comorbidity measures in administrative data. Because life expectancy algorithms using administrative data underestimate the life expectancy of patients who undergo screening, they can overestimate the problem of cancer screening in patients with limited life expectancy.

HE4 as a biomarker for ovarian and endometrial cancer management

PubMed Central

Li, Jinping; Dowdy, Sean; Tipton, Tracy; Podratz, Karl; Lu, Wei-Guo; Xie, Xing; Jiang, Shi-Wen

2012-01-01

Ovarian and endometrial cancer will be diagnosed in over 63,000 women in 2009, resulting in 22,000 deaths in the USA. Histologic screening, such as pap smears for detection of cervical cancer, is not feasible for these diseases given difficulty with access to the tissue. Thus, a serum-screening test using a biomarker or panel of biomarkers would be useful to aid in cancer diagnosis, detection of recurrence and as a means to monitor response to therapy. In this review, we focus on the human epididymis protein (HE)4 gene, which appears to have potential as a biomarker for both of these diseases. The structure and methods of detection of HE4 are discussed. Preliminary data show that HE4 may have more potential than cancer antigen 125 in discriminating benign from cancerous ovarian masses, and has the strongest correlation with endometrial cancer of all markers tested to date. Utilizing risk stratification, a panel of biomarkers including HE4 may ultimately be useful for detecting ovarian and endometrial cancer at an early stage in patients at high risk. PMID:19732003

Early results of urothelial carcinoma screening in a risk population of coke workers: urothelial carcinoma among coke workers.

PubMed

Giberti, C; Gallo, F; Schenone, M; Genova, A

2010-08-01

To present the protocol and the early results of a urothelial carcinoma (UC) screening analysis performed in a risk population of coke workers. Between June 2006 and October 2008, 171 male workers (mean age 43 years), employed in a Ligurian coke plant (Italiana Coke S.r.l) and exposed to polycyclic aromatic hydrocarbons (PAHs) for a median period of 16 years, underwent screening for UC. Urological evaluation included medical history, physical examination, routine laboratory tests, urine analysis, urinary cytology and uCyt+ assay. In the event of signs and symptoms suggestive of UC or positive urinary tests, the workers were also subjected to urinary ultrasonography and cystoscopy with biopsy of any suspicious lesions. Regarding the laboratory tests, 19/171 (11%) uCyt+ samples were considered inadequate and were excluded from the outcomes assessment. Overall, urine analysis, cytology and uCyt+ were positive in 18/152 (12%) subjects who showed no evidence of UC at the scheduled check-ups. No significant association was identified between marker positivity and occupational activity. Our results fail to show an increased risk of UC among the coke workers evaluated. However, they will need to be confirmed in the future by a larger enrollment and a longer follow-up in order to assess the definitive risk for UC after exposure to coke. Copyright © 2010 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Mapping QTL for popping expansion volume in popcorn with simple sequence repeat markers.

PubMed

Lu, H-J; Bernardo, R; Ohm, H W

2003-02-01

Popping expansion volume is the most important quality trait in popcorn ( Zea mays L.), but its genetics is not well understood. The objectives of this study were to map quantitative trait loci (QTLs) responsible for popping expansion volume in a popcorn x dent corn cross, and to compare the predicted efficiencies of phenotypic selection, marker-based selection, and marker-assisted selection for popping expansion volume. Of 259 simple sequence repeat (SSR) primer pairs screened, 83 pairs were polymorphic between the H123 (dent corn) and AG19 (popcorn) parental inbreds. Popping test data were obtained for 160 S(1) families developed from the [AG19(H123 x AG19)] BC(1) population. The heritability ( h(2)) for popping expansion volume on an S(1) family mean basis was 0.73. The presence of the gametophyte factor Ga1(s) in popcorn complicates the analysis of popcorn x dent corn crosses. But, from a practical perspective, the linkage between a favorable QTL allele and Ga1(s) in popcorn will lead to selection for the favorable QTL allele. Four QTLs, on chromosomes 1S, 3S, 5S and 5L, jointly explained 45% of the phenotypic variation. Marker-based selection for popping expansion volume would require less time and work than phenotypic selection. But due to the high h(2) of popping expansion volume, marker-based selection was predicted to be only 92% as efficient as phenotypic selection. Marker-assisted selection, which comprises index selection on phenotypic and marker scores, was predicted to be 106% as efficient as phenotypic selection. Overall, our results suggest that phenotypic selection will remain the preferred method for selection in popcorn x dent corn crosses.

Remarkable Variation in the Informativeness of RFLP Markers Linked to Hemophilia B Locus in Indian Population Groups: Implication in the Strategy for Carrier Detection

PubMed Central

Mukherjee, S.; Saha, A.; Kumar P., Senthil; Chandak, G. R.; Majumder, P. P.; Ray, K.

2006-01-01

Hemophilia B, an X-linked recessive bleeding disorder, is caused by heterogeneous mutations in the factor IX (F9) gene. Hence, carriers of the disease are usually detected by F9 gene linked RFLP analysis. We aimed to test a set of RFLP markers (DdeI, XmnI, MnlI, TaqI & HhaI), used worldwide for carrier detection, to estimate its heterozygosity in different population groups of India, and identify additional single nucleotide polymorphisms (SNPs) if necessary. A total of 8 population groups encompassing different regions of India, consisting of 107 unrelated normal females without any history of hemophilia B in the family and 13 unrelated obligate carriers were recruited in the study. Regions of F9 gene were amplified by PCR from genomic DNA of the donors followed by restriction enzyme digestion and/or sequencing as appropriate. Combined informativeness for the markers varied between 52–86% among normal females belonging to different geographical locations of India. Haplotype analysis revealed that the most prevalent haplotype lacked the restriction sites for all five RFLP markers. Screening regions of F9 gene that harbor 10 SNPs reported in dbSNP yielded only two SNPs, which increased the overall informativeness in each population group and heterozygosity in the obligate carriers for the disease from 38% to 69%. Our data show that heterozygosity of commonly used RFLP markers is remarkably variable across different regions of India. Thus prudent selection of the markers based on specific population groups including usage of additional markers is recommended for efficient carrier detection. PMID:17264403

Development of goose- and duck-specific DNA markers to determine sources of Escherichia coli in waterways.

PubMed

Hamilton, Matthew J; Yan, Tao; Sadowsky, Michael J

2006-06-01

The contamination of waterways with fecal material is a persistent threat to public health. Identification of the sources of fecal contamination is a vital component for abatement strategies and for determination of total maximum daily loads. While phenotypic and genotypic techniques have been used to determine potential sources of fecal bacteria in surface waters, most methods require construction of large known-source libraries, and they often fail to adequately differentiate among environmental isolates originating from different animal sources. In this study, we used pooled genomic tester and driver DNAs in suppression subtractive hybridizations to enrich for host source-specific DNA markers for Escherichia coli originating from locally isolated geese. Seven markers were identified. When used as probes in colony hybridization studies, the combined marker DNAs identified 76% of the goose isolates tested and cross-hybridized, on average, with 5% of the human E. coli strains and with less than 10% of the strains obtained from other animal hosts. In addition, the combined probes identified 73% of the duck isolates examined, suggesting that they may be useful for determining the contribution of waterfowl to fecal contamination. However, the hybridization probes reacted mainly with E. coli isolates obtained from geese in the upper midwestern United States, indicating that there is regional specificity of the markers identified. Coupled with high-throughput, automated macro- and microarray screening, these markers may provide a quantitative, cost-effective, and accurate library-independent method for determining the sources of genetically diverse E. coli strains for use in source-tracking studies. However, future efforts to generate DNA markers specific for E. coli must include isolates obtained from geographically diverse animal hosts.

Metabolite and transcript markers for the prediction of potato drought tolerance.

PubMed

Sprenger, Heike; Erban, Alexander; Seddig, Sylvia; Rudack, Katharina; Thalhammer, Anja; Le, Mai Q; Walther, Dirk; Zuther, Ellen; Köhl, Karin I; Kopka, Joachim; Hincha, Dirk K

2018-04-01

Potato (Solanum tuberosum L.) is one of the most important food crops worldwide. Current potato varieties are highly susceptible to drought stress. In view of global climate change, selection of cultivars with improved drought tolerance and high yield potential is of paramount importance. Drought tolerance breeding of potato is currently based on direct selection according to yield and phenotypic traits and requires multiple trials under drought conditions. Marker-assisted selection (MAS) is cheaper, faster and reduces classification errors caused by noncontrolled environmental effects. We analysed 31 potato cultivars grown under optimal and reduced water supply in six independent field trials. Drought tolerance was determined as tuber starch yield. Leaf samples from young plants were screened for preselected transcript and nontargeted metabolite abundance using qRT-PCR and GC-MS profiling, respectively. Transcript marker candidates were selected from a published RNA-Seq data set. A Random Forest machine learning approach extracted metabolite and transcript markers for drought tolerance prediction with low error rates of 6% and 9%, respectively. Moreover, by combining transcript and metabolite markers, the prediction error was reduced to 4.3%. Feature selection from Random Forest models allowed model minimization, yielding a minimal combination of only 20 metabolite and transcript markers that were successfully tested for their reproducibility in 16 independent agronomic field trials. We demonstrate that a minimum combination of transcript and metabolite markers sampled at early cultivation stages predicts potato yield stability under drought largely independent of seasonal and regional agronomic conditions. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Serum Metabonomics of Mild Acute Pancreatitis.

PubMed

Xu, Hongmin; Zhang, Lei; Kang, Huan; Zhang, Jiandong; Liu, Jie; Liu, Shuye

2016-11-01

Mild acute pancreatitis (MAP) is a common acute abdominal disease, and exhibits rising incidence in recent decades. As an important component of systemic biology, metabonomics is a new discipline developed following genomics and proteomics. In this study, the objective was to analyze the serum metabonomics of patients with MAP, aiming to screen metabolic markers with potential diagnostic values. An analysis platform with ultra performance liquid chromatography-high-resolution mass spectrometry was used to screen the difference metabolites related to MAP diagnosis and disease course monitoring. A total of 432 endogenous metabolites were screened out from 122 serum samples, and 49 difference metabolites were verified, among which 12 difference metabolites were identified by nonparametric test. After material identification, eight metabolites exhibited reliable results, and their levels in MAP serum were higher than those in healthy serum. Four metabolites exhibited gradual downward trend with treatment process going on, and the differences were statistically significant (P < 0.05). Metabonomic analysis has revealed eight metabolites with potential diagnostic values toward MAP, among which four metabolites can be used to monitor the disease course. © 2016 Wiley Periodicals, Inc.

Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries.

PubMed

Schuster, Daniela; Nashev, Lyubomir G; Kirchmair, Johannes; Laggner, Christian; Wolber, Gerhard; Langer, Thierry; Odermatt, Alex

2008-07-24

17Beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) plays a pivotal role in the local synthesis of the most potent estrogen estradiol. Its expression is a prognostic marker for the outcome of patients with breast cancer and inhibition of 17beta-HSD1 is currently under consideration for breast cancer prevention and treatment. We aimed to identify nonsteroidal 17beta-HSD1 inhibitor scaffolds by virtual screening with pharmacophore models built from crystal structures containing steroidal compounds. The most promising model was validated by comparing predicted and experimentally determined inhibitory activities of several flavonoids. Subsequently, a virtual library of nonsteroidal compounds was screened against the 3D pharmacophore. Analysis of 14 selected compounds yielded four that inhibited the activity of human 17beta-HSD1 (IC 50 below 50 microM). Specificity assessment of identified 17beta-HSD1 inhibitors emphasized the importance of including related short-chain dehydrogenase/reductase (SDR) members to analyze off-target effects. Compound 29 displayed at least 10-fold selectivity over the related SDR enzymes tested.

Mitigation of NADPH Oxidase 2 Activity as a Strategy to Inhibit Peroxynitrite Formation*

PubMed Central

Zielonka, Jacek; Zielonka, Monika; VerPlank, Lynn; Cheng, Gang; Hardy, Micael; Ouari, Olivier; Ayhan, Mehmet Menaf; Podsiadły, Radosław; Sikora, Adam; Lambeth, J. David; Kalyanaraman, Balaraman

2016-01-01

Using high throughput screening-compatible assays for superoxide and hydrogen peroxide, we identified potential inhibitors of the NADPH oxidase (Nox2) isoform from a small library of bioactive compounds. By using multiple probes (hydroethidine, hydropropidine, Amplex Red, and coumarin boronate) with well defined redox chemistry that form highly diagnostic marker products upon reaction with superoxide (O2˙̄), hydrogen peroxide (H2O2), and peroxynitrite (ONOO−), the number of false positives was greatly decreased. Selected hits for Nox2 were further screened for their ability to inhibit ONOO− formation in activated macrophages. A new diagnostic marker product for ONOO− is reported. We conclude that the newly developed high throughput screening/reactive oxygen species assays could also be used to identify potential inhibitors of ONOO− formed from Nox2-derived O2˙̄ and nitric oxide synthase-derived nitric oxide. PMID:26839313

Salicylic and jasmonic acid pathways are necessary for defence against Dickeya solani as revealed by a novel method for Blackleg disease screening of in vitro grown potato.

PubMed

Burra, D D; Mühlenbock, P; Andreasson, E

2015-09-01

Potato is major crop ensuring food security in Europe, and blackleg disease is increasingly causing losses in yield and during storage. Recently, one blackleg pathogen, Dickeya solani has been shown to be spreading in Northern Europe that causes aggressive disease development. Currently, identification of tolerant commercial potato varieties has been unsuccessful; this is confounded by the complicated etiology of the disease and a strong environmental influence on disease development. There is currently a lack of efficient testing systems. Here, we describe a system for quantification of blackleg symptoms on shoots of sterile in vitro potato plants, which saves time and space compared to greenhouse and existing field assays. We found no evidence for differences in infection between the described in vitro-based screening method and existing greenhouse assays. This system facilitates efficient screening of blackleg disease response of potato plants independent of other microorganisms and variable environmental conditions. We therefore used the in vitro screening method to increase understanding of plant mechanisms involved in blackleg disease development by analysing disease response of hormone- related (salicylic and jasmonic acid) transgenic potato plants. We show that both jasmonic (JA) and salicylic (SA) acid pathways regulate tolerance to blackleg disease in potato, a result unlike previous findings in Arabidopsis defence response to necrotrophic bacteria. We confirm this by showing induction of a SA marker, pathogenesis-related protein 1 (StPR1), and a JA marker, lipoxygenase (StLOX), in Dickeya solani infected in vitro potato plants. We also observed that tubers of transgenic potato plants were more susceptible to soft rot compared to wild type, suggesting a role for SA and JA pathways in general tolerance to Dickeya. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

Discerning morpho-anatomical, physiological and molecular multiformity in cultivated and wild genotypes of lentil with reconciliation to salinity stress

PubMed Central

Singh, Chandan Kumar; Kumari, Shanti; Singh Tomar, Ram Sewak; Karwa, Sourabh; Singh, Rajendra; Singh, Raja Bahadur; Sarkar, Susheel Kumar; Pal, Madan

2017-01-01

One hundred and sixty two genotypes of different Lens species were screened for salinity tolerance in hydroponics at 40, 80 and 120 mM sodium chloride (NaCl) for 30 d. The germination, seedling growth, biomass accumulation, seedling survivability, salinity scores, root and shoot anatomy, sodium ion (Na+), chloride ion (Cl-) and potassium ion (K+) concentrations, proline and antioxidant activities were measured to evaluate the performance of all the genotypes. The results were compared in respect of physiological (Na+, K+ and Cl-) and seed yield components obtained from field trials for salinity stress conducted during two years. Expression of salt tolerance in hydroponics was found to be reliable indicator for similarity in salt tolerance between genotypes and was evident in saline soil based comparisons. Impressive genotypic variation for salinity tolerance was observed among the genotypes screened under hydroponic and saline field conditions. Plant concentrations of Na+ and Cl- at 120 mM NaCl were found significantly correlated with germination, root and shoot length, fresh and dry weight of roots and shoots, seedling survivability, salinity scores and K+ under controlled conditions and ranked the genotypes along with their seed yield in the field. Root and shoot anatomy of tolerant line (PDL-1) and wild accession (ILWL-137) showed restricted uptake of Na+ and Cl- due to thick layer of their epidermis and endodermis as compared to sensitive cultigen (L-4076). All the genotypes were scanned using SSR markers for genetic diversity, which generated high polymorphism. On the basis of cluster analysis and population structure the contrasting genotypes were grouped into different classes. These markers may further be tested to explore their potential in marker-assisted selection. PMID:28542267

Milk Donor Blood Screening for HIV, Syphilis and Hepatitis B Markers in a Brazilian Human Milk Bank: Prevalence Time-trends Over the 2005- 2015 Period.

PubMed

Kupek, Emil; Savi, Estela Olivo

2017-01-01

Human milk banking has been promoted to provide donated breast milk for at-risk children whose mothers cannot breastfeed them but this effort was hindered by the advent of HIV epidemic. To estimate the seroprevalence of HIV, syphilis and hepatitis B in the blood of human milk donors registered in a major maternity hospital in the northern region of the Santa Catarina State, Brazil. A retrospective study included serological tests for HIV, syphilis and hepatitis B screening of milk donor candidates in the 2005-2015 period. The 95% confidence intervals were calculated using the Poisson distribution. For HIV, the prevalence per 100.000 pregnant women was 155, 170 and zero over the three periods analyzed (2005-2009, 2010-2012 and 2013-2015), respectively. Syphilis prevalence per 100,000 pregnant women was 509, 460 and 1749 in the three periods analyzed. For the HBsAg marker of recent hepatitis B infection, the prevalence on the same scale was 254, 231 and 299, respectively, while the anti-HBc prevalence, a marker of lifetime risk for hepatitis B infection, was 7339 in the 2010-2012 period and 3874 in the 2013-2015 period. High prevalence of HIV, syphilis and hepatitis B was found for the 2005-2015 period among breastfeeding mothers who offered to donate their exceeding milk to a human milk bank in Brazil. Despite apparent elimination of the HIV by the end of the period, the decline was not statistically significant. There was no significant change in the acute hepatitis B prevalence over time but the increased syphilis prevalence in the most recent period was statistically significant. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Discerning morpho-anatomical, physiological and molecular multiformity in cultivated and wild genotypes of lentil with reconciliation to salinity stress.

PubMed

Singh, Dharmendra; Singh, Chandan Kumar; Kumari, Shanti; Singh Tomar, Ram Sewak; Karwa, Sourabh; Singh, Rajendra; Singh, Raja Bahadur; Sarkar, Susheel Kumar; Pal, Madan

2017-01-01

One hundred and sixty two genotypes of different Lens species were screened for salinity tolerance in hydroponics at 40, 80 and 120 mM sodium chloride (NaCl) for 30 d. The germination, seedling growth, biomass accumulation, seedling survivability, salinity scores, root and shoot anatomy, sodium ion (Na+), chloride ion (Cl-) and potassium ion (K+) concentrations, proline and antioxidant activities were measured to evaluate the performance of all the genotypes. The results were compared in respect of physiological (Na+, K+ and Cl-) and seed yield components obtained from field trials for salinity stress conducted during two years. Expression of salt tolerance in hydroponics was found to be reliable indicator for similarity in salt tolerance between genotypes and was evident in saline soil based comparisons. Impressive genotypic variation for salinity tolerance was observed among the genotypes screened under hydroponic and saline field conditions. Plant concentrations of Na+ and Cl- at 120 mM NaCl were found significantly correlated with germination, root and shoot length, fresh and dry weight of roots and shoots, seedling survivability, salinity scores and K+ under controlled conditions and ranked the genotypes along with their seed yield in the field. Root and shoot anatomy of tolerant line (PDL-1) and wild accession (ILWL-137) showed restricted uptake of Na+ and Cl- due to thick layer of their epidermis and endodermis as compared to sensitive cultigen (L-4076). All the genotypes were scanned using SSR markers for genetic diversity, which generated high polymorphism. On the basis of cluster analysis and population structure the contrasting genotypes were grouped into different classes. These markers may further be tested to explore their potential in marker-assisted selection.

Case-Control Study of Candidate Gene Methylation and Adenomatous Polyp Formation

PubMed Central

M, Alexander; JB, Burch; SE, Steck; C-F, Chen; TG, Hurley; P, Cavicchia; N, Shivappa; J, Guess; H, Zhang; SD, Youngstedt; KE, Creek; S, Lloyd; K, Jones; JR, Hébert

2016-01-01

Purpose Colorectal cancer (CRC) is one of the most common and preventable forms of cancer, but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70–90% of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation. Methods Patients recruited from a local endoscopy clinic provided informed consent, and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors. Cases were individuals with a histopathologically confirmed adenoma, and controls included patients with a normal colonoscopy, or those with histopathological findings not requiring heightened surveillance (normal biopsy, hyperplastic polyp). Methylation-specific polymerase chain reaction was used to characterize candidate gene promoter methylation. Odds ratios and 95% confidence intervals (OR, 95% CI) were calculated using unconditional multivariable logistic regression to test the hypothesis that candidate gene methylation differed between cases and controls, after adjustment for confounders. Results Complete data were available for 107 participants; 36% had adenomas (men: 40%, women: 31%). Hypomethylation of the MINT1 locus (OR: 5.3, 95% CI: 1.0–28.2), and the PER1 (OR: 2.9, 95% CI: 1.1–7.7) and PER3 (OR: 11.6, 95% CI: 1.6–78.5) clock gene promoters was more common among adenoma cases. While specificity was moderate to high for the three markers (71–97%), sensitivity was relatively low (18–45%). Conclusion Follow-up of these epigenetic markers is suggested to further evaluate their utility for adenoma screening or surveillance. PMID:27771773

Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status.

PubMed

Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis

2017-09-01

Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis.

PubMed

Nicholas, B; Rudrasingham, V; Nash, S; Kirov, G; Owen, M J; Wimpory, D C

2007-06-01

Clock gene anomalies have been suggested as causative factors in autism. We screened eleven clock/clock-related genes in a predominantly high-functioning Autism Genetic Resource Exchange sample of strictly diagnosed autistic disorder progeny and their parents (110 trios) for association of clock gene variants with autistic disorder. We found significant association (P<0.05) for two single-nucleotide polymorphisms in per1 and two in npas2. Analysis of all possible combinations of two-marker haplotypes for each gene showed that in npas2 40 out of the 136 possible two-marker combinations were significant at the P<0.05 level, with the best result between markers rs1811399 and rs2117714, P=0.001. Haplotype analysis within per1 gave a single significant result: a global P=0.027 for the markers rs2253820-rs885747. No two-marker haplotype was significant in any of the other genes, despite the large number of tests performed. Our findings support the hypothesis that these epistatic clock genes may be involved in the etiology of autistic disorder. Problems in sleep, memory and timing are all characteristics of autistic disorder and aspects of sleep, memory and timing are each clock-gene-regulated in other species. We identify how our findings may be relevant to theories of autism that focus on the amygdala, cerebellum, memory and temporal deficits. We outline possible implications of these findings for developmental models of autism involving temporal synchrony/social timing.

Evaluation of surrogate markers for human immunodeficiency virus infection among blood donors at the blood bank of "Hospital Universitário Regional Norte do Paraná", Londrina, PR, Brazil.

PubMed

Reiche, Edna Maria Vissoci; Vogler, Ingridt Hildegard; Morimoto, Helena Kaminami; Bortoliero, André Luis; Matsuo, Tiemi; Yuahasi, Kátia Kioko; Cancian, Sanderson Júnior; Koguichi, Roberto Setsuo

2003-01-01

This study evaluated the usefulness of the anti-HBc, hepatitis C virus antibodies (anti-HCV), human T cell lymphotropic virus I and II antibodies (anti-HTLV I/II), serologic tests for syphilis, and surface antigen of hepatitis B virus (HBsAg) as surrogate markers for the risk for HIV infection in 80,284 serum samples from blood donors from the Blood Bank of "Hospital Universitário Regional Norte do Paraná", Londrina, Paraná State, Brazil, analyzed from July 1994 to April 2001. Among 39 blood donors with positive serology for HIV, 12 (30.8%) were anti-HBc positive, 10 (25.6%) for anti-HCV, 1 (2.6%) for anti-HTLV I/I, 1 (2.6%) was positive for syphilis, and 1 (2.6%) for HBsAg. Among the donors with negative serology for HIV, these markers were detected in 8,407 (10.5%), 441 (0.5%), 189 (0.2%), 464 (0.6%), and 473 (0.6%) samples, respectively. The difference was statistically significant (p < 0.001) for anti-HBc and anti-HCV. Although the predictive positive values for these surrogate markers were low for HIV infection, the results confirmed the anti-HBc and anti-HCV as useful surrogate markers for HIV infection thus reinforcing the maintenance of them in the screening for blood donors contributing to the prevention of the small number of cases in which HIV is still transmitted by transfusion.

The Promise of Novel Molecular Markers in Bladder Cancer

PubMed Central

Miremami, Jahan; Kyprianou, Natasha

2014-01-01

Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a molecular signature for an individual’s disease that can help predict progression, prognosis, and potential therapeutic response. Markers have shown potential value in improving diagnostic accuracy when used as an adjunct to current modalities, risk-stratification of patients that could aid the clinician in determining aggressiveness of surveillance, and allowing for a decrease in invasive surveillance procedures. This review discusses the current understanding of emerging biomarkers, including miRNAs, gene signatures and detection of circulating tumor cells in the blood, and their potential clinical value in bladder cancer diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practice. PMID:25535079

Cytogenetic and molecular markers for detecting Aegilops uniaristata chromosomes in a wheat background.

PubMed

Gong, Wenping; Li, Guangrong; Zhou, Jianping; Li, Genying; Liu, Cheng; Huang, Chengyan; Zhao, Zhendong; Yang, Zujun

2014-09-01

Aegilops uniaristata has many agronomically useful traits that can be used for wheat breeding. So far, a Triticum turgidum - Ae. uniaristata amphiploid and one set of Chinese Spring (CS) - Ae. uniaristata addition lines have been produced. To guide Ae. uniaristata chromatin transformation from these lines into cultivated wheat through chromosome engineering, reliable cytogenetic and molecular markers specific for Ae. uniaristata chromosomes need to be developed. Standard C-banding shows that C-bands mainly exist in the centromeric regions of Ae. uniaristata but rarely at the distal ends. Fluorescence in situ hybridization (FISH) using (GAA)8 as a probe showed that the hybridization signal of chromosomes 1N-7N are different, thus (GAA)8 can be used to identify all Ae. uniaristata chromosomes in wheat background simultaneously. Moreover, a total of 42 molecular markers specific for Ae. uniaristata chromosomes were developed by screening expressed sequence tag - sequence tagged site (EST-STS), expressed sequence tag - simple sequence repeat (EST-SSR), and PCR-based landmark unique gene (PLUG) primers. The markers were subsequently localized using the CS - Ae. uniaristata addition lines and different wheat cultivars as controls. The cytogenetic and molecular markers developed herein will be helpful for screening and identifying wheat - Ae. uniaristata progeny.

Weak cation magnetic separation technology and MALDI-TOF-MS in screening serum protein markers in primary type I osteoporosis.

PubMed

Shi, X L; Li, C W; Liang, B C; He, K H; Li, X Y

2015-11-30

We investigated weak cation magnetic separation technology and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) in screening serum protein markers of primary type I osteoporosis. We selected 16 postmenopausal women with osteoporosis and nine postmenopausal women as controls to find a new method for screening biomarkers and establishing a diagnostic model for primary type I osteoporosis. Serum samples were obtained from controls and patients. Serum protein was extracted with the WCX protein chip system; protein fingerprints were examined using MALDI-TOF-MS. The preprocessed and model construction data were handled by the ProteinChip system. The diagnostic models were established using a genetic arithmetic model combined with a support vector machine (SVM). The SVM model with the highest Youden index was selected. Combinations with the highest accuracy in distinguishing different groups of data were selected as potential biomarkers. From the two groups of serum proteins, 123 cumulative MS protein peaks were selected. Significant intensity differences in the protein peaks of 16 postmenopausal women with osteoporosis were screened. The difference in Youden index between the four groups of protein peaks showed that the highest peaks had mass-to-charge ratios of 8909.047, 8690.658, 13745.48, and 15114.52. A diagnosis model was established with these four markers as the candidates, and the model specificity and sensitivity were found to be 100%. Two groups of specimens in the SVM results on the scatterplot were distinguishable. We established a diagnosis model, and provided a new serological method for screening and diagnosis of osteoporosis with high sensitivity and specificity.

Investigation of tracking systems properties in CAVE-type virtual reality systems

NASA Astrophysics Data System (ADS)

Szymaniak, Magda; Mazikowski, Adam; Meironke, Michał

2017-08-01

In recent years, many scientific and industrial centers in the world developed a virtual reality systems or laboratories. One of the most advanced solutions are Immersive 3D Visualization Lab (I3DVL), a CAVE-type (Cave Automatic Virtual Environment) laboratory. It contains two CAVE-type installations: six-screen installation arranged in a form of a cube, and four-screen installation, a simplified version of the previous one. The user feeling of "immersion" and interaction with virtual world depend on many factors, in particular on the accuracy of the tracking system of the user. In this paper properties of the tracking systems applied in I3DVL was investigated. For analysis two parameters were selected: the accuracy of the tracking system and the range of detection of markers by the tracking system in space of the CAVE. Measurements of system accuracy were performed for six-screen installation, equipped with four tracking cameras for three axes: X, Y, Z. Rotation around the Y axis was also analyzed. Measured tracking system shows good linear and rotating accuracy. The biggest issue was the range of the monitoring of markers inside the CAVE. It turned out, that the tracking system lose sight of the markers in the corners of the installation. For comparison, for a simplified version of CAVE (four-screen installation), equipped with eight tracking cameras, this problem was not occur. Obtained results will allow for improvement of cave quality.

Screening of a Brassica napus bacterial artificial chromosome library using highly parallel single nucleotide polymorphism assays

PubMed Central

2013-01-01

Background Efficient screening of bacterial artificial chromosome (BAC) libraries with polymerase chain reaction (PCR)-based markers is feasible provided that a multidimensional pooling strategy is implemented. Single nucleotide polymorphisms (SNPs) can be screened in multiplexed format, therefore this marker type lends itself particularly well for medium- to high-throughput applications. Combining the power of multiplex-PCR assays with a multidimensional pooling system may prove to be especially challenging in a polyploid genome. In polyploid genomes two classes of SNPs need to be distinguished, polymorphisms between accessions (intragenomic SNPs) and those differentiating between homoeologous genomes (intergenomic SNPs). We have assessed whether the highly parallel Illumina GoldenGate® Genotyping Assay is suitable for the screening of a BAC library of the polyploid Brassica napus genome. Results A multidimensional screening platform was developed for a Brassica napus BAC library which is composed of almost 83,000 clones. Intragenomic and intergenomic SNPs were included in Illumina’s GoldenGate® Genotyping Assay and both SNP classes were used successfully for screening of the multidimensional BAC pools of the Brassica napus library. An optimized scoring method is proposed which is especially valuable for SNP calling of intergenomic SNPs. Validation of the genotyping results by independent methods revealed a success of approximately 80% for the multiplex PCR-based screening regardless of whether intra- or intergenomic SNPs were evaluated. Conclusions Illumina’s GoldenGate® Genotyping Assay can be efficiently used for screening of multidimensional Brassica napus BAC pools. SNP calling was specifically tailored for the evaluation of BAC pool screening data. The developed scoring method can be implemented independently of plant reference samples. It is demonstrated that intergenomic SNPs represent a powerful tool for BAC library screening of a polyploid genome. PMID:24010766

Identification of Novel, Inherited Genetic Markers for Aggressive PCa in European and African Americans Using Whole Genome Sequencing

DTIC Science & Technology

2013-09-01

DATES COVERED (From - To) 22 August 2012 – 21 August 2013 4. TITLE AND SUBTITLE Identification of Novel, Inherited Genetic Markers for Aggressive... Inherited markers of aggressive PCa could be used for screening and diagnosis of aggressive PCa at an early stage while reducing over-diagnosis and...treatment for others. The overall hypothesis is that inherited sequence variants in the genome are associated with a lethal (aggressive) form of PCa but not

Electronic Device of Didactic and Electrometric Interest for the Study of RLC Circuits.

ERIC Educational Resources Information Center

Rodriguez, Angel L. Perez; And Others

1979-01-01

Presents a method of studying RLC circuits with the help of the oscilloscope in the XYZ mode, complemented by an electronic device which generates a marker-trace on the screen and which is used to measure frequencies without the need of a reference point on the screen. (Author/GA)

Comparison of accessions from the UK and US national pear germplasm collections with a standardized set of microsatellite markers

USDA-ARS?s Scientific Manuscript database

A standardized set of 12 microsatellite markers, previously agreed upon following an ECP/GR workshop in 2006, was used to screen accessions from the UK National Pear Collection at Brogdale and from the US National Pear Germplasm Repository (NCGR), Corvallis. Eight standard varieties were chosen from...

Results from a Multi-Modal Program Evaluation of a Four Year Statewide Juvenile Sex Offender Treatment and Reentry Program

ERIC Educational Resources Information Center

Underwood, Lee A.; Dailey, Frances L. L.; Merino, Carrie; Crump, Yolanda

2015-01-01

The results of the Program Evaluation show the OJJ Statewide Sex Offender Treatment program is exceptionally productive in meeting over 90% of its established performance markers. These markers included successful screening and assessment of risk and psychosocial needs, completion of initial and master treatment plans, establishment of sex…

Mitosis Is a Source of Potential Markers for Screening and Survival and Therapeutic Targets in Cervical Cancer

PubMed Central

Espinosa, Ana María; Alfaro, Ana; Roman-Basaure, Edgar; Guardado-Estrada, Mariano; Palma, Ícela; Serralde, Cyntia; Medina, Ingrid; Juárez, Eligia; Bermúdez, Miriam; Márquez, Edna; Borges-Ibáñez, Manuel; Muñoz-Cortez, Sergio; Alcántara-Vázquez, Avissai; Alonso, Patricia; Curiel-Valdez, José; Kofman, Susana; Villegas, Nicolas; Berumen, Jaime

2013-01-01

The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it’s still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR = 5.9, 95%CI = 1.4–23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether it’s indispensable for tumor growth remains to be demonstrated. PMID:23405241

Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention

PubMed Central

Karimi, Parisa; Islami, Farhad; Anandasabapathy, Sharmila; Freedman, Neal D.; Kamangar, Farin

2014-01-01

Less than a century ago, gastric cancer (GC) was the most common cancer in the United States and perhaps throughout the world. Despite its worldwide decline in incidence over the past century, GC remains a major killer across the globe. This article reviews the epidemiology, screening, and prevention of gastric cancer. We first discuss the descriptive epidemiology of GC, including its incidence, survival, and mortality, including trends over time. Next, we characterize the risk factors for gastric cancer, both environmental and genetic. Serological markers and histological precursor lesions of GC and early detection of GC of using these markers is reviewed. Finally, we discuss prevention strategies and provide suggestions for further research. PMID:24618998

Nested methylation-specific polymerase chain reaction cancer detection method

DOEpatents

Belinsky, Steven A [Albuquerque, NM; Palmisano, William A [Edgewood, NM

2007-05-08

A molecular marker-based method for monitoring and detecting cancer in humans. Aberrant methylation of gene promoters is a marker for cancer risk in humans. A two-stage, or "nested" polymerase chain reaction method is disclosed for detecting methylated DNA sequences at sufficiently high levels of sensitivity to permit cancer screening in biological fluid samples, such as sputum, obtained non-invasively. The method is for detecting the aberrant methylation of the p16 gene, O 6-methylguanine-DNA methyltransferase gene, Death-associated protein kinase gene, RAS-associated family 1 gene, or other gene promoters. The method offers a potentially powerful approach to population-based screening for the detection of lung and other cancers.

Impact of the May 12, 2008, Earthquake on blood donations across five Chinese blood centers.

PubMed

Liu, Jing; Huang, Yi; Wang, Jingxing; Bi, Xinhong; Li, Julin; Lu, Yunlai; Wen, Xiuqiong; Yao, Fuzhu; Dong, Xiangdong; He, Weilan; Huang, Mei; Ma, Hongli; Mei, Heili; King, Melissa; Wright, David J; Ness, Paul M; Shan, Hua

2010-09-01

On May 12, 2008, a severe earthquake struck China's Sichuan Province. The nationwide outpouring of charity resulted in a surge of subsequent blood donations. The quantity and quality of these donations were examined in comparison with routine donations. Whole blood and apheresis donations from five geographically different blood centers collected within 1 week postearthquake were compared with those collected during the rest of the year. Regional differences, demographic characteristics, first-time and repeat donor status, and infectious disease screening markers associated with these donations were compared by earthquake status using chi-square statistics. Poisson regression analysis examined the number of daily donations by earthquake status after adjusting for center, day of week, and seasonal variations. The number of daily donations across five blood centers increased from 685 on a typical day to 1151 in the postearthquake week. The surge was observed in both sexes and across different education levels, age, and ethnicity groups and three blood centers and was significant after adjusting for confounding covariates. The influx of first-time donors (89.5%) was higher than that of repeat donors (34%). There was a significant change in the overall screening reactive marker rates excluding alanine aminotransferase (2.06% vs. 1.72%% vs. 4.96%). However, when the individual screening test was analyzed separately, no significant differences were found. Timely donations in response to a disaster are crucial to ensure emergency blood transfusion. The dramatically increased postearthquake donations suggest that Chinese blood centers are capable of handling emergency blood needs. Measures to maintain blood safety should be taken in times of emergency. © 2010 American Association of Blood Banks.

Genomics-based precision breeding approaches to improve drought tolerance in rice.

PubMed

Swamy, B P Mallikarjuna; Kumar, Arvind

2013-12-01

Rice (Oryza sativa L.), the major staple food crop of the world, faces a severe threat from widespread drought. The development of drought-tolerant rice varieties is considered a feasible option to counteract drought stress. The screening of rice germplasm under drought and its characterization at the morphological, genetic, and molecular levels revealed the existence of genetic variation for drought tolerance within the rice gene pool. The improvements made in managed drought screening and selection for grain yield under drought have significantly contributed to progress in drought breeding programs. The availability of rice genome sequence information, genome-wide molecular markers, and low-cost genotyping platforms now makes it possible to routinely apply marker-assisted breeding approaches to improve grain yield under drought. Grain yield QTLs with a large and consistent effect under drought have been indentified and successfully pyramided in popular rice mega-varieties. Various rice functional genomics resources, databases, tools, and recent advances in "-omics" are facilitating the characterization of genes and pathways involved in drought tolerance, providing the basis for candidate gene identification and allele mining. The transgenic approach is successful in generating drought tolerance in rice under controlled conditions, but field-level testing is necessary. Genomics-assisted drought breeding approaches hold great promise, but a well-planned integration with standardized phenotyping is highly essential to exploit their full potential. Copyright © 2013 Elsevier Inc. All rights reserved.

Multi-locus genotyping of bottom fermenting yeasts by single nucleotide polymorphisms indicative of brewing characteristics.

PubMed

Ikushima, Shigehito; Tateishi, Yoshiyuki; Kanai, Keiko; Shimada, Emiko; Tanaka, Misa; Ishiguro, Tatsuji; Mizutani, Satoru; Kobayashi, Osamu

2012-04-01

Yeast plays a capital role in brewing fermentation and has a direct impact on flavor and aroma. For the evaluation of competent brewing strains during quality control or development of novel strains it is standard practice to perform fermentation tests, which are costly and time-consuming. Here, we have categorized DNA markers which enable to distinguish and to screen brewing strains more efficiently than ever before. Sequence analysis at 289 loci in the genomes of six bottom fermenting Saccharomyces pastorianus strains revealed that 30 loci contained single nucleotide polymorphisms (SNPs). By determining the nucleotide sequences at the SNP-loci in 26 other S. pastorianus strains and 20 strains of the top fermenting yeast Saccharomyces cerevisiae, almost all these strains could be discriminated solely on the basis of the SNPs. By comparing the fermentative phenotypes of these strains we found that some DNA markers showed a strong association with brewing characteristics, such as the production of ethyl acetate and hydrogen sulphide (H2S). Therefore, the DNA markers we identified will facilitate quality control and the efficient development of brewing yeast strains. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection

PubMed Central

Wang, Yu; Chen, Pei-Min; Liu, Rong-Bin

2018-01-01

This review article summarizes the research advances of the plasma-based SEPT9 gene methylation assay for the clinical detection of colorectal cancer and its limitations. Colorectal cancer is a common malignancy with a poor prognosis and a high mortality, for which early detection and diagnosis are particularly crucial for the high-risk groups. Increasing evidence supported that SEPT9 gene methylation is associated with the pathogenesis of colorectal cancer and that detecting the level of methylation of SEPT9 in the peripheral blood can be used for screening of colorectal cancer in susceptible populations. In recent years, the data obtained in clinical studies demonstrated that the SEPT9 gene methylation assay has a good diagnostic performance with regard to both sensitivity and specificity with the advantage of better acceptability, convenience and compliance with serological testing compared with fecal occult blood tests and carcinoembryonic antigen for colorectal cancer (CRC). Furthermore, the combination of multiple methods or markers has become a growing trend for CRC detection and screening. Nevertheless, the clinical availability of the methylated SEPT9 assay is still limited because of the large degree of sample heterogeneity caused by demographic characteristics, pathological features, comorbidities and/or technique selection. Another factor is the cost-effectiveness of colorectal cancer screening strategies that hinders its large-scale application. In addition, improvements in its accuracy in detecting adenomas and premalignant polyps are required. PMID:29375744

Sub-tesla-field magnetization of vibrated magnetic nanoreagents for screening tumor markers

NASA Astrophysics Data System (ADS)

Chieh, Jen-Jie; Huang, Kai-Wen; Shi, Jin-Cheng

2015-02-01

Magnetic nanoreagents (MNRs), consisting of liquid solutions and magnetic nanoparticles (MNPs) coated with bioprobes, have been widely used in biomedical disciplines. For in vitro tests of serum biomarkers, numerous MNR-based magnetic immunoassay methods or schemes have been developed; however, their applications are limited. In this study, a vibrating sample magnetometer (VSM) was used for screening tumor biomarkers based on the same MNRs as those used in other immunoassay methods. The examination mechanism is that examined tumor biomarkers are typically conjugated to the bioprobes coated on MNPs to form magnetic clusters. Consequently, the sub-Tesla-field magnetization (Msub-T) of MNRs, including magnetic clusters, exceeds that of MNRs containing only separate MNPs. For human serum samples, proteins other than the targeted biomarkers induce the formation of magnetic clusters with increased Msub-T because of weak nonspecific binding. In this study, this interference problem was suppressed by the vibration condition in the VSM and analysis. Based on a referenced Msub-T,0 value defined by the average Msub-T value of a normal person's serum samples, including general proteins and few tumor biomarkers, the difference ΔMsub-T between the measured Msub-T and the reference Msub-T,0 determined the expression of only target tumor biomarkers in the tested serum samples. By using common MNRs with an alpha-fetoprotein-antibody coating, this study demonstrated that a current VSM can perform clinical screening of hepatocellular carcinoma.

Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection.

PubMed

Wang, Yu; Chen, Pei-Min; Liu, Rong-Bin

2018-01-15

This review article summarizes the research advances of the plasma-based SEPT9 gene methylation assay for the clinical detection of colorectal cancer and its limitations. Colorectal cancer is a common malignancy with a poor prognosis and a high mortality, for which early detection and diagnosis are particularly crucial for the high-risk groups. Increasing evidence supported that SEPT9 gene methylation is associated with the pathogenesis of colorectal cancer and that detecting the level of methylation of SEPT9 in the peripheral blood can be used for screening of colorectal cancer in susceptible populations. In recent years, the data obtained in clinical studies demonstrated that the SEPT9 gene methylation assay has a good diagnostic performance with regard to both sensitivity and specificity with the advantage of better acceptability, convenience and compliance with serological testing compared with fecal occult blood tests and carcinoembryonic antigen for colorectal cancer (CRC). Furthermore, the combination of multiple methods or markers has become a growing trend for CRC detection and screening. Nevertheless, the clinical availability of the methylated SEPT9 assay is still limited because of the large degree of sample heterogeneity caused by demographic characteristics, pathological features, comorbidities and/or technique selection. Another factor is the cost-effectiveness of colorectal cancer screening strategies that hinders its large-scale application. In addition, improvements in its accuracy in detecting adenomas and premalignant polyps are required.

GMO detection in food and feed through screening by visual loop-mediated isothermal amplification assays.

PubMed

Wang, Cong; Li, Rong; Quan, Sheng; Shen, Ping; Zhang, Dabing; Shi, Jianxin; Yang, Litao

2015-06-01

Isothermal DNA/RNA amplification techniques are the primary methodology for developing on-spot rapid nucleic acid amplification assays, and the loop-mediated isothermal amplification (LAMP) technique has been developed and applied in the detection of foodborne pathogens, plant/animal viruses, and genetically modified (GM) food/feed contents. In this study, one set of LAMP assays targeting on eight frequently used universal elements, marker genes, and exogenous target genes, such as CaMV35S promoter, FMV35S promoter, NOS, bar, cry1Ac, CP4 epsps, pat, and NptII, were developed for visual screening of GM contents in plant-derived food samples with high efficiency and accuracy. For these eight LAMP assays, their specificity was evaluated by testing commercial GM plant events and their limits of detection were also determined, which are 10 haploid genome equivalents (HGE) for FMV35S promoter, cry1Ac, and pat assays, as well as five HGE for CaMV35S promoter, bar, NOS terminator, CP4 epsps, and NptII assays. The screening applicability of these LAMP assays was further validated successfully using practical canola, soybean, and maize samples. The results suggested that the established visual LAMP assays are applicable and cost-effective for GM screening in plant-derived food samples.

Advances in pancreatic cancer research: moving towards early detection.

PubMed

He, Xiang-Yi; Yuan, Yao-Zong

2014-08-28

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India.

PubMed

Maity, Susmita; Nandi, Srijita; Biswas, Subrata; Sadhukhan, Salil Kumar; Saha, Malay Kumar

2012-11-26

HIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance. A comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.); ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd.) gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd.), Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd.) did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100%) except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.). The kit efficiency didn't vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p < 0.01) among three kit types. ELISA is a good screening assay for markers of HIV, HBV and HCV infections. Rapid tests are useful for further detection of false positive samples. ELISA seems the appropriate assay in blood bank. For availability of quality commercial diagnostic assays, evaluation of kit may be helpful.

Performance and diagnostic usefulness of commercially available enzyme linked immunosorbent assay and rapid kits for detection of HIV, HBV and HCV in India

PubMed Central

2012-01-01

Background HIV, HBV and HCV pose a major public health problem throughout the world. Detection of infection markers for these agents is a major challenge for testing laboratories in a resource poor setting. As blood transfusion is an important activity saving millions of live every year, it also carries a risk of transfusion transmissible infections caused by these fatal blood borne pathogens if the quality of testing is compromised. Conventional ELISA is regarded as the mostly used screening technique but due to limitations like high cost, unavailability in many blood banks and testing sites, involvement of costly instruments, time taking nature and requirement of highly skilled personnel for interpretation, rapid tests are gaining more importance and warrants comparison of performance. Results A comparative study between these two techniques has been performed using commercially available diagnostic kits to assess their efficacy for detection of HIV, HBV and HCV infections. Rapid kits were more efficient in specificity with synthetic antigens along with high PPV than ELISA in most cases. Comparison between different ELISA kits revealed that Microlisa HIV and Hepalisa (J. Mitra & Co. Pvt. Ltd.); ERBA LISA HIV1 + 2, ERBA LISA Hepatitis B and ERBA LISA HCV (Transasia Bio-medicals Ltd.) gives uniform result with good performance in terms of sensitivity, specificity, PPV, NPV and efficiency, whereas, Microlisa HCV (J. Mitra & Co. Pvt. Ltd.), Microscreen HBsAg ELISA and INNOVA HCV (Span Diagnostics Ltd.) did not perform well. Rapid kits were also having high degree of sensitivity and specificity (100%) except in HIV Comb and HCV Comb (J. Mitra & Co. Pvt. Ltd.). The kit efficiency didn’t vary significantly among different companies and lots in all the cases except for HCV ELISA showing statistically significant variation (p < 0.01) among three kit types. Conclusions ELISA is a good screening assay for markers of HIV, HBV and HCV infections. Rapid tests are useful for further detection of false positive samples. ELISA seems the appropriate assay in blood bank. For availability of quality commercial diagnostic assays, evaluation of kit may be helpful. PMID:23181517

Comparisons of the oxidative stress biomarkers levels in gestational diabetes mellitus (GDM) and non-GDM among Thai population: cohort study.

PubMed

Rueangdetnarong, Hathairat; Sekararithi, Rattanaporn; Jaiwongkam, Thidarat; Kumfu, Sirinart; Chattipakorn, Nipon; Tongsong, Theera; Jatavan, Phudit

2018-05-01

The primary objective of this study was to compare the levels of oxidative stress biomarkers between pregnancies with gestational diabetes mellitus (GDM) and normoglycemic pregnancies. A prospective study was conducted on pregnant women at average risk for GDM. The participants were screened for GDM with glucose challenge test and confirmed by 100 g, 3-h oral glucose tolerance test and categorized into the control (non-GDM) and GDM groups. Maternal blood was collected from all participants at gestational age (GA) 24-28 weeks and early labor and fetal cord blood was collected for measurements of 8 Isoprostane (8Isop) (oxidative stress marker), TNF-α (inflammatory marker) and IL-10 (anti-inflammatory marker) and were followed up for maternal and neonatal outcomes. A total of 62 women, 30 in GDM and 32 in control group, met the inclusion criteria. At 24-28 weeks of gestation, maternal serum 8Isop and TNF-α levels were significantly higher in GDM group ( P  = 0.032 and P  = 0.047), in spite of good glycemic control. At early labor, maternal 8Isop levels were significantly higher in GDM ( P  = 0.001). The biomarkers in the cord blood as well as maternal and neonatal outcomes in both groups were not significantly different. GDM is significantly associated with inflammatory process when compared to normal pregnancy, as indicated by higher oxidative stress and apoptosis markers. However, such levels were not correlated with the pregnancy outcomes. An increase in oxidative stress could not be prevented by good glycemic control. Cord blood biomarker levels in pregnancy with GDM were not changed, suggesting that the placenta could be the barrier for the oxidative stress and cytokines. © 2018 The authors.

Screening for pre-eclampsia in the first trimester: role of maternal hemodynamics and bioimpedance in non-obese patients.

PubMed

Gagliardi, G; Tiralongo, G M; LoPresti, D; Pisani, I; Farsetti, D; Vasapollo, B; Novelli, G P; Andreoli, A; Valensise, H

2017-11-01

To test if maternal hemodynamics and bioimpedance, assessed at the time of combined screening for PE, are able to identify in the first trimester of gestation normotensive non-obese patients at risk for pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). One hundred and fifty healthy nulliparous non-obese women (body mass index < 30 kg/m 2 ) in the first trimester of pregnancy underwent assessment by UltraSonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters, bioimpedance analysis to characterize body composition, and combined screening for PE (assessment of maternal history, biophysical and maternal biochemical markers). Patients were followed until term, noting the appearance of PE and/or IUGR. One hundred and thirty-eight patients had an uneventful pregnancy (controls), while 12 (8%) developed complications (cases). USCOM showed, in cases compared with controls, lower cardiac output (5.6 ± 0.3 vs 6.7 ± 1.1 L/min, P < 0.001), lower inotropy index (1.54 ± 0.38 vs 1.91 ± 0.32 W/m 2 , P < 0.001) and higher total vascular resistance (1279.8 ± 166.4 vs 1061.4 ± 179.5 dynes × s/cm 5 , P < 0.001). Bioimpedance analysis showed, in cases compared with controls, lower total body water (53.7 ± 3.3% vs 57.2 ± 5.6%, P = 0.037). Combined screening was positive for PE in 8% of the controls and in 50% of the cases (P < 0.001). After identification of cut-off values for USCOM and bioimpedance parameters, forward multivariate logistic regression analysis identified as independent predictors of complications in pregnancy the inotropy index (derived by USCOM), fat mass (derived from bioimpedance analysis) and combined screening. Combined screening for PE and assessment of bioimpedance and maternal hemodynamics can be used to identify early markers of impaired cardiovascular adaptation and body composition that may lead to complications in the third trimester of pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The evolution of lung cancer screening.

PubMed

Wilkinson, Neal W; Loewen, Gregory M; Klippenstein, Donald L; Litwin, Alan M; Anderson, Timothy M

2003-12-01

In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.

High-throughput multiplexed T-cell-receptor excision circle quantitative PCR assay with internal controls for detection of severe combined immunodeficiency in population-based newborn screening.

PubMed

Gerstel-Thompson, Jacalyn L; Wilkey, Jonathan F; Baptiste, Jennifer C; Navas, Jennifer S; Pai, Sung-Yun; Pass, Kenneth A; Eaton, Roger B; Comeau, Anne Marie

2010-09-01

Real-time quantitative PCR (qPCR) targeting a specific marker of functional T cells, the T-cell-receptor excision circle (TREC), detects the absence of functional T cells and has a demonstrated clinical validity for detecting severe combined immunodeficiency (SCID) in infants. There is need for a qPCR TREC assay with an internal control to monitor DNA quality and the relative cellular content of the particular dried blood spot punch sampled in each reaction. The utility of the qPCR TREC assay would also be far improved if more tests could be performed on the same newborn screening sample. We approached the multiplexing of qPCR for TREC by attenuating the reaction for the reference gene, with focus on maintaining tight quality assurance for reproducible slopes and for prevention of sample-to-sample cross contamination. Statewide newborn screening for SCID using the multiplexed assay was implemented, and quality-assurance data were recorded. The multiplex qPCR TREC assay showed nearly 100% amplification efficiency for each of the TREC and reference sequences, clinical validity for multiple forms of SCID, and an analytic limit of detection consistent with prevention of contamination. The eluate and residual ghost from a 3.2-mm dried blood spot could be used as source material for multiplexed immunoassays and multiplexed DNA tests (Multiplex Plus), with no disruption to the multiplex TREC qPCR. Population-based SCID newborn screening programs should consider multiplexing for quality assurance purposes. Potential benefits of using Multiplex Plus include the ability to perform multianalyte profiling.

Protective effect of an aphrodisiac herb Tribulus terrestris Linn on cadmium-induced testicular damage

PubMed Central

Rajendar, B.; Bharavi, K.; Rao, G. S.; Kishore, P.V.S; Kumar, P. Ravi; Kumar, C.S.V Satish; Patel, T. Pankaj

2011-01-01

Aim: The aim of the present study was to investigate whether Tribulus terrestris Linn (TT) could protect the cadmium (Cd)-induced testicular tissue peroxidation in rats and to explore the underlying mechanism of the same. Materials and Methods: In vitro and in vivo studies were conducted to know the protective effect of ethanolic extract of TT (eTT) in Cd toxicity. In in vitro studies, total antioxidant and ferrous metal ion chelating activity of TT was studied. In vivo studies were conducted in rats. A total of 40 Wistar strain adult male rats were divided into four groups. Group 1 served as control, while group 2 to 4 received CdCl2 (3 mg/kg b. wt. s/c once a week). In addition to Cd, group 3 and 4 rats also received eTT (5 mg/kg b.wt. daily as oral gavage) and α-tocopherol (75 mg/kg daily by oral gavage), respectively. At the end of 6th week, all the rats were sacrificed and the separated testes were weighted and processed for estimation of tissue peroxidation markers, antioxidant markers, functional markers, and Cd concentration. The testes were also subjected to histopathological screening. Results: In in vitro studies, the percentage of metal ion chelating activity of 50 μg/ml of eTT and α-tocopherol were 2.76 and 9.39, respectively, and the antioxidant capacity of eTT was equivalent to 0.063 μg of α-tocopherol/μg of eTT. In in vivo studies, administration of Cd significantly reduced the absolute and relative testicular weight, antioxidant markers such as superoxide dismutase and glutathione, and functional markers such as LDH and ALP, along with significant increase in peroxidation markers such as malondialdehyde and protein carbonyls in testicular tissue. Testes of Cd only-treated group showed histological insults like necrotic changes in seminiferous tubules and interstitium, shrunken tubules with desquamated basal lamina, vacuolization and destruction of sertoli cells, and degenerating Leydig cells. This group also had higher Cd levels in testicular tissue. Co-treatment with eTT and α-tocopherol significantly reduced the Cd burden in the testes along with reversal of the Cd-induced changes. Conclusions: eTT exhibited protective effect against Cd-induced testicular damage. The protective effect appears to be mediated through inhibition of testicular tissue peroxidation by antioxidant and metal chelator activity and also, may be indirectly by stimulating the testosterone production from Leydig cells. PMID:22022002

ON MODEL SELECTION STRATEGIES TO IDENTIFY GENES UNDERLYING BINARY TRAITS USING GENOME-WIDE ASSOCIATION DATA.

PubMed

Wu, Zheyang; Zhao, Hongyu

2012-01-01

For more fruitful discoveries of genetic variants associated with diseases in genome-wide association studies, it is important to know whether joint analysis of multiple markers is more powerful than the commonly used single-marker analysis, especially in the presence of gene-gene interactions. This article provides a statistical framework to rigorously address this question through analytical power calculations for common model search strategies to detect binary trait loci: marginal search, exhaustive search, forward search, and two-stage screening search. Our approach incorporates linkage disequilibrium, random genotypes, and correlations among score test statistics of logistic regressions. We derive analytical results under two power definitions: the power of finding all the associated markers and the power of finding at least one associated marker. We also consider two types of error controls: the discovery number control and the Bonferroni type I error rate control. After demonstrating the accuracy of our analytical results by simulations, we apply them to consider a broad genetic model space to investigate the relative performances of different model search strategies. Our analytical study provides rapid computation as well as insights into the statistical mechanism of capturing genetic signals under different genetic models including gene-gene interactions. Even though we focus on genetic association analysis, our results on the power of model selection procedures are clearly very general and applicable to other studies.

ON MODEL SELECTION STRATEGIES TO IDENTIFY GENES UNDERLYING BINARY TRAITS USING GENOME-WIDE ASSOCIATION DATA

PubMed Central

Wu, Zheyang; Zhao, Hongyu

2013-01-01

For more fruitful discoveries of genetic variants associated with diseases in genome-wide association studies, it is important to know whether joint analysis of multiple markers is more powerful than the commonly used single-marker analysis, especially in the presence of gene-gene interactions. This article provides a statistical framework to rigorously address this question through analytical power calculations for common model search strategies to detect binary trait loci: marginal search, exhaustive search, forward search, and two-stage screening search. Our approach incorporates linkage disequilibrium, random genotypes, and correlations among score test statistics of logistic regressions. We derive analytical results under two power definitions: the power of finding all the associated markers and the power of finding at least one associated marker. We also consider two types of error controls: the discovery number control and the Bonferroni type I error rate control. After demonstrating the accuracy of our analytical results by simulations, we apply them to consider a broad genetic model space to investigate the relative performances of different model search strategies. Our analytical study provides rapid computation as well as insights into the statistical mechanism of capturing genetic signals under different genetic models including gene-gene interactions. Even though we focus on genetic association analysis, our results on the power of model selection procedures are clearly very general and applicable to other studies. PMID:23956610

Development of Genomic Simple Sequence Repeats (SSR) by Enrichment Libraries in Date Palm.

PubMed

Al-Faifi, Sulieman A; Migdadi, Hussein M; Algamdi, Salem S; Khan, Mohammad Altaf; Al-Obeed, Rashid S; Ammar, Megahed H; Jakse, Jerenj

2017-01-01

Development of highly informative markers such as simple sequence repeats (SSR) for cultivar identification and germplasm characterization and management is essential for date palms genetic studies. The present study documents the development of SSR markers and assesses genetic relationships of commonly grown date palm (Phoenix dactylifera L.) cultivars in different geographical regions of Saudi Arabia. A total of 93 novel simple sequence repeat (SSR) markers were screened for their ability to detect polymorphism in date palm. Around 71% of genomic SSRs are dinucleotide, 25% trinucleotide, 3% tetranucleotide, and 1% pentanucleotide motives and show 100% polymorphism. The Unweighted Pair Group Method with Arithmetic Mean (UPGMA) cluster analysis illustrates that cultivars trend to group according to their class of maturity, region of cultivation, and fruit color. Analysis of molecular variations (AMOVA) reveals genetic variation among and within cultivars of 27% and 73%, respectively, according to the geographical distribution of the cultivars. Developed microsatellite markers are of additional value to date palm characterization, tools which can be used by researchers in population genetics, cultivar identification, as well as genetic resource exploration and management. The cultivars tested exhibited a significant amount of genetic diversity and could be suitable for successful breeding programs. Genomic sequences generated from this study are available at the National Center for Biotechnology Information (NCBI), Sequence Read Archive (Accession numbers. LIBGSS_039019).

Chip-Based Dynamic Real-Time Quantification of Drug-Induced Cytotoxicity in Human Tumor Cells

PubMed Central

Wlodkowic, Donald; Skommer, Joanna; McGuinness, Dagmara; Faley, Shannon; Kolch, Walter; Darzynkiewicz, Zbigniew; Cooper, Jonathan M.

2013-01-01

Cell cytotoxicity tests are among the most common bioassays using flow cytometry and fluorescence imaging analysis. The permeability of plasma membranes to charged fluorescent probes serves, in these assays, as a marker distinguishing live from dead cells. Since it is generally assumed that probes, such as propidium iodide (PI) or 7-amino-actinomycin D (7-AAD), are themselves cytotoxic, they are currently generally used only as the end-point markers of assays for live versus dead cells. In the current study, we provide novel insights into potential applications of these classical plasma membrane integrity markers in the dynamic tracking of drug-induced cytotoxicity. We show that treatment of a number of different human tumor cell lines in cultures for up to 72 h with the PI, 7-AAD, SYTOX Green (SY-G), SYTOX Red (SYR), TO-PRO, and YO-PRO had no effect on cell viability assessed by the integrity of plasma membrane, cell cycle progression, and rate of proliferation. We subsequently explore the potential of dynamic labeling with these markers in real-time analysis, by comparing results from both conventional cytometry and microfluidic chips. Considering the simplicity of the staining protocols and their low cost combined with the potential for real-time data collection, we show how that real-time fluorescent imaging and Lab-on-a-Chip platforms have the potential to be used for automated drug screening routines. PMID:19572560

Methods for detecting additional genes underlying Alzheimer disease

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

Locke, P.A.; Haines, J.L.; Ter-Minassian, M.

1994-09-01

Alzheimer`s disease (AD) is a complex inherited disorder with proven genetic heterogeneity. To date, genes on chromosome 21 (APP) and 14 (not yet identified) are associated with early-onset familial AD, while the APOE gene on chromosome 19 is associated with both late onset familial and sporadic AD and early onset sporadic AD. Although these genes likely account for the majority of AD, many familial cases cannot be traced to any of these genes. From a set of 127 late-onset multiplex families screened for APOE, 43 (34%) families have at least one affected individual with no APOE-4 allele, suggesting an alternativemore » genetic etiology. Simulation studies indicated that additional loci could be identified through a genomic screen with a 10 cM sieve on a subset of 21 well documented, non-APOE-4 families. Given the uncertainties in the mode of inheritance, reliance on a single analytical method could result in a missed linkage. Therefore, we have developed a strategy of using multiple overlapping yet complementary methods to detect linkage. These include sib-pair analysis and affected-pedigree-member analysis, neither of which makes assumptions about mode of inheritance, and lod score analysis (using two predefined genetic models). In order for a marker to qualify for follow-up, it must fit at least two of three criteria. These are nominal P values of 0.05 or less for the non-parametric methods, and/or a lod score greater than 1.0. Adjacent markers each fulfilling a single criterion also warrant follow-up. To date, we have screened 61 markers on chromosomes 1, 2, 3, 18, 19, 21, and 22. One marker, D2S163, generated a lod score of 1.06 ({theta} = 0.15) and an APMT statistic of 3.68 (P < 0.001). This region is currently being investigated in more detail. Updated results of this region plus additional screening data will be presented.« less

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection

PubMed Central

Ibekwe, Titus S.; Nwegbu, Maxwell M.; Asogun, Daniel; Adomeh, Donatus I.; Okokhere, Peter O.

2012-01-01

Background: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. Patients and Methods: A prospective case–control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Results: Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. Conclusion: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF “rapid screening kit” since RT-PCR is unavailable in most centers. In the interim, “high clinical index of suspicion,” irrespective of IgM status, requires urgent referral to confirmatory centers. PMID:23661877

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection.

PubMed

Ibekwe, Titus S; Nwegbu, Maxwell M; Asogun, Daniel; Adomeh, Donatus I; Okokhere, Peter O

2012-10-01

Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. A prospective case-control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF "rapid screening kit" since RT-PCR is unavailable in most centers. In the interim, "high clinical index of suspicion," irrespective of IgM status, requires urgent referral to confirmatory centers.

Alcohol consumption, smoking, and drug use in pregnancy: Prevalence and risk factors in Southern Thailand.

PubMed

Assanangkornchai, Sawitri; Saingam, Darika; Apakupakul, Nualta; Edwards, J Guy

2017-03-01

Substance use during pregnancy contributes to the risk of adverse health outcomes in mothers and children-in utero and during later development. In this study, we investigated the prevalence of substance use and associated factors in pregnant women receiving antenatal care in public hospitals in Thailand. Women (3578) attending 7 antenatal care clinics in Songkhla for the first time during their current pregnancy were interviewed with a structured questionnaire focusing on demographic data, obstetric history, use of alcohol, tobacco, and other substances, and the General Health Questionnaire was administered. The use of substances was confirmed with the ultrarapid version of the Alcohol, Smoking, and Substance Involvement Screening Test and urine tests, which were also administered to 1 in 5 to 10 randomly selected women whose screening results were negative. Based on self-reports and General Health Questionnaire results, the weighted prevalence of alcohol, tobacco, or illicit substance use and that of "mental health problems" were 5.6% (95% confidence interval [CI], 4.9-6.4) and 29.2% (95% CI, 27.5-30.9), respectively. On the basis of the ultrarapid version of the Alcohol, Smoking, and Substance Involvement Screening Test and urine tests, the prevalence of likely substance use disorder during the 3 months prior to assessment was 1.2% (95% CI, 0.8-1.5) and 7.7% (95% CI, 4.6-10.7), respectively. Factors associated with substance use were religion, unmarried status, unplanned pregnancy, previous abortion, and current mental health problem. Our results emphasize the need for identification of substance use and mental health problems, with the help of questionnaires and biological markers, followed by early intervention. © 2016 John Wiley & Sons Australia, Ltd.

Seroprevalence and trends in transfusion transmitted infections among blood donors in a university hospital blood bank: a 5 year study.

PubMed

Pallavi, P; Ganesh, C K; Jayashree, K; Manjunath, G V

2011-03-01

Blood is life. Transfusion of blood and blood components, as a specialized modality of patient management saves millions of lives worldwide each year and reduce morbidity. It is well known that blood transfusion is associated with a large number of complications, some are only trivial and others are potentially life threatening, demanding for meticulous pretransfusion testing and screening particularly for transfusion transmissible infections (TTI). These TTI are a threat to blood safety. The priority objective of BTS is thus to ensure safety, adequacy, accessibility and efficiency of blood supply at all levels. The objective of the present study was to assess the prevalence and trend of transfusion transmitted infections (TTI) among voluntary and replacement donors in the Department of Blood bank and transfusion Medicine of JSS College Hospital, a teaching hospital of Mysore during the period from 2004 to 2008. A retrospective review of donors record covering the period between 2004 and 2008 at the blood bank, JSS Hospital, Mysore was carried out. All samples were screened for HIV, HBsAg, HCV, syphilis and malaria. Of the 39,060, 25,303 (64.78%) were voluntary donors and the remaining 13,757 (35.22%) were replacement donors. The overall prevalence of HIV, HbsAg, HCV and syphilis were 0.44, 1.27, 0.23 and 0.28%, respectively. No blood donor tested showed positivity for malarial parasite. Majority were voluntary donors with male preponderance. In all the markers tested there was increased prevalence of TTI among the replacement donors as compared to voluntary donors. With the implementation of strict donor criteria and use of sensitive screening tests, it may be possible to reduce the incidence of TTI in the Indian scenario.

Three-dimensional paper-based electrochemiluminescence immunodevice for multiplexed measurement of biomarkers and point-of-care testing.

PubMed

Ge, Lei; Yan, Jixian; Song, Xianrang; Yan, Mei; Ge, Shenguang; Yu, Jinghua

2012-02-01

In this work, electrochemiluminescence (ECL) immunoassay was introduced into the recently proposed microfluidic paper-based analytical device (μPADs) based on directly screen-printed electrodes on paper for the very first time. The screen-printed paper-electrodes will be more important for further development of this paper-based ECL device in simple, low-cost and disposable application than commercialized ones. To further perform high-performance, high-throughput, simple and inexpensive ECL immunoassay on μPAD for point-of-care testing, a wax-patterned three-dimensional (3D) paper-based ECL device was demonstrated for the very first time. In this 3D paper-based ECL device, eight carbon working electrodes including their conductive pads were screen-printed on a piece of square paper and shared the same Ag/AgCl reference and carbon counter electrodes on another piece of square paper after stacking. Using typical tris-(bipyridine)-ruthenium (Ⅱ) - tri-n-propylamine ECL system, the application test of this 3D paper-based ECL device was performed through the diagnosis of four tumor markers in real clinical serum samples. With the aid of a facile device-holder and a section-switch assembled on the analyzer, eight working electrodes were sequentially placed into the circuit to trigger the ECL reaction in the sweeping range from 0.5 to 1.1 V at room temperature. In addition, this 3D paper-based ECL device can be easily integrated and combined with the recently emerging paper electronics to further develop simple, sensitive, low-cost, disposable and portable μPAD for point-of-care testing, public health and environmental monitoring in remote regions, developing or developed countries. Copyright © 2011 Elsevier Ltd. All rights reserved.

Visual Iconic Patterns of Instant Messaging: Steps Towards Understanding Visual Conversations

NASA Astrophysics Data System (ADS)

Bays, Hillary

An Instant Messaging (IM) conversation is a dynamic communication register made up of text, images, animation and sound played out on a screen with potentially several parallel conversations and activities all within a physical environment. This article first examines how best to capture this unique gestalt using in situ recording techniques (video, screen capture, XML logs) which highlight the micro-phenomenal level of the exchange and the macro-social level of the interaction. Of particular interest are smileys first as cultural artifacts in CMC in general then as linguistic markers. A brief taxonomy of these markers is proposed in an attempt to clarify their frequency and patterns of their use. Then, focus is placed on their importance as perceptual cues which facilitate communication, while also serving as emotive and emphatic functional markers. We try to demonstrate that the use of smileys and animation is not arbitrary but an organized interactional and structured practice. Finally, we discuss how the study of visual markers in IM could inform the study of other visual conversation codes, such as sign languages, which also have co-produced, physical behavior, suggesting the possibility of a visual phonology.

Development of a language screening instrument for Swedish 4-year-olds.

PubMed

Lavesson, Ann; Lövdén, Martin; Hansson, Kristina

2018-05-01

The Swedish Program for health surveillance of preschool children includes screening of language and communication abilities. One important language screening is carried out at age 4 years as part of a general screening conducted by health nurses at child health centres. The instruments presently in use for this screening mainly focus on expressive phonology. This may result in both over-referral of children with phonological difficulties and under-referral of children with language disorders (LDs), involving difficulties with vocabulary, grammar and/or language comprehension. Previous research has proposed non-word repetition as a clinical marker for LD. It has also been found that higher predictive power is achieved when non-word repetition is combined with the assessment of lexical/semantic skills. Taking these findings into account, the construction of a language screening instrument may yield more adequate referrals to speech-language therapists (SLTs). To construct a new standardized language screening instrument for 4-year-olds and to test its properties. An instrument was developed and revised after piloting. A population of 352 children was screened at the regular 4-year check-up by 11 health nurses. The final sample consisted of 328 children aged 46-53 months (23% multilingual). Children performing below a preliminary cut-off were referred to an SLT (n = 52). Five SLTs carried out an assessment on average within 5 weeks using a gold standard language test battery. Children who screened negatively were followed up with a parent questionnaire at age 5;6. Thirty-one true-positives and 11 false-positives were identified after SLT assessment. A further six children were identified as false-negatives (two through referral to an SLT and four through parent questionnaire at age 5;6). A receiver-operating characteristics curve with a C statistic of .94 was calculated. Based on optimal cut-off, the sensitivity of the screening instrument was found to be .84, and specificity was .96. Multilingual children performed similar to monolingual children; boys performed significantly lower than girls; and children with a family history of language-related problems performed lower than those without. Interrater reliability was high, as was Cronbach's alpha. The screening instrument seems sufficiently valid for its purpose to identify children who need further assessment by an SLT. A follow-up study including SLT assessment for all children to check for false-negatives would be interesting in future, as would studies comparing results from the 4-year screening with those from earlier screens. © 2018 Royal College of Speech and Language Therapists.

Incomplete Lineage Sorting and Hybridization Statistics for Large-Scale Retroposon Insertion Data

PubMed Central

Kuritzin, Andrej; Kischka, Tabea

2016-01-01

Ancient retroposon insertions can be used as virtually homoplasy-free markers to reconstruct the phylogenetic history of species. Inherited, orthologous insertions in related species offer reliable signals of a common origin of the given species. One prerequisite for such a phylogenetically informative insertion is that the inserted element was fixed in the ancestral population before speciation; if not, polymorphically inserted elements may lead to random distributions of presence/absence states during speciation and possibly to apparently conflicting reconstructions of their ancestry. Fortunately, such misleading fixed cases are relatively rare but nevertheless, need to be considered. Here, we present novel, comprehensive statistical models applicable for (1) analyzing any pattern of rare genomic changes, (2) testing and differentiating conflicting phylogenetic reconstructions based on rare genomic changes caused by incomplete lineage sorting or/and ancestral hybridization, and (3) differentiating between search strategies involving genome information from one or several lineages. When the new statistics are applied, in non-conflicting cases a minimum of three elements present in both of two species and absent in a third group are considered significant support (p<0.05) for the branching of the third from the other two, if all three of the given species are screened equally for genome or experimental data. Five elements are necessary for significant support (p<0.05) if a diagnostic locus derived from only one of three species is screened, and no conflicting markers are detected. Most potentially conflicting patterns can be evaluated for their significance and ancestral hybridization can be distinguished from incomplete lineage sorting by considering symmetric or asymmetric distribution of rare genomic changes among possible tree configurations. Additionally, we provide an R-application to make the new KKSC insertion significance test available for the scientific community at http://retrogenomics.uni-muenster.de:3838/KKSC_significance_test/. PMID:26967525

Screening Applications to Test Cellular Fitness in Transwell® Models After Nanoparticle Treatment.

PubMed

Christ, Bastian; Fey, Christina; Cubukova, Alevtina; Walles, Heike; Dembski, Sofia; Metzger, Marco

2017-01-01

Nanoparticles (NPs) in biotechnology hold great promise for revolutionizing medical treatments and therapies. In order to bring NPs into clinical application there is a number of preclinical in vitro and in vivo tests, which have to be applied before. The initial in vitro evaluation includes a detailed physicochemical characterization as well as biocompatibility tests, among others. For determination of biocompatibility at the cellular level, the correct choice of the in vitro assay as well as NP pretreatment is absolutely essential. There are a variety of assay technologies available that use standard plate readers to measure metabolic markers to estimate the number of viable cells in culture. Each cell viability assay has its own set of advantages and disadvantages. Regardless of the assay method chosen, the major factors critical for reproducibility and success include: (1) choosing the right assay after comparing optical NP properties with the read-out method of the assay, (2) verifying colloidal stability of NPs in cell culture media, (3) preparing a sterile and stable NP dispersion in cell culture media used in the assay, (4) using a tightly controlled and consistent cell model allowing appropriate characterization of NPs. This chapter will briefly summarize these different critical points, which can occur during biocompatibility screening applications of NPs.

Recent advances in the diagnosis and treatment of niemann-pick disease type C in children: a guide to early diagnosis for the general pediatrician.

PubMed

Alobaidy, Hanna

2015-01-01

Niemann-Pick disease (NP-C) is a lysosomal storage disease in which impaired intracellular lipid transport leads to accumulation of cholesterol and glycosphingolipids in various neurovisceral tissues. It is an autosomal recessive disorder, caused by mutations in the NPC1 or NPC2 genes. The clinical spectrum is grouped by the age of onset and onset of neurological manifestation: pre/perinatal; early infantile; late infantile; and juvenile periods. The NP-C Suspicion Index (SI) screening tool was developed to identify suspected patients with this disease. It is especially good at recognizing the disease in patients older than four years of age. Biochemical tests involving genetic markers and Filipin staining of skin fibroblast are being employed to assist diagnosis. Therapy is mostly supportive and since 2009, the first specific therapy approved for use was Miglustat (Zavesca) aimed at stabilizing the rate of progression of neurological manifestation. The prognosis correlates with age at onset of neurological signs; patients with early onset form progress faster. The NP-C disease has heterogeneous neurovisceral manifestations. A SI is a screening tool that helps in diagnostic process. Filipin staining test is a specific biomarker diagnostic test. Miglustat is the first disease-specific therapy.

Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes.

PubMed

Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J; Chung, Woonbok; Estecio, Marcos R H; Kondo, Kimie; Guo, Yi; Ahmed, Saira S; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J

2009-06-01

Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 nonneoplastic gastric mucosa samples. Six genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test, and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer, whereas PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r = 0.5-0.9, P = .03-.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the receiver operating characteristic curve (0.961) in terms of tumor detection in gastric washes. These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally, we have developed a new method for gastric cancer detection by DNA methylation in gastric washes.

Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

PubMed Central

Bancroft, Elizabeth K.; Page, Elizabeth C.; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S.; Mitchell, Gillian; Drew, Kate; Mæhle, Lovise; Axcrona, Karol; Evans, D. Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A.; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J.; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A.; Oosterwijk, Jan C.; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J.; Buys, Saundra; Conner, Tom; Ausems, Margreet G.; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R.; Maia, Sofia; Foulkes, William D.; Taherian, Nassim; Ruijs, Marielle; den Enden, Apollonia T. Helderman-van; Izatt, Louise; Davidson, Rosemarie; Adank, Muriel A.; Walker, Lisa; Schmutzler, Rita; Tucker, Kathy; Kirk, Judy; Hodgson, Shirley; Harris, Marion; Douglas, Fiona; Lindeman, Geoffrey J.; Zgajnar, Janez; Tischkowitz, Marc; Clowes, Virginia E.; Susman, Rachel; Ramón y Cajal, Teresa; Patcher, Nicholas; Gadea, Neus; Spigelman, Allan; van Os, Theo; Liljegren, Annelie; Side, Lucy; Brewer, Carole; Brady, Angela F.; Donaldson, Alan; Stefansdottir, Vigdis; Friedman, Eitan; Chen-Shtoyerman, Rakefet; Amor, David J.; Copakova, Lucia; Barwell, Julian; Giri, Veda N.; Murthy, Vedang; Nicolai, Nicola; Teo, Soo-Hwang; Greenhalgh, Lynn; Strom, Sara; Henderson, Alex; McGrath, John; Gallagher, David; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Dearnaley, David; Costello, Philandra; Eyfjord, Jorunn; Rothwell, Jeanette; Falconer, Alison; Gronberg, Henrik; Hamdy, Freddie C.; Johannsson, Oskar; Khoo, Vincent; Kote-Jarai, Zsofia; Lubinski, Jan; Axcrona, Ulrika; Melia, Jane; McKinley, Joanne; Mitra, Anita V.; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Wilson, Penny; Killick, Emma; Moss, Sue; Eeles, Rosalind A.

2014-01-01

Background Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40–69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%—double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. Conclusions The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. Patient summary In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment. PMID:24484606

Association between leprosy and hepatitis B infection. A survey in Goiânia, central Brazil.

PubMed

Rosa, H; Costa, A P; Ferraz, M L; Pedroza, S C; Andrade, A L; Martelli, C M; Zicker, F

1992-01-01

This investigation presents the results of hepatitis B virus screening among leprosy patients conducted in central Brazil as a preliminary information for a HBV vaccination programme. The main objectives were to assess the seroprevalence of HBV serum markers among lepromatous patients and to analyse institutionalization as risk factor for HBV infection in this population. Two groups of lepromatous patients were studied, 83 outpatients and 171 institutionalized ones. Screening for HBV serum markers included the detection of HBsAg, anti-HBc by radioimmune assay (RIA). The prevalence of carrier state (HBsAg) was 4.8% and 8.8% among outpatients and institutionalized, respectively, (p > 0.05). Seroprevalence of exposure (all markers) was statistically significant different between outpatients (16.9%) and institutionalized ones (50.3%). Institutionalized patients had an almost four fold risk of HBV infection when compared to the outpatients, and the highest risks were among patients with more than 21 years of residence in the colony, after adjusting for age and sex.

Identification of chemical markers in Cordyceps sinensis by HPLC-MS/MS.

PubMed

Hu, Hankun; Xiao, Ling; Zheng, Baogen; Wei, Xin; Ellis, Alexis; Liu, Yi-Ming

2015-10-01

Authentication and quality assessment of Cordyceps sinensis, a precious and pricey natural product that offers a variety of health benefits, is highly significant. To identify effective chemical markers, authentic C. sinensis was thoroughly screened by using HPLC-MS/MS. In addition to many previously reported ingredients, two glycosides, i.e., cyclo-Ala-Leu-rhamnose and Phe-o-glucose, were detected for the first time in this material. Six ingredients detected, including cordycepin, D-mannitol, Phe, Phe-o-glucose, cyclo-Gly-Pro, and cyclo-Ala-Leu-rhamnose, were selected as a collection of chemical markers. An HPLC-MS/MS method was developed to simultaneously quantify them with sensitivity and specificity. The method had limits of detection ranging from 0.008 μg mL(-1) for cordycepin to 0.75 μg mL(-1) for cyclo-Gly-Pro. Recovery was found between 96 and 103 % in all tests. To evaluate the effectiveness of the marker collection proposed, five authentic C. sinensis samples and five samples of its substitutes were analyzed. Cordycepin, D-mannitol, and Phe were found present in all samples. The contents ranged from 0.0076 to 0.029 % (w/w) for cordycepin, 0.33 to 18.9 % for mannitol, and 0.0013 to 0.642 % for Phe. Interestingly, the two glycosides, Phe-o-glucose and cyclo-Ala-Leu-rhamnose, were detected only in authentic C. sinensis samples. These results indicated that the proposed protocol based on HPLC-MS/MS quantification of the markers might have a great potential in authentication and quality assessment of C. sinensis. Graphical abstract Chemical markers of C. sinensis identified in this work.

Infection by hepatitis B and C virus in female and transsexual Greek prostitutes with serological evidence of active syphilis.

PubMed

Tsakris, A; Kyriakis, K P; Chryssou, S; Papoutsakis, G

1997-11-01

Two hundred and thirty female and 43 male-to-female transsexual Greek prostitutes were screened for serological evidence of active syphilis as judged by positivity in both rapid plasma reagin (RPR) test and treponemal (FTA-ABS and TPHA) tests. The rate of active syphilis was 20.9% in the male-to-female transsexual prostitutes and 4.3% in the female ones (P < 0.001, odds ratio = 5.82). In the former group 65.1% had evidence of hepatitis B virus (HBV) infection, and 4.7% of hepatitis C virus (HCV) infection while the respective rates among the latter group were 50.4% and 3.9%. There was no correlation of viral hepatitis marker prevalence with positive syphilis serology.

Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy

PubMed Central

Oberdörster, Günter; Maynard, Andrew; Donaldson, Ken; Castranova, Vincent; Fitzpatrick, Julie; Ausman, Kevin; Carter, Janet; Karn, Barbara; Kreyling, Wolfgang; Lai, David; Olin, Stephen; Monteiro-Riviere, Nancy; Warheit, David; Yang, Hong

2005-01-01

The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicity screening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays. There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity. In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability, protein interactions, complement activation, and pro-oxidant activity is also considered. Tier 1 in vivo assays are proposed for pulmonary, oral, skin and injection exposures, and Tier 2 evaluations for pulmonary exposures are also proposed. Tier 1 evaluations include markers of inflammation, oxidant stress, and cell proliferation in portal-of-entry and selected remote organs and tissues. Tier 2 evaluations for pulmonary exposures could include deposition, translocation, and toxicokinetics and biopersistence studies; effects of multiple exposures; potential effects on the reproductive system, placenta, and fetus; alternative animal models; and mechanistic studies. PMID:16209704

Identification and validation of FaP1D7, a putative marker associated with the biosynthesis of methyl butanoate in cultivated strawberry (Fragaria x ananassa).

PubMed

Gor, Mian Chee; Candappa, Chrishani; de Silva, Thishakya; Mantri, Nitin; Pang, Edwin

2017-12-12

Breeding strawberry (Fragaria x ananassa) with enhanced fruit flavour is one of the top breeding goals of many strawberry-producing countries. Although several genes involved in the biosynthetic pathways of key aroma compounds have been identified, the development and application of molecular markers associated with fruit flavour remain limited. This study aims to identify molecular markers closely linked to genes controlling strawberry aroma. A purpose-built Subtracted Diversity Array (SDA) known as Fragaria Discovery Panel (FDP) was used for marker screening. Polymorphic sequences associated with key aroma compounds were identified from two DNA bulks with extreme phenotypes, established using 50 F 1 progeny plants derived from Juliette X 07-102-41 cross, two strawberry genotypes differing in aroma profile. A total of 49 polymorphic markers for eight key aroma compounds were detected using genotypic data of the extreme DNA bulks and phenotypic data obtained from gas chromatography-mass spectrometry (GC-MS). A similarity search against the physical maps of Fragaria vesca revealed that FaP1D7 is linked to genes potentially involved in the synthesis of methyl butanoate. A C/T SNP was detected within the feature, which could possibly be converted to a molecular tool for rapid screening of the strawberry accessions for their methyl butanoate production capacity.

Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia.

PubMed

De Villiers, Carin P; Hedley, Paula L; Placing, Sophie; Wøjdemann, Karen R; Shalmi, Anne-Cathrine; Carlsen, Anting L; Rode, Line; Sundberg, Karin; Tabor, Ann; Christiansen, Michael

2017-11-27

Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified. PP13 was measured in first trimester (week 10+3-13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation. In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8-85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1-50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4-142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI. PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

[Mapping of seedlessness gene in grapes using SCAR markers].

PubMed

Yang, Ke-Qiang; Wang, Yue-Jin; Zhang, Jin-Jin; Wang, Xi-Ping; W A N, Yi-Zhen; Zhang, Jian-Xia

2005-03-01

Nine primers (including UBC-269 and GSLP1) were designed and synthesized based on DNA sequences of UBC-269(484) and GSLP1(569). The template DNA from Red Globe (seeded paternal parent) and Flame Seedless (seedless maternal parent) were screened using these primers. For Flame Seedless,GSLP1 yielded specific marker GSLP1(569); No. 39970524-5 primer yielded specific marker 39970524-5-564; and No. 6 primer yielded specific marker 39970524-6-1538 and 39970524-6-1200. GSLP1, No. 39970524-5, and No. 39970524-6 primers were used specifically to screen template DNA from the experimental plant materials. The results showed that the specific markers GSLP1(569), 39970524-5-564,39970524-6-1538 and 39970524-6-1200 were cosegregating with the major seedlessness gene. All these specific loci were also present in Thompson Seedless which was the initial donor of the seedlessness gene. It suggests that these SCAR markers are linked to a major grape seedlessness gene S. Markers order and map distance were estimated using the software 'QTXb17'. This showed that GSLP1(569), 39970524-5-564,39970524-6-1538 and 39970524-6-1200 were tightly linked to gene S. When P = 0.01,confidence limits for map distance ranged from 0.2 to 9.9; standard errors of map distance were from 0.6 to 1.9; LOD for linkage were from 32.7 to 46.4. These markers and the gene S were found to be in the same group. The markers were located on either side of gene S, covering 12.3 cM of the grape genome. The genetic distances between gene S and 39970524-5-564, GSLP1(569), 39970524-6-1538 and 39970524-6-1200 were 0.6 cM, 1.2 cM, 4.9 cM and 11.1 cM respectively.

Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map

PubMed Central

Haile, Jemanesh K.; Cory, Aron T.; Clarke, Fran R.; Clarke, John M.; Knox, Ron E.; Pozniak, Curtis J.

2017-01-01

Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype-based analysis over single marker analysis to detect loci associated with colour traits in durum wheat. PMID:28135299

Monitoring of 30 marker candidates in early Parkinson disease as progression markers

PubMed Central

Zimmermann, Johannes; Sixel-Döring, Friederike; Focke, Niels K.; Wicke, Tamara; Ebentheuer, Jens; Schaumburg, Martina; Lang, Elisabeth; Trautmann, Ellen; Zetterberg, Henrik; Taylor, Peggy; Friede, Tim; Trenkwalder, Claudia

2016-01-01

Objective: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). Methods: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). Results: A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09–0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06–0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24–0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25–0.64), and RBD by PSG (d 0.37; CI 0.19–0.55) as well as VBM units of cortical gray matter (d −0.2; CI −0.3 to −0.09) and hippocampus (d −0.15; CI −0.27 to −0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d −0.19; CI −0.36 to −0.02) and 2 depression scales (Beck Depression Inventory d −0.18; CI −0.36 to 0; Montgomery-Åsberg Depression Rating Scale d −0.26; CI −0.47 to −0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. Conclusions: Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression. PMID:27164658

Seroprevalence of hepatitis B virus serological markers among pregnant Nigerian women

PubMed Central

Aba, Henrietta Oneh; Aminu, Maryam

2016-01-01

Background: Chronic hepatitis B infection is a global problem; however, Asia and sub-Saharan Africa are most affected by it. Hepatitis B status of pregnant women is essential for the effective management of the disease and prevention of mother to child transmission. Materials and Methods: The study was conducted at the antenatal care unit of four hospitals within Kaduna Metropolis, Nigeria, between August and December 2011. After obtaining ethical clearance, blood samples were collected from 800 consenting pregnant women, the plasma were screened for hepatitis B surface antigen (HBsAg) using first response HBsAg card and the reactive sera were confirmed with enzyme-linked immunosorbent assay. Other serological markers of hepatitis B virus (HBV) were detected using the one-step HBV multi-5 test kit. Results: Of the 800 pregnant women screened, 31 (3.9%) tested positive for HBsAg. Only one of the 31 HBsAg positive women had developed the hepatitis B surface antibody, 16 (51.6%) had the envelop antibody, 18 (58.1%) had the hepatitis B core antibody (anti-HBc), and two (6.5%) had hepatitis B envelop antigen (HBeAg). The highest prevalence of HBsAg was recorded among women in age group 21–25 years old (P = 0.968). Similarly, married women (P = 0.772), women in their second trimester of pregnancy (P = 0.938), women with tertiary education (P = 0.972), women from the South-East geopolitical zone (P = 0.250) and those whose husbands were in polygamous relationships (P = 0.944) had the highest seroprevalence of HBsAg. Conclusion: HBV was detected with a prevalence of 3.9% among pregnant women in Kaduna Metropolis, Nigeria. About 96.8% (29) of the reactive women had HBeAg negative chronic hepatitis while 6.5% (2) had HBeAg positive chronic hepatitis B infection. About 58.1% of the women had anti-HBc, hence, did not have immunity and probably had chronic infection with reduced risk of vertical transmission. Pregnant women should be screened for HBsAg at the first antenatal clinic visit for appropriate clinical management and effective prevention of vertical transmission. PMID:26857933

Discovery of Genome-Wide Microsatellite Markers in Scombridae: A Pilot Study on Albacore Tuna

PubMed Central

Nikolic, Natacha; Duthoy, Stéphanie; Destombes, Antoine; Bodin, Nathalie; West, Wendy; Puech, Alexis; Bourjea, Jérôme

2015-01-01

Recent developments in sequencing technologies and bioinformatics analysis provide a greater amount of DNA sequencing reads at a low cost. Microsatellites are the markers of choice for a variety of population genetic studies, and high quality markers can be discovered in non-model organisms, such as tuna, with these recent developments. Here, we use a high-throughput method to isolate microsatellite markers in albacore tuna, Thunnus alalunga, based on coupling multiplex enrichment and next-generation sequencing on 454 GS-FLX Titanium pyrosequencing. The crucial minimum number of polymorphic markers to infer evolutionary and ecological processes for this species has been described for the first time. We provide 1670 microsatellite design primer pairs, and technical and molecular genetics selection resulting in 43 polymorphic microsatellite markers. On this panel, we characterized 34 random and selectively neutral markers («neutral») and 9 «non-neutral» markers. The variability of «neutral» markers was screened with 136 individuals of albacore tuna from southwest Indian Ocean (42), northwest Indian Ocean (31), South Africa (31), and southeast Atlantic Ocean (32). Power analysis demonstrated that the panel of genetic markers can be applied in diversity and population genetics studies. Global genetic diversity for albacore was high with a mean number of alleles at 16.94; observed heterozygosity 66% and expected heterozygosity 77%. The number of individuals was insufficient to provide accurate results on differentiation. Of the 9 «non-neutral» markers, 3 were linked to a sequence of known function. The one is located to a sequence having an immunity function (ThuAla-Tcell-01) and the other to a sequence having energy allocation function (ThuAla-Hki-01). These two markers were genotyped on the 136 individuals and presented different diversity levels. ThuAla-Tcell-01 has a high number of alleles (20), heterozygosity (87–90%), and assignment index. ThuAla-Hki-01 has a lower number of alleles (9), low heterozygosity (24–27%), low assignment index and significant inbreeding. Finally, the 34 «neutral» and 3 «non-neutral» microsatellites markers were tested on four economically important Scombridae species—Thunnus albacares, Thunnus thynnus, Thunnus obesus, and Acanthocybium solandri. PMID:26544051

Projected future impact of HPV vaccination and primary HPV screening on cervical cancer rates from 2017-2035: Example from Australia.

PubMed

Hall, Michaela T; Simms, Kate T; Lew, Jie-Bin; Smith, Megan A; Saville, Marion; Canfell, Karen

2018-01-01

Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017. Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18-20 to 69, to recommending HPV screening every five years for women aged 25-74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males). Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16-24% and 11-14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40-44% and 42-51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34-45% by 2035. Over the period 2018-2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives. Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10-15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success.

Characterization and Separation of Cancer Cells with a Wicking Fiber Device.

PubMed

Tabbaa, Suzanne M; Sharp, Julia L; Burg, Karen J L

2017-12-01

Current cancer diagnostic methods lack the ability to quickly, simply, efficiently, and inexpensively screen cancer cells from a mixed population of cancer and normal cells. Methods based on biomarkers are unreliable due to complexity of cancer cells, plasticity of markers, and lack of common tumorigenic markers. Diagnostics are time intensive, require multiple tests, and provide limited information. In this study, we developed a novel wicking fiber device that separates cancer and normal cell types. To the best of our knowledge, no previous work has used vertical wicking of cells through fibers to identify and isolate cancer cells. The device separated mouse mammary tumor cells from a cellular mixture containing normal mouse mammary cells. Further investigation showed the device separated and isolated human cancer cells from a heterogeneous mixture of normal and cancerous human cells. We report a simple, inexpensive, and rapid technique that has potential to identify and isolate cancer cells from large volumes of liquid samples that can be translated to on-site clinic diagnosis.

Do Circulating Tumor Cells, Exosomes, and Circulating Tumor Nucleic Acids Have Clinical Utility?

PubMed Central

Gold, Bert; Cankovic, Milena; Furtado, Larissa V.; Meier, Frederick; Gocke, Christopher D.

2016-01-01

Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided. PMID:25908243

Hypersensitivity reactions to metal implants: laboratory options.

PubMed

Carossino, Anna Maria; Carulli, Christian; Ciuffi, Simone; Carossino, Roberto; Zappoli Thyrion, Giorgia Donata; Zonefrati, Roberto; Innocenti, Massimo; Brandi, Maria Luisa

2016-11-23

All implant compounds undergo an electrochemical process when in contact with biological fluids, as well as mechanical corrosion due to abrasive wear, with production of metal debris that may inhibit repair processes. None of the commonly-used methods can diagnose implant allergies when used singly, therefore a panel of tests should be performed on allergic patients as pre-operative screening, or when a postoperative metal sensitisation is suspected. We analysed patients with painful prostheses and subjects prone to allergies using the Patch Test in comparison with the Lymphocyte Transformation Test. Cytokine production was evaluated to identify prognostic markers for early diagnosis of aseptic loosening. Metal debris endocytosis and cytoskeletal rearrangement was visualised by confocal microscopy. Our results demonstrate that the Lymphocyte Transformation Test can identify patients who have a predisposition to develop allergic reactions and can confirm the diagnosis of hypersensitivity in patients with painful prostheses. The prevalence of a Th2-cytokine pattern may be used to identify predisposition to the development of allergic diseases, while the selective presence of osteoclastogenic cytokines may be used as predictor of a negative outcome in patients with painful prosthesis. The hypothesis of the prognostic value of these cytokines as early markers of aseptic loosening is attractive, but its confirmation would require extensive testing. The Lymphocyte Transformation Test is the most suitable method for testing systemic allergies. We suggest that the combined use of the Patch Test and the Lymphocyte Transformation Test, associated with cytokine detection in selected patients, could provide a useful tool for preventive evaluation of immune reactivity in patients undergoing primary joint replacement surgery, and for clinical monitoring of the possible onset of a metal sensitization in patients with implanted devices.

Evaluation of Different Blood Collection Tubes and Blood Storage Conditions for the Preservation and Stability of Cell-Free Circulating DNA for the Analysis of the Methylated mSEPT9 Colorectal Cancer Screening Marker.

PubMed

Distler, Jurgen; Tetzner, Reimo; Weiss, Gunter; König, Thomas; Schlegel, Anne; Bagrowski, Michal

2016-01-01

For the subsequent analysis of the methylated mSEPT9 colorectal cancer screening marker in plasma, different blood collection tubes and blood storage conditions were investigated. The study demonstrated that methylated Septin 9 ( m SEPT9) can be consistently detected in plasma samples derived from whole blood samples collected with S-Monovette® K3E and BD Vacutainer ® K2EDTA tubes stored at 2-8 °C for a maximum of 24 h and for samples collected in S-Monovette CPDA tubes stored at 18-25 °C for up to 48 h.

Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde

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

Python, Francois; Goebel, Carsten; Aeby, Pierre

2009-09-15

The number of studies involved in the development of in vitro skin sensitization tests has increased since the adoption of the EU 7th amendment to the cosmetics directive proposing to ban animal testing for cosmetic ingredients by 2013. Several studies have recently demonstrated that sensitizers induce a relevant up-regulation of activation markers such as CD86, CD54, IL-8 or IL-1{beta} in human myeloid cell lines (e.g., U937, MUTZ-3, THP-1) or in human peripheral blood monocyte-derived dendritic cells (PBMDCs). The present study aimed at the identification of new dendritic cell activation markers in order to further improve the in vitro evaluation ofmore » the sensitizing potential of chemicals. We have compared the gene expression profiles of PBMDCs and the human cell line MUTZ-3 after a 24-h exposure to the moderate sensitizer cinnamaldehyde. A list of 80 genes modulated in both cell types was obtained and a set of candidate marker genes was selected for further analysis. Cells were exposed to selected sensitizers and non-sensitizers for 24 h and gene expression was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. Results indicated that PIR, TRIM16 and two Nrf2-regulated genes, CES1 and NQO1, are modulated by most sensitizers. Up-regulation of these genes could also be observed in our recently published DC-activation test with U937 cells. Due to their role in DC activation, these new genes may help to further refine the in vitro approaches for the screening of the sensitizing properties of a chemical.« less

Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

PubMed Central

Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

2012-01-01

Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes.

PubMed

Terkelsen, Astrid J; Karlsson, Páll; Lauria, Giuseppe; Freeman, Roy; Finnerup, Nanna B; Jensen, Troels S

2017-11-01

Small fibre neuropathies are a heterogeneous group of disorders affecting thinly myelinated Aδ-fibres and unmyelinated C-fibres. Although multiple causes of small nerve fibre degeneration have been reported, including via genetic mutations, the cause of small fibre neuropathy remains unknown in up to 50% of cases. The typical clinical presentation of small fibre neuropathy is that of a symmetrical, length-dependent polyneuropathy associated with sensory or autonomic symptoms. More rarely, the clinical presentation is characterised by non-length-dependent, focal, or multifocal symptoms. The diagnostic tests to identify small fibre neuropathy include skin biopsy, quantitative sensory, and autonomic testing. Additional tests, such as those measuring small fibre-related evoked potentials and corneal confocal microscopy, might contribute to a better understanding of these neuropathies. Biochemical markers can also help in screening patients for the presence of small fibre neuropathy and to assess disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

First-trimester screening for trisomies 18 and 13, triploidy and Turner syndrome by detailed early anomaly scan.

PubMed

Wagner, P; Sonek, J; Hoopmann, M; Abele, H; Kagan, K O

2016-10-01

To examine the performance of first-trimester ultrasound screening for trisomies 18 and 13, triploidy and Turner syndrome based on fetal nuchal translucency thickness (NT), additional fetal ultrasound markers including anatomy of the nasal bone (NB), blood flow across the tricuspid valve (TV) and through the ductus venosus (DV) and a detailed fetal anomaly scan at 11-13 weeks' gestation. This was a retrospective case-matched study involving pregnant women at 11-13 weeks' gestation. The study population consisted of fetuses with trisomy 18, trisomy 13, triploidy or Turner syndrome. For each fetus with an abnormal karyotype, 50 randomly selected euploid fetuses were added to the study population. In all cases, the crown-rump length and NT were measured. In addition NB, TV flow and DV flow were examined. The summed risk for trisomies 21, 18 and 13 was computed based on: first, maternal age (MA); second, MA and fetal NT; third, MA, NT and one of the markers NB, TV flow or DV flow; fourth, MA, NT and all these markers combined; fifth, MA, NT and fetal anomalies; and, finally, MA, NT, all markers and fetal anomalies. The study population consisted of 4550 euploid and 91 aneuploid fetuses. Median NT was 1.8 mm in euploid fetuses and 4.8, 6.8, 1.8 and 10.0 mm in fetuses with trisomy 18, trisomy 13, triploidy and Turner syndrome, respectively. The NB, TV flow and DV flow were abnormal in 48 (1.1%), 34 (0.7%) and 99 (2.2%) euploid fetuses, respectively, and in 42 (46.2%), 31 (34.1%) and 62 (68.1%) aneuploid fetuses, respectively. At least one defect was found in 60 (1.3%) euploid and in 76 (83.5%) aneuploid fetuses. For a false-positive rate of 3%, the detection rate for screening based on MA and fetal NT was 75.8%. It increased to 84.6-86.8% when including one of the additional ultrasound markers and it was 90.1% when all three markers were included. When screening was based on MA, fetal NT and a detailed anomaly scan, the detection rate was 94.5% and increased to 95.6% with the addition of NB, TV flow and DV flow. A detailed anomaly scan at 11-13 weeks' gestation can identify about 95% of fetuses with trisomy 18, trisomy 13, triploidy and Turner syndrome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Tetany caused by chronic diarrhea in a child with celiac disease: A case report

PubMed Central

Hurtado-Valenzuela, Jaime Gabriel; Sotelo-Cruz, Norberto; López-Cervantes, Guillermo; de la Barca, Ana María Calderón

2008-01-01

There is no awareness about celiac disease (CD) in Mexico. A 2.9 year old mestizo boy was admitted to a Mexican hospital with muscle cramps and fine tremors. He suffered chronic diarrhea, abdominal distention, hypotrophic limbs, stunting and wasting, and presented hypocalcemia, anemia and high titers of serological markers. Diagnosis of CD was confirmed by a duodenal biopsy. After replacement of calcium and a gluten-free diet, the symptoms resolved within 6 weeks. After 2-months, serum analyses, anthropometric data as well as antibodies titers were normal after 4 years. CD screening tests are needed in chronic diarrhea for any ethnicity patients. PMID:18811963

Association mapping to discover significant marker-trait associations for resistance against fusarium wilt variant 2 in pigeonpea [Cajanus cajan (L.) Millspaugh] using SSR markers.

PubMed

Patil, Prakash G; Dubey, Jyotirmay; Bohra, Abhishek; Mishra, R K; Saabale, P R; Das, Alok; Rathore, Meenal; Singh, N P

2017-08-01

Pigeonpea production is severely constrained by wilt disease caused by Fusarium udum. In the current study, we discover the putative genomic regions that control resistance response to variant 2 of fusarium wilt using association mapping approach. The association panel comprised of 89 diverse pigeonpea genotypes including seven varieties, three landraces and 79 germplasm lines. The panel was screened rigorously for 3 consecutive years (2013-14, 2014-15 and 2015-2016) against variant 2 in a wilt-sick field. A total of 65 pigeonpea specific hypervariable SSR markers (HASSRs) were screened representing seven linkage groups and 29 scaffolds of the pigeonpea genome. A total of 181 alleles were detected, with average values of gene diversity and polymorphism information content (PIC) of 0.55 and 0.47, respectively. Further analysis using model based (STRUCTURE) and distance based (clustering) approaches separated the entire pigeonpea collection into two distinct subgroups (K = 2). The marker trait associations (MTAs) were established based on three-year wilt incidence data and SSR dataset using a unified mixed linear model. Consequently, six SSR markers were identified, which were significantly associated with wilt resistance and explained up to 6% phenotypic variance (PV) across the years. Among these SSRs, HASSR18 was found to be the most stable and significant, accounting for 5-6% PV across the years. To the best of our knowledge, this is the first report of identification of favourable alleles for resistance to variant 2 of Fusarium udum in pigeonpea using association mapping. The SSR markers identified here will greatly facilitate marker assisted resistance breeding against fusarium wilt in pigeonpea.

A rapid screening of ancestry for genetic association studies in an admixed population from Pernambuco, Brazil.

PubMed

Coelho, A V C; Moura, R R; Cavalcanti, C A J; Guimarães, R L; Sandrin-Garcia, P; Crovella, S; Brandão, L A C

2015-03-31

Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time.

Development of Novel SSR Markers for Flax (Linum usitatissimum L.) Using Reduced-Representation Genome Sequencing.

PubMed

Wu, Jianzhong; Zhao, Qian; Wu, Guangwen; Zhang, Shuquan; Jiang, Tingbo

2016-01-01

Flax ( Linum usitatissimum L.) is a major fiber and oil yielding crop grown in northeastern China. Identification of flax molecular markers is a key step toward improving flax yield and quality via marker-assisted breeding. Simple sequence repeat (SSR) markers, which are based on genomic structural variation, are considered the most valuable type of genetic marker for this purpose. In this study, we screened 1574 microsatellites from Linum usitatissimum L. obtained using reduced representation genome sequencing (RRGS) to systematically identify SSR markers. The resulting set of microsatellites consisted mainly of trinucleotide (56.10%) and dinucleotide (35.23%) repeats, with each motif consisting of 5-8 repeats. We then evaluated marker sensitivity and specificity based on samples of 48 flax isolates obtained from northeastern China. Using the new SSR panel, the results demonstrated that fiber flax and oilseed flax varieties clustered into two well separated groups. The novel SSR markers developed in this study show potential value for selection of varieties for use in flax breeding programs.

A Comparative Picture of the Ease of Use and Acceptance of Onscreen Marking by Markers across Subject Areas

ERIC Educational Resources Information Center

Coniam, David; Yan, Zi

2016-01-01

Onscreen marking (OSM) has been used for the majority of Hong Kong public examinations since 2012. The current study compares marker reactions to OSM, ie, perceived ease of use and acceptance of OSM, against the backdrop of virtually all subject areas being marked on screen. The data were collected from three major sources: (1) survey data…

The reverse boomerang sign: a marker for first-trimester transposition of great arteries.

PubMed

Bravo-Valenzuela, Nathalie Jeanne; Peixoto, Alberto Borges; Araujo Júnior, Edward; Da Silva Costa, Fabricio; Meagher, Simon

2017-10-12

To describe a new sonographic marker of transposition of great arteries (TGA) during the first-trimester screening. We reviewed six cases of TGA from 2013 to 2016 in which an antenatal diagnosis of TGA at first-trimester screening (11-13 + 6 weeks of gestation) was confirmed postnatally. We specifically assessed images obtained by scanning the fetal heart in three vessels (3V) and three-vessel with trachea (3VT) views using color Doppler. The "reverse boomerang" sign was defined as a reverse curvature of right ventricle outflow tract (RVOT) at level of the 3VT view. We described six cases of confirmed TGA, five singletons and one twin pregnancy, among which only two vessels and the reverse curvature of RVOT (reverse boomerang sign) was demonstrated in the first-trimester screening at level of 3VT view. Ventricular septal defects were observed in three cases, and double outlet right ventricle in one case. No other cardiac or extracardiac anomalies were identified. Termination of pregnancy was not performed in any case. Our series case suggests that the reverse boomerang sign may improve the early prenatal screening for TGA.

Metabolic profiling of rat hair and screening biomarkers using ultra performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry.

PubMed

Inagaki, Shinsuke; Noda, Takumi; Min, Jun Zhe; Toyo'oka, Toshimasa

2007-12-28

An exhaustive analysis of metabolites in hair samples has been performed for the first time using ultra performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry (UPLC-ESI-TOF-MS). The hair samples were collected from spontaneously hypertensive model rats (SHR/Izm), stroke-prone SHR (SHRSP/Izm) and Wistar Kyoto (WKY/Izm) rats, and were analyzed by UPLC-ESI-TOF-MS; a multivariate statistical analysis method, such as the principal component analysis (PCA), was then used for screening the biomarkers. From the samples derived from the group of SHRSP/Izm at weeks 10, 18, 26 and 34, we successfully detected a potential biomarker of stroke, which existed at much higher concentrations as compared with that in the other groups. However, a significant difference could not be found at weeks less than 7 before the rats were subjected to stroke and hypertension. In addition, the present method was applicable to screening not only the disease markers, but also the markers related to aging. The method utilizing hair samples is expected to be quite useful for screening biomarkers of many other diseases, and not limited to stroke and hypertension.

Relationship between first trimester aneuploidy screening test serum analytes and placenta accreta.

PubMed

Büke, Barış; Akkaya, Hatice; Demir, Sibel; Sağol, Sermet; Şimşek, Deniz; Başol, Güneş; Barutçuoğlu, Burcu

2018-01-01

The aim of this study is to determine whether there is a relationship between first trimester serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) MoM values and placenta accreta in women who had placenta previa. A total of 88 patients with placenta previa who had first trimester aneuploidy screening test results were enrolled in the study. Nineteen of these patients were also diagnosed with placenta accreta. As probable markers of excessive placental invasion, serum PAPP-A and fβhCG MoM values were compared in two groups with and without placenta accreta. Patients with placenta accreta had higher statistically significant serum PAPP-A (1.20 versus 0.865, respectively, p = 0.045) and fβhCG MoM (1.42 versus 0.93, respectively, p = 0.042) values than patients without accreta. Higher first trimester serum PAPP-A and fβhCG MoM values seem to be associated with placenta accreta in women with placenta previa. Further studies are needed to use these promising additional tools for early detection of placenta accreta.

Screening of trace elements in hair of the female population with different types of cancers in Wielkopolska region of Poland.

PubMed

Czerny, Bogusław; Krupka, Krzysztof; Ożarowski, Marcin; Seremak-Mrozikiewicz, Agnieszka

2014-01-01

Cancer constitutes a major health problem worldwide. Thus, search for reliable and practical markers of the disease process remains the key issue of the diagnostic process. The study aims at linking the trace element status of an organism, assessed by hair analysis, with the occurrence of cancer diseases. Hair samples were collected from 299 patients with cancer diseases confirmed by a histopathological test and from 100 controls. Cancer patients were divided into three groups, depending on cancer type: hormone-dependent cancer, cancer of the alimentary tract, and cancer with high glycolytic activity. Mineral element analysis of hair was performed using an atomic emission spectrophotometer with inductively coupled plasma (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). Statistically significantly lower concentrations of selenium, zinc, copper, germanium and boron, iron, and magnesium were observed in the three groups of cancer patients. Disturbance in the axis glucose-insulin and changes in concentrations of heavy metals and toxic elements were also noted. It seems safe to conclude that our results confirmed usefulness of hair element analysis in screening tests for the assessment of the biomarker of various cancer diseases in a female population.

Bacterial Artificial Chromosome Libraries for Mouse Sequencing and Functional Analysis

PubMed Central

Osoegawa, Kazutoyo; Tateno, Minako; Woon, Peng Yeong; Frengen, Eirik; Mammoser, Aaron G.; Catanese, Joseph J.; Hayashizaki, Yoshihide; de Jong, Pieter J.

2000-01-01

Bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) libraries providing a combined 33-fold representation of the murine genome have been constructed using two different restriction enzymes for genomic digestion. A large-insert PAC library was prepared from the 129S6/SvEvTac strain in a bacterial/mammalian shuttle vector to facilitate functional gene studies. For genome mapping and sequencing, we prepared BAC libraries from the 129S6/SvEvTac and the C57BL/6J strains. The average insert sizes for the three libraries range between 130 kb and 200 kb. Based on the numbers of clones and the observed average insert sizes, we estimate each library to have slightly in excess of 10-fold genome representation. The average number of clones found after hybridization screening with 28 probes was in the range of 9–14 clones per marker. To explore the fidelity of the genomic representation in the three libraries, we analyzed three contigs, each established after screening with a single unique marker. New markers were established from the end sequences and screened against all the contig members to determine if any of the BACs and PACs are chimeric or rearranged. Only one chimeric clone and six potential deletions have been observed after extensive analysis of 113 PAC and BAC clones. Seventy-one of the 113 clones were conclusively nonchimeric because both end markers or sequences were mapped to the other confirmed contig members. We could not exclude chimerism for the remaining 41 clones because one or both of the insert termini did not contain unique sequence to design markers. The low rate of chimerism, ∼1%, and the low level of detected rearrangements support the anticipated usefulness of the BAC libraries for genome research. [The sequence data described in this paper have been submitted to the GenBank data library under accession numbers AQ797173–AQ797398.] PMID:10645956

High-throughput microsphiltration to assess red blood cell deformability and screen for malaria transmission-blocking drugs.

PubMed

Duez, Julien; Carucci, Mario; Garcia-Barbazan, Irene; Corral, Matias; Perez, Oscar; Presa, Jesus Luis; Henry, Benoit; Roussel, Camille; Ndour, Papa Alioune; Rosa, Noemi Bahamontes; Sanz, Laura; Gamo, Francisco-Javier; Buffet, Pierre

2018-06-01

The mechanical retention of rigid erythrocytes in the spleen is central in major hematological diseases such as hereditary spherocytosis, sickle-cell disease and malaria. Here, we describe the use of microsphiltration (microsphere filtration) to assess erythrocyte deformability in hundreds to thousands of samples in parallel, by filtering them through microsphere layers in 384-well plates adapted for the discovery of compounds that stiffen Plasmodium falciparum gametocytes, with the aim of interrupting malaria transmission. Compound-exposed gametocytes are loaded into microsphiltration plates, filtered and then transferred to imaging plates for analysis. High-content imaging detects viable gametocytes upstream and downstream from filters and quantifies spleen-like retention. This screening assay takes 3-4 d. Unlike currently available methods used to assess red blood cell (RBC) deformability, microsphiltration enables high-throughput pharmacological screening (tens of thousands of compounds tested in a matter of months) and involves a cell mechanical challenge that induces a physiologically relevant dumbbell-shape deformation. It therefore directly assesses the ability of RBCs to cross inter-endothelial splenic slits in vivo. This protocol has potential applications in quality control for transfusion and in determination of phenotypic markers of erythrocytes in hematological diseases.

An Effective Counterselection System for Listeria monocytogenes and Its Use To Characterize the Monocin Genomic Region of Strain 10403S.

PubMed

Argov, Tal; Rabinovich, Lev; Sigal, Nadejda; Herskovits, Anat A

2017-03-15

Construction of Listeria monocytogenes mutants by allelic exchange has been laborious and time-consuming due to lack of proficient selection markers for the final recombination event, that is, a marker conveying substance sensitivity to the bacteria bearing it, enabling the exclusion of merodiploids and selection for plasmid loss. In order to address this issue, we engineered a counterselection marker based on a mutated phenylalanyl-tRNA synthetase gene ( pheS* ). This mutation renders the phenylalanine-binding site of the enzyme more promiscuous and allows the binding of the toxic p -chloro-phenylalanine analog ( p -Cl-phe) as a substrate. When pheS* is introduced into L. monocytogenes and highly expressed under control of a constitutively active promoter, the bacteria become sensitive to p -Cl-phe supplemented in the medium. This enabled us to utilize pheS* as a negative selection marker and generate a novel, efficient suicide vector for allelic exchange in L. monocytogenes We used this vector to investigate the monocin genomic region in L. monocytogenes strain 10403S by constructing deletion mutants of the region. We have found this region to be active and to cause bacterial lysis upon mitomycin C treatment. The future applications of such an effective counterselection system, which does not require any background genomic alterations, are vast, as it can be modularly used in various selection systems (e.g., genetic screens). We expect this counterselection marker to be a valuable genetic tool in research on L. monocytogenes IMPORTANCE L. monocytogenes is an opportunistic intracellular pathogen and a widely studied model organism. An efficient counterselection marker is a long-standing need in Listeria research for improving the ability to design and perform various genetic manipulations and screening systems for different purposes. We report the construction and utilization of an efficient suicide vector for allelic exchange which can be conjugated, leaves no marker in the bacterial chromosome, and does not require the use of sometimes leaky inducible promoters. This highly efficient genome editing tool for L. monocytogenes will allow for rapid sequential mutagenesis, introduction of point mutations, and design of screening systems. We anticipate that it will be extensively used by the research community and yield novel insights into the diverse fields studied using this model organism. Copyright © 2017 American Society for Microbiology.

New polymorphic markers in the vicinity of the pearl locus on mouse chromosome 13.

PubMed

Xu, H P; Yanak, B L; Wigler, M H; Gorin, M B

1996-01-01

We have used a Mus domesticus/-Mus spretus congenic animal that was selected for retention of Mus spretus DNA around the pearl locus to create a highly polymorphic region suitable for screening new markers. Representation difference analysis (RDA) was performed with either DNA from the congenic animal or C57BL/6J as the driver for subtraction. Four clones were identified, characterized, and converted to PCR-based polymorphic markers. Three of the four markers equally subdivide a 10-cM interval containing the pearl locus, with the fourth located centromeric to it. These markers have been placed on the mouse genetic map by use of an interspecific backcross panel between Mus domesticus (C57BL/6J) and Mus spretus generated by The Jackson Laboratory.

Factors associated with a second deferral among donors eligible for re-entry after a false-positive screening test for syphilis, HCV, HBV and HIV.

PubMed

Grégoire, Y; Germain, M; Delage, G

2018-05-01

Since 25 May 2010, all donors at our blood centre who tested false-positive for HIV, HBV, HCV or syphilis are eligible for re-entry after further testing. Donors who have a second false-positive screening test, either during qualification for or after re-entry, are deferred for life. This study reports on factors associated with the occurrence of such deferrals. Rates of second false-positive results were compared by year of deferral, transmissible disease marker, gender, age, donor status (new or repeat) and testing platform (same or different) both at qualification for re-entry and afterwards. Chi-square tests were used to compare proportions. Cox regression was used for multivariate analyses. Participation rates in the re-entry programme were 42·1%: 25·6% failed to qualify for re-entry [different platform: 2·7%; same platform: 42·9% (P < 0·0001)]. After re-entry, rates of deferral for second false-positive results were 8·4% after 3 years [different platform: 1·8%; same platform: 21·4% (P < 0·0001)]. Deferral rates were higher for HIV and HCV than for HBV at qualification when tested on the same platform. The risk, when analysed by multivariate analyses, of a second deferral for a false-positive result, both at qualification and 3 years after re-entry, was lower for donors deferred on a different platform; this risk was higher for HIV, HCV and syphilis than for HBV and for new donors if tested on the same platform. Re-entry is more often successful when donors are tested on a testing platform different from the one on which they obtained their first false-positive result. © 2018 International Society of Blood Transfusion.

Oral Fluid Testing for Drugs of Abuse

PubMed Central

Bosker, Wendy M.; Huestis, Marilyn A.

2011-01-01

BACKGROUND Oral fluid (OF) is an exciting alternative matrix for monitoring drugs of abuse in workplace, clinical toxicology, criminal justice, and driving under the influence of drugs (DUID) programs. During the last 5 years, scientific and technological advances in OF collection, point-of-collection testing devices, and screening and confirmation methods were achieved. Guidelines were proposed for workplace OF testing by the Substance Abuse and Mental Health Services Administration, DUID testing by the European Union’s Driving under the Influence of Drugs, Alcohol and Medicines (DRUID) program, and standardization of DUID research. Although OF testing is now commonplace in many monitoring programs, the greatest current limitation is the scarcity of controlled drug administration studies available to guide interpretation. CONTENT This review outlines OF testing advantages and limitations, and the progress in OF that has occurred during the last 5 years in collection, screening, confirmation, and interpretation of cannabinoids, opioids, amphetamines, cocaine, and benzodiazepines. We examine controlled drug administration studies, immunoassay and chromatographic methods, collection devices, point-of-collection testing device performance, and recent applications of OF testing. SUMMARY Substance Abuse and Mental Health Services Administration approval of OF testing was delayed because questions about drug OF disposition were not yet resolved, and collection device performance and testing assays required improvement. Here, we document the many advances achieved in the use of OF. Additional research is needed to identify new bio-markers, determine drug detection windows, characterize OF adulteration techniques, and evaluate analyte stability. Nevertheless, there is no doubt that OF offers multiple advantages as an alternative matrix for drug monitoring and has an important role in DUID, treatment, workplace, and criminal justice programs. PMID:19745062

Gestational dating by metabolic profile at birth: a California cohort study.

PubMed

Jelliffe-Pawlowski, Laura L; Norton, Mary E; Baer, Rebecca J; Santos, Nicole; Rutherford, George W

2016-04-01

Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (<37 weeks) from term births and to assign a specific gestational age in the PTB group. We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11-20 weeks' gestation. Using training and testing subsets (divided in a ratio of 3:1) we evaluated the association among PTB, target newborn characteristics, acylcarnitines, amino acids, thyroid-stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses to create a linear function for PTB and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. Along with birthweight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing PTBs and term births. Using a linear discriminate analyses-derived linear function, we were able to sort PTBs and term births accurately with sensitivities and specificities of ≥95% in both the training and testing subsets. Assignment of a specific week of gestation in those identified as PTBs resulted in the correct assignment of week ±2 weeks in 89.8% of all newborns in the training and 91.7% of those in the testing subset. When PTB rates were modeled using the metabolic dating algorithm compared to fetal ultrasound, PTB rates were 7.15% vs 6.11% in the training subset and 7.31% vs 6.25% in the testing subset. When considered in combination with birthweight and hours of age at test, metabolic profile evaluated within 8 days of birth appears to be a useful measure of PTB and, among those born preterm, of specific week of gestation ±2 weeks. Dating by metabolic profile may be useful in instances where there is no fetal ultrasound due to lack of availability or late entry into care. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Gestational dating by metabolic profile at birth: a California cohort study

PubMed Central

Jelliffe-Pawlowski, Laura L.; Norton, Mary E.; Baer, Rebecca J.; Santos, Nicole; Rutherford, George W.

2016-01-01

Background Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. Objective We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (<37 weeks) from term births and to assign a specific gestational age in the PTB group. Study Design We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11–20 weeks’ gestation. Using training and testing subsets (divided in a ratio of 3:1) we evaluated the association among PTB, target newborn characteristics, acylcarnitines, amino acids, thyroid-stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses to create a linear function for PTB and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. Results Along with birthweight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing PTBs and term births. Using a linear discriminate analyses-derived linear function, we were able to sort PTBs and term births accurately with sensitivities and specificities of ≥95% in both the training and testing subsets. Assignment of a specific week of gestation in those identified as PTBs resulted in the correct assignment of week ±2 weeks in 89.8% of all newborns in the training and 91.7% of those in the testing subset. When PTB rates were modeled using the metabolic dating algorithm compared to fetal ultrasound, PTB rates were 7.15% vs 6.11% in the training subset and 7.31% vs 6.25% in the testing subset. Conclusion When considered in combination with birthweight and hours of age at test, metabolic profile evaluated within 8 days of birth appears to be a useful measure of PTB and, among those born preterm, of specific week of gestation ±2 weeks. Dating by metabolic profile may be useful in instances where there is no fetal ultrasound due to lack of availability or late entry into care. PMID:26688490

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema: a prospective, multicentre, UK study.

PubMed

Olson, J; Sharp, P; Goatman, K; Prescott, G; Scotland, G; Fleming, A; Philip, S; Santiago, C; Borooah, S; Broadbent, D; Chong, V; Dodson, P; Harding, S; Leese, G; Styles, C; Swa, K; Wharton, H

2013-11-01

To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. This study has been registered as REC/IRAS 07/S0801/107, UKCRN ID 9063 and NIHR HTA 06/402/49. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 51. See the HTA programme website for further project information.

21 CFR 866.5065 - Human allotypic marker immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5065 Human allotypic marker immunological test system. (a) Identification. A human allotypic marker... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human allotypic marker immunological test system...

Genome-wide screening of DNA methylation associated with lymph node metastasis in esophageal squamous cell carcinoma.

PubMed

Nagata, Hiroaki; Kozaki, Ken-Ichi; Muramatsu, Tomoki; Hiramoto, Hidekazu; Tanimoto, Kousuke; Fujiwara, Naoto; Imoto, Seiya; Ichikawa, Daisuke; Otsuji, Eigo; Miyano, Satoru; Kawano, Tatsuyuki; Inazawa, Johji

2017-06-06

Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC. To identify DNA methylation markers associated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues using the Illumina Infinium HumanMethylation450 BeadChip. In this screening, we focused on differentially methylated regions (DMRs) that were associated with LNM of ESCC, as prime candidates for DNA methylation markers. We extracted three genes, HOXB2, SLC15A3, and SEPT9, as candidates predicting LNM of ESCC, using pyrosequencing and several statistical analyses in the discovery cohort. We confirmed that HOXB2 and SEPT9 were highly methylated in LNM-positive tumors in 59 ESCC validation samples. These results suggested that HOXB2 and SEPT9 may be useful epigenetic biomarkers for the prediction of the presence of LNM in ESCC.

Genome-wide screening of DNA methylation associated with lymph node metastasis in esophageal squamous cell carcinoma

PubMed Central

Nagata, Hiroaki; Kozaki, Ken-Ichi; Muramatsu, Tomoki; Hiramoto, Hidekazu; Tanimoto, Kousuke; Fujiwara, Naoto; Imoto, Seiya; Ichikawa, Daisuke; Otsuji, Eigo; Miyano, Satoru; Kawano, Tatsuyuki; Inazawa, Johji

2017-01-01

Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC. To identify DNA methylation markers associated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues using the Illumina Infinium HumanMethylation450 BeadChip. In this screening, we focused on differentially methylated regions (DMRs) that were associated with LNM of ESCC, as prime candidates for DNA methylation markers. We extracted three genes, HOXB2, SLC15A3, and SEPT9, as candidates predicting LNM of ESCC, using pyrosequencing and several statistical analyses in the discovery cohort. We confirmed that HOXB2 and SEPT9 were highly methylated in LNM-positive tumors in 59 ESCC validation samples. These results suggested that HOXB2 and SEPT9 may be useful epigenetic biomarkers for the prediction of the presence of LNM in ESCC. PMID:28465481

Antenatal screening for Toxoplasma gondii, Cytomegalovirus, rubella and Treponema pallidum infections in northern Benin.

PubMed

De Paschale, Massimo; Ceriani, Cristina; Cerulli, Teresa; Cagnin, Debora; Cavallari, Serena; Cianflone, Annalisa; Diombo, Kouma; Ndayaké, Joseph; Aouanou, Guy; Zaongo, Dieudonné; Priuli, Gianbattista; Viganò, Paolo; Clerici, Pierangelo

2014-06-01

Toxoplasma gondii, cytomegalovirus (HCMV) and rubella virus infections are among the most serious of those contracted during pregnancy in terms of foetal consequences. Toxoplasma, HCMV and rubella antibody screening is unusual in Africa, and there are few published data. The aim of this study was to evaluate the prevalence of these markers among pregnant women in northern Benin on the occasion of routine syphilis screening. Toxoplasma, HCMV and rubella IgG and IgM antibodies were determined in the serum of 283 women attending Saint Jean de Dieu de Tanguiéta hospital, using an enzyme immunoassay, and IgM were confirmed using an enzyme-linked fluorescent assay (ELFA). In the case of IgM positivity, the avidity of anti-HCMV and anti-Toxoplasma IgG was measured. Total anti-Treponema pallidum antibodies were determined using an enzyme immunoassay and confirmed by immunoblotting. In the case of positivity, the Venereal Disease Research Laboratory (VDRL) test was used. The prevalence of anti-Toxoplasma, anti-HCMV, anti-rubella IgG and total anti-Treponema antibodies was, respectively, 30.0%, 100%, 94% and 2.5%. The VDRL test was positive in 62.5% of the anti-Treponema-positive samples. The prevalence of anti-Toxoplasma, anti-HCMV and anti-rubella IgM was, respectively, 0.4%, 1.4% and 0%. There were no statistically significant differences in terms of age class or trimester of pregnancy. Anti-Toxoplasma and anti-HCMV IgG avidity was always high. The prevalence of HCMV and rubella antibodies is high in northern Benin, whereas that of Toxoplasma antibodies is lower. As nearly two-thirds of the pregnant women were anti-Toxoplasma seronegative, antibody screening should be introduced. © 2014 John Wiley & Sons Ltd.

Signature-tagged mutagenesis screening revealed a novel smooth-to-rough transition determinant of Salmonella enterica serovar Enteritidis.

PubMed

Jiao, Yang; Guo, Rongxian; Tang, Peipei; Kang, Xilong; Yin, Junlei; Wu, Kaiyue; Geng, Shizhong; Li, Qiuchun; Sun, Jun; Xu, Xiulong; Zhou, Xiaohui; Gan, Junji; Jiao, Xinan; Liu, Xiufan; Pan, Zhiming

2017-03-03

Salmonella enterica serovar Enteritidis (S. Enteritidis) has emerged as one of the most important food-borne pathogens for humans. Lipopolysaccharide (LPS), as a component of the outer membrane, is responsible for the virulence and smooth-to-rough transition in S. Enteritidis. In this study, we screened S. Enteritidis signature-tagged transposon mutant library using monoclonal antibody against somatic O 9 antigen (O 9 MAb) and O 9 factor rabbit antiserum to identify novel genes that are involved in smooth-to-rough transition. A total of 480 mutants were screened and one mutant with transposon insertion in rfbG gene had smooth-to-rough transition phenotype. In order to verify the role of rfbG gene, an rfbG insertion or deletion mutant was constructed using λ-Red recombination system. Phenotypic and biological analysis revealed that rfbG insertion or deletion mutants were similar to the wild-type strain in growth rate and biochemical properties, but the swimming motility was reduced. SE Slide Agglutination test and ELISA test showed that rfbG mutants do not stimulate animals to produce agglutinating antibody. In addition, the half-lethal dose (LD 50 ) of the rfbG deletion mutant strain was 10 6.6 -fold higher than that of the parent strain in a mouse model when injected intraperitoneally. These data indicate that the rfbG gene is involved in smooth-to-rough transition, swimming motility and virulence of S. Enteritidis. Furthermore, somatic O-antigen antibody-based approach to screen signature-tagged transposon mutants is feasible to clarify LPS biosynthesis and to find suitable markers in DIVA-vaccine research.

Applicability of the ParaDNA(®) Screening System to Seminal Samples.

PubMed

Tribble, Nicholas D; Miller, Jamie A D; Dawnay, Nick; Duxbury, Nicola J

2015-05-01

Seminal fluid represents a common biological material recovered from sexual assault crime scenes. Such samples can be prescreened using different techniques to determine cell type and relative amount before submitting for full STR profiling. The ParaDNA(®) Screening System is a novel forensic test which identifies the presence of DNA through amplification and detection of two common STR loci (D16S539 and TH01) and the Amelogenin marker. The detection of the Y allele in samples could provide a useful tool in the triage and submission of sexual assault samples by enforcement authorities. Male template material was detected on a range of common sexual assault evidence items including cotton pillow cases, condoms, swab heads and glass surfaces and shows a detection limit of 1 in 1000 dilution of neat semen. These data indicate this technology has the potential to be a useful tool for the detection of male donor DNA in sexual assault casework. © 2015 American Academy of Forensic Sciences.

Prevalence of celiac disease in patients with severe food allergy.

PubMed

Pillon, R; Ziberna, F; Badina, L; Ventura, A; Longo, G; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Patano, G; Not, T; Berti, I

2015-10-01

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Automatic colonic lesion detection and tracking in endoscopic videos

NASA Astrophysics Data System (ADS)

Li, Wenjing; Gustafsson, Ulf; A-Rahim, Yoursif

2011-03-01

The biology of colorectal cancer offers an opportunity for both early detection and prevention. Compared with other imaging modalities, optical colonoscopy is the procedure of choice for simultaneous detection and removal of colonic polyps. Computer assisted screening makes it possible to assist physicians and potentially improve the accuracy of the diagnostic decision during the exam. This paper presents an unsupervised method to detect and track colonic lesions in endoscopic videos. The aim of the lesion screening and tracking is to facilitate detection of polyps and abnormal mucosa in real time as the physician is performing the procedure. For colonic lesion detection, the conventional marker controlled watershed based segmentation is used to segment the colonic lesions, followed by an adaptive ellipse fitting strategy to further validate the shape. For colonic lesion tracking, a mean shift tracker with background modeling is used to track the target region from the detection phase. The approach has been tested on colonoscopy videos acquired during regular colonoscopic procedures and demonstrated promising results.

Optimization and Standardization of Fluorescent Cell Barcoding for Multiplexed Flow Cytometric Phenotyping

PubMed Central

Giudice, Valentina; Feng, Xingmin; Kajigaya, Sachiko; Young, Neal S.; Biancotto, Angélique

2017-01-01

Fluorescent cell barcoding (FCB) is a cell-based multiplexing technique for high-throughput flow cytometry. Barcoded samples can be stained and acquired collectively, minimizing staining variability and antibody consumption, and decreasing required sample volumes. Combined with functional measurements, FCB can be used for drug screening, signaling profiling, and cytokine detection, but technical issues are present. We optimized the FCB technique for routine utilization using DyLight 350, DyLight 800, Pacific Orange, and CBD500 for barcoding six, nine, or 36 human peripheral blood specimens. Working concentrations of FCB dyes ranging from 0 to 500 μg/ml were tested, and viability dye staining was optimized to increase robustness of data. A five-color staining with surface markers for Vβ usage analysis in CD4+ and CD8+ T cells was achieved in combination with nine sample barcoding. We provide improvements of the FCB technique that should be useful for multiplex drug screening and for lymphocyte characterization and perturbations in the diagnosis and during the course of disease. PMID:28692789

Breast Cancer Treatment in the Era of Molecular Imaging

PubMed Central

Edelhauser, Gundula; Funovics, Martin

2008-01-01

Summary Molecular imaging employs molecularly targeted probes to visualize and often quantify distinct disease-specific markers and pathways. Modalities like intravital confocal or multiphoton microscopy, near-infrared fluorescence combined with endoscopy, surface reflectance imaging, or fluorescence-mediated tomography, and radionuclide imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are increasingly used for small animal high-throughput screening, drug development and testing, and monitoring gene therapy experiments. In the clinical treatment of breast cancer, PET and SPECT as well as magnetic resonance-based molecular imaging are already established for the staging of distant disease and intrathoracic nodal status, for patient selection regarding receptor-directed treatments, and to gain early information about treatment efficacy. In the near future, reporter gene imaging during gene therapy and further spatial and qualitative characterization of the disease can become clinically possible with radionuclide and optical methods. Ultimately, it may be expected that every level of breast cancer treatment will be affected by molecular imaging, including screening. PMID:21048912

Combining in Vitro Diagnostics with in Vivo Imaging for Earlier Detection of Pancreatic Ductal Adenocarcinoma: Challenges and Solutions

PubMed Central

Laeseke, Paul F.; Chen, Ru; Jeffrey, R. Brooke; Brentnall, Teresa A.

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth-leading cause of cancer-related death in the United States and is associated with a dismal prognosis, particularly when diagnosed at an advanced stage. Overall survival is significantly improved if PDAC is detected at an early stage prior to the onset of symptoms. At present, there is no suitable screening strategy for the general population. Available diagnostic serum markers are not sensitive or specific enough, and clinically available imaging modalities are inadequate for visualizing early-stage lesions. In this article, the role of currently available blood biomarkers and imaging tests for the early detection of PDAC will be reviewed. Also, the emerging biomarkers and molecularly targeted imaging agents being developed to improve the specificity of current imaging modalities for PDAC will be discussed. A strategy incorporating blood biomarkers and molecularly targeted imaging agents could lead to improved screening and earlier detection of PDAC in the future. © RSNA, 2015 PMID:26599925

The clinical impact of the novel tumor marker DR-70 in unresectable gastric cancer patients.

PubMed

Hung, Yi-Ping; Chen, Ming-Huang; Lin, June-Seng; Hsiao, Chin-Fu; Shan, Yan-Shen; Chen, Yeu-Chin; Chen, Li-Tzong; Liu, Tsang-Wu; Li, Chung-Pin; Chao, Yee

2018-07-01

Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. DR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation. Copyright © 2018. Published by Elsevier Taiwan LLC.

Barrett's oesophagus: can meaningful screening and surveillance guidelines be formulated based on new data and rejigging the old paradigm?

PubMed

Rajendra, Shanmugarajah

2015-02-01

Gastro-oesophageal reflux disease (GORD) and Barrett's oesophagus (BO) have been considered to be the most important known risk factors for oesophageal adenocarcinoma (OAC). It has been the fastest growing cancer in the Western World and has occurred against a backdrop of progressive reduction in the risk estimate of malignancy associated with BO and no reduction in mortality from OAC using the prevailing screening and surveillance guidelines. The recently published link between high risk HPV and Barrett's dysplasia/cancer may be the 'missing' strong risk factor responsible for the significant rise of OAC since the 1970's, as has been the case with head and neck tumours, another viral associated cancer. P53 immunohistochemistry has been proposed as a good molecular marker for predicting disease progression in BD. Nevertheless, significant negative staining for this mutation in BD remains a major hurdle to widespread routine clinical use as a sole molecular marker. Recent data raises the distinct possibility of at least 2 (probably more) carcinogenic pathways operating in OAC. One is HPV mediated devoid largely of p53 mutations and the other p53 dependent. The joint use of both these markers as part of a molecular panel may represent the best bet yet of detecting the high risk group of progressors to OAC. Patients who are positive for either or both biomarkers i.e p53 or/and transcriptional markers of HPV may warrant more intensive screening. In future, genome wide technology may provide molecular signatures to aid diagnosis and risk stratification in BO. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Screening injured children for physical abuse or neglect in emergency departments: a systematic review.

PubMed

Woodman, J; Lecky, F; Hodes, D; Pitt, M; Taylor, B; Gilbert, Ruth

2010-03-01

Screening markers are used in emergency departments (EDs) to identify children who should be assessed for possible physical abuse and neglect. We conducted three systematic reviews evaluating age, repeat attendance and injury type as markers for physical abuse or neglect in injured children attending EDs. We included studies comparing markers in physically abused or neglected children and non-abused injured children attending ED or hospital. We calculated likelihood ratios (LRs) for age group, repeat attendance and injury type (head injury, bruises, fractures, burns or other). Given the low prevalence of abuse or neglect, we considered that an LR of 10 or more would be clinically useful. All studies were poor quality. Infancy increased the risk of physical abuse or neglect in severely injured or admitted children (LRs 7.7-13.0, 2 studies) but was not strongly associated in children attending the ED (LR 1.5, 95% CI: 0.9, 2.8; one study). Repeat attendance did not substantially increase the risk of abuse or neglect and may be confounded by chronic disease and socio-economic status (LRs 0.8-3.9, 3 studies). One study showed no evidence that the type of injury substantially increased the risk of physical abuse or neglect in severely injured children. There was no evidence that any of the markers (infancy, type of injury, repeated attendance) were sufficiently accurate (i.e. LR >or= 10) to screen injured children in the ED to identify those requiring paediatric assessment for possible physical abuse or neglect. Clinicians should be aware that among injured children at ED a high proportion of abused children will present without these characteristics and a high proportion of non-abused children will present with them. Information about age, injury type and repeat attendances should be interpreted in this context.

New chloroplast microsatellite markers suitable for assessing genetic diversity of Lolium perenne and other related grass species

PubMed Central

Diekmann, Kerstin; Hodkinson, Trevor R.; Barth, Susanne

2012-01-01

Background and Aims Lolium perenne (perennial ryegrass) is the most important forage grass species of temperate regions. We have previously released the chloroplast genome sequence of L. perenne ‘Cashel’. Here nine chloroplast microsatellite markers are published, which were designed based on knowledge about genetically variable regions within the L. perenne chloroplast genome. These markers were successfully used for characterizing the genetic diversity in Lolium and different grass species. Methods Chloroplast genomes of 14 Poaceae taxa were screened for mononucleotide microsatellite repeat regions and primers designed for their amplification from nine loci. The potential of these markers to assess genetic diversity was evaluated on a set of 16 Irish and 15 European L. perenne ecotypes, nine L. perenne cultivars, other Lolium taxa and other grass species. Key Results All analysed Poaceae chloroplast genomes contained more than 200 mononucleotide repeats (chloroplast simple sequence repeats, cpSSRs) of at least 7 bp in length, concentrated mainly in the large single copy region of the genome. Nucleotide composition varied considerably among subfamilies (with Pooideae biased towards poly A repeats). The nine new markers distinguish L. perenne from all non-Lolium taxa. TeaCpSSR28 was able to distinguish between all Lolium species and Lolium multiflorum due to an elongation of an A8 mononucleotide repeat in L. multiflorum. TeaCpSSR31 detected a considerable degree of microsatellite length variation and single nucleotide polymorphism. TeaCpSSR27 revealed variation within some L. perenne accessions due to a 44-bp indel and was hence readily detected by simple agarose gel electrophoresis. Smaller insertion/deletion events or single nucleotide polymorphisms detected by these new markers could be visualized by polyacrylamide gel electrophoresis or DNA sequencing, respectively. Conclusions The new markers are a valuable tool for plant breeding companies, seed testing agencies and the wider scientific community due to their ability to monitor genetic diversity within breeding pools, to trace maternal inheritance and to distinguish closely related species. PMID:22419761

New chloroplast microsatellite markers suitable for assessing genetic diversity of Lolium perenne and other related grass species.

PubMed

Diekmann, Kerstin; Hodkinson, Trevor R; Barth, Susanne

2012-11-01

Lolium perenne (perennial ryegrass) is the most important forage grass species of temperate regions. We have previously released the chloroplast genome sequence of L. perenne 'Cashel'. Here nine chloroplast microsatellite markers are published, which were designed based on knowledge about genetically variable regions within the L. perenne chloroplast genome. These markers were successfully used for characterizing the genetic diversity in Lolium and different grass species. Chloroplast genomes of 14 Poaceae taxa were screened for mononucleotide microsatellite repeat regions and primers designed for their amplification from nine loci. The potential of these markers to assess genetic diversity was evaluated on a set of 16 Irish and 15 European L. perenne ecotypes, nine L. perenne cultivars, other Lolium taxa and other grass species. All analysed Poaceae chloroplast genomes contained more than 200 mononucleotide repeats (chloroplast simple sequence repeats, cpSSRs) of at least 7 bp in length, concentrated mainly in the large single copy region of the genome. Nucleotide composition varied considerably among subfamilies (with Pooideae biased towards poly A repeats). The nine new markers distinguish L. perenne from all non-Lolium taxa. TeaCpSSR28 was able to distinguish between all Lolium species and Lolium multiflorum due to an elongation of an A(8) mononucleotide repeat in L. multiflorum. TeaCpSSR31 detected a considerable degree of microsatellite length variation and single nucleotide polymorphism. TeaCpSSR27 revealed variation within some L. perenne accessions due to a 44-bp indel and was hence readily detected by simple agarose gel electrophoresis. Smaller insertion/deletion events or single nucleotide polymorphisms detected by these new markers could be visualized by polyacrylamide gel electrophoresis or DNA sequencing, respectively. The new markers are a valuable tool for plant breeding companies, seed testing agencies and the wider scientific community due to their ability to monitor genetic diversity within breeding pools, to trace maternal inheritance and to distinguish closely related species.

[Development of UPLC-Q-TOF-MS/MS combined with reference herb approach to rapidly screen commercial sulfur-fumigated ginseng].

PubMed

Zhou, Shan-Shan; Xu, Jin-Di; Shen, Hong; Liu, Huan-Huan; Li, Song-Lin

2014-08-01

An ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) combined with reference herb method was developed to rapidly screen commercial sulfur-fumigated ginseng. Sufur-fumigated ginseng reference herb was prepared using genuine ginseng by conventional procedure. Then the reference sulfur-fumigated ginseng sample was analyzed by UPLC-Q-TOF-MS/MS to identify characteristic marker components. 25-hydroxyl-Re sulfate with higher abundance was se- lected as marker compound from 8 characteristic components identified in sulfur-fumigated ginseng reference herb. The fragmentation of 25-hydroxyl-Re sulfate was extensively investigated, fragment ion m/z 879.44 with higher intensity was chosen as the characteristic ion of sulfur-fumigated ginseng. The response of ion m/z 879. 44 was improved by optimizing the MS conditions so that this ion could be used as the characteristic marker ion for screening purpose in ion extracting screening mode. The established approach was successfully applied to inspect 21 commercial ginseng samples collected from different cities in China It was found that the chemical profiles of 9 samples were similar to that of sulfur-fumigated ginseng reference herb, and the characteristic ion m/z 879. 44 of 25-hydroxyl-Re sulfate was also detected in these samples, suggesting that there were nearly 43% ginseng samples analyzed being sulfur-fumigated. This findng agreed well with the results of sulfur dioxide residues of these 21 commercial ginseng samples determined with the method documented in Chinese Pharmacopeia Compared with the method documented in Chinese Pharmacopeia, the proposed approach is more rapid and specific for screening sulfur-fumigated ginseng. SFDA of China should strengthen the enforcement to prohibit ginseng being sulfur-fumigated, so that ginseng and it preparations could be effectively and safely benefit to the health of human beings.

Screening and Characterization of RAPD Markers in Viscerotropic Leishmania Parasites

PubMed Central

Mkada–Driss, Imen; Talbi, Chiraz; Guerbouj, Souheila; Driss, Mehdi; Elamine, Elwaleed M.; Cupolillo, Elisa; Mukhtar, Moawia M.; Guizani, Ikram

2014-01-01

Visceral leishmaniasis (VL) is mainly due to the Leishmania donovani complex. VL is endemic in many countries worldwide including East Africa and the Mediterranean region where the epidemiology is complex. Taxonomy of these pathogens is under controversy but there is a correlation between their genetic diversity and geographical origin. With steady increase in genome knowledge, RAPD is still a useful approach to identify and characterize novel DNA markers. Our aim was to identify and characterize polymorphic DNA markers in VL Leishmania parasites in diverse geographic regions using RAPD in order to constitute a pool of PCR targets having the potential to differentiate among the VL parasites. 100 different oligonucleotide decamers having arbitrary DNA sequences were screened for reproducible amplification and a selection of 28 was used to amplify DNA from 12 L. donovani, L. archibaldi and L. infantum strains having diverse origins. A total of 155 bands were amplified of which 60.65% appeared polymorphic. 7 out of 28 primers provided monomorphic patterns. Phenetic analysis allowed clustering the parasites according to their geographical origin. Differentially amplified bands were selected, among them 22 RAPD products were successfully cloned and sequenced. Bioinformatic analysis allowed mapping of the markers and sequences and priming sites analysis. This study was complemented with Southern-blot to confirm assignment of markers to the kDNA. The bioinformatic analysis identified 16 nuclear and 3 minicircle markers. Analysis of these markers highlighted polymorphisms at RAPD priming sites with mainly 5′ end transversions, and presence of inter– and intra– taxonomic complex sequence and microsatellites variations; a bias in transitions over transversions and indels between the different sequences compared is observed, which is however less marked between L. infantum and L. donovani. The study delivers a pool of well-documented polymorphic DNA markers, to develop molecular diagnostics assays to characterize and differentiate VL causing agents. PMID:25313833

[The possibility of prenatal diagnosis of autism spectrum disorder].

PubMed

Vanya, Melinda; Szücs, Szabina; Szili, Károly; Vetró, Ágnes; Bártfai, György

2015-01-01

Autism spectrum disorder (ASD) is an idiopathic multifactorial disease. Chromosomal abnormalities could be found only in a few percent (0.3-0.6) of cases. The estimated prevalence is 0.6 in Europe and the prevalence of the disease has been increased in last few decades. ASD have an impact on the quality of life of the patient and his family. The early diagnosis of ASD is most important. There are limited data regarding the measure of biparietal diameter (BPD) of the fetus in the first trimester of pregnancy. These data suggested the BPD is an important screening marker for ASD, but the complex prenatal screening is unresolved. There is a need for further investigations of the genetic background of ASD and to identify potentially first trimester ultrasound markers for ASD.

Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses.

PubMed

Rouzier, Roman; Pronzato, Paolo; Chéreau, Elisabeth; Carlson, Josh; Hunt, Barnaby; Valentine, William J

2013-06-01

Breast cancer is the most common female cancer and is associated with a significant clinical and economic burden. Multigene assays and molecular markers represent an opportunity to direct chemotherapy only to patients likely to have significant benefit. This systematic review examines published health economic analyses to assess the support for adjuvant therapy decision making. Literature searches of PubMed, the Cochrane Library, and congress databases were carried out to identify economic evaluations of multigene assays and molecular markers published between 2002 and 2012. After screening and data extraction, study quality was assessed using the Quality of Health Economic Studies instrument. The review identified 29 publications that reported evaluations of two assays: Oncotype DX(®) and MammaPrint. Studies of both tests provided evidence that their routine use was cost saving or cost-effective versus conventional approaches. Benefits were driven by optimal allocation of adjuvant chemotherapy and reduction in chemotherapy utilization. Findings were sensitive to variation in the frequency of chemotherapy prescription, chemotherapy costs, and patients' risk profiles. Evidence suggests that multigene assays are likely cost saving or cost-effective relative to current approaches to adjuvant therapy. They should benefit decision making in early-stage breast cancer in a variety of settings worldwide.

Multiplexed microsatellite recovery using massively parallel sequencing

USGS Publications Warehouse

Jennings, T.N.; Knaus, B.J.; Mullins, T.D.; Haig, S.M.; Cronn, R.C.

2011-01-01

Conservation and management of natural populations requires accurate and inexpensive genotyping methods. Traditional microsatellite, or simple sequence repeat (SSR), marker analysis remains a popular genotyping method because of the comparatively low cost of marker development, ease of analysis and high power of genotype discrimination. With the availability of massively parallel sequencing (MPS), it is now possible to sequence microsatellite-enriched genomic libraries in multiplex pools. To test this approach, we prepared seven microsatellite-enriched, barcoded genomic libraries from diverse taxa (two conifer trees, five birds) and sequenced these on one lane of the Illumina Genome Analyzer using paired-end 80-bp reads. In this experiment, we screened 6.1 million sequences and identified 356958 unique microreads that contained di- or trinucleotide microsatellites. Examination of four species shows that our conversion rate from raw sequences to polymorphic markers compares favourably to Sanger- and 454-based methods. The advantage of multiplexed MPS is that the staggering capacity of modern microread sequencing is spread across many libraries; this reduces sample preparation and sequencing costs to less than $400 (USD) per species. This price is sufficiently low that microsatellite libraries could be prepared and sequenced for all 1373 organisms listed as 'threatened' and 'endangered' in the United States for under $0.5M (USD).

Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy.

PubMed

Zhou, Yu; Du, Juan; Hou, Hong-Yan; Lu, Yan-Fang; Yu, Jing; Mao, Li-Yan; Wang, Feng; Sun, Zi-Yong

2017-01-01

Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI. The pathogen-detecting methods such as acid-fast staining and culture, all have limitations in clinical application. ImmunoScore (IS) is a new promising prognostic tool which was commonly used in tumor. However, the importance of host immunity has also been demonstrated in TB pathogenesis, which implies the possibility of using IS model for ATB diagnosis and therapy monitoring. In the present study, we focused on the performance of IS model in the differentiation between ATB and LTBI and in treatment monitoring of TB disease. We have totally screened five immunological markers (four non-specific markers and one TB-specific marker) and successfully established IS model by using Lasso logistic regression analysis. As expected, the IS model can effectively distinguish ATB from LTBI (with a sensitivity of 95.7% and a specificity of 92.1%) and also has potential value in the treatment monitoring of TB disease.

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer

PubMed Central

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening. PMID:22076164

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer.

PubMed

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.

Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer

PubMed Central

de Paula, Ana Caroline L.; Medeiros, Julliane D.; de Azevedo, Analice C.; Chagas, Jéssica M. de Assis; da Silva, Vânia L.

2018-01-01

Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)—a typical Brazilian white soft cheese—and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota. PMID:29463055

Evolution of apomixis loci in Pilosella and Hieracium (Asteraceae) inferred from the conservation of apomixis-linked markers in natural and experimental populations

PubMed Central

Hand, M L; Vít, P; Krahulcová, A; Johnson, S D; Oelkers, K; Siddons, H; Chrtek, J; Fehrer, J; Koltunow, A M G

2015-01-01

The Hieracium and Pilosella (Lactuceae, Asteraceae) genera of closely related hawkweeds contain species with two different modes of gametophytic apomixis (asexual seed formation). Both genera contain polyploid species, and in wild populations, sexual and apomictic species co-exist. Apomixis is known to co-exist with sexuality in apomictic Pilosella individuals, however, apomictic Hieracium have been regarded as obligate apomicts. Here, a developmental analysis of apomixis within 16 Hieracium species revealed meiosis and megaspore tetrad formation in 1 to 7% of ovules, for the first time indicating residual sexuality in this genus. Molecular markers linked to the two independent, dominant loci LOSS OF APOMEIOSIS (LOA) and LOSS OF PARTHENOGENESIS (LOP) controlling apomixis in Pilosella piloselloides subsp. praealta were screened across 20 phenotyped Hieracium individuals from natural populations, and 65 phenotyped Pilosella individuals from natural and experimental cross populations, to examine their conservation, inheritance and association with reproductive modes. All of the tested LOA and LOP-linked markers were absent in the 20 Hieracium samples irrespective of their reproductive mode. Within Pilosella, LOA and LOP-linked markers were essentially absent within the sexual plants, although they were not conserved in all apomictic individuals. Both loci appeared to be inherited independently, and evidence for additional genetic factors influencing quantitative expression of LOA and LOP was obtained. Collectively, these data suggest independent evolution of apomixis in Hieracium and Pilosella and are discussed with respect to current knowledge of the evolution of apomixis. PMID:25026970

Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer.

PubMed

de Paula, Ana Caroline L; Medeiros, Julliane D; de Azevedo, Analice C; de Assis Chagas, Jéssica M; da Silva, Vânia L; Diniz, Cláudio G

2018-02-19

Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)-a typical Brazilian white soft cheese-and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry.

PubMed

Vikingsson, Svante; Gréen, Henrik; Brinkhagen, Linda; Mukhtar, Shahzabe; Josefsson, Martin

2016-09-01

Synthetic cannabinoids are a group of psychoactive drugs presently widespread among drug users in Europe. Analytical methods to measure these compounds in urine are in demand as urine is a preferred matrix for drug testing. For most synthetic cannabinoids, the parent compounds are rarely detected in urine. Therefore urinary metabolites are needed as markers of drug intake. AB-FUBINACA was one of the top three synthetic cannabinoids most frequently found in seizures and toxicological drug screening in Sweden (2013-2014). Drug abuse is also reported from several other countries such as the USA and Japan. In this study, 28 authentic case samples were used to identify urinary markers of AB-FUBINACA intake using liquid chromatography quadrupole tandem time of flight mass spectrometry and human liver microsomes. Three metabolites suitable as markers of drug intake were identified and at least two of them were detected in all but one case. In total, 15 urinary metabolites of AB-FUBINACA were reported, including hydrolxylations on the indazole ring and the amino-oxobutane moiety, dealkylations and hydrolysis of the primary amide. No modifications on the fluorobenzyl side-chain were observed. The parent compound was detected in 54% of the case samples. Also, after three hours of incubation with human liver microsomes, 77% of the signal from the parent compound remained. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.

PubMed

Balti, Eric V; Vandemeulebroucke, Evy; Weets, Ilse; Van De Velde, Ursule; Van Dalem, Annelien; Demeester, Simke; Verhaeghen, Katrijn; Gillard, Pieter; De Block, Christophe; Ruige, Johannes; Keymeulen, Bart; Pipeleers, Daniel G; Decochez, Katelijn; Gorus, Frans K

2015-02-01

In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D). The design is a registry-based study. Functional tests were performed in a hospital setting. Persistently autoAb(+) first-degree relatives of patients with T1D (n = 81; age 5-39 years). We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC(5-10 min); min 5-10) was determined in all relatives and second-phase release (AUC(120-150 min); min 120-150) in those aged 12-39 years (n = 62). Overall, the predictive ability of AUC(5-10 min) was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80-0.98] vs 0.81 [0.70-0.93]). Fasting blood glucose (FBG) and AUC(5-10 min) provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC(5-10 min)) (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC(5-10 min) below percentile 10 of controls was associated with 50-70% progression to T1D regardless of age. Similar results were obtained for AUC(120-150 min). Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb(+) offspring and siblings of T1D patients to predict impending diabetes.

Assessing cortical excitability in migraine: reliability of magnetic suppression of perceptual accuracy technique over time.

PubMed

Custers, Anouk; Mulleners, Wim M; Chronicle, Edward P

2005-10-01

To examine test-retest reliability of magnetic suppression of perceptual accuracy (MSPA) prior to its use as a marker of cortical excitability in a trial of migraine prophylactic agents. MSPA is a relatively novel avenue of research in headache, providing an opportunity to study cortical responsiveness objectively and noninvasively. However, little is known about the reliability of magnetic stimulation protocols such as MSPA in longitudinal research designs. We tested 10 healthy headache-free volunteers who had no family history of migraine. In 54 trials, they were briefly presented different three-letter combinations, flashed on a computer screen for 24 ms (target). After a brief interval, each target was followed by a single magnetic pulse through a 90-mm circular coil centered 7 cm above inion in the midline. The interval between target and magnetic pulse was systematically varied. Volunteers were requested to report as many letters as they had possibly identified. After 2 weeks, all volunteers were retested using identical methods. MSPA performance is expressed as a profile of response accuracy (ie, percentage of correctly identified letters) across target-pulse intervals. Profiles were characteristic of normal headache-free subjects at the first test. Analysis of variance revealed no significant difference in profiles between test and retest (F= 2.05; P= .136): the retest profiles are almost coincidental with the test profiles. MSPA is a safe and objective measure of cortical excitability, which is reliable over time. MSPA, therefore, shows excellent promise as a biological marker of cortical response in trials of migraine prophylactics.

Construction and Analysis of Siberian Tiger Bacterial Artificial Chromosome Library with Approximately 6.5-Fold Genome Equivalent Coverage

PubMed Central

Liu, Changqing; Bai, Chunyu; Guo, Yu; Liu, Dan; Lu, Taofeng; Li, Xiangchen; Ma, Jianzhang; Ma, Yuehui; Guan, Weijun

2014-01-01

Bacterial artificial chromosome (BAC) libraries are extremely valuable for the genome-wide genetic dissection of complex organisms. The Siberian tiger, one of the most well-known wild primitive carnivores in China, is an endangered animal. In order to promote research on its genome, a high-redundancy BAC library of the Siberian tiger was constructed and characterized. The library is divided into two sub-libraries prepared from blood cells and two sub-libraries prepared from fibroblasts. This BAC library contains 153,600 individually archived clones; for PCR-based screening of the library, BACs were placed into 40 superpools of 10 × 384-deep well microplates. The average insert size of BAC clones was estimated to be 116.5 kb, representing approximately 6.46 genome equivalents of the haploid genome and affording a 98.86% statistical probability of obtaining at least one clone containing a unique DNA sequence. Screening the library with 19 microsatellite markers and a SRY sequence revealed that each of these markers were present in the library; the average number of positive clones per marker was 6.74 (range 2 to 12), consistent with 6.46 coverage of the tiger genome. Additionally, we identified 72 microsatellite markers that could potentially be used as genetic markers. This BAC library will serve as a valuable resource for physical mapping, comparative genomic study and large-scale genome sequencing in the tiger. PMID:24608928

Characterization of some bread wheat genotypes using molecular markers for drought tolerance.

PubMed

Ateş Sönmezoğlu, Özlem; Terzi, Begüm

2018-02-01

Because of its wide geographical adaptation and importance in human nutrition, wheat is one of the most important crops in the world. However, wheat yield has reduced due to drought stress posing threat to sustainability and world food security in agricultural production. The first stage of drought tolerant variety breeding occurs on the molecular and biochemical characterization and classification of wheat genotypes. The aim of the present study is characterization of widely grown bread wheat cultivars and breeding lines for drought tolerance so as to be adapted to different regions in Turkey. The genotypes were screened with molecular markers for the presence of QTLs mapped to different chromosomes. Results of the molecular studies identified and detected 15 polymorphic SSR markers which gave the clearest PCR bands among the control genotypes. At the end of the research, bread wheat genotypes which were classified for tolerance or sensitivity to drought and the genetic similarity within control varieties were determined by molecular markers. According to SSR based dendrogram, two main groups were obtained for drought tolerance. At end of the molecular screening with SSR primers, genetic similarity coefficients were obtained that ranged from 0.14 to 0.71. The ones numbered 8 and 11 were the closest genotypes to drought tolerant cultivar Gerek 79 and the furthest genotypes from this cultivar were number 16 and to drought sensitive cultivar Sultan 95. The genotypes as drought tolerance due to their SSR markers scores are expected to provide useful information for drought related molecular breeding studies.

Homogeneity tests of clustered diagnostic markers with applications to the BioCycle Study

PubMed Central

Tang, Liansheng Larry; Liu, Aiyi; Schisterman, Enrique F.; Zhou, Xiao-Hua; Liu, Catherine Chun-ling

2014-01-01

Diagnostic trials often require the use of a homogeneity test among several markers. Such a test may be necessary to determine the power both during the design phase and in the initial analysis stage. However, no formal method is available for the power and sample size calculation when the number of markers is greater than two and marker measurements are clustered in subjects. This article presents two procedures for testing the accuracy among clustered diagnostic markers. The first procedure is a test of homogeneity among continuous markers based on a global null hypothesis of the same accuracy. The result under the alternative provides the explicit distribution for the power and sample size calculation. The second procedure is a simultaneous pairwise comparison test based on weighted areas under the receiver operating characteristic curves. This test is particularly useful if a global difference among markers is found by the homogeneity test. We apply our procedures to the BioCycle Study designed to assess and compare the accuracy of hormone and oxidative stress markers in distinguishing women with ovulatory menstrual cycles from those without. PMID:22733707

Screening and identification of a microsatellite marker associated with sex in Wami tilapia, Oreochromis urolepis hornorum.

PubMed

Zhu, Huaping; Liu, Zhigang; Lu, Maixin; Gao, Fengying; Ke, Xiaoli; Ma, Dongmei; Huang, Zhanghan; Cao, Jianmeng; Wang, Miao

2016-06-01

In this study, primer pairs of 15 microsatellite markers associated with sex determination of tilapia were selected and amplified in Wami tilapia, Oreochromis urolepis hornorum. While one marker, UNH168, on linkage group 3 (LG3) was associated (P <0.001) with the phenotypic sex in the experimental population, nine genotypes were detected in both sexes. Only 99-bp allele was detected in the female samples, while 141, 149 and 157-bp alleles were present in both male and female samples. UNH168 was localized by fluorescence in situ hybridization (FISH) on the long arm of the largest tilapia chromosome pair (chromosome 1, equivalent to LG3). This sex-linked microsatellite marker could potentially be used for marker-assisted selection in tilapia breeding programmes to produce monosex male tilapia.

Antihyperlipidemic Effect of Different Fractions Obtained from Teucrium polium Hydroalcoholic Extract in Rats.

PubMed

Safaeian, Leila; Ghanadian, Mustafa; Shafiee-Moghadam, Zahra

2018-01-01

This study was aimed to screen the antihyperlipidemic effect of different fractions of Teucrium polium to obtain the most efficient herbal fraction for isolation of bioactive constituents responsible for hypolipidemic activity. Chloroform, butanol, and aqueous fractions were obtained from hydroalcoholic extract of T. polium aerial parts using partitioning process. To induce hyperlipidemia, dexamethasone (Dex) was injected 10 mg/kg/day (s.c.) for 8 days. In the test groups, animals received 50, 100 and 150 mg/kg of T. polium hydroalcoholic extract and different fractions orally simultaneously with Dex. Serum lipid profile and hepatic marker enzymes were evaluated using biochemical kits. All treatments, especially chloroform and aqueous fractions, reversed serum lipid markers in hyperlipidemic rats. Maximum reduction in triglyceride (60.2%, P < 0.001) and maximum elevation in high-density lipoprotein (HDL) (35.0%, P < 0.01) was observed for chloroform fraction. Maximum cholesterol-lowering effect (29.0%, P < 0.001) and maximum reduction in low-density lipoprotein were found for hydroalcoholic extract (72.9%, P < 0.001). Aqueous fraction improved all lipid markers at the highest dose. Butanol fraction decreased triglyceride at the lowest dose (43.9%, P < 0.001) and increased HDL (33%, P < 0.05) at the highest dose. There was a significant increase in alanine aminotransferase and aspartate aminotransferase levels in all tested groups compared to normal group ( P < 0.001). This study showed strong antihyperlipidemic effect of various fractions derived from hydroalcoholic extract of T. polium . Chloroform and aqueous fractions may be worthy candidates for isolation of bioactive hypolipidemic constituents. However, possible hepatotoxicity should be considered for clinical application.

Sensitive and Specific Detection of Early Gastric Cancer Using DNA Methylation Analysis of Gastric Washes

PubMed Central

Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J.; Chung, Woonbok; Estecio, Marcos R. H.; Kondo, Kimie; Guo, Yi; Ahmed, Saira S.; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J.

2009-01-01

Background & Aims Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 non-neoplastic gastric mucosa samples. Results 6 genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer while PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r=0.5 to 0.9, p=0.03 to 0.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the ROC curve (0.961) in terms of tumor detection in gastric washes. Conclusions These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally we have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes. PMID:19375421

Associations between Markers of Glucose and Insulin Function and Cognitive Function in Healthy African American Elders

PubMed Central

Skinner, Jeannine S.; Morgan, Amy; Hernandez-Saucedo, Hector; Hansen, Angela; Corbett, Selena; Arbuckle, Matthew; Leverenz, James BA; Wilkins, Consuelo H.; Craft, Suzanne; Baker, Laura D.

2015-01-01

Background Glucose and insulin are important moderators of cognitive function. African Americans have poorer glycemic control across the glycemic spectrum and are at increased risk for type 2 diabetes and poor cognitive health. It is unclear which glucoregulatory markers predict cognitive function in this at-risk population. The purpose of this study was to examine the association between cognitive function and common markers of glucoregulation in non-diabetic African Americans elders. Methods Thirty-four, community-dwelling African Americans, aged 50-75 years completed cognitive testing and blood collection as part of a health screening assessment. Cognitive outcomes were composite scores derived from neuropsychological tests of executive function and verbal memory. Linear regression was used to examine relationships between cognitive composite scores and fasting blood levels of glucose, insulin, and hemoglobin A1C, with adjustments for age, education, body mass index, and antihypertensive medication use. Results Fasting plasma glucose was negatively associated with executive function (β=−0.41, p=0.03). There was a trend of an association between fasting plasma glucose and verbal memory (β=−0.34, p=0.06). Fasting insulin and hemoglobin A1c were not associated with cognitive function. Conclusion High non-diabetic fasting glucose levels were associated with poorer executive function and verbal memory. These results provide preliminary support for proactive glucose control in older African Americans even before glycemic criteria for type 2 diabetes are met. Our findings suggests that high-normal FPG levels may represent an early red-flag to signify increased risk of cognitive impairment or decline. PMID:26798567

Comparison of four commercially available avidity tests for Toxoplasma gondii-specific IgG antibodies.

PubMed

Villard, O; Breit, L; Cimon, B; Franck, J; Fricker-Hidalgo, H; Godineau, N; Houze, S; Paris, L; Pelloux, H; Villena, I; Candolfi, E

2013-02-01

Toxoplasma infection in pregnant women may cause congenital toxoplasmosis. Diagnosis of infection is based on serological tests aimed at detecting IgM and IgG antibodies against Toxoplasma gondii. However, IgM antibodies are not an accurate marker for discriminating between acute and latent infection. Detection of residual or persistent IgM may occur months or even years after primary infection, while the IgG avidity test is a rapid means of identifying latent infections in pregnant women who exhibit both IgG and IgM anti-Toxoplasma antibodies on initial testing during pregnancy. In this study, we assessed and compared the performances of four commercially available Toxoplasma IgG avidity tests in immunocompetent and immunocompromised patients with acute and latent toxoplasmosis. The positive predictive value of high avidity to confirm latent toxoplasmosis was 100% for all the assays, indicating that high avidity is a hallmark of latent infection. However, the negative predictive value of high avidity ranged from 99.2% (bioMérieux) to 95.3% (Abbott), indicating that acute toxoplasmosis could not be reliably diagnosed based on low IgG avidity alone. Thus, the avidity test provides a rapid means for identifying latent Toxoplasma infection in immunocompetent pregnant women presenting both IgG and IgM anti-Toxoplasma antibodies on initial testing. In terms of cost-effectiveness, avidity testing is a powerful tool that optimizes screening and follow-up of pregnant women while minimizing the costs of screening by avoiding subsequent costly maternal and fetal investigation and unnecessary treatment. The cheapest assay, Vidas Toxo IgG Avidity, also had the best performance for the diagnosis of latent toxoplasmosis.

Comparison of Four Commercially Available Avidity Tests for Toxoplasma gondii-Specific IgG Antibodies

PubMed Central

Breit, L.; Cimon, B.; Franck, J.; Fricker-Hidalgo, H.; Godineau, N.; Houze, S.; Paris, L.; Pelloux, H.; Villena, I.

2013-01-01

Toxoplasma infection in pregnant women may cause congenital toxoplasmosis. Diagnosis of infection is based on serological tests aimed at detecting IgM and IgG antibodies against Toxoplasma gondii. However, IgM antibodies are not an accurate marker for discriminating between acute and latent infection. Detection of residual or persistent IgM may occur months or even years after primary infection, while the IgG avidity test is a rapid means of identifying latent infections in pregnant women who exhibit both IgG and IgM anti-Toxoplasma antibodies on initial testing during pregnancy. In this study, we assessed and compared the performances of four commercially available Toxoplasma IgG avidity tests in immunocompetent and immunocompromised patients with acute and latent toxoplasmosis. The positive predictive value of high avidity to confirm latent toxoplasmosis was 100% for all the assays, indicating that high avidity is a hallmark of latent infection. However, the negative predictive value of high avidity ranged from 99.2% (bioMérieux) to 95.3% (Abbott), indicating that acute toxoplasmosis could not be reliably diagnosed based on low IgG avidity alone. Thus, the avidity test provides a rapid means for identifying latent Toxoplasma infection in immunocompetent pregnant women presenting both IgG and IgM anti-Toxoplasma antibodies on initial testing. In terms of cost-effectiveness, avidity testing is a powerful tool that optimizes screening and follow-up of pregnant women while minimizing the costs of screening by avoiding subsequent costly maternal and fetal investigation and unnecessary treatment. The cheapest assay, Vidas Toxo IgG Avidity, also had the best performance for the diagnosis of latent toxoplasmosis. PMID:23239801

HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women.

PubMed

Duvlis, Sotirija; Popovska-Jankovic, Katerina; Arsova, Zorica Sarafinovska; Memeti, Shaban; Popeska, Zaneta; Plaseska-Karanfilska, Dijana

2015-09-01

High risk types of human papillomaviruses E6/E7 oncogenes and their association with tumor suppressor genes products are the key factors of cervical carcinogenesis. This study proposed them as specific markers for cervical dysplasia screening. The aim of the study is to compare the clinical and prognostic significance of HPV E6/E7 mRNA as an early biomarker versus HPV DNA detection and cytology in triage of woman for cervical cancer. The study group consists of 413 women: 258 NILM, 26 ASC-US, 81 LSIL, 41 HSIL, and 7 unsatisfactory cytology. HPV4AACE screening, real-time multiplex PCR and MY09/11 consensus PCR primers methods were used for the HPV DNA detection. The real-time multiplex nucleic acid sequence-based assay (NucliSENS EasyQ HPV assay) was used for HPV E6/E7 mRNA detection of the five most common high risk HPV types in cervical cancer (16, 18, 31, 33, and 45). The results show that HPV E6/E7 mRNA testing had a higher specificity 50% (95% CI 32-67) and positive predictive value (PPV) 62% (95% CI 46-76) for CIN2+ compared to HPV DNA testing that had specificity of 18% (95% CI 7-37) and PPV 52% (95% CI 39-76) respectively. The higher specificity and PPV of HPV E6/E7 mRNA testing are valuable in predicting insignificant HPV DNA infection among cases with borderline cytological finding. It can help in avoiding aggressive procedures (biopsies and over-referral of transient HPV infections) as well as lowering patient's anxiety and follow up period. © 2015 Wiley Periodicals, Inc.

Recommendations for newborn screening for galactokinase deficiency: A systematic review and evaluation of Dutch newborn screening data.

PubMed

Stroek, Kevin; Bouva, Marelle J; Schielen, Peter C J I; Vaz, Frédéric M; Heijboer, Annemieke C; de Jonge, Robert; Boelen, Anita; Bosch, Annet M

2018-03-21

Galactokinase (GALK) deficiency causes cataract leading to severe developmental consequences unless treated early. Because of the easy prevention and rapid reversibility of cataract with treatment, the Dutch Health Council advised to include GALK deficiency in the Dutch newborn screening program. The aim of this study is to establish the optimal screening method and cut-off value (COV) for GALK deficiency screening by performing a systematic review of the literature of screening strategies and total galactose (TGAL) values and by evaluating TGAL values in the first week of life in a cohort of screened newborns in the Netherlands. Systematic literature search strategies in OVID MEDLINE and OVID EMBASE were developed and study selection, data collection and analyses were performed by two independent investigators. A range of TGAL values measured by the Quantase Neonatal Total Galactose screening assay in a cohort of Dutch newborns in 2007 was evaluated. Eight publications were included in the systematic review. All four studies describing screening strategies used TGAL as the primary screening marker combined with galactose-1-phosphate uridyltransferase (GALT) measurement that is used for classical galactosemia screening. TGAL COVs of 2200 μmol/L, 1665 μmol/L and 1110 μmol/L blood resulted in positive predictive values (PPV) of 100%, 82% and 10% respectively. TGAL values measured in the newborn period were reported for 39 GALK deficiency patients with individual values ranging from 3963 to 8159 μmol/L blood and 2 group values with mean 8892 μmol/L blood (SD ± 5243) and 4856 μmol/L blood (SD ± 461). Dutch newborn screening data of 72,786 newborns from 2007 provided a median TGAL value of 110 μmol/L blood with a range of 30-2431 μmol/L blood. Based on TGAL values measured in GALK deficiency patients reported in the literature and TGAL measurements in the Dutch cohort by newborn screening we suggest to perform the GALK screening with TGAL as a primary marker with a COV of 2500 μmol/L blood, combined with GALT enzyme activity measurement as used in the classical galactosemia screening, to ensure detection of GALK deficiency patients and minimize false positive referrals. Copyright © 2018. Published by Elsevier Inc.

Polymorphic microsatellite loci for Haumania danckelmaniana and transferability to H. liebrechtsiana (Marantaceae).

PubMed

Ley, Alexandra C; Hardy, Olivier J

2016-03-01

Microsatellite markers were developed for the species Haumania danckelmaniana (Marantaceae) from central tropical Africa. Microsatellite isolation was performed simultaneously on three different species of Marantaceae through a procedure that combines multiplex microsatellite enrichment and next-generation sequencing. From 80 primers selected for initial screening, 20 markers positively amplified in H. danckelmaniana, of which 10 presented unambiguous amplification products within the expected size range and eight were polymorphic with four to nine alleles per locus. Positive transferability with the related species H. liebrechtsiana was observed for the same 10 markers. The polymorphic microsatellite markers are suitable for studies in genetic diversity and structure, mating system, and gene flow in H. danckelmaniana and the closely related species H. liebrechtsiana.

Development of SSR Markers Linked to Low Hydrocyanic Acid Content in Sorghum-Sudan Grass Hybrid Based on BSA Method.

PubMed

Xiao-Xia, Yu; Zhi-Hua, Liu; Zhuo, Yu; Yue, Shi; Xiao-Yu, Li

2016-01-01

Sorghum-Sudan grass hybrid containing high hydrocyanic acid content can cause hydrocyanic acid poisoning to the livestock and limit the popularization of this forage crop. Molecular markers associated with low hydrocyanic acid content can speed up the process of identification of genotypes with low hydrocyanic acid content. In the present study, 11 polymorphic SSR primers were screened and used for bulked segregant analysis and single marker analysis. Three SSR markers Xtxp7230, Xtxp7375 and Bnlg667960 associated with low hydrocyanic acid content were rapidly identified by BSA. In single marker analysis, six markers Xtxp7230, Xtxp7375, Bnlg667960, Xtxp67-11, Xtxp295-7 and Xtxp12-9 were linked to low hydrocyanic acid content, which explained the proportion of phenotypic variation from 7.6 % to 41.2 %. The markers identified by BSA were also verified by single marker analysis. The three SSR marker bands were then cloned and sequenced for sequence homology analysis in NCBI. It is the first report on the development of molecular markers associated with low hydrocyanic acid content in sorghum- Sudan grass hybrid. These markers will be useful for genetic improvement of low hydrocyanic acid sorghum-Sudan grass hybrid by marker-assisted breeding.

Development of Novel SSR Markers for Flax (Linum usitatissimum L.) Using Reduced-Representation Genome Sequencing

PubMed Central

Wu, Jianzhong; Zhao, Qian; Wu, Guangwen; Zhang, Shuquan; Jiang, Tingbo

2017-01-01

Flax (Linum usitatissimum L.) is a major fiber and oil yielding crop grown in northeastern China. Identification of flax molecular markers is a key step toward improving flax yield and quality via marker-assisted breeding. Simple sequence repeat (SSR) markers, which are based on genomic structural variation, are considered the most valuable type of genetic marker for this purpose. In this study, we screened 1574 microsatellites from Linum usitatissimum L. obtained using reduced representation genome sequencing (RRGS) to systematically identify SSR markers. The resulting set of microsatellites consisted mainly of trinucleotide (56.10%) and dinucleotide (35.23%) repeats, with each motif consisting of 5–8 repeats. We then evaluated marker sensitivity and specificity based on samples of 48 flax isolates obtained from northeastern China. Using the new SSR panel, the results demonstrated that fiber flax and oilseed flax varieties clustered into two well separated groups. The novel SSR markers developed in this study show potential value for selection of varieties for use in flax breeding programs. PMID:28133461

Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties

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

Liu, Miao; Zheng, Mingjing; Xu, Hanying

Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control.more » Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. - Highlights: • Fibrogenesis was accompanied with the changes of cyto-biophysical properties. • Cyto-biophysical properties could be markers for anti-fibrotic drugs screening. • Stiffness is a leading index among all biophysical markers. • SalB was detected to protect TGF-β1-stimulated A549 cells against stiffening. • SalB treatment ameliorated pulmonary fibrosis induced by BLM in rats.« less

Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.

PubMed

Chen, Wei-Hsin; Hsieh, Sheau-Ling; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

2013-05-23

A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets collected in year 2011 were used as predicting cases. The feature selection strategies were implemented and the optimal markers for PKU, hypermethioninemia, and 3-MCC deficiency were obtained. The results of the machine learning approach were compared with the cutoff scheme. The number of the false positive cases were reduced from 21 to 2 for PKU, from 30 to 10 for hypermethioninemia, and 209 to 46 for 3-MCC deficiency. This SOA Web service-based newborn screening system can accelerate screening procedures effectively and efficiently. An SVM learning methodology for PKU, hypermethioninemia, and 3-MCC deficiency metabolic diseases classification, including optimal feature selection strategies, is presented. By adopting the results of this study, the number of suspected cases could be reduced dramatically.

Web-Based Newborn Screening System for Metabolic Diseases: Machine Learning Versus Clinicians

PubMed Central

Chen, Wei-Hsin; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

2013-01-01

Background A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. Objective The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. Methods The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets collected in year 2011 were used as predicting cases. Results The feature selection strategies were implemented and the optimal markers for PKU, hypermethioninemia, and 3-MCC deficiency were obtained. The results of the machine learning approach were compared with the cutoff scheme. The number of the false positive cases were reduced from 21 to 2 for PKU, from 30 to 10 for hypermethioninemia, and 209 to 46 for 3-MCC deficiency. Conclusions This SOA Web service–based newborn screening system can accelerate screening procedures effectively and efficiently. An SVM learning methodology for PKU, hypermethioninemia, and 3-MCC deficiency metabolic diseases classification, including optimal feature selection strategies, is presented. By adopting the results of this study, the number of suspected cases could be reduced dramatically. PMID:23702487

Projected future impact of HPV vaccination and primary HPV screening on cervical cancer rates from 2017–2035: Example from Australia

PubMed Central

Smith, Megan A.; Saville, Marion; Canfell, Karen

2018-01-01

Background Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017. Methods Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18–20 to 69, to recommending HPV screening every five years for women aged 25–74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males). Findings Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16–24% and 11–14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40–44% and 42–51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34–45% by 2035. Over the period 2018–2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives. Conclusions Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10–15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success. PMID:29444073

Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis

PubMed Central

Monach, Paul A; Warner, Roscoe L; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Iklé, David; Kallenberg, Cees GM; Krischer, Jeffrey; Langford, Carol A; Mueller, Mark; Seo, Philip; St. Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Johnson, Kent J; Merkel, Peter A

2016-01-01

Objective To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. Methods Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). Results All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. Conclusions Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV. PMID:22975753

Performance characteristics of an ELISA screening assay for urinary synthetic cannabinoids.

PubMed

Spinelli, Eliani; Barnes, Allan J; Young, Sheena; Castaneto, Marisol S; Martin, Thomas M; Klette, Kevin L; Huestis, Marilyn A

2015-06-01

Synthetic cannabinoids are marketed as legal alternatives to cannabis, as routine urine cannabinoid immunoassays do not detect synthetic cannabinoids. Laboratories are challenged to identify these new designer drugs that are widely available and represent a major public health and safety problem. Immunoassay testing offers rapid separation of presumptive positive and negative specimens, prior to more costly and time-consuming chromatographic confirmation. The Neogen SPICE ELISA kit targets JWH-018 N-pentanoic acid as a marker for urinary synthetic cannabinoids. Assay performance was evaluated by analyzing 2469 authentic urine samples with the Neogen immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two immunoassay cut-off concentrations, 5 and 10 µg/L, classified samples as presumptive positive or negative, followed by qualitative LC-MS/MS confirmation for 29 synthetic cannabinoids markers with limits of detection of 0.5-10 µg/L to determine the assay's sensitivity, specificity and efficacy. Challenges at ±25% of each cut-off also were investigated to determine performance around the cut-off and intra- and inter-plate imprecision. The immunoassay was linear from 1 to 250 µg/L (r(2)  = 0.992) with intra- and inter-plate imprecision of ≤5.3% and <9%, respectively. Sensitivity, specificity, and efficiency results with the 5 µg/L cut-off were 79.9%, 99.7%, and 97.4% and with the 10 µg/L cut-off 69.3%, 99.8%, and 96.3%, respectively. Cross-reactivity was shown for 18 of 73 synthetic cannabinoids markers evaluated. Good sensitivity, specificity, and efficiency, lack of sample preparation requirements, and rapid semi-automation documented that the Neogen SPICE ELISA kit is a viable method for screening synthetic cannabinoids in urine targeting JWH-018 N-pentanoic acid. Copyright © 2014 John Wiley & Sons, Ltd.

Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on existing biomarkers?

PubMed

Savolainen, Otto; Fagerberg, Björn; Vendelbo Lind, Mads; Sandberg, Ann-Sofie; Ross, Alastair B; Bergström, Göran

2017-01-01

The aim was to determine if metabolomics could be used to build a predictive model for type 2 diabetes (T2D) risk that would improve prediction of T2D over current risk markers. Gas chromatography-tandem mass spectrometry metabolomics was used in a nested case-control study based on a screening sample of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were identified in plasma obtained at baseline and the power to predict diabetes was tested in 69 incident cases occurring during 5.5 years follow-up. The metabolomics results were used as a standalone prediction model and in combination with established T2D predictive biomarkers for building eight T2D prediction models that were compared with each other based on their sensitivity and selectivity for predicting T2D. Established markers of T2D (impaired fasting glucose, impaired glucose tolerance, insulin resistance (HOMA), smoking, serum adiponectin)) alone, and in combination with metabolomics had the largest areas under the curve (AUC) (0.794 (95% confidence interval [0.738-0.850]) and 0.808 [0.749-0.867] respectively), with the standalone metabolomics model based on nine fasting plasma markers having a lower predictive power (0.657 [0.577-0.736]). Prediction based on non-blood based measures was 0.638 [0.565-0.711]). Established measures of T2D risk remain the best predictor of T2D risk in this population. Additional markers detected using metabolomics are likely related to these measures as they did not enhance the overall prediction in a combined model.

Developing expressed sequence tag libraries and the discovery of simple sequence repeat markers for two species of raspberry (Rubus L.).

PubMed

Bushakra, Jill M; Lewers, Kim S; Staton, Margaret E; Zhebentyayeva, Tetyana; Saski, Christopher A

2015-10-26

Due to a relatively high level of codominant inheritance and transferability within and among taxonomic groups, simple sequence repeat (SSR) markers are important elements in comparative mapping and delineation of genomic regions associated with traits of economic importance. Expressed sequence tags (ESTs) are a source of SSRs that can be used to develop markers to facilitate plant breeding and for more basic research across genera and higher plant orders. Leaf and meristem tissue from 'Heritage' red raspberry (Rubus idaeus) and 'Bristol' black raspberry (R. occidentalis) were utilized for RNA extraction. After conversion to cDNA and library construction, ESTs were sequenced, quality verified, assembled and scanned for SSRs.  Primers flanking the SSRs were designed and a subset tested for amplification, polymorphism and transferability across species. ESTs containing SSRs were functionally annotated using the GenBank non-redundant (nr) database and further classified using the gene ontology database. To accelerate development of EST-SSRs in the genus Rubus (Rosaceae), 1149 and 2358 cDNA sequences were generated from red raspberry and black raspberry, respectively. The cDNA sequences were screened using rigorous filtering criteria which resulted in the identification of 121 and 257 SSR loci for red and black raspberry, respectively. Primers were designed from the surrounding sequences resulting in 131 and 288 primer pairs, respectively, as some sequences contained more than one SSR locus. Sequence analysis revealed that the SSR-containing genes span a diversity of functions and share more sequence identity with strawberry genes than with other Rosaceous species. This resource of Rubus-specific, gene-derived markers will facilitate the construction of linkage maps composed of transferable markers for studying and manipulating important traits in this economically important genus.

Biomarkers for predicting type 2 diabetes development—Can metabolomics improve on existing biomarkers?

PubMed Central

Savolainen, Otto; Fagerberg, Björn; Vendelbo Lind, Mads; Sandberg, Ann-Sofie; Ross, Alastair B.; Bergström, Göran

2017-01-01

Aim The aim was to determine if metabolomics could be used to build a predictive model for type 2 diabetes (T2D) risk that would improve prediction of T2D over current risk markers. Methods Gas chromatography-tandem mass spectrometry metabolomics was used in a nested case-control study based on a screening sample of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were identified in plasma obtained at baseline and the power to predict diabetes was tested in 69 incident cases occurring during 5.5 years follow-up. The metabolomics results were used as a standalone prediction model and in combination with established T2D predictive biomarkers for building eight T2D prediction models that were compared with each other based on their sensitivity and selectivity for predicting T2D. Results Established markers of T2D (impaired fasting glucose, impaired glucose tolerance, insulin resistance (HOMA), smoking, serum adiponectin)) alone, and in combination with metabolomics had the largest areas under the curve (AUC) (0.794 (95% confidence interval [0.738–0.850]) and 0.808 [0.749–0.867] respectively), with the standalone metabolomics model based on nine fasting plasma markers having a lower predictive power (0.657 [0.577–0.736]). Prediction based on non-blood based measures was 0.638 [0.565–0.711]). Conclusions Established measures of T2D risk remain the best predictor of T2D risk in this population. Additional markers detected using metabolomics are likely related to these measures as they did not enhance the overall prediction in a combined model. PMID:28692646

41. View of electro/mechanical fiber optic system panel in transmitter ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

41. View of electro/mechanical fiber optic system panel in transmitter building no. 102. Images projected to screen (panel at upper left) are projected to back side of screen located in MWOC to display changing information. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

An efficient platform for genetic selection and screening of gene switches in Escherichia coli

PubMed Central

Muranaka, Norihito; Sharma, Vandana; Nomura, Yoko; Yokobayashi, Yohei

2009-01-01

Engineered gene switches and circuits that can sense various biochemical and physical signals, perform computation, and produce predictable outputs are expected to greatly advance our ability to program complex cellular behaviors. However, rational design of gene switches and circuits that function in living cells is challenging due to the complex intracellular milieu. Consequently, most successful designs of gene switches and circuits have relied, to some extent, on high-throughput screening and/or selection from combinatorial libraries of gene switch and circuit variants. In this study, we describe a generic and efficient platform for selection and screening of gene switches and circuits in Escherichia coli from large libraries. The single-gene dual selection marker tetA was translationally fused to green fluorescent protein (gfpuv) via a flexible peptide linker and used as a dual selection and screening marker for laboratory evolution of gene switches. Single-cycle (sequential positive and negative selections) enrichment efficiencies of >7000 were observed in mock selections of model libraries containing functional riboswitches in liquid culture. The technique was applied to optimize various parameters affecting the selection outcome, and to isolate novel thiamine pyrophosphate riboswitches from a complex library. Artificial riboswitches with excellent characteristics were isolated that exhibit up to 58-fold activation as measured by fluorescent reporter gene assay. PMID:19190095

Response variability in rapid automatized naming predicts reading comprehension

PubMed Central

Li, James J.; Cutting, Laurie E.; Ryan, Matthew; Zilioli, Monica; Denckla, Martha B.; Mahone, E. Mark

2009-01-01

A total of 37 children ages 8 to 14 years, screened for word-reading difficulties (23 with attention-deficit/hyperactivity disorder, ADHD; 14 controls) completed oral reading and rapid automatized naming (RAN) tests. RAN trials were segmented into pause and articulation time and intraindividual variability. There were no group differences on reading or RAN variables. Color- and letter-naming pause times and number-naming articulation time were significant predictors of reading fluency. In contrast, number and letter pause variability were predictors of comprehension. Results support analysis of subcomponents of RAN and add to literature emphasizing intraindividual variability as a marker for response preparation, which has relevance to reading comprehension. PMID:19221923

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait.

PubMed

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-12-31

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits.

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait

PubMed Central

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-01-01

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits. PMID:14975142

Informative markers identification and multivariate analysis of selected DxP for the purpose of QTL mapping

NASA Astrophysics Data System (ADS)

Hazirah S., Z.; Maizura, I.; Rajinder, S.; Mohd Isa Z., A.; Ismanizan, I.

2014-09-01

A study was carried out to generate a linkage map of oil palm dura x pisifera (DXP) population. A subset of sample from a DXP mapping family was screened using 325 SSR primers, of which 221 were informative. To date, 150 SSRs have been genotyped across the entire DxP population via capillary sequencer, where 73 SSRs had 1:1 segregation ratio, 64 had 1:1:1:1, 3 had 3:1 and ten had 1:2:1 segregation ratios. Kolmogorov-Smirnov tests by SPSS revealed that most of the bunch quality components had normal distribution which fulfilled one of the pre-requisites to carry out phenotype-genotype correlation association.