Correcting for batch effects in case-control microbiome studies

PubMed Central

Gibbons, Sean M.; Duvallet, Claire

2018-01-01

High-throughput data generation platforms, like mass-spectrometry, microarrays, and second-generation sequencing are susceptible to batch effects due to run-to-run variation in reagents, equipment, protocols, or personnel. Currently, batch correction methods are not commonly applied to microbiome sequencing datasets. In this paper, we compare different batch-correction methods applied to microbiome case-control studies. We introduce a model-free normalization procedure where features (i.e. bacterial taxa) in case samples are converted to percentiles of the equivalent features in control samples within a study prior to pooling data across studies. We look at how this percentile-normalization method compares to traditional meta-analysis methods for combining independent p-values and to limma and ComBat, widely used batch-correction models developed for RNA microarray data. Overall, we show that percentile-normalization is a simple, non-parametric approach for correcting batch effects and improving sensitivity in case-control meta-analyses. PMID:29684016

Overcoming Heparin-Associated RT-qPCR Inhibition and Normalization Issues for microRNA Quantification in Patients with Acute Myocardial Infarction.

PubMed

Coelho-Lima, Jose; Mohammed, Ashfaq; Cormack, Suzanne; Jones, Samuel; Das, Rajiv; Egred, Mohaned; Panahi, Pedram; Ali, Simi; Spyridopoulos, Ioakim

2018-06-11

 Cardiac-enriched micro ribonucleic acids (miRNAs) are released into the circulation following ST-elevation myocardial infarction (STEMI). Lack of standardized approaches for reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) data normalization and presence of RT-qPCR inhibitors (e.g. heparin) in patient blood samples have prevented reproducible miRNA quantification in this cohort and subsequent translation of these biomarkers to clinical practice.  Using a RT-qPCR miRNA screening platform, we identified and validated an endogenous circulating miRNA as a normalization control. In addition, we assessed the effects of in vivo and in vitro anticoagulant drugs administration (heparin and bivalirudin) on three RT-qPCR normalization strategies (global miRNA mean, exogenous spike-in control [cel-miR-39] and endogenous miRNA control). Finally, we evaluated the effect of heparin and its in vitro inhibition with heparinase on the quantification of cardiac-enriched miRNAs in STEMI patients.  miR-425-5p was validated as an endogenous miRNA control. Heparin administration in vitro and in vivo inhibited all RT-qPCR normalization strategies. In contrast, bivalirudin had no effects on cel-miR-39 or miR-425-5p quantification. In vitro RNA sample treatment with 0.3 U of heparinase overcame heparin-induced over-estimation of cardiac-enriched miRNA levels and improved their correlation with high-sensitivity troponin T.  miRNA quantification in STEMI patients receiving heparin is jeopardized by its effect on all RT-qPCR normalization approaches. Use of samples from bivalirudin-treated patients or in vitro treatment of heparin-contaminated samples with heparinase are suitable alternatives for miRNA quantification in this cohort. Finally, we reinforce the evidence that cardiac-enriched miRNAs early after myocardial reperfusion reflect the severity of cardiac injury. Schattauer GmbH Stuttgart.

Is this the right normalization? A diagnostic tool for ChIP-seq normalization.

PubMed

Angelini, Claudia; Heller, Ruth; Volkinshtein, Rita; Yekutieli, Daniel

2015-05-09

Chip-seq experiments are becoming a standard approach for genome-wide profiling protein-DNA interactions, such as detecting transcription factor binding sites, histone modification marks and RNA Polymerase II occupancy. However, when comparing a ChIP sample versus a control sample, such as Input DNA, normalization procedures have to be applied in order to remove experimental source of biases. Despite the substantial impact that the choice of the normalization method can have on the results of a ChIP-seq data analysis, their assessment is not fully explored in the literature. In particular, there are no diagnostic tools that show whether the applied normalization is indeed appropriate for the data being analyzed. In this work we propose a novel diagnostic tool to examine the appropriateness of the estimated normalization procedure. By plotting the empirical densities of log relative risks in bins of equal read count, along with the estimated normalization constant, after logarithmic transformation, the researcher is able to assess the appropriateness of the estimated normalization constant. We use the diagnostic plot to evaluate the appropriateness of the estimates obtained by CisGenome, NCIS and CCAT on several real data examples. Moreover, we show the impact that the choice of the normalization constant can have on standard tools for peak calling such as MACS or SICER. Finally, we propose a novel procedure for controlling the FDR using sample swapping. This procedure makes use of the estimated normalization constant in order to gain power over the naive choice of constant (used in MACS and SICER), which is the ratio of the total number of reads in the ChIP and Input samples. Linear normalization approaches aim to estimate a scale factor, r, to adjust for different sequencing depths when comparing ChIP versus Input samples. The estimated scaling factor can easily be incorporated in many peak caller algorithms to improve the accuracy of the peak identification. The diagnostic plot proposed in this paper can be used to assess how adequate ChIP/Input normalization constants are, and thus it allows the user to choose the most adequate estimate for the analysis.

Metabolomic analysis of urine samples by UHPLC-QTOF-MS: Impact of normalization strategies.

PubMed

Gagnebin, Yoric; Tonoli, David; Lescuyer, Pierre; Ponte, Belen; de Seigneux, Sophie; Martin, Pierre-Yves; Schappler, Julie; Boccard, Julien; Rudaz, Serge

2017-02-22

Among the various biological matrices used in metabolomics, urine is a biofluid of major interest because of its non-invasive collection and its availability in large quantities. However, significant sources of variability in urine metabolomics based on UHPLC-MS are related to the analytical drift and variation of the sample concentration, thus requiring normalization. A sequential normalization strategy was developed to remove these detrimental effects, including: (i) pre-acquisition sample normalization by individual dilution factors to narrow the concentration range and to standardize the analytical conditions, (ii) post-acquisition data normalization by quality control-based robust LOESS signal correction (QC-RLSC) to correct for potential analytical drift, and (iii) post-acquisition data normalization by MS total useful signal (MSTUS) or probabilistic quotient normalization (PQN) to prevent the impact of concentration variability. This generic strategy was performed with urine samples from healthy individuals and was further implemented in the context of a clinical study to detect alterations in urine metabolomic profiles due to kidney failure. In the case of kidney failure, the relation between creatinine/osmolality and the sample concentration is modified, and relying only on these measurements for normalization could be highly detrimental. The sequential normalization strategy was demonstrated to significantly improve patient stratification by decreasing the unwanted variability and thus enhancing data quality. Copyright © 2016 Elsevier B.V. All rights reserved.

Internal Kinematics of AGN Hosts

NASA Astrophysics Data System (ADS)

Masegosa, Josefa; Márquez, Isabel; Durret, Florence; DEGAS Consortium

In order to understand the fueling mechanism to power AGNs, a large effort has been done by the DEGAS (Dynamics and nuclear Engine of GAlaxies of Spiral type) consortium to collect the necessary observational material. We defined an AGN sample which is not contaminated by interacting galaxies and a control sample made of normal spirals with the same properties than the AGN sample, i.e. luminosity and redshift distribution, morphology and percentage of bars. In total we have analyzed a sample of 17 active galaxies and 16 normal spirals. All the galaxies are isolated with the following criteria: not having a companion within 0.4 Mpc and cz < 500 km/s. We want to stress this aspect of our sample, since claimed differences between active and normal galaxies (Knapen et al. 2000) disappear when the samples are decontaminated of interacting systems.

Colon Cancer Associated Transcript-1 (CCAT1) Expression in Adenocarcinoma of the Stomach.

PubMed

Mizrahi, Ido; Mazeh, Haggi; Grinbaum, Ronit; Beglaibter, Nahum; Wilschanski, Michael; Pavlov, Vera; Adileh, Muchamad; Stojadinovic, Alexander; Avital, Itzhak; Gure, Ali Osmay; Halle, David; Nissan, Aviram

2015-01-01

Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance.

Average of delta: a new quality control tool for clinical laboratories.

PubMed

Jones, Graham R D

2016-01-01

Average of normals is a tool used to control assay performance using the average of a series of results from patients' samples. Delta checking is a process of identifying errors in individual patient results by reviewing the difference from previous results of the same patient. This paper introduces a novel alternate approach, average of delta, which combines these concepts to use the average of a number of sequential delta values to identify changes in assay performance. Models for average of delta and average of normals were developed in a spreadsheet application. The model assessed the expected scatter of average of delta and average of normals functions and the effect of assay bias for different values of analytical imprecision and within- and between-subject biological variation and the number of samples included in the calculations. The final assessment was the number of patients' samples required to identify an added bias with 90% certainty. The model demonstrated that with larger numbers of delta values, the average of delta function was tighter (lower coefficient of variation). The optimal number of samples for bias detection with average of delta was likely to be between 5 and 20 for most settings and that average of delta outperformed average of normals when the within-subject biological variation was small relative to the between-subject variation. Average of delta provides a possible additional assay quality control tool which theoretical modelling predicts may be more valuable than average of normals for analytes where the group biological variation is wide compared with within-subject variation and where there is a high rate of repeat testing in the laboratory patient population. © The Author(s) 2015.

A comprehensive quality control workflow for paired tumor-normal NGS experiments.

PubMed

Schroeder, Christopher M; Hilke, Franz J; Löffler, Markus W; Bitzer, Michael; Lenz, Florian; Sturm, Marc

2017-06-01

Quality control (QC) is an important part of all NGS data analysis stages. Many available tools calculate QC metrics from different analysis steps of single sample experiments (raw reads, mapped reads and variant lists). Multi-sample experiments, as sequencing of tumor-normal pairs, require additional QC metrics to ensure validity of results. These multi-sample QC metrics still lack standardization. We therefore suggest a new workflow for QC of DNA sequencing of tumor-normal pairs. With this workflow well-known single-sample QC metrics and additional metrics specific for tumor-normal pairs can be calculated. The segmentation into different tools offers a high flexibility and allows reuse for other purposes. All tools produce qcML, a generic XML format for QC of -omics experiments. qcML uses quality metrics defined in an ontology, which was adapted for NGS. All QC tools are implemented in C ++ and run both under Linux and Windows. Plotting requires python 2.7 and matplotlib. The software is available under the 'GNU General Public License version 2' as part of the ngs-bits project: https://github.com/imgag/ngs-bits. christopher.schroeder@med.uni-tuebingen.de. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Electron Micrographs of Quail Limb Bones formed in microgravity

NASA Technical Reports Server (NTRS)

2003-01-01

Electron micrographs of quail limb bones that formed under the influence of microgravity show decreased mineralization compared to bones formed in normal gravity. The letters B and C indicate bone and cartilage sides of the sample, respectively, with the arrows marking the junction between bone and cartilage cells. The asterisks indicate where mineralization begins. The bone that developed during spaceflight (top) shows less mineral compared to the control sample (bottom); the control sample clearly shows mineral deposits (dark spots) that are absent in the flight sample. Quail eggs are small and develop quickly, making them ideal for space experiments. In late 2001, the Avian Development Facility (ADF) made its first flight and carried eggs used in two investigations, development and function of the irner-ear balance system in normal and altered gravity environments, and skeletal development in embryonic quail.

Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples.

PubMed

Elloumi, Fathi; Hu, Zhiyuan; Li, Yan; Parker, Joel S; Gulley, Margaret L; Amos, Keith D; Troester, Melissa A

2011-06-30

Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification. To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors. Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability. Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor.

Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls.

PubMed

Xu, Wuhua; Kawarabayashi, Takeshi; Matsubara, Etsuro; Deguchi, Kentaro; Murakami, Tetsuro; Harigaya, Yasuo; Ikeda, Masaki; Amari, Masakuni; Kuwano, Ryozo; Abe, Koji; Shoji, Mikio

2008-07-11

Antibodies to amyloid beta protein (Abeta) are present naturally or after Abeta vaccine therapy in human plasma. To clarify their clinical role, we examined plasma samples from 113 patients with Alzheimer's disease (AD) and 205 normal controls using the tissue amyloid plaque immunoreactivity (TAPIR) assay. A high positive rate of TAPIR was revealed in AD (45.1%) and age-matched controls (41.2%), however, no significance was observed. No significant difference was observed in the MMS score or disease duration between TAPIR-positive and negative samples. TAPIR-positive plasma reacted with the Abeta40 monomer and dimer, and the Abeta42 monomer weakly, but not with the Abeta42 dimer. TAPIR was even detected in samples from young normal subjects and young Tg2576 transgenic mice. Although the Abeta40 level and Abeta40/42 ratio increased, and Abeta42 was significantly decreased in plasma from AD groups when compared to controls, no significant correlations were revealed between plasma Abeta levels and TAPIR grading. Thus an immune response to Abeta40 and immune tolerance to Abeta42 occurred naturally in humans without a close relationship to the Abeta burden in the brain. Clarification of the mechanism of the immune response to Abeta42 is necessary for realization of an immunotherapy for AD.

Economic consequences of improved temperature forecasts: An experiment with the Florida citrus growers (an update of control group results)

NASA Technical Reports Server (NTRS)

Braen, C.

1978-01-01

The economic experiment, the results obtained to date and the work which still remains to be done are summarized. Specifically, the experiment design is described in detail as are the developed data collection methodology and procedures, sampling plan, data reduction techniques, cost and loss models, establishment of frost severity measures, data obtained from citrus growers, National Weather Service and Federal Crop Insurance Corp. Resulting protection costs and crop losses for the control group sample, extrapolation of results of control group to the Florida citrus industry and the method for normalization of these results to a normal or average frost season so that results may be compared with anticipated similar results from test group measurements are discussed.

Effects of spaceflight on the spermatogonial population of rat seminiferous epithelium

NASA Technical Reports Server (NTRS)

Sapp, Walter J.; Philpott, Delbert E.; Williams, Carol S.; Kato, Katharine; Stevenson, Joann; Vasquez, M.; Serova, L. V.

1990-01-01

Testes from rats flown on Cosmos 1887 were compared with vivarium control and synchronous control samples. The mean weights of flight testes, normalized for weight per 100 g, were 6.4 percent less when compared with the vivarium controls. Counts of spermatogonia from tissue sections (seminiferous tubules in maturation stage 6) from five animals in each group revealed 4 percent fewer spermatogonia in flight testes compared with synchronous controls and 11 percent fewer spermatogonia in flight samples compared with vivarium controls.

Colon Cancer Associated Transcript-1 (CCAT1) Expression in Adenocarcinoma of the Stomach

PubMed Central

Mizrahi, Ido; Mazeh, Haggi; Grinbaum, Ronit; Beglaibter, Nahum; Wilschanski, Michael; Pavlov, Vera; Adileh, Muchamad; Stojadinovic, Alexander; Avital, Itzhak; Gure, Ali Osmay; Halle, David; Nissan, Aviram

2015-01-01

Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Methods: Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Results: Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). Conclusion: CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance. PMID:25561974

Detection of equine herpesvirus in horses with idiopathic keratoconjunctivitis and comparison of three sampling techniques.

PubMed

Hollingsworth, Steven R; Pusterla, Nicola; Kass, Philip H; Good, Kathryn L; Brault, Stephanie A; Maggs, David J

2015-09-01

To determine the role of equine herpesvirus (EHV) in idiopathic keratoconjunctivitis in horses and to determine whether sample collection method affects detection of EHV DNA by quantitative polymerase chain reaction (qPCR). Twelve horses with idiopathic keratoconjunctivitis and six horses without signs of ophthalmic disease. Conjunctival swabs, corneal scrapings, and conjunctival biopsies were collected from 18 horses: 12 clinical cases with idiopathic keratoconjunctivitis and six euthanized controls. In horses with both eyes involved, the samples were taken from the eye judged to be more severely affected. Samples were tested with qPCR for EHV-1, EHV-2, EHV-4, and EHV-5 DNA. Quantity of EHV DNA and viral replicative activity were compared between the two populations and among the different sampling techniques; relative sensitivities of the sampling techniques were determined. Prevalence of EHV DNA as assessed by qPCR did not differ significantly between control horses and those with idiopathic keratoconjunctivitis. Sampling by conjunctival swab was more likely to yield viral DNA as assessed by qPCR than was conjunctival biopsy. EHV-1 and EHV-4 DNA were not detected in either normal or IKC-affected horses; EHV-2 DNA was detected in two of 12 affected horses but not in normal horses. EHV-5 DNA was commonly found in ophthalmically normal horses and horses with idiopathic keratoconjunctivitis. Because EHV-5 DNA was commonly found in control horses and in horses with idiopathic keratoconjunctivitis, qPCR was not useful for the etiological diagnosis of equine keratoconjunctivitis. Conjunctival swabs were significantly better at obtaining viral DNA samples than conjunctival biopsy in horses in which EHV-5 DNA was found. © 2015 American College of Veterinary Ophthalmologists.

Maximizing PTH Anabolic Osteoporosis Therapy

DTIC Science & Technology

2015-09-01

SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c...normalization or endogenous controls and calculates fold 263 changes with P values. Gene expression data were normalized to five endogenous controls ( 18S ...adapters were ligated and the sample was size-fractionated (200-300 bp) on an agarose gel. After a final 294 PCR amplification step ( 18 cycles), the

SNP rs16906252C>T is an expression and methylation quantitative trait locus associated with an increased risk of developing MGMT-methylated colorectal cancer

PubMed Central

Kuroiwa-Trzmielina, Joice; Wang, Fan; Rapkins, Robert W.; Ward, Robyn L.; Buchanan, Daniel D.; Win, Aung Ko; Clendenning, Mark; Rosty, Christophe; Southey, Melissa C.; Winship, Ingrid M.; Hopper, John L.; Jenkins, Mark A.; Olivier, Jake; Hawkins, Nicholas J.; Hitchins, Megan P.

2016-01-01

Purpose Methylation of the MGMT promoter is the major cause of O6-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter-enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer (CRC) featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues. Experimental design By applying a molecular pathological epidemiology case-control study design, associations between rs16906252C>T and risk for CRC overall, and CRC stratified by MGMT methylation status, were estimated using multinomial logistic regression in two independent retrospective series of CRC cases and controls. The test sample comprised 1054 CRC cases and 451 controls from Sydney, Australia. The validation sample comprised 612 CRC cases and 245 controls from the Australasian Colon Cancer Family Registry (ACCFR). To determine if rs16906252C>T was linked to a constitutively altered epigenetic state, quantitative allelic expression and methylation analyses were performed in normal tissues. Results An association between rs16906252C>T and increased risk of developing MGMT-methylated CRC in the Sydney sample was observed (OR 3.3; 95%CI=2.0–5.3; P<0.0001), which was replicated in the ACCFR sample (OR 4.0; 95%CI=2.4–6.8; P<0.0001). The T allele demonstrated ~2.5-fold reduced transcription in normal colorectal mucosa from cases and controls, and was selectively methylated in a minority of normal cells, indicating rs16906252C>T represents an expression and methylation quantitative trait locus. Conclusions We provide evidence that rs16906252C>T is associated with elevated risk for MGMT-methylated CRC, likely mediated by constitutive epigenetic repression of the T allele. PMID:27267851

Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients.

PubMed

Meintker, Lisa; Haimerl, Maria; Ringwald, Jürgen; Krause, Stefan W

2013-11-01

Measurement of immature platelets was introduced into routine diagnostics by Sysmex as immature platelet fraction (IPF) some years ago and recently by Abbott as reticulated platelet fraction (rPT). Here, we compare both methods. We evaluated the precision and agreement of these parameters between Sysmex XE-5000 and Abbott CD-Sapphire in three distinct thrombocytopaenic cohorts: 30 patients with beginning thrombocytopaenia and 64 patients with recovering platelets (PLT) after chemotherapy, 16 patients with immune thrombocytopaenia (ITP) or heparin-induced thrombocytopaenia type 2 (HIT) and 110 additional normal controls. Furthermore, we analysed, how IPF/rPT differed between these thrombocytopaenic cohorts and controls. Both analysers demonstrated acceptable overall precision (repeatability) of IPF/rPT with lower precision at low PLT counts. IPF/rPT artificially increased during storage of blood samples overnight. Inter-instrument comparison showed a moderate correlation (Pearson r²=0.38) and a systematic bias of 1.04 towards higher IPF-values with the XE-5000. IPF/rPT was highest in recovering thrombopoesis after chemotherapy and moderately increased in ITP/HIT. The normal range deduced from control samples was much narrower with CD-Sapphire (1.0%-3.8%, established here for the first time) in comparison to XE-5000 (0.8%-7.9%) leading to a smaller overlap of samples with increased PLT turnover and normal controls. IPF and rPT both give useful information on PLT turnover, although the two analysers only show a moderate inter-instrument correlation and have different reference ranges. A better separation of patient groups with high PLT turnover like ITP/HIT from normal controls is obtained by CD-Sapphire.

Mixture model normalization for non-targeted gas chromatography/mass spectrometry metabolomics data.

PubMed

Reisetter, Anna C; Muehlbauer, Michael J; Bain, James R; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Metzger, Boyd E; Newgard, Christopher B; Lowe, William L; Scholtens, Denise M

2017-02-02

Metabolomics offers a unique integrative perspective for health research, reflecting genetic and environmental contributions to disease-related phenotypes. Identifying robust associations in population-based or large-scale clinical studies demands large numbers of subjects and therefore sample batching for gas-chromatography/mass spectrometry (GC/MS) non-targeted assays. When run over weeks or months, technical noise due to batch and run-order threatens data interpretability. Application of existing normalization methods to metabolomics is challenged by unsatisfied modeling assumptions and, notably, failure to address batch-specific truncation of low abundance compounds. To curtail technical noise and make GC/MS metabolomics data amenable to analyses describing biologically relevant variability, we propose mixture model normalization (mixnorm) that accommodates truncated data and estimates per-metabolite batch and run-order effects using quality control samples. Mixnorm outperforms other approaches across many metrics, including improved correlation of non-targeted and targeted measurements and superior performance when metabolite detectability varies according to batch. For some metrics, particularly when truncation is less frequent for a metabolite, mean centering and median scaling demonstrate comparable performance to mixnorm. When quality control samples are systematically included in batches, mixnorm is uniquely suited to normalizing non-targeted GC/MS metabolomics data due to explicit accommodation of batch effects, run order and varying thresholds of detectability. Especially in large-scale studies, normalization is crucial for drawing accurate conclusions from non-targeted GC/MS metabolomics data.

A Spiking Strategy for ChIP-chip Data Normalization in S. cerevisiae.

PubMed

Jeronimo, Célia; Robert, François

2017-01-01

Chromatin immunoprecipitation coupled to DNA microarrays (ChIP-chip) is widely used in the chromatin field, notably to map the position of histone variants or histone modifications along the genome. Often, the position and the occupancy of these epigenetic marks are to be compared between different experiments. It is now increasingly recognized that such cross-sample comparison is better done using externally added exogenous controls for normalization but no such method has been described for ChIP-chip. Here we describe a spiking normalization strategy that makes use of phiX174 phage DNA as a spiked control for normalization of ChIP-chip signals across different experiments.

Robust gene network analysis reveals alteration of the STAT5a network as a hallmark of prostate cancer.

PubMed

Reddy, Anupama; Huang, C Chris; Liu, Huiqing; Delisi, Charles; Nevalainen, Marja T; Szalma, Sandor; Bhanot, Gyan

2010-01-01

We develop a general method to identify gene networks from pair-wise correlations between genes in a microarray data set and apply it to a public prostate cancer gene expression data from 69 primary prostate tumors. We define the degree of a node as the number of genes significantly associated with the node and identify hub genes as those with the highest degree. The correlation network was pruned using transcription factor binding information in VisANT (http://visant.bu.edu/) as a biological filter. The reliability of hub genes was determined using a strict permutation test. Separate networks for normal prostate samples, and prostate cancer samples from African Americans (AA) and European Americans (EA) were generated and compared. We found that the same hubs control disease progression in AA and EA networks. Combining AA and EA samples, we generated networks for low low (<7) and high (≥7) Gleason grade tumors. A comparison of their major hubs with those of the network for normal samples identified two types of changes associated with disease: (i) Some hub genes increased their degree in the tumor network compared to their degree in the normal network, suggesting that these genes are associated with gain of regulatory control in cancer (e.g. possible turning on of oncogenes). (ii) Some hubs reduced their degree in the tumor network compared to their degree in the normal network, suggesting that these genes are associated with loss of regulatory control in cancer (e.g. possible loss of tumor suppressor genes). A striking result was that for both AA and EA tumor samples, STAT5a, CEBPB and EGR1 are major hubs that gain neighbors compared to the normal prostate network. Conversely, HIF-lα is a major hub that loses connections in the prostate cancer network compared to the normal prostate network. We also find that the degree of these hubs changes progressively from normal to low grade to high grade disease, suggesting that these hubs are master regulators of prostate cancer and marks disease progression. STAT5a was identified as a central hub, with ~120 neighbors in the prostate cancer network and only 81 neighbors in the normal prostate network. Of the 120 neighbors of STAT5a, 57 are known cancer related genes, known to be involved in functional pathways associated with tumorigenesis. Our method is general and can easily be extended to identify and study networks associated with any two phenotypes.

Telomere length in normal and neoplastic canine tissues.

PubMed

Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

2007-12-01

To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

High resolution DNA melting analysis: an application for prenatal control of alpha-thalassemia.

PubMed

Sirichotiyakul, Supatra; Wanapirak, Chanane; Saetung, Rattika; Sanguansermsri, Torpong

2010-04-01

To report the use of real-time gap-PCR using SYTO9 with high-resolution melting analysis (HRMA) in prenatal diagnosis of alpha-thalassemia 1. Real-time gap-PCR using SYTO9 with HRMA was performed in 33 DNA samples from chorionic villi sampling (8 normal, 16 heterozygous, and 9 homozygous) to determine the alpha-thalassemia 1 gene [normal and Southeast Asia (-SEA) allele]. The dissociation curve analysis in normal and - SEA allele gave a peak of T(m) at 91.80 +/- 0.14 degrees C and 88.67 +/- 0.08 degrees C, respectively. Normal genotype and homozygous alpha-thalassemia 1 showed a single peak of T(m) that corresponded to their alleles. The heterozygotes gave both peaks with higher normal peak and smaller - SEA peak. Thirty one samples showed consistent results with the conventional gap-PCR. Two samples with ambiguous results were confirmed to be maternal DNA contamination on real-time quantitative PCR and microsatellite assay. HRMA from both samples showed similar pattern to that of heterozygotes. However, they showed much smaller normal peak compared with the - SEA peak, which is in contrast to those of heterozygotes and can readily be distinguished. HRMA with SYTO9 is feasible for prenatal diagnosis of alpha-thalassemia. It had potential advantage of prompt detection maternal DNA contamination. Copyright (c) 2010 John Wiley & Sons, Ltd.

Relationship of 24-hour urinary free cortisol to 4-hour salivary morning and afternoon cortisol and cortisone as measured by a time-integrated oral diffusion sink.

PubMed

Kathol, R G; Poland, R E; Stokes, P E; Wade, S

1995-05-01

The relationship between salivary corticosteroids integrated over 4-hour periods and urinary free cortisol collected over 24 hours was investigated in normal controls. Twenty-one normal volunteers wore "oral diffusion sink" sampling devices in their mouths for two 4-hour periods (08:00-12:00 hours and 13:00-17:00 hours) and on the same day collected a 24-hour urine specimen. Time-integrated salivary corticosteroid concentrations were determined from the sample devices and urinary free cortisol was measured. Salivary corticosteroids were not consistently higher in the morning than in the afternoon period and did not differ between men and women. Urinary free cortisol levels were higher in women. No salivary corticosteroids measure was significantly correlated with urinary free cortisol. We conclude that time-integrated salivary corticosteroids do not reflect urinary free cortisol levels in normal controls.

Can a combination of average of normals and "real time" External Quality Assurance replace Internal Quality Control?

PubMed

Badrick, Tony; Graham, Peter

2018-03-28

Internal Quality Control and External Quality Assurance are separate but related processes that have developed independently in laboratory medicine over many years. They have different sample frequencies, statistical interpretations and immediacy. Both processes have evolved absorbing new understandings of the concept of laboratory error, sample material matrix and assay capability. However, we do not believe at the coalface that either process has led to much improvement in patient outcomes recently. It is the increasing reliability and automation of analytical platforms along with improved stability of reagents that has reduced systematic and random error, which in turn has minimised the risk of running less frequent IQC. We suggest that it is time to rethink the role of both these processes and unite them into a single approach using an Average of Normals model supported by more frequent External Quality Assurance samples. This new paradigm may lead to less confusion for laboratory staff and quicker responses to and identification of out of control situations.

Identification of osteosarcoma-related specific proteins in serum samples using surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry.

PubMed

Gu, Jianli; Li, Jitian; Huang, Manyu; Zhang, Zhiyong; Li, Dongsheng; Song, Guoying; Ding, Xingpo; Li, Wuyin

2014-01-01

Osteosarcoma (OS) is the most common malignant bone tumor. To identify OS-related specific proteins for early diagnosis of OS, a novel approach, surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF-MS) to serum samples from 25 OS patients, 16 osteochondroma, and 26 age-matched normal human volunteers as controls, was performed. Two proteins showed a significantly different expression in OS serum samples from control groups. Proteomic profiles and external leave-one-out cross-validation analysis showed that the correct rate of allocation, the sensitivity, and the specificity of diagnosis were 100%. These two proteins were further identified by searching the EPO-KB database, and one of the proteins identified as Serine rich region profile is involved in various cellular signaling cascades and tumor genesis. The presence of these two proteins in OS patients but absence from premalignant and normal human controls implied that they can be potential biomarkers for early diagnosis of OS.

Vitamin D receptor levels in colorectal cancer. Possible role of BsmI polymorphism.

PubMed

Parisi, Eva; Reñé, Josep Maria; Cardús, Anna; Valcheva, Petya; Piñol-Felis, Carme; Valdivielso, José Manuel; Fernández, Elvira

2008-07-01

A high expression of vitamin D receptor (VDR) in colorectal cancer (CRC) tumoral tissue has been related to a good prognosis and it has been proposed that it could be a good biological marker of CRC progression. Nevertheless, there are no previous studies that compare the VDR expression in tumoral towards normal tissue of the same CRC patient in relation to VDR BsmI genotype. We collected normal and tumoral tissue samples, as well as blood samples, from CRC patients (n=170) and controls (n=122). VDR genotyping was performed and BsmI homozygous patients were selected (CRC=50, Cont=32). VDR mRNA and protein levels were analyzed. We also measured 25-Hydroxyvitamin D serum levels. We found no differences in the polymorphism distribution in tumoral versus normal tissue (control: BB=15.7%, bb=41.3%, Bb=43%; CRC: BB=14.2%, bb=41.9%, Bb=43.9%). Furthermore, VDR levels decreased in colonic cancer tissue (mean: 3.03) versus normal mucosa (11.62) from the same patient (p<0.001), but this decrease was similar in both genotypes. There were differences in 25-Hydroxyvitamin D(3) levels between the CRC and the control group (CRC=8.65 ng/ml, Cont=18.15 ng/ml). In conclusion, we found a decrease in VDR levels in tumoral compared with normal mucosa from the same patient. This difference is independent of the BsmI polymorphism.

A Unique Four-Hub Protein Cluster Associates to Glioblastoma Progression

PubMed Central

Simeone, Pasquale; Trerotola, Marco; Urbanella, Andrea; Lattanzio, Rossano; Ciavardelli, Domenico; Di Giuseppe, Fabrizio; Eleuterio, Enrica; Sulpizio, Marilisa; Eusebi, Vincenzo; Pession, Annalisa; Piantelli, Mauro; Alberti, Saverio

2014-01-01

Gliomas are the most frequent brain tumors. Among them, glioblastomas are malignant and largely resistant to available treatments. Histopathology is the gold standard for classification and grading of brain tumors. However, brain tumor heterogeneity is remarkable and histopathology procedures for glioma classification remain unsatisfactory for predicting disease course as well as response to treatment. Proteins that tightly associate with cancer differentiation and progression, can bear important prognostic information. Here, we describe the identification of protein clusters differentially expressed in high-grade versus low-grade gliomas. Tissue samples from 25 high-grade tumors, 10 low-grade tumors and 5 normal brain cortices were analyzed by 2D-PAGE and proteomic profiling by mass spectrometry. This led to identify 48 differentially expressed protein markers between tumors and normal samples. Protein clustering by multivariate analyses (PCA and PLS-DA) provided discrimination between pathological samples to an unprecedented extent, and revealed a unique network of deranged proteins. We discovered a novel glioblastoma control module centered on four major network hubs: Huntingtin, HNF4α, c-Myc and 14-3-3ζ. Immunohistochemistry, western blotting and unbiased proteome-wide meta-analysis revealed altered expression of this glioblastoma control module in human glioma samples as compared with normal controls. Moreover, the four-hub network was found to cross-talk with both p53 and EGFR pathways. In summary, the findings of this study indicate the existence of a unifying signaling module controlling glioblastoma pathogenesis and malignant progression, and suggest novel targets for development of diagnostic and therapeutic procedures. PMID:25050814

Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma.

PubMed

Morelatto, Rosana; Itoiz, María-Elina; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

2014-05-01

The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes.

Expression of heat shock protein 70 in transport-stressed broiler pectoralis major muscle and its relationship with meat quality.

PubMed

Xing, T; Wang, M F; Han, M Y; Zhu, X S; Xu, X L; Zhou, G H

2017-09-01

Omics research has indicated that heat shock protein 70 (HSP70) is a potential biomarker of meat quality. However, the specific changes and the potential role of HSP70 in postmortem meat quality development need to be further defined. In this study, Arbor Acres broiler chickens (n=126) were randomly categorized into three treatment groups of unstressed control (C), 0.5-h transport (T) and subsequent water shower spray following transport (T/W). Each treatment consisted of six replicates with seven birds each. The birds were transported according to a designed protocol. The pectoralis major (PM) muscles of the transport-stressed broilers were categorized as normal and pale, soft and exudative (PSE)-like muscle samples according to L* and pH24 h values to test the expression and location of HSP70. Results revealed that the activities of plasma creatine kinase and lactate dehydrogenase increased significantly (P<0.05) in normal and PSE-like muscle samples after transportation. The mRNA expression of HSP70 in normal muscle samples increased significantly (P<0.05) compared with that in the controls after stress. The protein expression of HSP70 increased significantly in normal muscle samples and decreased significantly (P<0.05) in PSE-like muscles. Immuno-fluorescence showed that HSP70 was present in the cytoplasm and on surface membranes of PM muscle cells in the normal samples following stress. Meanwhile, HSP70 was present on the surface membranes and extracellular matrix but was barely visible in the cytoplasm of the PSE-like samples. Principal component analysis showed high correlations between HSP70 and meat quality and stress indicators. In conclusion, this research suggests that the variation in HSP70 expression may provide a novel insight into the pathways underlying meat quality development.

Antibacterial Efficacy of Tender Coconut Water (Cocos nucifera L) on Streptococcus mutans: An In-Vitro Study

PubMed Central

Rukmini, J. N.; Manasa, Sunkari; Rohini, Chenna; Sireesha, Lavanya Putchla; Ritu, Sachan; Umashankar, G. K.

2017-01-01

Objective: The antibacterial property of coconut, the presence of lauric acid, and the ability to extract antimicrobial peptides Cn-AMP (1, 2, and 3) from tender coconut water has drawn attention on its effectiveness in normal consumption. An in-vitro experimental study was conducted to evaluate the antimicrobial efficacy of tender coconut water in its natural state on Streptococcus mutans. Materials and Methods: Fresh tender coconut water and pasteurized tender coconut water were taken as test samples, dimethyl formamide was used as the negative control, and 0.2% chlorhexidine was used as the positive control. Pure strain of S. mutans (MTCC 890) was used for determining the antibacterial effects. The test samples along with the controls were subjected to antimicrobial sensitivity test procedure and the zone of inhibition was examined. Kruskal–Wallis test was used to check for any significant differences in the antibacterial efficacy between the samples. Result: There was no zone of inhibition with the tender coconut water, fresh and pasteurised, and negative control (dimethyl formamide). Zone of inhibition was seen in positive control (0.2% Chlorhexidine). Conclusion: No antimicrobial activity was demonstrated with tender coconut water in its normal state (in vitro). PMID:28462183

Antibacterial Efficacy of Tender Coconut Water (Cocos nucifera L) on Streptococcus mutans: An In-Vitro Study.

PubMed

Rukmini, J N; Manasa, Sunkari; Rohini, Chenna; Sireesha, Lavanya Putchla; Ritu, Sachan; Umashankar, G K

2017-01-01

The antibacterial property of coconut, the presence of lauric acid, and the ability to extract antimicrobial peptides Cn-AMP (1, 2, and 3) from tender coconut water has drawn attention on its effectiveness in normal consumption. An in-vitro experimental study was conducted to evaluate the antimicrobial efficacy of tender coconut water in its natural state on Streptococcus mutans . Fresh tender coconut water and pasteurized tender coconut water were taken as test samples, dimethyl formamide was used as the negative control, and 0.2% chlorhexidine was used as the positive control. Pure strain of S. mutans (MTCC 890) was used for determining the antibacterial effects. The test samples along with the controls were subjected to antimicrobial sensitivity test procedure and the zone of inhibition was examined. Kruskal-Wallis test was used to check for any significant differences in the antibacterial efficacy between the samples. There was no zone of inhibition with the tender coconut water, fresh and pasteurised, and negative control (dimethyl formamide). Zone of inhibition was seen in positive control (0.2% Chlorhexidine). No antimicrobial activity was demonstrated with tender coconut water in its normal state ( in vitro ).

Increased Steady-State Mutant Huntingtin mRNA in Huntington's Disease Brain.

PubMed

Liu, Wanzhao; Chaurette, Joanna; Pfister, Edith L; Kennington, Lori A; Chase, Kathryn O; Bullock, Jocelyn; Vonsattel, Jean Paul G; Faull, Richard L M; Macdonald, Douglas; DiFiglia, Marian; Zamore, Phillip D; Aronin, Neil

2013-01-01

Huntington's disease is caused by expansion of CAG trinucleotide repeats in the first exon of the huntingtin gene, which is essential for both development and neurogenesis. Huntington's disease is autosomal dominant. The normal allele contains 6 to 35 CAG triplets (average, 18) and the mutant, disease-causing allele contains >36 CAG triplets (average, 42). We examined 279 postmortem brain samples, including 148 HD and 131 non-HD controls. A total of 108 samples from 87 HD patients that are heterozygous at SNP rs362307, with a normal allele (18 to 27 CAG repeats) and a mutant allele (39 to 73 CAG repeats) were used to measure relative abundance of mutant and wild-type huntingtin mRNA. We used allele-specific, quantitative RT-PCR based on SNP heterozygosity to estimate the relative amount of mutant versus normal huntingtin mRNA in postmortem brain samples from patients with Huntington's disease. In the cortex and striatum, the amount of mRNA from the mutant allele exceeds that from the normal allele in 75% of patients. In the cerebellum, no significant difference between the two alleles was evident. Brain tissues from non-HD controls show no significant difference between two alleles of huntingtin mRNAs. Allelic differences were more pronounced at early neuropathological grades (grades 1 and 2) than at late grades (grades 3 and 4). More mutant HTT than normal could arise from increased transcription of mutant HTT allele, or decreased clearance of mutant HTT mRNA, or both. An implication is that equimolar silencing of both alleles would increase the mutant HTT to normal HTT ratio.

Vitamin D deficiency and insufficiency among patients with prostate cancer

PubMed Central

Trump, Donald L.; Chadha, Manpreet K.; Sunga, Annette Y.; Fakih, Marwan G.; Ashraf, Umeer; Silliman, Carrie G.; Hollis, Bruce W.; Nesline, Mary K.; Tian, Lili; Tan, Wei; Johnson, Candace S.

2009-01-01

Objective To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. Patients, subjects and methods The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. Results The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (< 20 ng/mL) and insufficiency (20–31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32–100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Conclusions Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region. PMID:19426195

Vitamin D deficiency and insufficiency among patients with prostate cancer.

PubMed

Trump, Donald L; Chadha, Manpreet K; Sunga, Annette Y; Fakih, Marwan G; Ashraf, Umeer; Silliman, Carrie G; Hollis, Bruce W; Nesline, Mary K; Tian, Lili; Tan, Wei; Johnson, Candace S

2009-10-01

To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (<20 ng/mL) and insufficiency (20-31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32-100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.

An analytical approach to reduce between-plate variation in multiplex assays that measure antibodies to Plasmodium falciparum antigens.

PubMed

Fang, Rui; Wey, Andrew; Bobbili, Naveen K; Leke, Rose F G; Taylor, Diane Wallace; Chen, John J

2017-07-17

Antibodies play an important role in immunity to malaria. Recent studies show that antibodies to multiple antigens, as well as, the overall breadth of the response are associated with protection from malaria. Yet, the variability and reliability of antibody measurements against a combination of malarial antigens using multiplex assays have not been well characterized. A normalization procedure for reducing between-plate variation using replicates of pooled positive and negative controls was investigated. Sixty test samples (30 from malaria-positive and 30 malaria-negative individuals), together with five pooled positive-controls and two pooled negative-controls, were screened for antibody levels to 9 malarial antigens, including merozoite antigens (AMA1, EBA175, MSP1, MSP2, MSP3, MSP11, Pf41), sporozoite CSP, and pregnancy-associated VAR2CSA. The antibody levels were measured in triplicate on each of 3 plates, and the experiments were replicated on two different days by the same technician. The performance of the proposed normalization procedure was evaluated with the pooled controls for the test samples on both the linear and natural-log scales. Compared with data on the linear scale, the natural-log transformed data were less skewed and reduced the mean-variance relationship. The proposed normalization procedure using pooled controls on the natural-log scale significantly reduced between-plate variation. For malaria-related research that measure antibodies to multiple antigens with multiplex assays, the natural-log transformation is recommended for data analysis and use of the normalization procedure with multiple pooled controls can improve the precision of antibody measurements.

Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide.

PubMed

Nurliyani; Harmayani, Eni; Sunarti

2015-01-01

The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells.

The Properties of the Massive Star-forming Galaxies with an Outside-in Assembly Mode

NASA Astrophysics Data System (ADS)

Wang, Enci; Kong, Xu; Wang, Huiyuan; Wang, Lixin; Lin, Lin; Gao, Yulong; Liu, Qing

2017-08-01

Previous findings show that massive ({M}* > {10}10 {M}⊙ ) star-forming (SF) galaxies usually have an “inside-out” stellar mass assembly mode. In this paper, we have for the first time selected a sample of 77 massive SF galaxies with an “outside-in” assembly mode (called the “targeted sample”) from the Mapping Nearby Galaxies at the Apache Point Observatory (MaNGA) survey. For comparison, two control samples are constructed from the MaNGA sample matched in stellar mass: a sample of 154 normal SF galaxies and a sample of 62 quiescent galaxies. In contrast to normal SF galaxies, the targeted galaxies appear to be smoother and more bulge-dominated and have a smaller size and higher concentration, star formation rate, and gas-phase metallicity as a whole. However, they have a larger size and lower concentration than quiescent galaxies. Unlike the normal SF sample, the targeted sample exhibits a slightly positive gradient of the 4000 Å break and a pronounced negative gradient of Hα equivalent width. Furthermore, the median surface mass density profile is between those of the normal SF and quiescent samples, indicating that the gas accretion of quiescent galaxies is not likely to be the main approach for the outside-in assembly mode. Our results suggest that the targeted galaxies are likely in the transitional phase from normal SF galaxies to quiescent galaxies, with rapid ongoing central stellar mass assembly (or bulge growth). We discuss several possible formation mechanisms for the outside-in mass assembly mode.

Learning with sublexical information from emerging reading vocabularies in exceptionally early and normal reading development.

PubMed

Thompson, G Brian; Fletcher-Flinn, Claire M; Wilson, Kathryn J; McKay, Michael F; Margrain, Valerie G

2015-03-01

Predictions from theories of the processes of word reading acquisition have rarely been tested against evidence from exceptionally early readers. The theories of Ehri, Share, and Byrne, and an alternative, Knowledge Sources theory, were so tested. The former three theories postulate that full development of context-free letter sounds and awareness of phonemes are required for normal acquisition, while the claim of the alternative is that with or without such, children can use sublexical information from their emerging reading vocabularies to acquire word reading. Results from two independent samples of children aged 3-5, and 5 years, with mean word reading levels of 7 and 9 years respectively, showed underdevelopment of their context-free letter sounds and phoneme awareness, relative to their word reading levels and normal comparison samples. Despite such underdevelopment, these exceptional readers engaged in a form of phonological recoding that enabled pseudoword reading, at the level of older-age normal controls matched on word reading level. Moreover, in the 5-year-old sample further experiments showed that, relative to normal controls, they had a bias toward use of sublexical information from their reading vocabularies for phonological recoding of heterophonic pseudowords with irregular consistent spelling, and were superior in accessing word meanings independently of phonology, although only if the readers were without exposure to explicit phonics. The three theories were less satisfactory than the alternative theory in accounting for the learning of the exceptionally early readers. Copyright © 2014 Elsevier B.V. All rights reserved.

Sexual self-esteem in mothers of normal and mentally-retarded children.

PubMed

Tavakolizadeh, Jahanshir; Amiri, Mostafa; Nejad, Fahimeh Rastgoo

2017-06-01

Sexual self-esteem is negatively influenced by the stressful experiences in lifetime. This study compared the sexual self-esteem and its components in mothers with normal and mentally-retarded children in Qaen city, in 2014. A total of 120 mothers were selected and assigned into two groups of 60 samples based on convenient sampling method and randomized multiple stage sampling. Both groups completed sexual self-esteem questionnaire. The data were analyzed employing t-test through SPSS software version15. The results showed that the rate of sexual self-esteem in mothers of mentally-retarded children decreased significantly compared with that of mothers with normal children (p<0.05). Moreover, the mean scores of all components of sexual self-esteem including skill and experience, attractiveness, control, moral judgment, and adaptiveness in mothers of mentally-retarded children were significantly less than those of mothers with normal children (p <0.05). Therefore, it is recommended that self-esteem, especially the sexual one, be taught to mothers of mentally-retarded children by specialists.

The Power of Exclusion using Automated Osteometric Sorting: Pair-Matching.

PubMed

Lynch, Jeffrey James; Byrd, John; LeGarde, Carrie B

2018-03-01

This study compares the original pair-matching osteometric sorting model (J Forensic Sci 2003;48:717) against two new models providing validation and performance testing across three samples. The samples include the Forensic Data Bank, USS Oklahoma, and the osteometric sorting reference used within the Defense POW/MIA Accounting Agency. A computer science solution to generating dynamic statistical models across a commingled assemblage is presented. The issue of normality is investigated showing the relative robustness against non-normality and a data transformation to control for normality. A case study is provided showing the relative exclusion power of all three models from an active commingled case within the Defense POW/MIA Accounting Agency. In total, 14,357,220 osteometric t-tests were conducted. The results indicate that osteometric sorting performs as expected despite reference samples deviating from normality. The two new models outperform the original, and one of those is recommended to supersede the original for future osteometric sorting work. © 2017 American Academy of Forensic Sciences.

High Rhodotorula sequences in skin transcriptome of patients with diffuse systemic sclerosis

PubMed Central

Arron, Sarah T.; Dimon, Michelle T.; Li, Zhenghui; Johnson, Michael E.; Wood, Tammara; Feeney, Luzviminda; Angeles, Jorge Gil; Lafyatis, Robert; Whitfield, Michael L.

2014-01-01

Previous studies have suggested a role for pathogens as a trigger of systemic sclerosis (SSc), though neither a pathogen nor a mechanism of pathogenesis is known. Here we show enrichment of Rhodotorula sequences in the skin of patients with early, diffuse SSc compared to normal controls. RNA-seq was performed on four SSc and four controls, to a depth of 200 million reads per patient. Data were analyzed to quantify the non-human sequence reads in each sample. We found little difference between bacterial microbiome and viral read counts, but found a significant difference between the read counts for a mycobiome component, R. glutinis. Normal samples contained almost no detected R. glutinis or other Rhodotorula sequence reads (mean score 0.021 for R. glutinis, 0.024 for all Rhodotorula). In contrast, SSc samples had a mean score of 5.039 for R. glutinis (5.232 for Rhodotorula). We were able to assemble the D1–D2 hypervariable region of the 28S rRNA of R. glutinis from each of the SSc samples. Taken together, these results suggest R. glutinis may be present in the skin of early SSc patients at higher levels than normal skin, raising the possibility that it may be triggering the inflammatory response found in SSc. PMID:24608988

High Rhodotorula sequences in skin transcriptome of patients with diffuse systemic sclerosis.

PubMed

Arron, Sarah T; Dimon, Michelle T; Li, Zhenghui; Johnson, Michael E; Wood, Tammara A; Feeney, Luzviminda; Angeles, Jorge G; Lafyatis, Robert; Whitfield, Michael L

2014-08-01

Previous studies have suggested a role for pathogens as a trigger of systemic sclerosis (SSc), although neither a pathogen nor a mechanism of pathogenesis is known. Here we show enrichment of Rhodotorula sequences in the skin of patients with early, diffuse SSc compared with that in normal controls. RNA-seq was performed on four SSc patients and four controls, to a depth of 200 million reads per patient. Data were analyzed to quantify the nonhuman sequence reads in each sample. We found little difference between bacterial microbiome and viral read counts, but found a significant difference between the read counts for a mycobiome component, R. glutinis. Normal samples contained almost no detected R. glutinis or other Rhodotorula sequence reads (mean score 0.021 for R. glutinis, 0.024 for all Rhodotorula). In contrast, SSc samples had a mean score of 5.039 for R. glutinis (5.232 for Rhodotorula). We were able to assemble the D1-D2 hypervariable region of the 28S ribosomal RNA (rRNA) of R. glutinis from each of the SSc samples. Taken together, these results suggest that R. glutinis may be present in the skin of early SSc patients at higher levels than in normal skin, raising the possibility that it may be triggering the inflammatory response found in SSc.

Rarity of the Alzheimer Disease–Protective APP A673T Variant in the United States

PubMed Central

Wang, Li-San; Naj, Adam C.; Graham, Robert R.; Crane, Paul K.; Kunkle, Brian W.; Cruchaga, Carlos; Gonzalez Murcia, Josue D.; Cannon-Albright, Lisa; Baldwin, Clinton T.; Zetterberg, Henrik; Blennow, Kaj; Kukull, Walter A.; Faber, Kelley M.; Schupf, Nicole; Norton, Maria C.; Tschanz, JoAnn T.; Munger, Ronald G.; Corcoran, Christopher D.; Rogaeva, Ekaterina; Lin, Chiao-Feng; Dombroski, Beth A.; Cantwell, Laura B.; Partch, Amanda; Valladares, Otto; Hakonarson, Hakon; St George-Hyslop, Peter; Green, Robert C.; Goate, Alison M.; Foroud, Tatiana M.; Carney, Regina M.; Larson, Eric B.; Behrens, Timothy W.; Kauwe, John S. K.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Mayeux, Richard; Schellenberg, Gerard D.

2015-01-01

IMPORTANCE Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States. OBJECTIVE To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden. DESIGN, SETTING, AND PARTICIPANTS Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific sampling methods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources. MAIN OUTCOMES AND MEASURES Genotypes for the APP A673T variant were determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies). RESULTS The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls. We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673. CONCLUSIONS AND RELEVANCE The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations. PMID:25531812

Discrimination between stages of Alzheimer's disease with subsets of Mini-Mental State Examination items. An analysis of Consortium to Establish a Registry for Alzheimer's Disease data.

PubMed

Fillenbaum, G G; Wilkinson, W E; Welsh, K A; Mohs, R C

1994-09-01

To identify minimal sets of Mini-Mental State Examination (MMSE) items that can distinguish normal control subjects from patients with mild Alzheimer's disease (AD), patients with mild from those with moderate AD, and those with moderate from those with severe AD. Two randomly selected equivalent half samples. Results of logistic regression analysis from data from the first half of the sample were confirmed by receiver operating characteristic curves on the second half. Memory disorders clinics at major medical centers in the United States affiliated with the Consortium to establish a Registry for Alzheimer's Disease (CERAD). White, normal control subjects (n = 412) and patients with AD (n = 621) who met CERAD criteria; nonwhite subjects (n = 165) and persons with missing data (n = 27) were excluded. Three four-item sets of MMSE items that discriminate, respectively, (1) normal controls from patients with mild AD, (2) patients with mild from those with moderate AD, and (3) patients with moderate from those with severe AD. The MMSE items discriminating normal controls from patients with mild AD were day, date, recall of apple, and recall of penny; those discriminating patients with mild from those with moderate AD were month, city, spelling world backward, and county, and those discriminating patients with moderate from those with severe AD were floor of building, repeating the word table, naming watch, and folding paper in half. Performance on the first two four-item sets was comparable with that of the full MMSE; the third set distinguished patients with moderate from those with severe AD better than chance. A minimum set of MMSE items can effectively discriminate normal controls from patients with mild AD and between successive levels of severity of AD. Data apply only to white patients with AD. Performance in minorities, more heterogeneous groups, or normal subjects with questionable cognitive status has not been assessed.

Effects of age and amyloid deposition on Aβ dynamics in the human central nervous system.

PubMed

Huang, Yafei; Potter, Rachel; Sigurdson, Wendy; Santacruz, Anna; Shih, Shirley; Ju, Yo-El; Kasten, Tom; Morris, John C; Mintun, Mark; Duntley, Stephen; Bateman, Randall J

2012-01-01

The amyloid hypothesis predicts that increased production or decreased clearance of β-amyloid (Aβ) leads to amyloidosis, which ultimately culminates in Alzheimer disease (AD). To investigate whether dynamic changes in Aβ levels in the human central nervous system may be altered by aging or by the pathology of AD and thus contribute to the risk of AD. Repeated-measures case-control study. Washington University School of Medicine in St Louis, Missouri. Participants with amyloid deposition, participants without amyloid deposition, and younger normal control participants. In this study, hourly cerebrospinal fluid (CSF) Aβ concentrations were compared with age, status of amyloid deposition, electroencephalography, and video recording data. Linear increases were observed over time in the Aβ levels in CSF samples obtained from the younger normal control participants and the older participants without amyloid deposition, but not from the older participants with amyloid deposition. Significant circadian patterns were observed in the Aβ levels in CSF samples obtained from the younger control participants; however, circadian amplitudes decreased in both older participants without amyloid deposition and older participants with amyloid deposition. Aβ diurnal concentrations were correlated with the amount of sleep but not with the various activities that the participants participated in while awake. A reduction in the linear increase in the Aβ levels in CSF samples that is associated with amyloid deposition and a decreased CSF Aβ diurnal pattern associated with increasing age disrupt the normal physiology of Aβ dynamics and may contribute to AD.

Association of anti-sperm antibodies with chronic prostatitis: A systematic review and meta-analysis.

PubMed

Jiang, Yumei; Cui, Dong; Du, Yuefeng; Lu, Jun; Yang, Lin; Li, Jinmei; Zhang, Jing; Bai, Xiaojing

2016-11-01

Chronic prostatitis is a risk factor for impaired male fertility potential, and anti-sperm antibodies (ASAs) cause the autoimmune disease immune infertility, which has a negative effect on semen parameters. Current studies have investigated the ASA-positive relationship between chronic prostatitis versus normal controls, but have shown inconsistent results. Hence, we systematic searched the PubMed, EMBASE, Science Direct/Elsevier, Medline, and the Cochrane Library up to October 2015 for case-control studies that involved the ASA-positive relationship between chronic prostatitis patients versus normal controls. The meta-analysis was performed with Review Manager and Stata software. After literature search, six studies were identified, including 721 cases of chronic prostatitis and 160 normal controls. Our results illustrated a significant correlation of the ASA-positive relationship between chronic prostatitis patients versus normal controls. The combined odds ratio of the ASA-positive rate in chronic prostatitis patients and normal controls was 3.26 (1.86-5.71). There was also a significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) III versus normal controls, and the combined OR was 2.46 (1.10-5.51). However, there was no significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) II versus normal controls. The present study illustrates that the positive rate of ASAs in chronic prostatitis patients was significantly higher than in the control group, suggesting that chronic prostatitis has a negative effect on male reproductive function. However, studies with larger samples are needed to better illuminate the correlation between ASAs and chronic prostatitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Normalization to specific gravity prior to analysis improves information recovery from high resolution mass spectrometry metabolomic profiles of human urine.

PubMed

Edmands, William M B; Ferrari, Pietro; Scalbert, Augustin

2014-11-04

Extraction of meaningful biological information from urinary metabolomic profiles obtained by liquid-chromatography coupled to mass spectrometry (MS) necessitates the control of unwanted sources of variability associated with large differences in urine sample concentrations. Different methods of normalization either before analysis (preacquisition normalization) through dilution of urine samples to the lowest specific gravity measured by refractometry, or after analysis (postacquisition normalization) to urine volume, specific gravity and median fold change are compared for their capacity to recover lead metabolites for a potential future use as dietary biomarkers. Twenty-four urine samples of 19 subjects from the European Prospective Investigation into Cancer and nutrition (EPIC) cohort were selected based on their high and low/nonconsumption of six polyphenol-rich foods as assessed with a 24 h dietary recall. MS features selected on the basis of minimum discriminant selection criteria were related to each dietary item by means of orthogonal partial least-squares discriminant analysis models. Normalization methods ranked in the following decreasing order when comparing the number of total discriminant MS features recovered to that obtained in the absence of normalization: preacquisition normalization to specific gravity (4.2-fold), postacquisition normalization to specific gravity (2.3-fold), postacquisition median fold change normalization (1.8-fold increase), postacquisition normalization to urinary volume (0.79-fold). A preventative preacquisition normalization based on urine specific gravity was found to be superior to all curative postacquisition normalization methods tested for discovery of MS features discriminant of dietary intake in these urinary metabolomic datasets.

Postural control assessment in students with normal hearing and sensorineural hearing loss.

PubMed

Melo, Renato de Souza; Lemos, Andrea; Macky, Carla Fabiana da Silva Toscano; Raposo, Maria Cristina Falcão; Ferraz, Karla Mônica

2015-01-01

Children with sensorineural hearing loss can present with instabilities in postural control, possibly as a consequence of hypoactivity of their vestibular system due to internal ear injury. To assess postural control stability in students with normal hearing (i.e., listeners) and with sensorineural hearing loss, and to compare data between groups, considering gender and age. This cross-sectional study evaluated the postural control of 96 students, 48 listeners and 48 with sensorineural hearing loss, aged between 7 and 18 years, of both genders, through the Balance Error Scoring Systems scale. This tool assesses postural control in two sensory conditions: stable surface and unstable surface. For statistical data analysis between groups, the Wilcoxon test for paired samples was used. Students with hearing loss showed more instability in postural control than those with normal hearing, with significant differences between groups (stable surface, unstable surface) (p<0.001). Students with sensorineural hearing loss showed greater instability in the postural control compared to normal hearing students of the same gender and age. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Metabolomic Profiling of Extracellular Vesicles and Alternative Normalization Methods Reveal Enriched Metabolites and Strategies to Study Prostate Cancer-Related Changes

PubMed Central

Puhka, Maija; Takatalo, Maarit; Nordberg, Maria-Elisa; Valkonen, Sami; Nandania, Jatin; Aatonen, Maria; Yliperttula, Marjo; Laitinen, Saara; Velagapudi, Vidya; Mirtti, Tuomas; Kallioniemi, Olli; Rannikko, Antti; Siljander, Pia R-M; af Hällström, Taija Maria

2017-01-01

Body fluids are a rich source of extracellular vesicles (EVs), which carry cargo derived from the secreting cells. So far, biomarkers for pathological conditions have been mainly searched from their protein, (mi)RNA, DNA and lipid cargo. Here, we explored the small molecule metabolites from urinary and platelet EVs relative to their matched source samples. As a proof-of-concept study of intra-EV metabolites, we compared alternative normalization methods to profile urinary EVs from prostate cancer patients before and after prostatectomy and from healthy controls. Methods: We employed targeted ultra-performance liquid chromatography-tandem mass spectrometry to profile over 100 metabolites in the isolated EVs, original urine samples and platelets. We determined the enrichment of the metabolites in the EVs and analyzed their subcellular origin, pathways and relevant enzymes or transporters through data base searches. EV- and urine-derived factors and ratios between metabolites were tested for normalization of the metabolomics data. Results: Approximately 1 x 1010 EVs were sufficient for detection of metabolite profiles from EVs. The profiles of the urinary and platelet EVs overlapped with each other and with those of the source materials, but they also contained unique metabolites. The EVs enriched a selection of cytosolic metabolites including members from the nucleotide and spermidine pathways, which linked to a number of EV-resident enzymes or transporters. Analysis of the urinary EVs from the patients indicated that the levels of glucuronate, D-ribose 5-phosphate and isobutyryl-L-carnitine were 2-26-fold lower in all pre-prostatectomy samples compared to the healthy control and post-prostatectomy samples (p < 0.05). These changes were only detected from EVs by normalization to EV-derived factors or with metabolite ratios, and not from the original urine samples. Conclusions: Our results suggest that metabolite analysis of EVs from different samples is feasible using a high-throughput platform and relatively small amount of sample material. With the knowledge about the specific enrichment of metabolites and normalization methods, EV metabolomics could be used to gain novel biomarker data not revealed by the analysis of the original EV source materials. PMID:29109780

[Salivary microbiome in people with obesity: a pilot study].

PubMed

Wu, Y J; Chi, X P; Chen, F; Deng, X L

2018-02-18

To investigate the characterization of the salivary microbiome in people with obesity and the differences in microbial composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight controls. The study was carried out in people with obesity and age- and sex-matched normal weight controls. None of these selected participants had the systemic disease, oral mucosal disease or periodontal disease. Unstimulated saliva samples were collected and oral examination was conducted. DNAs from saliva samples were extracted and sequenced in an Illumina NextSeq 500 platform. Community composition, linear discriminant analysis of taxonomic differences,gene prediction, gene set construction and annotation of gene function were performed. The classified bacterial reads of the samples were 2 630 428 for each sample. A total of 11 phyla, 19 classes, 26 orders, 41 families, 62 genera and 164 species were detected ultimately. All samples had the same predominant phyla (Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria). There were statistical differences between the groups at the class, order, family, genus and species levels. At the class level, Negativicutes and Erysipelotrichia were more abundant in the obesity group, while Flavobacteriia and Bateroidetes dominated in normal weight group (P<0.05). At the species level, 16 showed significant differences in relative abundance among the groups, in which Prevotella melaninogenica,Prevotella salivae,Solobacterium moorei and Atopobium parvulum ware more abundant in the obesity group, whereas Streptococcus sanguinis dominated in normal weight group (P<0.05). The people with obesity had a higher number of salivary microbial genes (P<0.05). We produced statistics on gene prediction and found salivary microbiome of obesity group had a higher number of genes (P < 0.05). Genes associated with the pathways of metabolism and environmental information processing and human diseases were significantly enriched in the saliva samples of people with obesity (P < 0.01). Significant differences were seen in composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight people. We hope to go on further study with larger sample size in the near future.

Using an Animal Group Vigilance Practical Session to Give Learners a "Heads-Up" to Problems in Experimental Design

ERIC Educational Resources Information Center

Rands, Sean A.

2011-01-01

The design of experimental ecological fieldwork is difficult to teach to classes, particularly when protocols for data collection are normally carefully controlled by the class organiser. Normally, reinforcement of the some problems of experimental design such as the avoidance of pseudoreplication and appropriate sampling techniques does not occur…

Smooth quantile normalization.

PubMed

Hicks, Stephanie C; Okrah, Kwame; Paulson, Joseph N; Quackenbush, John; Irizarry, Rafael A; Bravo, Héctor Corrada

2018-04-01

Between-sample normalization is a critical step in genomic data analysis to remove systematic bias and unwanted technical variation in high-throughput data. Global normalization methods are based on the assumption that observed variability in global properties is due to technical reasons and are unrelated to the biology of interest. For example, some methods correct for differences in sequencing read counts by scaling features to have similar median values across samples, but these fail to reduce other forms of unwanted technical variation. Methods such as quantile normalization transform the statistical distributions across samples to be the same and assume global differences in the distribution are induced by only technical variation. However, it remains unclear how to proceed with normalization if these assumptions are violated, for example, if there are global differences in the statistical distributions between biological conditions or groups, and external information, such as negative or control features, is not available. Here, we introduce a generalization of quantile normalization, referred to as smooth quantile normalization (qsmooth), which is based on the assumption that the statistical distribution of each sample should be the same (or have the same distributional shape) within biological groups or conditions, but allowing that they may differ between groups. We illustrate the advantages of our method on several high-throughput datasets with global differences in distributions corresponding to different biological conditions. We also perform a Monte Carlo simulation study to illustrate the bias-variance tradeoff and root mean squared error of qsmooth compared to other global normalization methods. A software implementation is available from https://github.com/stephaniehicks/qsmooth.

A bias in the "mass-normalized" DTT response - An effect of non-linear concentration-response curves for copper and manganese

NASA Astrophysics Data System (ADS)

Charrier, Jessica G.; McFall, Alexander S.; Vu, Kennedy K.-T.; Baroi, James; Olea, Catalina; Hasson, Alam; Anastasio, Cort

2016-11-01

The dithiothreitol (DTT) assay is widely used to measure the oxidative potential of particulate matter. Results are typically presented in mass-normalized units (e.g., pmols DTT lost per minute per microgram PM) to allow for comparison among samples. Use of this unit assumes that the mass-normalized DTT response is constant and independent of the mass concentration of PM added to the DTT assay. However, based on previous work that identified non-linear DTT responses for copper and manganese, this basic assumption (that the mass-normalized DTT response is independent of the concentration of PM added to the assay) should not be true for samples where Cu and Mn contribute significantly to the DTT signal. To test this we measured the DTT response at multiple PM concentrations for eight ambient particulate samples collected at two locations in California. The results confirm that for samples with significant contributions from Cu and Mn, the mass-normalized DTT response can strongly depend on the concentration of PM added to the assay, varying by up to an order of magnitude for PM concentrations between 2 and 34 μg mL-1. This mass dependence confounds useful interpretation of DTT assay data in samples with significant contributions from Cu and Mn, requiring additional quality control steps to check for this bias. To minimize this problem, we discuss two methods to correct the mass-normalized DTT result and we apply those methods to our samples. We find that it is possible to correct the mass-normalized DTT result, although the correction methods have some drawbacks and add uncertainty to DTT analyses. More broadly, other DTT-active species might also have non-linear concentration-responses in the assay and cause a bias. In addition, the same problem of Cu- and Mn-mediated bias in mass-normalized DTT results might affect other measures of acellular redox activity in PM and needs to be addressed.

Investigating the relationship between FMR1 allele length and cognitive ability in children: a subtle effect of the normal allele range on the normal ability range?

PubMed

Loat, C S; Craig, G; Plomin, R; Craig, I W

2006-09-01

The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.

Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma

PubMed Central

Itoiz, María E.; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

2014-01-01

The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Study Design: Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Results: Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. Conclusions: NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes. Key words:Field cancerization, oral squamous cell carcinoma, Nitric Oxide Synthase 2 (NOS2), malignity markers. PMID:24316703

Childrearing Style of Anxiety-Disordered Parents

ERIC Educational Resources Information Center

Lindhout, Ingeborg; Markus, Monica; Hoogendijk, Thea; Borst, Sophie; Maingay, Ragna; Spinhoven, Philip; van Dyck, Richard; Boer, Frits

2006-01-01

This study investigated whether anxiety-disordered (AD) parents differ in their childrearing style from non-disordered parents. A clinical sample of 36 AD parents with children aged 6-18 was compared with a normal control sample of 36 parents. Childrearing was assessed through parent report and child report. The results demonstrated significant…

The Utility of Robust Means in Statistics

ERIC Educational Resources Information Center

Goodwyn, Fara

2012-01-01

Location estimates calculated from heuristic data were examined using traditional and robust statistical methods. The current paper demonstrates the impact outliers have on the sample mean and proposes robust methods to control for outliers in sample data. Traditional methods fail because they rely on the statistical assumptions of normality and…

EEG based topography analysis in string recognition task

NASA Astrophysics Data System (ADS)

Ma, Xiaofei; Huang, Xiaolin; Shen, Yuxiaotong; Qin, Zike; Ge, Yun; Chen, Ying; Ning, Xinbao

2017-03-01

Vision perception and recognition is a complex process, during which different parts of brain are involved depending on the specific modality of the vision target, e.g. face, character, or word. In this study, brain activities in string recognition task compared with idle control state are analyzed through topographies based on multiple measurements, i.e. sample entropy, symbolic sample entropy and normalized rhythm power, extracted from simultaneously collected scalp EEG. Our analyses show that, for most subjects, both symbolic sample entropy and normalized gamma power in string recognition task are significantly higher than those in idle state, especially at locations of P4, O2, T6 and C4. It implies that these regions are highly involved in string recognition task. Since symbolic sample entropy measures complexity, from the perspective of new information generation, and normalized rhythm power reveals the power distributions in frequency domain, complementary information about the underlying dynamics can be provided through the two types of indices.

Identification of Highly Methylated Genes across Various Types of B-Cell Non-Hodgkin Lymphoma

PubMed Central

Bethge, Nicole; Honne, Hilde; Hilden, Vera; Trøen, Gunhild; Eknæs, Mette; Liestøl, Knut; Holte, Harald; Delabie, Jan; Smeland, Erlend B.; Lind, Guro E.

2013-01-01

Epigenetic alterations of gene expression are important in the development of cancer. In this study, we identified genes which are epigenetically altered in major lymphoma types. We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified 233 genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples (n = 480) when compared to normal B cells (n = 5). The top 30 genes were further analyzed by methylation specific PCR (MSP) in 18 lymphoma cell lines. Seven of the genes were methylated in more than 70% of the cell lines and were further subjected to quantitative MSP in 37 B-cell lymphoma patient samples (diffuse large B-cell lymphoma (activated B-cell like and germinal center B-cell like subtypes), follicular lymphoma and Burkitt`s lymphoma) and normal B lymphocytes from 10 healthy donors. The promoters of DSP, FZD8, KCNH2, and PPP1R14A were methylated in 28%, 67%, 22%, and 78% of the 36 tumor samples, respectively, but not in control samples. Validation using a second series of healthy donor controls (n = 42; normal B cells, peripheral blood mononuclear cells, bone marrow, tonsils and follicular hyperplasia) and fresh-frozen lymphoma biopsies (n = 25), confirmed the results. The DNA methylation biomarker panel consisting of DSP, FZD8, KCNH2, and PPP1R14A was positive in 89% (54/61) of all lymphomas. Receiver operating characteristic analysis to determine the discriminative power between lymphoma and healthy control samples showed a c-statistic of 0.96, indicating a possible role for the biomarker panel in monitoring of lymphoma patients. PMID:24260260

Rapid Communication: MiR-92a as a housekeeping gene for analysis of bovine mastitis-related microRNA in milk.

PubMed

Lai, Y C; Fujikawa, T; Ando, T; Kitahara, G; Koiwa, M; Kubota, C; Miura, N

2017-06-01

Our aim was to identify a suitable microRNA housekeeping gene for real-time PCR analysis of bovine mastitis-related microRNA in milk. We identified , , and as housekeeping gene candidates on the basis of previous Solexa sequencing results. Threshold cycle (CT) values for , , and did not differ between milk from control cows and milk from mastitis-affected cows. NormFinder software identified as the most stable single housekeeping gene. We evaluated the suitability of the housekeeping gene candidates by using them to assess expression levels of the inflammation-related gene . Regardless of the housekeeping gene candidates used for normalization, relative expression levels of were significantly higher in mastitis-affected samples than in control samples. However, of all the housekeeping genes and gene combinations investigated, normalization with alone generated the difference in relative expression between mastitis-affected and control samples with the highest significance. These results suggest that is suitable for use as a housekeeping gene for analysis of bovine mastitis-related microRNA in milk.

Copy Number Variations of TBK1 in Australian Patients With Primary Open-Angle Glaucoma

PubMed Central

AWADALLA, MONA S.; FINGERT, JOHN H.; ROOS, BENJAMIN E.; CHEN, SIMON; HOLMES, RICHARD; GRAHAM, STUART L.; CHEHADE, MARK; GALANOPOLOUS, ANNA; RIDGE, BRONWYN; SOUZEAU, EMMANUELLE; ZHOU, TIGER; SIGGS, OWEN M.; HEWITT, ALEX W.; MACKEY, DAVID A.; BURDON, KATHRYN P.; CRAIG, JAMIE E.

2015-01-01

PURPOSE To investigate the presence of TBK1 copy number variations in a large, well-characterized Australian cohort of patients with glaucoma comprising both normal-tension glaucoma and high-tension glaucoma cases. DESIGN A retrospective cohort study. METHODS DNA samples from patients with normal-tension glaucoma and high-tension glaucoma and unaffected controls were screened for TBK1 copy number variations using real-time quantitative polymerase chain reaction. Samples with additional copies of the TBK1 gene were further tested using custom comparative genomic hybridization arrays. RESULTS Four out of 334 normal-tension glaucoma cases (1.2%) were found to carry TBK1 copy number variations using quantitative polymerase chain reaction. One extra dose of the TBK1 gene (duplication) was detected in 3 normal-tension glaucoma patients, while 2 extra doses of the gene (triplication) were detected in a fourth normal-tension glaucoma patient. The results were further confirmed by custom comparative genomic hybridization arrays. Further, the TBK1 copy number variation segregated with normal-tension glaucoma in the family members of the probands, showing an autosomal dominant pattern of inheritance. No TBK1 copy number variations were detected in 1045 Australian patients with high-tension glaucoma or in 254 unaffected controls. CONCLUSION We report the presence of TBK1 copy number variations in our Australian normal-tension glaucoma cohort, including the first example of more than 1 extra copy of this gene in glaucoma patients (gene triplication). These results confirm TBK1 to be an important cause of normal-tension glaucoma, but do not suggest common involvement in high-tension glaucoma. PMID:25284765

IgG subclass alterations in adult asthma.

PubMed

Outschoorn, I M; Natta, C L

1992-01-01

Immunoglobulin levels were measured in serum samples of 12 black adult non-smoking asthmatic patients, 11 females and 1 male, and compared with 15 age-, sex-matched normal controls. Their total IgG, IgA and IgM levels were within the normal range. However, on quantitation of subclasses, IgG1 levels were significantly above normal, while IgG2 and IgG3 levels were significantly lower than those of controls. No significant differences were found between the two groups when IgG4 levels were compared. These studies as well as those of others suggest that immunoglobulin administration, particularly of individual subclasses, might prove to be a beneficial addition in the management of this condition.

Nitric Oxide, Inflammation, Lipid Profile, and Cortisol in Normal- and Overweight Women With Fibromyalgia.

PubMed

Rus, Alma; Molina, Francisco; Gassó, Manuela; Camacho, Maria Victoria; Peinado, Maria Ángeles; del Moral, Maria Luisa

2016-03-01

Research has identified many factors associated with fibromyalgia (FM), but findings have been inconsistent. This study aimed to investigate changes in levels of nitric oxide (NO), inflammatory markers, lipid profile, and cortisol in normal- and overweight patients with FM and controls. Since most patients with FM are overweight, we explored possible changes in these markers according to body mass index (BMI). This preliminary study was performed on serum samples of women with FM and age-matched controls, grouped according to their BMI: 12 normal-weight patients and 12 controls and 13 overweight patients and 8 controls. Ozone-based chemiluminescence assay was used to measure NO. Inflammatory mediators and cortisol were determined by immunoassay. Lipid profile was measured by a spectrophotometric procedure. Functional capacity was assessed by the fibromyalgia impact questionnaire (FIQ). Normal-weight patients showed higher levels of C-reactive protein (CRP) and apolipoprotein B compared to controls (both p < .05). CRP, apolipoprotein B, and triglycerides were higher in overweight patients versus overweight controls (all p < .05) and in overweight versus normal-weight patients (CRP p < .01; apolipoprotein B, triglycerides p < .05). The other markers were unaffected. Apolipoprotein B (r = .762; p < .05) and NO (r = -.921; p < .05) levels correlated with FIQ score in normal-weight patients. CRP level correlated with FIQ (r = .912; p < .05) in overweight patients. CRP and apolipoprotein B, biomarkers linked to cardiovascular events, may be associated with FM-related dysfunction in normal- and overweight women with FM. Their increased levels in these patients may indicate an increased risk of cardiovascular disease. © The Author(s) 2015.

Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide

PubMed Central

Harmayani, Eni; Sunarti

2015-01-01

The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells. PMID:26877646

Formation of a xerogel in reduced gravity using the acid catalysed silica sol-gel reaction

NASA Astrophysics Data System (ADS)

Pienaar, Christine L.; Steinberg, Theodore A.

2006-01-01

An acid catalysed silica sol-gel reaction was used to create a xerogel in reduced gravity. Samples were formed in a special apparatus which utilised vacuum and heating to speed up the gelation process. Testing was conducted aboard NASA's KC-135 aircraft which flies a parabolic trajectory, producing a series of 25 second reduced gravity periods. The samples formed in reduced gravity were compared against a control sample formed in normal gravity. 29Si NMR and nitrogen adsorption/desorption techniques yielded information on the molecular and physical structure of the xerogels. The microstructure of the reduced gravity samples contained more Q 4 groups and less Q 3 and Q2 groups than the control sample. The pore size of the reduced gravity samples was also larger than the control sample. This indicated that in a reduced gravity environment, where convection is lessened due to the removal of buoyancy forces, the microstructure formed through cyclisation reactions rather than bimolecularisation reactions. The latter requires the movement of molecules for reactions to occur whereas cyclisation only requires a favourable configuration. Q 4 groups are stabilised when contained in a ring structure and are unlikely to undergo repolymerisation. Thus reduced gravity favoured the formation of a xerogel through cyclisation, producing a structure with more highly coordinated Q groups. The xerogel formed in normal gravity contained both chain and ring structures as bimolecularisation reactions were able to effectively compete with cyclisation.

Differentiating oral lesions in different carcinogenesis stages with optical coherence tomography

NASA Astrophysics Data System (ADS)

Tsai, Meng-Tsan; Lee, Cheng-Kuang; Lee, Hsiang-Chieh; Chen, Hsin-Ming; Chiang, Chun-Pin; Wang, Yih-Ming; Yang, Chih-Chung

2009-07-01

A swept-source optical coherence tomography (SS-OCT) system is used to clinically scan oral lesions in different oral carcinogenesis stages, including normal oral mucosa control, mild dysplasia (MiD), moderate dysplasia (MoD), early-stage squamous cell carcinoma (ES-SCC), and well-developed SCC (WD-SCC), for diagnosis purpose. On the basis of the analyses of the SS-OCT images, the stages of dysplasia (MiD and MoD), and SCC (ES-SCC and WD-SCC) can be differentiated from normal control by evaluating the depth-dependent standard deviation (SD) values of lateral variations. In the dysplasia stage, the boundary between the epithelium (EP) and lamina propria (LP) layers can still be identified and the EP layer becomes significantly thicker than that of normal control. Also, in a certain range of the EP layer above the EP/LP boundary, the SD value becomes larger than a certain percentage of the maximum level, which is observed around the EP/LP boundary. On the other hand, in the ES-SCC and WD-SCC stages, the EP/LP boundary disappears. Because of the higher density of connective tissue papillae in the ES-SCC stage, the SD values of the slowly varying lateral scan profiles in the ES-SCC samples are significantly larger than those in the WD-SCC sample. Also, ES-SCC can be differentiated from WD-SCC by comparing the exponential decay constants of averaged A-mode scan profiles. Because of the higher tissue absorption in the WD-SCC lesion, the decay constants in the WD-SCC samples are significantly higher than those in the ES-SCC samples.

Tissue-aware RNA-Seq processing and normalization for heterogeneous and sparse data.

PubMed

Paulson, Joseph N; Chen, Cho-Yi; Lopes-Ramos, Camila M; Kuijjer, Marieke L; Platig, John; Sonawane, Abhijeet R; Fagny, Maud; Glass, Kimberly; Quackenbush, John

2017-10-03

Although ultrahigh-throughput RNA-Sequencing has become the dominant technology for genome-wide transcriptional profiling, the vast majority of RNA-Seq studies typically profile only tens of samples, and most analytical pipelines are optimized for these smaller studies. However, projects are generating ever-larger data sets comprising RNA-Seq data from hundreds or thousands of samples, often collected at multiple centers and from diverse tissues. These complex data sets present significant analytical challenges due to batch and tissue effects, but provide the opportunity to revisit the assumptions and methods that we use to preprocess, normalize, and filter RNA-Seq data - critical first steps for any subsequent analysis. We find that analysis of large RNA-Seq data sets requires both careful quality control and the need to account for sparsity due to the heterogeneity intrinsic in multi-group studies. We developed Yet Another RNA Normalization software pipeline (YARN), that includes quality control and preprocessing, gene filtering, and normalization steps designed to facilitate downstream analysis of large, heterogeneous RNA-Seq data sets and we demonstrate its use with data from the Genotype-Tissue Expression (GTEx) project. An R package instantiating YARN is available at http://bioconductor.org/packages/yarn .

Plasma homovanillic acid in the prodromal phase of schizophrenia.

PubMed

Sumiyoshi, T; Kurachi, M; Kurokawa, K; Yotsutsuji, T; Uehara, T; Itoh, H; Saitoh, O

2000-03-01

Plasma levels of homovanillic acid (pHVA) have been used as a peripheral measure of central dopaminergic activity. Despite a large body of studies investigating pHVA in schizophrenia, little is known about pHVA in patients in the prodromal phase of the illness. Plasma HVA levels of 12 male outpatients meeting DSM-III-R criteria for the prodromal phase of schizophrenia at the time of blood sampling (who later developed psychotic symptoms) were compared with those of 12 normal male healthy volunteers. Task amounts in the Kraepelin arithmetic test at the time of blood sampling were compared between the prodromal patients and normal controls and were correlated with pHVA levels. The prodromal patients had significantly higher pHVA levels compared with normal control subjects. The mean amount of the arithmetic task for the prodromal patients was significantly less than that for controls. In the patient group, a significant negative correlation was observed between pHVA levels and the task amounts. Data from the present study indicate the presence of dopaminergic dysfunction in the prodromal stage of schizophrenia that is associated with neuropsychological impairment. Increased pHVA levels in the prodromal patients may have implications for early detection of schizophrenia.

[A semimicroquality evaluation method on Panax notoginseng and its application in analysis of continuous cropping obstacles research samples].

PubMed

Cao, Yi; Wang, Chao-Qun; Xu, Feng; Jia, Xiu-Hong; Liu, Guang-Xue; Yang, Sheng-Chao; Long, Guang-Qiang; Chen, Zhong-Jian; Wei, Fu-Zhou; Yang, Shao-Zhou; Fukuda, Kozo; Wang, Xuan; Cai, Shao-Qing

2016-10-01

Panax notoginseng is a commonly used traditional Chinese medicine with blood activating effect while has continuous cropping obstacle problem in planting process. In present study, a semimicroextraction method with water-saturated n-butanol on 0.1 g notoginseng sample was established with good repeatability (RSD<2.5%) and 9.6%-20.6% higher extraction efficiency of seven saponins than the conventional method. A total of 16 characteristic peaks were identified by LC-MS-IT-TOF, including eight 20(S)-protopanaxatriol (PPT) type saponins and eight 20(S)-protopanaxadiol (PPD) type saponins. The established method was utilized to evaluate the quality of notoginseng samples cultivated by manual intervened methods to overcome continuous cropping obstacles.As a result, HPLC fingerprint similarity, content of Fa and ratio of notoginsenoside K and notoginsenoside Fa (N-K/Fa) were found out to be as valuatable markers of the quality of samples in continuous cropping obstacle research, of which N-K/Fa could also be applied to the analysis of notoginseng samples with different growth years.Notoginseng samples with continuous cropping obstacle had HPLC fingerprint similarity lower than 0.87, in consistent with normal sample, and had significant lower content of notoginsenoside Fa and significant higher N-K/Fa (2.35-4.74) than normal group (0.45-1.33). All samples in the first group with manual intervention showed high similarity with normal group (>0.87), similar content of common peaks and N-K/Fa (0.42-2.06). The content of notoginsenoside K in the second group with manual intervention was higher than normal group. All samples except two displayed similarity higher than 0.87 and possessed content of 16 saponins close to normal group. The result showed that notoginseng samples with continuous cropping obstacle had lower quality than normal sample. And manual intervened methods could improve their quality in different levels.The method established in this study was simple, fast and accurate, and the markers may provide new guides for quality control in continuous cropping obstacle research of notoginseng. Copyright© by the Chinese Pharmaceutical Association.

Diagnostic Performance and Utility of Quantitative EEG Analyses in Delirium: Confirmatory Results From a Large Retrospective Case-Control Study.

PubMed

Fleischmann, Robert; Tränkner, Steffi; Bathe-Peters, Rouven; Rönnefarth, Maria; Schmidt, Sein; Schreiber, Stephan J; Brandt, Stephan A

2018-03-01

The lack of objective disease markers is a major cause of misdiagnosis and nonstandardized approaches in delirium. Recent studies conducted in well-selected patients and confined study environments suggest that quantitative electroencephalography (qEEG) can provide such markers. We hypothesize that qEEG helps remedy diagnostic uncertainty not only in well-defined study cohorts but also in a heterogeneous hospital population. In this retrospective case-control study, EEG power spectra of delirious patients and age-/gender-matched controls (n = 31 and n = 345, respectively) were fitted in a linear model to test their performance as binary classifiers. We subsequently evaluated the diagnostic performance of the best classifiers in control samples with normal EEGs (n = 534) and real-world samples including pathologic findings (n = 4294). Test reliability was estimated through split-half analyses. We found that the combination of spectral power at F3-P4 at 2 Hz (area under the curve [AUC] = .994) and C3-O1 at 19 Hz (AUC = .993) provided a sensitivity of 100% and a specificity of 99% to identify delirious patients among normal controls. These classifiers also yielded a false positive rate as low as 5% and increased the pretest probability of being delirious by 57% in an unselected real-world sample. Split-half reliabilities were .98 and .99, respectively. This retrospective study yielded preliminary evidence that qEEG provides excellent diagnostic performance to identify delirious patients even outside confined study environments. It furthermore revealed reduced beta power as a novel specific finding in delirium and that a normal EEG excludes delirium. Prospective studies including parameters of pretest probability and delirium severity are required to elaborate on these promising findings.

Obesity and risk taking. A male phenomenon.

PubMed

Koritzky, Gilly; Yechiam, Eldad; Bukay, Irit; Milman, Uzi

2012-10-01

There is a growing tendency to regard overeating as an addiction, with obesity as its primary symptom. We propose that similar to other addictions, obesity is associated with excessive risk-taking in men, though not in women. To examine this suggestion we conducted two studies, one involving a sample of overweight and normal-weight students, and the other involving obese adults drawn from a dataset of health care clients, and a control sample of normal-weight adults. In both of these studies, we found that overweight and obese men took more risk in a laboratory task than normal-weight men, while overweight and obese women did not differ from normal-weight women in this respect. At the same time, obese women (but not overweight women) displayed higher impulsivity levels than normal-weight women. These findings shed light on the cognitive characteristics of obesity in men, and accent the importance of taking gender into account when developing research paradigms and treatment methods for obesity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sample entropy analysis of cervical neoplasia gene-expression signatures

PubMed Central

Botting, Shaleen K; Trzeciakowski, Jerome P; Benoit, Michelle F; Salama, Salama A; Diaz-Arrastia, Concepcion R

2009-01-01

Background We introduce Approximate Entropy as a mathematical method of analysis for microarray data. Approximate entropy is applied here as a method to classify the complex gene expression patterns resultant of a clinical sample set. Since Entropy is a measure of disorder in a system, we believe that by choosing genes which display minimum entropy in normal controls and maximum entropy in the cancerous sample set we will be able to distinguish those genes which display the greatest variability in the cancerous set. Here we describe a method of utilizing Approximate Sample Entropy (ApSE) analysis to identify genes of interest with the highest probability of producing an accurate, predictive, classification model from our data set. Results In the development of a diagnostic gene-expression profile for cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the cervix, we identified 208 genes which are unchanging in all normal tissue samples, yet exhibit a random pattern indicative of the genetic instability and heterogeneity of malignant cells. This may be measured in terms of the ApSE when compared to normal tissue. We have validated 10 of these genes on 10 Normal and 20 cancer and CIN3 samples. We report that the predictive value of the sample entropy calculation for these 10 genes of interest is promising (75% sensitivity, 80% specificity for prediction of cervical cancer over CIN3). Conclusion The success of the Approximate Sample Entropy approach in discerning alterations in complexity from biological system with such relatively small sample set, and extracting biologically relevant genes of interest hold great promise. PMID:19232110

Urinary Virome Perturbations in Kidney Transplantation.

PubMed

Sigdel, Tara K; Mercer, Neil; Nandoe, Sharvin; Nicora, Carrie D; Burnum-Johnson, Kristin; Qian, Wei-Jun; Sarwal, Minnie M

2018-01-01

The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.

An enzyme-linked immunosorbent assay for the evaluation of thrombocytopenia induced by heparin.

PubMed

Howe, S E; Lynch, D M

1985-05-01

Five patients with heparin-associated thrombocytopenia (HAT) were evaluated by platelet aggregation and quantitation of immunoglobulin binding to intact target platelets in both the presence and absence of heparin. These patients developed thrombocytopenia (12,000 to 70,000 platelets/microliter) 7 to 15 days and embolic and hemorrhagic complications 9 to 15 days after the initiation of heparin therapy. Platelet aggregation after the addition of heparin was demonstrated in two of four HAT serum samples, whereas normal serum samples showed no significant platelet aggregation. The five HAT serum samples showed normal to elevated baseline serum platelet-bindable immunoglobulin (SPBIg) with a range of 4.3 to 11.4 fg/platelet (normal less than or equal to 1.0 to 6.5 fg/platelet). When HAT sera were incubated with target platelets and heparin (5 U/ml), the SPBIg increased to 8.5 to 37.5 fg/platelet, a mean increase of 148% in the presence of heparin. Normal and control serum samples (from 10 normal laboratory volunteers, nine patients without thrombocytopenia receiving heparin, nine patients with autoimmune thrombocytopenic purpura, and nine patients with nonimmune thrombocytopenia not receiving heparin) showed only a slight increase in SPBIg of 0 to 2.8 fg/platelet above baseline, a mean increase of 15% after heparin incubation with the serum samples. The measurement of SPBIg of washed platelets incubated with test serum samples in the presence and absence of heparin is potentially a specific and sensitive in vitro test for the diagnosis of HAT and may prove more sensitive than platelet aggregation studies with heparin.

Detection of septicemia in chicken livers by spectroscopy,.

PubMed

Dey, B P; Chen, Y R; Hsieh, C; Chan, D E

2003-02-01

To establish a procedure for differentiating normal chickens from chickens with septicemia/toxemia (septox) by machine inspection under the Hazard Analysis and Critical Control Point-Based Inspection Models Project, spectral measurements of 300 chicken livers, of which half were normal and half were condemned due to septox conditions, were collected and analyzed. Neural network classification of the spectral data after principal component analysis (PCA) indicated that normal and septox livers were correctly differentiated by spectroscopy at a rate of 96%. Analysis of the data established 100% correlation between the spectroscopic identification and the subset of samples, both normal and septox, that were histopathologically diagnosed. In an attempt to establish the microbiological etiology of the diseased livers, isolates from 30 livers indicated that the poultry carcasses were contaminated mostly with coliforms present in the environment, hindering the isolation of pathogenic microorganisms. Therefore, to establish the cause of diseased livers, a strictly aseptic environment and procedure for sample collection is required.

Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene.

PubMed

Surendran, S; Sacksteder, K A; Gould, S J; Coldwell, J G; Rady, P L; Tyring, S K; Matalon, R

2001-09-15

Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a -5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency. Copyright 2001 Wiley-Liss, Inc.

Is Season of Birth Related to Developmental Dyslexia?

ERIC Educational Resources Information Center

Donfrancesco, Renato; Iozzino, Roberto; Caruso, Barbara; Ferrante, Laura; Mugnaini, Daniele; Talamo, Alessandra; Miano, Silvia; Dimitri, Andrea; Masi, Gabriele

2010-01-01

Different moderators/mediators of risk are involved in developmental dyslexia (DD), but data are inconsistent. We explored the prevalence of season of birth and its association with gender and age of school entry in an Italian sample of dyslexic children compared to an Italian normal control group. The clinical sample included 498 children (345…

Epstein-Barr Virus and Gastric Cancer Risk: A Meta-analysis With Meta-regression of Case-control Studies.

PubMed

Bae, Jong-Myon; Kim, Eun Hee

2016-03-01

Research on how the risk of gastric cancer increases with Epstein-Barr virus (EBV) infection is lacking. In a systematic review that investigated studies published until September 2014, the authors did not calculate the summary odds ratio (SOR) due to heterogeneity across studies. Therefore, we include here additional studies published until October 2015 and conduct a meta-analysis with meta-regression that controls for the heterogeneity among studies. Using the studies selected in the previously published systematic review, we formulated lists of references, cited articles, and related articles provided by PubMed. From the lists, only case-control studies that detected EBV in tissue samples were selected. In order to control for the heterogeneity among studies, subgroup analysis and meta-regression were performed. In the 33 case-control results with adjacent non-cancer tissue, the total number of test samples in the case and control groups was 5280 and 4962, respectively. In the 14 case-control results with normal tissue, the total number of test samples in case and control groups was 1393 and 945, respectively. Upon meta-regression, the type of control tissue was found to be a statistically significant variable with regard to heterogeneity. When the control tissue was normal tissue of healthy individuals, the SOR was 3.41 (95% CI, 1.78 to 6.51; I-squared, 65.5%). The results of the present study support the argument that EBV infection increases the risk of gastric cancer. In the future, age-matched and sex-matched case-control studies should be conducted.

Evaluation of the repeatability of a crude adult indirect Ostertagia ostertagi ELISA and methods of expressing test results.

PubMed

Sanchez, J; Dohoo, I R; Markham, F; Leslie, K; Conboy, G

2002-10-16

An indirect enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against Ostertagia ostertagi using a crude adult worm antigen was evaluated using serum and milk samples from adult cows, as well as from bulk tank milk. Within and between plate repeatabilities were determined. In addition, the effects of factors such as antigen batch, freezing, preserving of the samples and somatic cell counts (SCCs) of the samples were evaluated. Raw optical densities (ODs) and normalized values were compared using the concordance correlation coefficient (CCC), the coefficient of variation (CV), Bland-Altman plots (BA). Based on raw OD values, there was a high repeatability within a plate (CCC approximately 0.96 and CV<10%). Repeatability between plates was evaluated following normalization of OD values by four methods. Computing normalized values as (OD-Nt)/(Pst-Nt), gave the most repeatable results, with the CCC being approximately 0.95 and the CV approximately 11%. When the OD values were higher than 1.2 and 0.3 for the positive and the negative controls, respectively, none of the normalization methods evaluated provided highly repeatable results and it was necessary to repeat the test. Two batches of the crude antigen preparation were evaluated for repeatability, and no difference was found (CCC=0.96). The use of preservative (bronopol) did not affect test results, nor did freezing the samples for up to 8 months. A significant positive relationship between ELISA OD for milk samples and SCC score was found. Therefore, the use of composite milk samples, which have less variable SCC than samples taken from each quarter, would be more suitable when the udder health status is unknown. The analytical methods used to evaluate repeatability provided a practical way to select among normalization procedures.

Bioassay of procoagulant albumin in human plasma.

PubMed

Grosset, A; Liu, L; Parker, C J; Rodgers, G M

1994-09-01

Procoagulant albumin (P-Al) is present in normal human plasma and increases monocyte and endothelial cell expression of tissue factor activity. To develop a bioassay for P-Al, we partially purified plasma from healthy volunteers and several patient groups using BaCl2 and (NH4)2SO4 precipitation. The samples were assayed for tissue factor (TF) inducing activity, expressed as a percentage increase compared to a serum-free media control. Over six months, the assay was reproducible in stored samples and in serial samples from normal volunteers. The plasma P-Al activities of 35 volunteers averaged 141 +/- 8.2% (SEM). There was no diurnal variation. There was no difference in the P-Al activity after a 12 hour fast and 2 hours after a large meal in 4 healthy volunteers. There was no increase in activity (r = 0.16) with the subject's age. The average activity from 16 poorly-controlled diabetics was 131 +/- 11% (SEM). No alteration in activity was seen with samples from patients with uremia, liver dysfunction, hemophilia, thrombotic events, or adenocarcinoma. These results indicate that P-Al activity can be bioassayed in individual patient samples; however, pathologic states associated with abnormal P-Al-induced tissue factor activity presently remain unidentified.

Psychometric characteristics in normal and social phobic samples for a Spanish version of the Rosenberg Self-Esteem Scale.

PubMed

Baños, R M; Guillén, V

2000-08-01

The present paper had three purposes: (a) presenting normative data for the Rosenberg Self-esteem Scale in a Spanish sample, (b) studying whether there are significant sex or age differences in self-esteem, and (c) studying whether there are significant differences between a Control group with no psychological diagnosis and a group of social phobics. Of the total sample of 266 persons, 214 belonged to the Control group and 52 to the Social Phobic group. Item-total score correlations and alpha reliabilities supported the internal consistency of the scale. There were statistically significant differences between the Control and Social Phobic groups, but not by sex or age.

Pregnancy rates after artificial insemination with cooled stallion spermatozoa either with or without single layer centrifugation.

PubMed

Morrell, J M; Richter, J; Martinsson, G; Stuhtmann, G; Hoogewijs, M; Roels, K; Dalin, A-M

2014-11-01

A successful outcome after artificial insemination with cooled semen is dependent on many factors, the sperm quality of the ejaculate being one. Previous studies have shown that spermatozoa with good motility, normal morphology, and good chromatin integrity can be selected by means of colloid centrifugation, particularly single layer centrifugation (SLC) using species-specific colloids. The purpose of the present study was to conduct an insemination trial with spermatozoa from "normal" ejaculates, i.e., from stallions with no known fertility problem, to determine whether the improvements in sperm quality seen in SLC-selected sperm samples compared with uncentrifuged controls in laboratory tests are reflected in an increased pregnancy rate after artificial insemination. In a multicentre study, SLC-selected sperm samples and uncentrifuged controls from eight stallions were inseminated into approximately 10 mares per treatment per stallion. Ultrasound examination was carried out approximately 16 days after insemination to detect an embryonic vesicle. The pregnancy rates per cycle were 45% for controls and 69% for SLC-selected sperm samples, which is statistically significant (P < 0.0018). Thus, the improvement in sperm quality reported previously for SLC-selected sperm samples is associated with an increase in pregnancy rate, even for ejaculates from stallions with no known fertility problem. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparing the Effects of Particulate Matter on the Ocular Surfaces of Normal Eyes and a Dry Eye Rat Model.

PubMed

Han, Ji Yun; Kang, Boram; Eom, Youngsub; Kim, Hyo Myung; Song, Jong Suk

2017-05-01

To compare the effect of exposure to particulate matter on the ocular surface of normal and experimental dry eye (EDE) rat models. Titanium dioxide (TiO2) nanoparticles were used as the particulate matter. Rats were divided into 4 groups: normal control group, TiO2 challenge group of the normal model, EDE control group, and TiO2 challenge group of the EDE model. After 24 hours, corneal clarity was compared and tear samples were collected for quantification of lactate dehydrogenase, MUC5AC, and tumor necrosis factor-α concentrations. The periorbital tissues were used to evaluate the inflammatory cell infiltration and detect apoptotic cells. The corneal clarity score was greater in the EDE model than in the normal model. The score increased after TiO2 challenge in each group compared with each control group (normal control vs. TiO2 challenge group, 0.0 ± 0.0 vs. 0.8 ± 0.6, P = 0.024; EDE control vs. TiO2 challenge group, 2.2 ± 0.6 vs. 3.8 ± 0.4, P = 0.026). The tear lactate dehydrogenase level and inflammatory cell infiltration on the ocular surface were higher in the EDE model than in the normal model. These measurements increased significantly in both normal and EDE models after TiO2 challenge. The tumor necrosis factor-α levels and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were also higher in the EDE model than in the normal model. TiO2 nanoparticle exposure on the ocular surface had a more prominent effect in the EDE model than it did in the normal model. The ocular surface of dry eyes seems to be more vulnerable to fine dust of air pollution than that of normal eyes.

Eating Disorder Inventory-3, validation in Swedish patients with eating disorders, psychiatric outpatients and a normal control sample.

PubMed

Nyman-Carlsson, Erika; Engström, Ingemar; Norring, Claes; Nevonen, Lauri

2015-02-01

The Eating Disorder Inventory-3 (EDI-3) is designed to assess eating disorder psychopathology and the associated psychological symptoms. The instrument has been revised and has not yet been validated for Swedish conditions in its current form. The aim of this study was to investigate the validity and reliability of this inventory and present national norms for Swedish females. Data from patients with eating disorders (n = 292), psychiatric outpatients (n = 140) and normal controls (n = 648), all females, were used to study the internal consistency, the discriminative ability, and the sensitivity and specificity of the inventory using preliminary cut-offs for each subscale and diagnosis separately. Swedish norms were compared with those from Denmark, USA, Canada, Europe and Australian samples. The reliability was acceptable for all subscales except Asceticism among normal controls. Analysis of variance showed that the EDI-3 discriminates significantly between eating disorders and normal controls. Anorexia nervosa was significantly discriminated from bulimia nervosa and eating disorder not otherwise specified on the Eating Disorder Risk Scales. Swedish patients scored significantly lower than patients from other countries on the majority of the subscales. Drive for Thinness is the second best predictor for an eating disorder. The best predictor for anorexia nervosa was Interoceptive Deficits and Bulimia for the other diagnoses. Conclusions/clinical implications: The EDI-3 is valid for use with Swedish patients as a clinical assessment tool for the treatment planning and evaluation of patients with eating-related problems. However, it still exist some uncertainty regarding its use as a screening tool.

Evaluation of endogenous control genes for gene expression studies across multiple tissues and in the specific sets of fat- and muscle-type samples of the pig.

PubMed

Gu, Y R; Li, M Z; Zhang, K; Chen, L; Jiang, A A; Wang, J Y; Li, X W

2011-08-01

To normalize a set of quantitative real-time PCR (q-PCR) data, it is essential to determine an optimal number/set of housekeeping genes, as the abundance of housekeeping genes can vary across tissues or cells during different developmental stages, or even under certain environmental conditions. In this study, of the 20 commonly used endogenous control genes, 13, 18 and 17 genes exhibited credible stability in 56 different tissues, 10 types of adipose tissue and five types of muscle tissue, respectively. Our analysis clearly showed that three optimal housekeeping genes are adequate for an accurate normalization, which correlated well with the theoretical optimal number (r ≥ 0.94). In terms of economical and experimental feasibility, we recommend the use of the three most stable housekeeping genes for calculating the normalization factor. Based on our results, the three most stable housekeeping genes in all analysed samples (TOP2B, HSPCB and YWHAZ) are recommended for accurate normalization of q-PCR data. We also suggest that two different sets of housekeeping genes are appropriate for 10 types of adipose tissue (the HSPCB, ALDOA and GAPDH genes) and five types of muscle tissue (the TOP2B, HSPCB and YWHAZ genes), respectively. Our report will serve as a valuable reference for other studies aimed at measuring tissue-specific mRNA abundance in porcine samples. © 2011 Blackwell Verlag GmbH.

Optimal consistency in microRNA expression analysis using reference-gene-based normalization.

PubMed

Wang, Xi; Gardiner, Erin J; Cairns, Murray J

2015-05-01

Normalization of high-throughput molecular expression profiles secures differential expression analysis between samples of different phenotypes or biological conditions, and facilitates comparison between experimental batches. While the same general principles apply to microRNA (miRNA) normalization, there is mounting evidence that global shifts in their expression patterns occur in specific circumstances, which pose a challenge for normalizing miRNA expression data. As an alternative to global normalization, which has the propensity to flatten large trends, normalization against constitutively expressed reference genes presents an advantage through their relative independence. Here we investigated the performance of reference-gene-based (RGB) normalization for differential miRNA expression analysis of microarray expression data, and compared the results with other normalization methods, including: quantile, variance stabilization, robust spline, simple scaling, rank invariant, and Loess regression. The comparative analyses were executed using miRNA expression in tissue samples derived from subjects with schizophrenia and non-psychiatric controls. We proposed a consistency criterion for evaluating methods by examining the overlapping of differentially expressed miRNAs detected using different partitions of the whole data. Based on this criterion, we found that RGB normalization generally outperformed global normalization methods. Thus we recommend the application of RGB normalization for miRNA expression data sets, and believe that this will yield a more consistent and useful readout of differentially expressed miRNAs, particularly in biological conditions characterized by large shifts in miRNA expression.

Expression and clinicopathological significance of microRNA-21 and programmed cell death 4 in malignant melanoma.

PubMed

Jiao, Jian; Fan, Yu; Zhang, Yan

2015-10-01

To measure levels of microRNA (miR)-21 and its target gene, programmed cell death 4 (PDCD4), in samples of human cutaneous malignant melanoma and normal non-malignant control skin. Relative levels of miR-21 and PDCD4 mRNA were measured using a quantitative real-time reverse transcription-polymerase chain reaction. Correlations between the levels of the two molecules and the clinicopathological characteristics of malignant melanoma were analysed. A total of 67 cases of human cutaneous malignant melanoma were analysed and compared with 67 samples of normal nonmalignant control skin. Compared with normal skin samples, the relative level of miR-21 was significantly higher and the relative level of PDCD4 mRNA was significantly lower in the melanoma specimens. A significant negative correlation between PDCD4 mRNA and miR-21 was demonstrated in malignant melanoma (r = -0.602). Elevated miR-21 and reduced PDCD4 mRNA levels were both significantly correlated with increased tumour size, a higher Clark classification level and the presence of lymph node metastases in malignant melanoma. These findings suggest that miR-21 and PDCD4 might be potential biomarkers for malignant melanoma and might provide treatment targets in the future. © The Author(s) 2015.

Acoustic plane waves normally incident on a clamped panel in a rectangular duct. [to explain noise reduction curves for reducing interior noise in aircraft

NASA Technical Reports Server (NTRS)

Unz, H.; Roskam, J.

1979-01-01

The theory of acoustic plane wave normally incident on a clamped panel in a rectangular duct is developed. The coupling theory between the elastic vibrations of the panel (plate) and the acoustic wave propagation in infinite space and in the rectangular duct is considered. The partial differential equation which governs the vibration of the panel (plate) is modified by adding to its stiffness (spring) forces and damping forces, and the fundamental resonance frequency and the attenuation factor are discussed. The noise reduction expression based on the theory is found to agree well with the corresponding experimental data of a sample aluminum panel in the mass controlled region, the damping controlled region, and the stiffness controlled region. All the frequency positions of the upward and downward resonance spikes in the sample experimental data are identified theoretically as resulting from four cross interacting major resonance phenomena: the cavity resonance, the acoustic resonance, the plate resonance, and the wooden back panel resonance.

Array-based comparative genomic hybridization-guided identification of reference genes for normalization of real-time quantitative polymerase chain reaction assay data for lymphomas, histiocytic sarcomas, and osteosarcomas of dogs.

PubMed

Tsai, Pei-Chien; Breen, Matthew

2012-09-01

To identify suitable reference genes for normalization of real-time quantitative PCR (RT-qPCR) assay data for common tumors of dogs. Malignant lymph node (n = 8), appendicular osteosarcoma (9), and histiocytic sarcoma (12) samples and control samples of various nonneoplastic canine tissues. Array-based comparative genomic hybridization (aCGH) data were used to guide selection of 9 candidate reference genes. Expression stability of candidate reference genes and 4 commonly used reference genes was determined for tumor samples with RT-qPCR assays and 3 software programs. LOC611555 was the candidate reference gene with the highest expression stability among the 3 tumor types. Of the commonly used reference genes, expression stability of HPRT was high in histiocytic sarcoma samples, and expression stability of Ubi and RPL32 was high in osteosarcoma samples. Some of the candidate reference genes had higher expression stability than did the commonly used reference genes. Data for constitutively expressed genes with high expression stability are required for normalization of RT-qPCR assay results. Without such data, accurate quantification of gene expression in tumor tissue samples is difficult. Results of the present study indicated LOC611555 may be a useful RT-qPCR assay reference gene for multiple tissue types. Some commonly used reference genes may be suitable for normalization of gene expression data for tumors of dogs, such as lymphomas, osteosarcomas, or histiocytic sarcomas.

Assessment of 1H NMR-based metabolomics analysis for normalization of urinary metals against creatinine.

PubMed

Cassiède, Marc; Nair, Sindhu; Dueck, Meghan; Mino, James; McKay, Ryan; Mercier, Pascal; Quémerais, Bernadette; Lacy, Paige

2017-01-01

Proton nuclear magnetic resonance ( 1 H NMR, or NMR) spectroscopy and inductively coupled plasma-mass spectrometry (ICP-MS) are commonly used for metabolomics and metal analysis in urine samples. However, creatinine quantification by NMR for the purpose of normalization of urinary metals has not been validated. We assessed the validity of using NMR analysis for creatinine quantification in human urine samples in order to allow normalization of urinary metal concentrations. NMR and ICP-MS techniques were used to measure metabolite and metal concentrations in urine samples from 10 healthy subjects. For metabolite analysis, two magnetic field strengths (600 and 700MHz) were utilized. In addition, creatinine concentrations were determined by using the Jaffe method. Creatinine levels were strongly correlated (R 2 =0.99) between NMR and Jaffe methods. The NMR spectra were deconvoluted with a target database containing 151 metabolites that are present in urine. A total of 50 metabolites showed good correlation (R 2 =0.7-1.0) at 600 and 700MHz. Metal concentrations determined after NMR-measured creatinine normalization were comparable to previous reports. NMR analysis provided robust urinary creatinine quantification, and was sufficient for normalization of urinary metal concentrations. We found that NMR-measured creatinine-normalized urinary metal concentrations in our control subjects were similar to general population levels in Canada and the United Kingdom. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Interleukin-17 and Interleukin-23 in Pterygium: Immunohistochemistry Study.

PubMed

Tiong, Kiew Ing; Mohd Zahidin, Aida Zairani; Sumugam, S Kala A/P; Uchang, Joseph; Mohd Isa, Hazlita Dato'

2017-01-01

To compare the interleukin-17 (IL-17) and interleukin-23 (IL-23) positive cell counts between pterygium and normal conjunctiva. A case-control study. This study received ethical approval (NMRR Research ID 23957) and informed consent was obtained from all participants. It involved 20 participants with 20 samples of pterygium and 20 samples of normal conjunctiva that were obtained from the same eye of each participant. All the participants underwent history taking, slit lamp examination, and pterygium excision surgery. Both samples underwent immunohistochemistry procedure. Pretreatment procedure was conducted using heat-induced epitope retrieval with PT link, subsequently followed by EnVision FLEX staining procedure and incubation with anti‒IL-17 antibody and anti‒IL-23 antibody. Slides were examined in high-power fields (400x) for both samples in 3 different fields. Total positive stained cell counts in all 3 fields with IL-17 and IL-23 between pterygium and normal conjunctiva were analyzed by using Wilcoxon signed rank test. IL-17 positive cell counts for normal conjunctiva showed mean 196.10 ± 80.487 but for pterygium was 331.10 ± 108.416. As for IL-23, the mean for positive cell counts for normal conjunctiva was 62.10 ± 33.462 and IL-23 positive cell counts for pterygium showed mean 102.95 ± 41.378. Both IL-17 and IL-23 were significantly increased in pterygium compared with normal conjunctiva (P < 0.001). Both IL-17 and IL-23 were found to be significantly higher in the pterygium group than in the normal conjunctiva group with P < 0.001 by Wilcoxon signed rank test. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Interidentity amnesia for neutral, episodic information in dissociative identity disorder.

PubMed

Huntjens, Rafaële J C; Postma, Albert; Peters, Madelon L; Woertman, Liesbeth; van der Hart, Onno

2003-05-01

Interidentity amnesia is considered a hallmark of dissociative identity disorder (DID) in clinical practice. In this study, objective methods of testing episodic memory transfer between identities were used. Tests of both recall (interference paradigm) and recognition were used. A sample of 31 DID patients was included. Additionally, 50 control subjects participated, half functioning as normal controls and the other half simulating interidentity amnesia. Twenty-one patients subjectively reported complete one-way amnesia for the learning episode. However, objectively, neither recall nor recognition scores of patients were different from those of normal controls. It is suggested that clinical models of amnesia in DID may be specified to exclude episodic memory impairments for emotionally neutral material.

Tooth contact in patients with temporomandibular disorders.

PubMed

Glaros, Alan G; Williams, Karen; Lausten, Leonard; Friesen, Lynn R

2005-07-01

Both experimental and retrospective studies suggest a link between parafunctions and pain in temporomandibular disorder (TMD) patients. To investigate the role of parafunctions in TMD, experience sampling methodology was used as a prospective test of the hypothesis that patients with TMD have higher levels of tooth contact and tension than non-TMD controls. Three groups of TMD patients and a group of normal controls carried pagers for one week, were contacted approximately every two hours by an automated calling system, and completed questionnaires assessing tooth contact, tension, and pain at each contact. Results showed that tooth contact was much more frequent among normal controls than is commonly presumed. Patients with myofascial pain with/without arthralgia reported more frequent contact, higher intensity contact, and more tension than patients with disk displacement or normal controls. Increased masticatory muscle activity responsible for tooth contact and tension may be an important mechanism in the etiology and maintenance of the myofascial pain and arthralgia of TMD.

Irradiation Does Not Increase the Penetration Depth of Doxorubicin in Normal Tissue After Pressurized Intra-peritoneal Aerosol Chemotherapy (PIPAC) in an Ex Vivo Model.

PubMed

Khosrawipour, Veria; Bellendorf, Alexander; Khosrawipour, Carolina; Hedayat-Pour, Yousef; Diaz-Carballo, David; Förster, Eckart; Mücke, Ralph; Kabakci, Burak; Adamietz, Irenäus Anton; Fakhrian, Khashayar

To compare the impact of single fractional with bi-fractional irradiation on the depth of doxorubicin penetration into the normal tissue after pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in our ex vivo model. Fresh post mortem swine peritoneum was cut into 12 proportional sections. Two control samples were treated with PIPAC only (no irradiation), one sample on day 1, the other on day 2. Five samples were irradiated with 1, 2, 4, 7 or 14 Gy followed by PIPAC. Four samples were treated on day one with 0.5, 1, 2, 3.5 or 7 Gy and with the same radiation dose 24 h later followed by PIPAC. Doxorubicin was aerosolized in an ex vivo PIPAC model at 12 mmHg/36°C. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. Doxorubicin penetration (DP) after PIPAC for the control samples was 407 μm and 373 μm, respectively. DP for samples with single fraction irradiation was 396 μm after 1 Gy, 384 μm after 2 Gy, 327 μm after 4 Gy, 280 μm after 7 Gy and 243 μm after 14 Gy. DP for samples with 2 fractions of irradiation was 376 μm after 0.5+0.5 Gy, 363 μm after 1+1 Gy, 372 μm after 2+2 Gy, 341 μm after 3.5+3.5 and 301 μm after 7+7 Gy irradiation. Fractionating of the irradiation did not significantly change DP into normal tissue. Irradiation does not increase the penetration depth of doxorubicin into the normal tissue but might have a limiting impact on penetration and distribution of doxorubicin. Further studies are warranted to investigate the impact of addition of irradiation to PIPAC of tumor cells and to find out if irradiation can be used safely as chemopotenting agent for patients with peritoneal metastases treated with PIPAC. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Palynological Investigation of Mummified Human Remains.

PubMed

Reinhard, Karl J; Amaral, Marina Milanello do; Wall, Nicole

2018-01-01

Pollen analysis was applied to a mummified homicide victim in Nebraska, U.S.A., to determine the location of death. A control sample showed the normal ambient pollen in the garage crime scene. Ambient windborne types, common in the air of the region, dominated the control. Internal samples were analyzed from the sacrum, intestine, and diaphragm. Microfossils were recovered from the rehydrated intestine lumen. The intestinal sample was dominated by Brassica (broccoli). The sacrum sample was high in dietary types but with a showing of ambient types. The pollen from the diaphragm was dominated by ambient pollen similar to the control samples. The discovery of diverse pollen spectra from within a single mummy was unexpected. They show that ingested and inhaled pollen mixed in the corpse. The data linked the decedent to a specific crime scene in her Nebraska home in the southern tier of eastern counties on the border with Kansas. © 2017 American Academy of Forensic Sciences.

Implicit Threat Vigilance among Violent Offenders Diagnosed with Antisocial Personality Disorder: The Impact of Ostracism and Control Threat

ERIC Educational Resources Information Center

Çelik, Pinar; van Beest, Ilja; Lammers, Joris; Bekker, Marrie

2013-01-01

The present study investigated the role of control as a moderator in reaction to ostracism among male violent offenders diagnosed with ASPD (N = 33) compared to a control sample consisting of males from the normal population without a known history of violence, or diagnosis of ASPD, matched for age and educational level (N = 35). Participants…

Establishment of a cervical cancer bio-bank for the Chinese population: from project-based sample collection to routine management.

PubMed

Yang, Ru; Li, Xiong; Zhou, Hang; Jia, Yao; Zhou, Jin; Huang, Kecheng; Tang, Fangxu; Hu, Ting; Shen, Jian; Chen, Zhilan; Wang, Shaoshuai; Sun, Haiying; Guo, Lili; Wang, Lin; Wang, Hui; Ma, Ding; Li, Shuang

2015-08-01

There is an increasing need for the establishment of a cervical cancer bio-bank that will facilitate both clinical and basic research. The cervical cancer bio-bank was first established in January 1999 and included two stages. First, a GWAS-based sample collection was conducted with special emphasis on the diagnosis and the retrieval of the corresponding bio-specimens, especially blood samples. Second, clinical data and their corresponding bio-specimens were routinely collected and handled. Notably, these bio-specimens also included samples from Wufeng Tujia Autonomous County, which has the highest incidence of cervical cancer in China. The specimens were collected from patients with cervical cancer and those with cervical intraepithelial neoplasia, while the control samples were collected from normal individuals. With special emphasis on clinical data and blood samples for the GWAS analysis, the collection of other bio-specimens was slow, and the pairing of specimens and clinical data was poor during the first stage. However, in the second stage, the pairing of the clinical data and its corresponding bio-specimens improved. At present, the samples procured and preserved in the bio-bank cover most regions of China and different ethnic groups for both the normal controls and cervical cancer patients of different pathological categories. This bio-bank of cervical cancer specimens from the Chinese population will greatly promote the studies of cervical cancer in China.

Elevated basal intestinal mucosal cytokine levels in asymptomatic first-degree relatives of patients with Crohn’s disease

PubMed Central

Indaram, Anant VK; Nandi, Santa; Weissman, Sam; Lam, Sing; Bailey, Beverly; Blumstein, Meyer; Greenberg, Ronald; Bank, Simmy

2000-01-01

AIM: To determine levels of cytokines in colonic mucosa of asymptomatic first degree relatives of Crohn’s disease patients. METHODS: Cytokines (Interleukin (IL) 1-Beta, IL-2, IL-6 and IL-8) were measured using ELISA in biopsy samples of normal looking colonic mucosa of first degree relatives of Crohn’s disease patients (n = 9) and fro m normal controls (n = 10) with no family history of Crohn’s disease. RESULTS: Asymptomatic first degree relatives of patients with Crohn’s disease had significantly higher levels of basal intestinal mucosal cytokines (IL-2, IL-6 and IL-8) than normal controls. Whether these increase d cytokine levels serve as phenotypic markers for a genetic predisposition to de veloping Crohn’s disease later on, or whether they indicate early (pre-cli nical) damage has yet to be further defined. CONCLUSION: Asymptomatic first degree relatives of Crohn’s disease patients have higher levels of cytokines in their normal-looking intestinal mucosa compared to normal controls. This supports the hypothesis that increased cytokines may be a cause or an early event in the inflammatory cascade of Crohn’s disease and are not merely a result of the inflammatory process. PMID:11819521

Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer.

PubMed

Karahan, Gurbet; Sayar, Nilufer; Gozum, Gokcen; Bozkurt, Betul; Konu, Ozlen; Yulug, Isik G

2015-06-01

Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter. However, the DNA methylation state of the 45 S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28 S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45 S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation between spliced rRNA expression levels, possibly due to changes in rRNA processing, which requires further investigation.

Verification of out-of-control situations detected by "average of normal" approach.

PubMed

Liu, Jiakai; Tan, Chin Hon; Loh, Tze Ping; Badrick, Tony

2016-11-01

"Average of normal" (AoN) or "moving average" is increasingly used as an adjunct quality control tool in laboratory practice. Little guidance exists on how to verify if an out-of-control situation in the AoN chart is due to a shift in analytical performance, or underlying patient characteristics. Through simulation based on clinical data, we examined 1) the location of the last apparently stable period in the AoN control chart after an analytical shift, and 2) an approach to verify if the observed shift is related to an analytical shift by repeat testing of archived patient samples from the stable period for 21 common analytes. The number of blocks of results to look back for the stable period increased with the duration of the analytical shift, and was larger when smaller AoN block sizes were used. To verify an analytical shift, 3 archived samples from the analytically stable period should be retested. In particular, the process is deemed to have shifted if a difference of >2 analytical standard deviations (i.e. 1:2s rejection rule) between the original and retested results are observed in any of the 3 samples produced. The probability of Type-1 error (i.e., false rejection) and power (i.e., detecting true analytical shift) of this rule are <0.1 and >0.9, respectively. The use of appropriately archived patient samples to verify an apparent analytical shift is preferred to quality control materials. Nonetheless, the above findings may also apply to quality control materials, barring matrix effects. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Selection of internal control genes for quantitative real-time RT-PCR studies during tomato development process

PubMed Central

Expósito-Rodríguez, Marino; Borges, Andrés A; Borges-Pérez, Andrés; Pérez, José A

2008-01-01

Background The elucidation of gene expression patterns leads to a better understanding of biological processes. Real-time quantitative RT-PCR has become the standard method for in-depth studies of gene expression. A biologically meaningful reporting of target mRNA quantities requires accurate and reliable normalization in order to identify real gene-specific variation. The purpose of normalization is to control several variables such as different amounts and quality of starting material, variable enzymatic efficiencies of retrotranscription from RNA to cDNA, or differences between tissues or cells in overall transcriptional activity. The validity of a housekeeping gene as endogenous control relies on the stability of its expression level across the sample panel being analysed. In the present report we describe the first systematic evaluation of potential internal controls during tomato development process to identify which are the most reliable for transcript quantification by real-time RT-PCR. Results In this study, we assess the expression stability of 7 traditional and 4 novel housekeeping genes in a set of 27 samples representing different tissues and organs of tomato plants at different developmental stages. First, we designed, tested and optimized amplification primers for real-time RT-PCR. Then, expression data from each candidate gene were evaluated with three complementary approaches based on different statistical procedures. Our analysis suggests that SGN-U314153 (CAC), SGN-U321250 (TIP41), SGN-U346908 ("Expressed") and SGN-U316474 (SAND) genes provide superior transcript normalization in tomato development studies. We recommend different combinations of these exceptionally stable housekeeping genes for suited normalization of different developmental series, including the complete tomato development process. Conclusion This work constitutes the first effort for the selection of optimal endogenous controls for quantitative real-time RT-PCR studies of gene expression during tomato development process. From our study a tool-kit of control genes emerges that outperform the traditional genes in terms of expression stability. PMID:19102748

Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease.

PubMed

Goel, N; Ulrich, D T; St Clair, E W; Fleming, J A; Lynch, D H; Seldin, M F

1995-12-01

To determine whether elevated soluble Fas/APO-1 (sFas/APO-1) levels are associated with either autoimmune disease or evidence of flares in autoimmune disease. Thirty-seven serum samples were retrospectively obtained from normal controls and patients with laboratory evidence of autoimmune disease activity. These samples were assayed for sFas/APO-1 levels by an enzyme-linked immunosorbent assay, and hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. Soluble Fas/APO-1 levels did not correlate with clinical diagnoses or laboratory abnormalities. The mean and range of sFas/APO-1 levels were similar in systemic lupus erythematosus patients (including those with active disease), patients with other autoimmune diseases, and normal controls. These data strongly suggest that measurement of sFas/APO-1 levels is unlikely to hold clinical value or play a role in the pathogenesis of autoimmune disease.

Androgen Responses to ACTH Infusion among Individual Women with Polycystic Ovary Syndrome

PubMed Central

Maas, Kevin H.; Chuan, Sandy; Harrison, Evan; Cook-Andersen, Heidi; Duleba, Antoni J; Chang, R. Jeffrey

2016-01-01

Objective To compare androgen responses during ACTH infusion among women with PCOS and normal women. Design Cross-sectional study. Setting Research center at an academic medical center. Participants Women with PCOS (n=13) and normal controls (n=15). Interventions Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. Main Outcome Measures Comparison of basal and stimulated levels of 17-OHP, androgens, and cortisol during ACTH infusion with those following hCG injection within individual subjects. Results In women with PCOS increased 17-OHP, A4, and DHEA responses during ACTH infusion were comparable to those observed in normal controls. The magnitude of responses was highly variable among PCOS women. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in PCOS and normal controls. Conclusion Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues. PMID:27473350

A protein anomaly in erythrocyte membranes of patients with Duchenne muscular dystrophy

PubMed Central

1983-01-01

Raman spectroscopic comparisons of erythrocyte membranes from 20 patients with Duchenne muscular dystrophy and 8 age-matched controls indicate a prominent and consistent protein anomaly in the patient samples. This was apparent in the following: (a) CH-stretching signals from control membranes reveal a thermotropic transition at 15.6 degrees C, attributable to a protein/lipid phase that is lacking in dystrophic membranes. (b) CH-stretching signals from control membranes also show a protein transition at 39 degrees C [pH 7.4] that is shifted to 45 degrees in dystrophic membranes. (c) A reduction in pH to 5.7 shifts this transition from 39 degrees C to 7 degrees C in normal membranes and from 45 degrees C to 24 degrees C in dystrophic membranes. (d) The Amide I/Amide III regions indicate a significant proportion of beta- structured peptide in dystrophic but not normal membranes. (e) Analysis of tyrosine signals indicates greater polar exposure of tyrosine hydroxyl groups in dystrophic vs normal membranes. All of the differences between dystrophic and normal membranes are highly significant (P less than 0.001). PMID:6854213

Sleep Misperception and Chronic Insomnia in the General Population: The Role of Objective Sleep Duration and Psychological Profiles

PubMed Central

Fernandez-Mendoza, Julio; Calhoun, Susan L.; Bixler, Edward O.; Karataraki, Maria; Liao, Duanping; Vela-Bueno, Antonio; Ramos-Platon, María Jose; Sauder, Katherine A.; Basta, Maria; Vgontzas, Alexandros N.

2011-01-01

Objective Sleep misperception is considered by some investigators a common characteristic of chronic insomnia, whereas others propose it as a separate diagnosis. The frequency and the determinants of sleep misperception in general population samples are unknown. In this study we examined the role of objective sleep duration, a novel marker in phenotyping insomnia, and psychological profiles on sleep misperception in a large, general population sample. Methods 142 insomniacs and 724 controls selected from a general random sample of 1,741 individuals (age ≥ 20 years) underwent a polysomnographic evaluation, completed the Minnesota Multiphasic Personality Inventory-2, and were split into two groups based on their objective sleep duration: “normal sleep duration” (≥ 6 hours) and “short sleep duration” (< 6 hours). Results The discrepancy between subjective and objective sleep duration was determined by two independent factors. Short sleepers reported more sleep than they objectively had and insomniacs reported less sleep than controls with similar objective sleep duration. The additive effect of these two factors resulted in underestimation only in insomniacs with normal sleep duration. Insomniacs with normal sleep duration showed a MMPI-2 profile of high depression and anxiety, and low ego strength, whereas insomniacs with short sleep duration showed a profile of a medical disorder. Conclusions Underestimation of sleep duration is prevalent among insomniacs with objective normal sleep duration. Anxious-ruminative traits and poor resources for coping with stress appear to mediate the underestimation of sleep duration. These data further support the validity and clinical utility of objective sleep measures in phenotyping insomnia. PMID:20978224

Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

PubMed Central

Fagge, Timothy J; Barclay, G Robin; Stove, G Colin; Stove, Gordon; Robinson, Michael J; Head, Mark W; Ironside, James W; Turner, Marc L

2007-01-01

Background Sub-clinical variant Creutzfeldt-Jakob disease (vCJD) infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrPSc), although achieving required sensitivity is a challenge. Methods We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS), which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples. Results Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system. Conclusion ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems. PMID:17760958

Children with minimal sensorineural hearing loss: prevalence, educational performance, and functional status.

PubMed

Bess, F H; Dodd-Murphy, J; Parker, R A

1998-10-01

This study was designed to determine the prevalence of minimal sensorineural hearing loss (MSHL) in school-age children and to assess the relationship of MSHL to educational performance and functional status. To determine prevalence, a single-staged sampling frame of all schools in the district was created for 3rd, 6th, and 9th grades. Schools were selected with probability proportional to size in each grade group. The final study sample was 1218 children. To assess the association of MSHL with educational performance, children identified with MSHL were assigned as cases into a subsequent case-control study. Scores of the Comprehensive Test of Basic Skills (4th Edition) (CTBS/4) then were compared between children with MSHL and children with normal hearing. School teachers completed the Screening Instrument for Targeting Education Risk (SIFTER) and the Revised Behavior Problem Checklist for a subsample of children with MSHL and their normally hearing counterparts. Finally, data on grade retention for a sample of children with MSHL were obtained from school records and compared with school district norm data. To assess the relationship between MSHL and functional status, test scores of all children with MSHL and all children with normal hearing in grades 6 and 9 were compared on the COOP Adolescent Chart Method (COOP), a screening tool for functional status. MSHL was exhibited by 5.4% of the study sample. The prevalence of all types of hearing impairment was 11.3%. Third grade children with MSHL exhibited significantly lower scores than normally hearing controls on a series of subtests of the CTBS/4; however, no differences were noted at the 6th and 9th grade levels. The SIFTER results revealed that children with MSHL scored poorer on the communication subtest than normal-hearing controls. Thirty-seven percent of the children with MSHL failed at least one grade. Finally, children with MSHL exhibited significantly greater dysfunction than children with normal hearing on several subtests of the COOP including behavior, energy, stress, social support, and self-esteem. The prevalence of hearing loss in the schools almost doubles when children with MSHL are included. This large, education-based study shows clinically important associations between MSHL and school behavior and performance. Children with MSHL experienced more difficulty than normally hearing children on a series of educational and functional test measures. Although additional research is necessary, results suggest the need for audiologists, speech-language pathologists, and educators to evaluate carefully our identification and management approaches with this population. Better efforts to manage these children could result in meaningful improvement in their educational progress and psychosocial well-being.

Human cytokine response to Texas crotaline envenomation before and after antivenom administration.

PubMed

Crocker, Patrick; Zad, Omid; Milling, Truman; Maxson, Todd; King, Benjamin; Whorton, Elbert

2010-10-01

The aim of this study was to characterize the human cytokine response to Texas crotaline envenomation before and after antivenom administration. This study enrolled crotaline bite victims presenting to a regional trauma center and children's hospital from March to November 2007 and age-matched unbitten controls. Blood spot cards were obtained from bite victims at presentation and at 1 and 6 hours after antivenom administration. One control sample was drawn from each of the age-matched controls selected from urgent care patients presenting for minor complaints. Samples were delivered to a laboratory using a proprietary method for quantitative evaluation of a large number of biomarkers in parallel with bead-based multiplex immunoassays. After obtaining informed consent, 14 crotaline bite victims (age range, 5-85 years; median age, 45 years; 50% female) (Snakebite Severity Score, 2-7; median, 3) and 14 age-matched controls were enrolled. There were 7 copperhead (Agkistrodon contortrix) bites, 4 rattlesnake (probably Western Diamondback Crotalus atrox) bites, 2 cottonmouth (Agkistrodon piscivorus) bites, and 1 bite from a snake that was not identified by the victim. In t tests, the means in the presentation samples for apolipoprotein A-I (Apo A-I), Apo C3, interleukin 4 (IL-4), myeloperoxidase, plasminogen activator inhibitor 1 (PAI-1), epidermal growth factor, and regulated upon activation, normal t-cell expressed and secreted were significantly lower and Apo H was significantly higher in the bite patients than in the controls. In the 1-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, eotaxin, IL-4, myeloperoxidase, and PAI-1 levels were lower and prostatic acid phosphatase and cancer antigen 125 levels were higher in the bite patients than in the controls. And in the 6-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, endothelin-1, IL-4, macrophage inflammatory protein 1β, myeloperoxidase, and epidermal growth factor levels were lower and Apo H level was higher in the bite patients than in controls (all P values < .05). Crotaline venom produces a broad cytokine response in human bite victims. In particular, IL-4, myeloperoxidase, and Apo A-I and C3 levels remain altered despite antivenom therapy, whereas PAI-1 and regulated upon activation, normal t-cell expressed and secreted levels seem to normalize after antivenin as other markers are affected. Understanding this profile and further study of the markers identified might lead to improved therapies and better prognostic indicators. Copyright © 2010 Elsevier Inc. All rights reserved.

Identification of suitable reference genes for hepatic microRNA quantitation.

PubMed

Lamba, Vishal; Ghodke-Puranik, Yogita; Guan, Weihua; Lamba, Jatinder K

2014-03-07

MicroRNAs (miRNAs) are short (~22 nt) endogenous RNAs that play important roles in regulating expression of a wide variety of genes involved in different cellular processes. Alterations in microRNA expression patterns have been associated with a number of human diseases. Accurate quantitation of microRNA levels is important for their use as biomarkers and in determining their functions. Real time PCR is the gold standard and the most frequently used technique for miRNA quantitation. Real time PCR data analysis includes normalizing the amplification data to suitable endogenous control/s to ensure that microRNA quantitation is not affected by the variability that is potentially introduced at different experimental steps. U6 (RNU6A) and RNU6B are two commonly used endogenous controls in microRNA quantitation. The present study was designed to investigate inter-individual variability and gender differences in hepatic microRNA expression as well as to identify the best endogenous control/s that could be used for normalization of real-time expression data in liver samples. We used Taqman based real time PCR to quantitate hepatic expression levels of 22 microRNAs along with U6 and RNU6B in 50 human livers samples (25 M, 25 F). To identify the best endogenous controls for use in data analysis, we evaluated the amplified candidates for their stability (least variability) in expression using two commonly used software programs: Normfinder and GeNormplus, Both Normfinder and GeNormplus identified U6 to be among the least stable of all the candidates analyzed, and RNU6B was also not among the top genes in stability. mir-152 and mir-23b were identified to be the two most stable candidates by both Normfinder and GeNormplus in our analysis, and were used as endogenous controls for normalization of hepatic miRNA levels. Measurements of microRNA stability indicate that U6 and RNU6B are not suitable for use as endogenous controls for normalizing microRNA relative quantitation data in hepatic tissue, and their use can led to possibly erroneous conclusions.

Psychosocial impact of dysthymia: a study among married patients.

PubMed

Subodh, B N; Avasthi, A; Chakrabarti, S

2008-07-01

Unlike major depression, the psychosocial impact of dysthymia has received far less research attention. This study attempted to assess the psychosocial consequences of dysthymia. The sample consisted of 30 married patients with DSM-IV dysthymic disorder and a matched control group of 30 married patients with recurrent major depressive disorder (RDD), diagnosed using structured interviews. Apart from ratings of severity of depression, assessments of psychosocial impact included quality of life (QOL), disability, perceived social support and marital adjustment. Psychosocial parameters were evaluated using vernacular versions of well-validated scales previously used in similar populations. Matched normal/medically ill controls were derived from Indian studies which had assessed the same parameters using the same instruments. Patients with dysthymia were significantly impaired on measures of QOL, disability, social support and marital adjustment compared to normal/medically ill controls. On the other hand, the two groups of dysthymia and RDD were comparable on these measures apart from significantly lower social support among patients with dysthymia. Duration of illness and severity of depression emerged as the most important correlates, particularly of impaired QOL and disability levels. Small hospital-based sample, normal/medically ill controls derived from other studies and cross-sectional assessments were the major limitations. Dysthymia had considerable adverse psychosocial impact in terms of QOL, functioning (disability), social support and marital adjustment. Severity and chronicity appeared to be important mediators of this negative psychosocial impact. Increased awareness, improved recognition and adequate treatment might help negate some of the untoward social consequences of this condition.

Diverse Vaginal Microbiomes in Reproductive-Age Women with Vulvovaginal Candidiasis

PubMed Central

Liu, Mu-Biao; Xu, Su-Rong; He, Yan; Deng, Guan-Hua; Sheng, Hua-Fang; Huang, Xue-Mei; Ouyang, Cai-Yan; Zhou, Hong-Wei

2013-01-01

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases. PMID:24265786

Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis.

PubMed

Liu, Mu-Biao; Xu, Su-Rong; He, Yan; Deng, Guan-Hua; Sheng, Hua-Fang; Huang, Xue-Mei; Ouyang, Cai-Yan; Zhou, Hong-Wei

2013-01-01

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases.

[Clinical Feature in Infants of Breast Feeding Allergy and Its Possible Relation with Gastrointestinal Peptide Change in Breast Milk].

PubMed

Xie, Yong-Mei; Gao, Shan; Wang, Li-Yuan; Wang, Zhi-Ling; Cai, Xiao-Tang; Zhou, Hui

2017-01-01

To investigate clinical features in infants of breast milk allergy(BMA), and the possible relationship with the changes of somatostatin (SST) and motilin (MTL) in breast milk. Twenty three cases of pure breast feeding infants with allergic gastroenteritis were collected, while another 23 normal infants with pure breast feeding were enrolled as normal controls. Samples of infant stools and breast milk were collected for the measurement of SST and MTL levels detected by by radioimmunity. The levels of SST and MTL in stool samples (pg/mg) were 32.6±8.9, 2.3±3.7 in BMA group and 56.2±12.7, 21.6±4.7 in normal control group, respectively. Those in breast milk (pg/mg) were 236.7±28.9, 159.4±36.7 in BMA group and 412.6±36.7, 216.8±59.7 in normal control group, respectively. All the differences were statistically significant ( P <0.05). In BMA infants, the clinical features were 91.3% (20/23) of diarrhea, 86.9% (21/23) of vomiting, 69.6% (16/23) of hematochezia, 95.7% (22/23) of C-reactive protein (CRP) increasing, 87.0% (20/23) of occult blood in stools, 73.9% (17/23) of neutrophil increasing, 39.1% (9/23) of WBC in stools. For those infants of breast feeding with persisting and repeated gastrointestinal symptoms, allergy for breast milk should be considered. Deficiency of SST and MTL in breast milk may be a possible cause for food allergy.

Dietary Habits and Nutritional Status in Mentally Retarded Children and Adolescents: A Study from North Western India

ERIC Educational Resources Information Center

Mathur, Manju; Bhargava, Rachna; Benipal, Ramandeep; Luthra, Neena; Basu, Sabita; Kaur, Jasbinder; Chavan, B. S.

2007-01-01

Objective: To compare the dietary habits and nutritional status of mentally retarded (MR) and normal (NG) subjects and to examine the relationship between the dietary habits and nutritional status and the level of mental retardation in the MR group. Method: A case control design was utilized: 117 MR (random sampling) and 100 NG (quota sampling)…

The Relationship between Theory of Mind and Executive Function in a Sample of Children from Mainland China

ERIC Educational Resources Information Center

Yang, Juan; Zhou, Shijie; Yao, Shuqiao; Su, Linyan; McWhinnie, Chad

2009-01-01

To explore the relationship between theory of mind (ToM) and executive function (EF) in a sample of individuals from mainland China, 20 children with autism spectrum disorders (ASD), 26 children with Attention Deficit Hyperactivity Disorder (ADHD), and 30 normal control subjects were compared on two batteries of ToM tasks and EF tasks. Children…

Comparison of CyTOF assays across sites: Results of a six-center pilot study.

PubMed

Leipold, Michael D; Obermoser, Gerlinde; Fenwick, Craig; Kleinstuber, Katja; Rashidi, Narges; McNevin, John P; Nau, Allison N; Wagar, Lisa E; Rozot, Virginie; Davis, Mark M; DeRosa, Stephen; Pantaleo, Giuseppe; Scriba, Thomas J; Walker, Bruce D; Olsen, Lars R; Maecker, Holden T

2018-02-01

For more than five years, high-dimensional mass cytometry has been employed to study immunology. However, these studies have typically been performed in one laboratory on one or few instruments. We present the results of a six-center study using healthy control human peripheral blood mononuclear cells (PBMCs) and commercially available reagents to test the intra-site and inter-site variation of mass cytometers and operators. We used prestained controls generated by the primary center as a reference to compare against samples stained at each individual center. Data were analyzed at the primary center, including investigating the effects of two normalization methods. All six sites performed similarly, with CVs for both Frequency of Parent and median signal intensity (MSI) values<30%. Increased background was seen when using the premixed antibody cocktail aliquots at each site, suggesting that cocktails are best made fresh. Both normalization methods tested performed adequately for normalizing MSI values between centers. Clustering algorithms revealed slight differences between the prestained and the sites-stained samples, due mostly to the increased background of a few antibodies. Therefore, we believe that multicenter mass cytometry assays are feasible. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

[677T mutation of the MTHFR gene in adenomas and colorectal cancer in a population sample from the Northeastern Mexico. Preliminary results].

PubMed

Delgado-Enciso, I; Martínez-Garza, S G; Rojas-Martínez, A; Ortiz-López, R; Bosques-Padilla, F; Calderón-Garcidueñas, A L; Zárate-Gómez, M; Barrera-Saldaña, H A

2001-01-01

Adequate intake of folates has been associated to low prevalence of colon cancer. Methylenetetrahydrofolate reductase enzyme (MTHFR) plays an important role in folate metabolism. The role of the 677 mutation at the MTHFR gene in the risk for colorectal cancer remains controversial. A recent report established that this mutation has a high prevalence in the healthy Mexican population. To analyze the prevalence of 677T MTHFR mutation in patients with colorectal cancer and controls without chronic gastrointestinal disorders. Seventy-four colorectal cancer, 32 adenomas and 110 normal samples were analyzed. Patients and controls were matched for sex and age. For each sample, DNA isolation, PCR, and mutation detection by restriction enzyme digestion were performed to determine the allele at the 677 position in the MTHFR gene. Genotype 677C/677C was found in 18.7, 20.3, and 30.9% in adenomas, cancer lesions and controls, respectively. Frequencies of the 677C/677T genotype were 59.4, 56.7, and 47.3%, in adenomas, cancer lesions, and controls, respectively. Genotype 677T/677T was found in 21.9, 23.0, and 21.8% in adenomas, cancer lesions, and controls, respectively. The odds ratio between genotypes carrying the mutation (T/T and C/T) and normal genotype (CC) was 1.81 (IC 95% 0.97-3.3), chi 2 = 3.5, p = 0.06. Our results showed that persons who carry the 677T mutation at MTHFR locus have a tendency for an increased risk for colorectal cancer. This study supports the basic concept that low levels of folic acid contribute with the colorectal cancer pathogenesis. Our lack of statistic significance may be due to reduced sample size.

Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

PubMed

de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

2015-02-01

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

Localised drug release using MRI-controlled focused ultrasound hyperthermia.

PubMed

Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

2011-01-01

Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo. Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue. Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test). The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.

The effect of science learning integrated with local potential to improve science process skills

NASA Astrophysics Data System (ADS)

Rahardini, Riris Riezqia Budy; Suryadarma, I. Gusti Putu; Wilujeng, Insih

2017-08-01

This research was aimed to know the effectiveness of science learning that integrated with local potential to improve student`s science process skill. The research was quasi experiment using non-equivalent control group design. The research involved all student of Muhammadiyah Imogiri Junior High School on grade VII as a population. The sample in this research was selected through cluster random sampling, namely VII B (experiment group) and VII C (control group). Instrument that used in this research is a nontest instrument (science process skill observation's form) adapted Desak Megawati's research (2016). The aspect of science process skills were making observation and communication. The data were using univariat (ANOVA) analyzed at 0,05 significance level and normalized gain score for science process skill increase's category. The result is science learning that integrated with local potential was effective to improve science process skills of student (Sig. 0,00). This learning can increase science process skill, shown by a normalized gain score value at 0,63 (medium category) in experiment group and 0,29 (low category) in control group.

Mast cells and matrix metalloproteinase 9 expression in actinic cheilitis and lip squamous cell carcinoma.

PubMed

Souza Freitas, Valéria; de Andrade Santos, Pedro Paulo; de Almeida Freitas, Roseana; Pereira Pinto, Leão; de Souza, Lélia Batista

2011-09-01

The aim of this study was to evaluate mast cell (MC) density and migration and their association with matrix metalloproteinase (MMP) 9 expression in squamous cell carcinoma (SCC) and actinic cheilitis (AC). Tryptase, c-Kit, and MMP-9 expression was evaluated in 20 cases of SCC, 20 cases of AC, and 7 cases of normal lip (control samples) by immunohistochemistry techniques. Tryptase(+) and c-Kit(+) MC densities were significantly higher in SCCs than in ACs and control samples (P < .001). However, no significant difference was found when comparing tryptase(+) and c-Kit(+) MC densities between ACs and control samples (P values .185 and .516, respectively). MMP-9 was strongly expressed in SCCs and moderately expressed in ACs and control samples. A highly significant association was found between tryptase(+) MC density and the expression of MMP-9 (P < .001). The increase in MC density associated with the strong expression of MMP-9 may favor SCC progression. Copyright © 2011 Mosby, Inc. All rights reserved.

Accounting for Dependence Induced by Weighted KNN Imputation in Paired Samples, Motivated by a Colorectal Cancer Study

PubMed Central

Suyundikov, Anvar; Stevens, John R.; Corcoran, Christopher; Herrick, Jennifer; Wolff, Roger K.; Slattery, Martha L.

2015-01-01

Missing data can arise in bioinformatics applications for a variety of reasons, and imputation methods are frequently applied to such data. We are motivated by a colorectal cancer study where miRNA expression was measured in paired tumor-normal samples of hundreds of patients, but data for many normal samples were missing due to lack of tissue availability. We compare the precision and power performance of several imputation methods, and draw attention to the statistical dependence induced by K-Nearest Neighbors (KNN) imputation. This imputation-induced dependence has not previously been addressed in the literature. We demonstrate how to account for this dependence, and show through simulation how the choice to ignore or account for this dependence affects both power and type I error rate control. PMID:25849489

DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

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

Ruebe, Claudia E., E-mail: claudia.ruebe@uks.e; Fricke, Andreas; Schneider, Ruth

Purpose: To evaluate, in a pilot study, the phosphorylated H2AX ({gamma}H2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting {gamma}H2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities,more » and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.« less

Low Water Activity Packaged White Bread.

DTIC Science & Technology

1985-12-31

this method is different in quality from the normal white pan bread. It has been well recognized that water activity is a key factor in controlling ...important in controlling microbial growth. The purpose of this project was to develop a shelf-stable white pan bread in a flexible pouch by utilizing...coded and randomized in order of presentation. Each judge was presented five samples: control , 5% sorbitol, 20% sorbitol, 8% glycerol, and 10% sorbitol-5

Personality correlates of criminals: A comparative study between normal controls and criminals.

PubMed

Sinha, Sudhinta

2016-01-01

Personality is a major factor in many kinds of behavior, one of which is criminal behavior. To determine what makes a criminal "a criminal," we must understand his/her personality. This study tries to identify different personality traits which link criminals to their personality. In the present study, 37 male criminals of district jail of Dhanbad (Jharkhand) and 36 normal controls were included on a purposive sampling basis. Each criminal was given a personal datasheet and Cattel's 16 personality factors (PFs) scale for assessing their sociodemographic variables and different personality traits. The objective of this study was to examine the relation between personality traits and criminal behavior, and to determine whether such factors are predictive of future recidivism. Results indicated high scores on intelligence, impulsiveness, suspicion, self-sufficient, spontaneity, self-concept control factors, and very low scores on emotionally less stable on Cattel's 16 PFs scale in criminals as compared with normal. Criminals differ from general population or non criminals in terms of personality traits.

Chromosome 17 Aneusomy Detected by Fluorescence in Situ Hybridization in Vulvar Squamous Cell Carcinomas and Synchronous Vulvar Skin

PubMed Central

Carlson, J. Andrew; Healy, Kara; Tran, Tien Anh; Malfetano, John; Wilson, Vincent L.; Rohwedder, Angela; Ross, Jeffrey S.

2000-01-01

Vulvar squamous cell carcinoma (SCC) affects a spectrum of women with granulomatous vulvar diseases, human papillomavirus (HPV) infections, and chronic inflammatory vulvar dermatoses. To determine whether there is evidence of chromosomal instability occurring in synchronous skin surrounding vulvar SCCs, we investigated abnormalities in chromosome 17 copy number. Samples of SCC, vulvar intraepithelial neoplasia (VIN), and surrounding vulvar skin were obtained from all vulvar excisions performed for squamous neoplasia at Albany Medical College from 1996 to 1997. Histological categorization, fluorescent in situ hybridization (FISH) for the α satellite region of chromosome 17, DNA content by image analysis, and Ki-67 labeling were evaluated. Controls of normal vulvar skin not associated with cancer were used for comparison. One hundred ten specimens were obtained from 33 patients with either SCC or VIN 3 and consisted of 49 neoplastic, 52 nonneoplastic, and 9 histologically normal vulvar skin samples. The majority of SCCs (88%) and a minority (18%) of VIN 3 excisions were associated with lichen sclerosus. Normal vulvar skin controls did not exhibit chromosome 17 polysomy (cells with more than four FISH signals), whereas 56% of normal vulvar skin associated with cancer did. Moreover, the frequency of polysomy significantly increased as the histological classification progressed from normal to inflammatory to neoplastic lesions. The largest mean value and variance for chromosome 17 copy number was identified in SCCs (2.4 ± 1.0) with intermediate values identified, in decreasing order, for SCC in situ (2.1 ± 1.0), VIN 2 (2.1 ± 0.8), lichen sclerosus (2.0 ± 0.5), lichen simplex chronicus (1.9 ± 0.4), and normal skin associated with SCC (1.8 ± 0.4) compared with control vulvar skin (1.5 ± 0.05). Concordance of chromosome 17 aneusomy between cancers and synchronous skin lesions was found in 48% of patients. Loss of chromosome 17 was identified 5% of all samples and was significantly associated with women with SCC in situ (HPV-related). Both DNA content and Ki-67 labeling positively and significantly correlated with mean chromosome 17 copy number (r = 0.1, P = 0.007). A high degree of genetic instability (aneuploidy) occurs in the skin surrounding vulvar carcinomas. As these events could be detected in histologically normal skin and inflammatory lesions (lichen sclerosus), chromosomal abnormalities may be a driving force in the early stages of carcinogenesis. Differences in chromosomal patterns (loss or gain) support the concept of at least two pathways in vulvar carcinogenesis. PMID:10980136

Chromosome 17 aneusomy detected by fluorescence in situ hybridization in vulvar squamous cell carcinomas and synchronous vulvar skin.

PubMed

Carlson, J A; Healy, K; Tran, T A; Malfetano, J; Wilson, V L; Rohwedder, A; Ross, J S

2000-09-01

Vulvar squamous cell carcinoma (SCC) affects a spectrum of women with granulomatous vulvar diseases, human papillomavirus (HPV) infections, and chronic inflammatory vulvar dermatoses. To determine whether there is evidence of chromosomal instability occurring in synchronous skin surrounding vulvar SCCs, we investigated abnormalities in chromosome 17 copy number. Samples of SCC, vulvar intraepithelial neoplasia (VIN), and surrounding vulvar skin were obtained from all vulvar excisions performed for squamous neoplasia at Albany Medical College from 1996 to 1997. Histological categorization, fluorescent in situ hybridization (FISH) for the alpha satellite region of chromosome 17, DNA content by image analysis, and Ki-67 labeling were evaluated. Controls of normal vulvar skin not associated with cancer were used for comparison. One hundred ten specimens were obtained from 33 patients with either SCC or VIN 3 and consisted of 49 neoplastic, 52 nonneoplastic, and 9 histologically normal vulvar skin samples. The majority of SCCs (88%) and a minority (18%) of VIN 3 excisions were associated with lichen sclerosus. Normal vulvar skin controls did not exhibit chromosome 17 polysomy (cells with more than four FISH signals), whereas 56% of normal vulvar skin associated with cancer did. Moreover, the frequency of polysomy significantly increased as the histological classification progressed from normal to inflammatory to neoplastic lesions. The largest mean value and variance for chromosome 17 copy number was identified in SCCs (2.4 +/- 1.0) with intermediate values identified, in decreasing order, for SCC in situ (2.1 +/- 1.0), VIN 2 (2.1 +/- 0.8), lichen sclerosus (2.0 +/- 0.5), lichen simplex chronicus (1.9 +/- 0.4), and normal skin associated with SCC (1.8 +/- 0.4) compared with control vulvar skin (1.5 +/- 0. 05). Concordance of chromosome 17 aneusomy between cancers and synchronous skin lesions was found in 48% of patients. Loss of chromosome 17 was identified 5% of all samples and was significantly associated with women with SCC in situ (HPV-related). Both DNA content and Ki-67 labeling positively and significantly correlated with mean chromosome 17 copy number (r = 0.1, P: = 0.007). A high degree of genetic instability (aneuploidy) occurs in the skin surrounding vulvar carcinomas. As these events could be detected in histologically normal skin and inflammatory lesions (lichen sclerosus), chromosomal abnormalities may be a driving force in the early stages of carcinogenesis. Differences in chromosomal patterns (loss or gain) support the concept of at least two pathways in vulvar carcinogenesis.

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data.

PubMed

Li, Xiaohong; Brock, Guy N; Rouchka, Eric C; Cooper, Nigel G F; Wu, Dongfeng; O'Toole, Timothy E; Gill, Ryan S; Eteleeb, Abdallah M; O'Brien, Liz; Rai, Shesh N

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level.

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data

PubMed Central

Li, Xiaohong; Brock, Guy N.; Rouchka, Eric C.; Cooper, Nigel G. F.; Wu, Dongfeng; O’Toole, Timothy E.; Gill, Ryan S.; Eteleeb, Abdallah M.; O’Brien, Liz

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level. PMID:28459823

Type I error probabilities based on design-stage strategies with applications to noninferiority trials.

PubMed

Rothmann, Mark

2005-01-01

When testing the equality of means from two different populations, a t-test or large sample normal test tend to be performed. For these tests, when the sample size or design for the second sample is dependent on the results of the first sample, the type I error probability is altered for each specific possibility in the null hypothesis. We will examine the impact on the type I error probabilities for two confidence interval procedures and procedures using test statistics when the design for the second sample or experiment is dependent on the results from the first sample or experiment (or series of experiments). Ways for controlling a desired maximum type I error probability or a desired type I error rate will be discussed. Results are applied to the setting of noninferiority comparisons in active controlled trials where the use of a placebo is unethical.

Perception of Smoking Risks and Motivation to Quit Among Nontreatment-Seeking Smokers With and Without Schizophrenia

PubMed Central

Kelly, Deanna L.; Raley, Heather G.; Lo, Suzanne; Wright, Katherine; Liu, Fang; McMahon, Robert P.; Moolchan, Eric T.; Feldman, Stephanie; Richardson, Charles M.; Wehring, Heidi J.; Heishman, Stephen J.

2012-01-01

Objective: We examined perceived consequences/benefits of cigarette smoking and motivation for quitting in nontreatment-seeking smokers who had schizophrenia or schizoaffective disorder (N = 100) or had no Axis I psychiatric disorder (normals, N = 100). Methods: Participants completed questionnaires and provided a breath carbon monoxide (CO) sample 10–15 minutes after smoking 1 preferred-brand cigarette. Primary assessments included the Smoking Consequences Questionnaire-Adult, the Reasons for Quitting Scale, and the Stages of Change. Results: There were no differences between the schizophrenia and control group in mean age of smoking onset (16.2 ± 5.4 vs 15.6 ± 5.5 y, P = .44), number of cigarettes daily (17.9 ± 11.6 vs 17.0 ± 7.9, P = 0.51), or in breath CO (28.0 ± 14.5 vs 22.9 ± 8.0 ppm, P = .61). Compared with normals, people with schizophrenia report greater stimulation/state enhancement (P < .0001) and social facilitation (P < .004) from smoking. People with schizophrenia had less appreciation of health risks associated with smoking than normal controls (P < .0001) and were less motivated to quit smoking than normal controls (P = .002), even though they were as likely to be in the preparation stage of change. Immediate reinforcement (P = .04) and health concerns (P = .002) were rated lower as motivators for considering quitting smoking in schizophrenia than normals. People with schizophrenia reported greater motivation to stop smoking due to social pressure/rewards than normals (P = .047). Conclusions: This study underscores the degree to which people with schizophrenia perceive the state-enhancing effects of smoking and their lower appreciation for health risks of smoking compared with normal controls. PMID:21041835

16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment.

PubMed

Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne; Rodríguez-Hilario, Arnold; González, Herminio; Bondy, Jessica; Lawson, Fahcina; Folawiyo, Oluwasina; Michailidi, Christina; Dziedzic, Amanda; Thangavel, Rajagowthamee; Hadar, Tal; Noordhuis, Maartje G; Westra, William; Koch, Wayne; Sidransky, David

2016-08-09

Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection.The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella, with lower numbers of Citrobacter and Neisseraceae genus Kingella. HNSCC patients had a significant loss in richness and diversity of microbiota species (p<0.05) compared to the controls. Overall, the Operational Taxonomic Units network shows that the relative abundance of OTU's within genus Streptococcus, Dialister, and Veillonella can be used to discriminate tumor from control samples (p<0.05). Tumor samples lost Neisseria, Aggregatibacter (Proteobacteria), Haemophillus (Firmicutes) and Leptotrichia (Fusobacteria). Paired taxa within family Enterobacteriaceae, together with genus Oribacterium, distinguish OCSCC samples from OPSCC and normal samples (p<0.05). Similarly, only HPV positive samples have an abundance of genus Gemellaceae and Leuconostoc (p<0.05). Longitudinal analyses of samples taken before and after surgery, revealed a reduction in the alpha diversity measure after surgery, together with an increase of this measure in patients that recurred (p<0.05). These results suggest that microbiota may be used as HNSCC diagnostic and prognostic biomonitors.

16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment

PubMed Central

Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne; Rodríguez-Hilario, Arnold; González, Herminio; Bondy, Jessica; Lawson, Fahcina; Folawiyo, Oluwasina; Michailidi, Christina; Dziedzic, Amanda; Thangavel, Rajagowthamee; Hadar, Tal; Noordhuis, Maartje G.; Westra, William; Koch, Wayne; Sidransky, David

2016-01-01

Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection. The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella, with lower numbers of Citrobacter and Neisseraceae genus Kingella. HNSCC patients had a significant loss in richness and diversity of microbiota species (p<0.05) compared to the controls. Overall, the Operational Taxonomic Units network shows that the relative abundance of OTU's within genus Streptococcus, Dialister, and Veillonella can be used to discriminate tumor from control samples (p<0.05). Tumor samples lost Neisseria, Aggregatibacter (Proteobacteria), Haemophillus (Firmicutes) and Leptotrichia (Fusobacteria). Paired taxa within family Enterobacteriaceae, together with genus Oribacterium, distinguish OCSCC samples from OPSCC and normal samples (p<0.05). Similarly, only HPV positive samples have an abundance of genus Gemellaceae and Leuconostoc (p<0.05). Longitudinal analyses of samples taken before and after surgery, revealed a reduction in the alpha diversity measure after surgery, together with an increase of this measure in patients that recurred (p<0.05). These results suggest that microbiota may be used as HNSCC diagnostic and prognostic biomonitors. PMID:27259999

Canine epidermal lipid sampling by skin scrub revealed variations between different body sites and normal and atopic dogs

PubMed Central

2014-01-01

Background Previously, we evaluated a minimally invasive epidermal lipid sampling method called skin scrub, which achieved reproducible and comparable results to skin scraping. The present study aimed at investigating regional variations in canine epidermal lipid composition using the skin scrub technique and its suitability for collecting skin lipids in dogs suffering from certain skin diseases. Eight different body sites (5 highly and 3 lowly predisposed for atopic lesions) were sampled by skin scrub in 8 control dogs with normal skin. Additionally, lesional and non-lesional skin was sampled from 12 atopic dogs and 4 dogs with other skin diseases by skin scrub. Lipid fractions were separated by high performance thin layer chromatography and analysed densitometrically. Results No significant differences in total lipid content were found among the body sites tested in the control dogs. However, the pinna, lip and caudal back contained significantly lower concentrations of ceramides, whereas the palmar metacarpus and the axillary region contained significantly higher amounts of ceramides and cholesterol than most other body sites. The amount of total lipids and ceramides including all ceramide classes were significantly lower in both lesional and non-lesional skin of atopic dogs compared to normal skin, with the reduction being more pronounced in lesional skin. The sampling by skin scrub was relatively painless and caused only slight erythema at the sampled areas but no oedema. Histological examinations of skin biopsies at 2 skin scrubbed areas revealed a potential lipid extraction from the transition zone between stratum corneum and granulosum. Conclusions The present study revealed regional variations in the epidermal lipid and ceramide composition in dogs without skin abnormalities but no connection between lipid composition and predilection sites for canine atopic dermatitis lesions. The skin scrub technique proved to be a practicable sampling method for canine epidermal lipids, revealed satisfying results regarding alterations of skin lipid composition in canine atopic dermatitis and might be suitable for epidermal lipid investigations of further canine skin diseases. Although the ceramide composition should be unaffected by the deeper lipid sampling of skin scrub compared to other sampling methods, further studies are required to determine methodological differences. PMID:25012966

Usual normalization strategies for gene expression studies impair the detection and analysis of circadian patterns.

PubMed

Figueredo, Diego de Siqueira; Barbosa, Mayara Rodrigues; Coimbra, Daniel Gomes; Dos Santos, José Luiz Araújo; Costa, Ellyda Fernanda Lopes; Koike, Bruna Del Vechio; Alexandre Moreira, Magna Suzana; de Andrade, Tiago Gomes

2018-03-01

Recent studies have shown that transcriptomes from different tissues present circadian oscillations. Therefore, the endogenous variation of total RNA should be considered as a potential bias in circadian studies of gene expression. However, normalization strategies generally include the equalization of total RNA concentration between samples prior to cDNA synthesis. Moreover, endogenous housekeeping genes (HKGs) frequently used for data normalization may exhibit circadian variation and distort experimental results if not detected or considered. In this study, we controlled experimental conditions from the amount of initial brain tissue samples through extraction steps, cDNA synthesis, and quantitative real time PCR (qPCR) to demonstrate a circadian oscillation of total RNA concentration. We also identified that the normalization of the RNA's yield affected the rhythmic profiles of different genes, including Per1-2 and Bmal1. Five widely used HKGs (Actb, Eif2a, Gapdh, Hprt1, and B2m) also presented rhythmic variations not detected by geNorm algorithm. In addition, the analysis of exogenous microRNAs (Cel-miR-54 and Cel-miR-39) spiked during RNA extraction suggests that the yield was affected by total RNA concentration, which may impact circadian studies of small RNAs. The results indicate that the approach of tissue normalization without total RNA equalization prior to cDNA synthesis can avoid bias from endogenous broad variations in transcript levels. Also, the circadian analysis of 2 -Cycle threshold (Ct) data, without HKGs, may be an alternative for chronobiological studies under controlled experimental conditions.

Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

PubMed

Ehinger, Johannes K; Morota, Saori; Hansson, Magnus J; Paul, Gesine; Elmér, Eskil

2015-06-01

Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease.

Autofluoresence spectroscopy for in-vivo diagnosis of human oral carcinogenesis

NASA Astrophysics Data System (ADS)

Wang, Chih-Yu; Tsai, Tsuimin; Chen, Hsin-Ming; Kuo, Ying-Shiung; Chen, Chin-Tin; Chiang, Chung-Ping

2002-09-01

An in vivo study of human oral cancer diagnosis by using autofluorescence spectroscopy is presented. A Xenon-lamp with a motor-controlled monochromator was adopted as the excitation light source. We chose the excitation wavelength of 330 nm, and the spectral measurement range was from 340 nm to 601 nm. A Y-type fiber bundle was used to guide the excitation light, and collect the autofluorescence of samples. The emitted light was detected by a motor-controlled monochromator and a PMT. After measurement, the measured sites were sectioned and sent for histological examination. In total 15 normal sites, 30 OSF (oral submucosa fibrosis) sites, 26 EH (epithelial hyperkratosis) sites, 13 ED (epithelial dysplasia) sites, and 13 SCC (squamous cell carcinoma) sites were measured. The discriminant algorithm was established by partial-least squares (PLS) method with cross-validation technique. By extracting the first two t-scores of each sample and make scattering plot, we found that the samples of different cancerous stages were in grouped distinct locations, except that samples of ED and EH were mixed together. It means that this algorithm can be used to classify normal, premalignant, and malignant tissues. We conclude that autofluorescence spectroscopy may be useful for in vivo detection of early stage oral cancer.

Hypermethylated APC in serous carcinoma based on a meta-analysis of ovarian cancer.

PubMed

Shen, Chunyan; Sheng, Qifang; Zhang, Xiaojie; Fu, Yuling; Zhu, Kemiao

2016-09-26

The reduced expression of the Adenomatous polyposis coli (APC) gene, a tumor suppressor gene, through promoter hypermethylation has been reported to play a key role in the carcinogenesis. However, the correlation between APC promoter hypermethylation and ovarian cancer (OC) remains to be clarified. A comprehensive literature search was carried out in related research databases. The overall odds ratio (OR) and corresponding 95 % confidence interval (CI) were used to evaluate the effects of APC promoter hypermethylation on OC and clinicopathological characteristics. Ultimately, 12 eligible studies were used in our study, including 806 OC samples, 429 normal controls, 109 benign lesions and 75 LMP samples. The pooled OR showed that APC promoter hypermethylation was significantly higher in OC than in normal and benign controls (OR = 6.18 and OR = 3.26, respectively). No significant correlation was observed between OC and low malignant potential (LMP) tumors (P = 0.436). In the comparison of OC and normal controls, subgroup analysis based on race showed that the overall OR of APC promoter hypermethylation was significant and similar in Asians and Caucasians (OR = 8.34 and OR = 5.39, respectively). A subgroup analysis based on sample type found that the pooled OR was significantly higher in blood than in tissue (OR = 18.71 and OR = 5.74, respectively). A significant association was not observed between APC promoter hypermethylation and tumor grade or tumor stage. The pooled OR indicated that APC promoter hypermethylation was significantly lower in serous carcinoma than in non-serous carcinoma (OR = 0.56, P = 0.02). No obvious publication bias was detected by Egger's test (all P > 0.05). APC promoter hypermethylation may be linked to the increased risk of OC. It was associated with histological type, but not with tumor grade or tumor stage. Moreover, hypermethylated APC may be a noninvasive biomarker using blood samples. Future studies are required to validate these results.

Identification of CSF fistulas by radionuclide counting

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

Yamamoto, Y.; Kunishio, K.; Sunami, N.

1990-07-01

A radionuclide counting method, performed with the patient prone and the neck flexed, was used successfully to diagnose CSF rhinorrhea in two patients. A normal radionuclide ratio (radionuclide counts in pledget/radionuclide counts in 1-ml blood sample) was obtained in 11 normal control subjects. Significance was determined to be a ratio greater than 0.37. Use of radionuclide counting method of determining CSF rhinorrhea is recommended when other methods have failed to locate a site of leakage or when posttraumatic meningitis suggests subclinical CSF rhinorrhea.

Influence of population versus convenience sampling on sample characteristics in studies of cognitive aging.

PubMed

Brodaty, Henry; Mothakunnel, Annu; de Vel-Palumbo, Melissa; Ames, David; Ellis, Kathryn A; Reppermund, Simone; Kochan, Nicole A; Savage, Greg; Trollor, Julian N; Crawford, John; Sachdev, Perminder S

2014-01-01

We examined whether differences in findings of studies examining mild cognitive impairment (MCI) were associated with recruitment methods by comparing sample characteristics in two contemporaneous Australian studies, using population-based and convenience sampling. The Sydney Memory and Aging Study invited participants randomly from the electoral roll in defined geographic areas in Sydney. The Australian Imaging, Biomarkers and Lifestyle Study of Ageing recruited cognitively normal (CN) individuals via media appeals and MCI participants via referrals from clinicians in Melbourne and Perth. Demographic and cognitive variables were harmonized, and similar diagnostic criteria were applied to both samples retrospectively. CN participants recruited via convenience sampling were younger, better educated, more likely to be married and have a family history of dementia, and performed better cognitively than those recruited via population-based sampling. MCI participants recruited via population-based sampling had better memory performance and were less likely to carry the apolipoprotein E ε4 allele than clinically referred participants but did not differ on other demographic variables. A convenience sample of normal controls is likely to be younger and better functioning and that of an MCI group likely to perform worse than a purportedly random sample. Sampling bias should be considered when interpreting findings. Copyright © 2014 Elsevier Inc. All rights reserved.

High-resolution microendoscope imaging of inverted papilloma and normal sinonasal mucosa: evaluation of interobserver concordance.

PubMed

Parasher, Arjun K; Kidwai, Sarah M; Schorn, Victor J; Goljo, Erden; Weinberg, Alan D; Richards-Kortum, Rebecca; Sikora, Andrew G; Iloreta, Alfred Marc; Govindaraj, Satish; Miles, Brett A

2015-12-01

High-resolution microendoscopy (HRME) enables real-time imaging of epithelial tissue. The utility of this novel imaging modality for inverted papilloma has not been previously described. This study examines the ability of otolaryngologists to differentiate between images of inverted papilloma and normal sinonasal mucosa obtained with a HRME. Inverted papilloma and normal sinonasal mucosa specimens were stained with a contrast agent, proflavine. HRME images were subsequently captured. Histopathological diagnosis was obtained for each sample. Quality-controlled images were used to assemble a training set. After reviewing the training images, 6 otolaryngologists without prior HRME experience reviewed and classified test images. Five samples of inverted papilloma and 2 normal sinonasal mucosa samples were collected. Four representative images from each specimen were used for the 28-image test set. The mean accuracy among all reviewers was 89.9% (95% confidence interval [CI], 84.3% to 94.0%). The sensitivity to correctly identify inverted papilloma was 86.7% (95% CI, 79.2% to 92.2%), and the specificity was 92.9% (95% CI, 89.0% to 100.0%). The Fleiss kappa interrater reliability score was 0.80 (95% CI, 0.70 to 0.89). Inverted papilloma and normal sinonasal mucosa have distinct HRME imaging characteristics. Otolaryngologists can be successfully trained to distinguish between inverted papilloma and normal sinonasal mucosa. HRME is a feasible tool for identification of inverted papilloma. By conducting future in vivo trials, HRME potentially may enable real-time surgical margin determination during surgical excision of inverted papilloma. © 2015 ARS-AAOA, LLC.

Statistical process control applied to mechanized peanut sowing as a function of soil texture.

PubMed

Zerbato, Cristiano; Furlani, Carlos Eduardo Angeli; Ormond, Antonio Tassio Santana; Gírio, Lucas Augusto da Silva; Carneiro, Franciele Morlin; da Silva, Rouverson Pereira

2017-01-01

The successful establishment of agricultural crops depends on sowing quality, machinery performance, soil type and conditions, among other factors. This study evaluates the operational quality of mechanized peanut sowing in three soil types (sand, silt, and clay) with variable moisture contents. The experiment was conducted in three locations in the state of São Paulo, Brazil. The track-sampling scheme was used for 80 sampling locations of each soil type. Descriptive statistics and statistical process control (SPC) were used to evaluate the quality indicators of mechanized peanut sowing. The variables had normal distributions and were stable from the viewpoint of SPC. The best performance for peanut sowing density, normal spacing, and the initial seedling growing stand was found for clayey soil followed by sandy soil and then silty soil. Sandy or clayey soils displayed similar results regarding sowing depth, which was deeper than in the silty soil. Overall, the texture and the moisture of clayey soil provided the best operational performance for mechanized peanut sowing.

[Study of the phase transformation of TiO2 with in-situ XRD in different gas].

PubMed

Ma, Li-Jing; Guo, Lie-Jin

2011-04-01

TiO2 sample was prepared by sol-gel method from chloride titanium. The phase transformation of the prepared TiO2 sample was studied by in-situ XRD and normal XRD in different gas. The experimental results showed that the phase transformation temperatures of TiO2 were different under in-situ or normal XRD in different kinds of gas. The transformation of amorphous TiO2 to anatase was controlled by kinetics before 500 degrees C. In-situ XRD showed that the growth of anatase was inhibited, but the transformation of anatase to rutile was accelerated under inactive nitrogen in contrast to air. Also better crystal was obtained under hydrogen than in argon. These all showed that external oxygen might accelerate the growth of TiO2, but reduced gas might partly counteract the negative influence of lack of external oxygen. The mechanism of phase transformation of TiO2 was studied by in-situ XRD in order to control the structure in situ.

Statistical process control applied to mechanized peanut sowing as a function of soil texture

PubMed Central

Furlani, Carlos Eduardo Angeli; da Silva, Rouverson Pereira

2017-01-01

The successful establishment of agricultural crops depends on sowing quality, machinery performance, soil type and conditions, among other factors. This study evaluates the operational quality of mechanized peanut sowing in three soil types (sand, silt, and clay) with variable moisture contents. The experiment was conducted in three locations in the state of São Paulo, Brazil. The track-sampling scheme was used for 80 sampling locations of each soil type. Descriptive statistics and statistical process control (SPC) were used to evaluate the quality indicators of mechanized peanut sowing. The variables had normal distributions and were stable from the viewpoint of SPC. The best performance for peanut sowing density, normal spacing, and the initial seedling growing stand was found for clayey soil followed by sandy soil and then silty soil. Sandy or clayey soils displayed similar results regarding sowing depth, which was deeper than in the silty soil. Overall, the texture and the moisture of clayey soil provided the best operational performance for mechanized peanut sowing. PMID:28742095

A multifunctional force microscope for soft matter with in situ imaging

NASA Astrophysics Data System (ADS)

Roberts, Paul; Pilkington, Georgia A.; Wang, Yumo; Frechette, Joelle

2018-04-01

We present the multifunctional force microscope (MFM), a normal and lateral force-measuring instrument with in situ imaging. In the MFM, forces are calculated from the normal and lateral deflection of a cantilever as measured via fiber optic sensors. The motion of the cantilever is controlled normally by a linear micro-translation stage and a piezoelectric actuator, while the lateral motion of the sample is controlled by another linear micro-translation stage. The micro-translation stages allow for travel distances that span 25 mm with a minimum step size of 50 nm, while the piezo has a minimum step size of 0.2 nm, but a 100 μm maximum range. Custom-designed cantilevers allow for the forces to be measured over 4 orders of magnitude (from 50 μN to 1 N). We perform probe tack, friction, and hydrodynamic drainage experiments to demonstrate the sensitivity, versatility, and measurable force range of the instrument.

Towards a new standardized method for circulating miRNAs profiling in clinical studies: Interest of the exogenous normalization to improve miRNA signature accuracy.

PubMed

Vigneron, Nicolas; Meryet-Figuière, Matthieu; Guttin, Audrey; Issartel, Jean-Paul; Lambert, Bernard; Briand, Mélanie; Louis, Marie-Hélène; Vernon, Mégane; Lebailly, Pierre; Lecluse, Yannick; Joly, Florence; Krieger, Sophie; Lheureux, Stéphanie; Clarisse, Bénédicte; Leconte, Alexandra; Gauduchon, Pascal; Poulain, Laurent; Denoyelle, Christophe

2016-08-01

Circulating miRNAs are promising biomarkers in oncology but have not yet been implemented in the clinic given the lack of concordance across studies. In order to increase the cross-studies reliability, we attempted to reduce and to control the circulating miRNA expression variability between patients. First, to maximize profiling signals and to reduce miRNA expression variability, three isolation kits were compared and the NucleoSpin(®) kit provided higher miRNA concentrations than the other widely used kits. Second, to control inter-sample variability during the profiling step, the exogenous miRNAs normalization method commonly used for RT-qPCR validation step was adapted to microarray experiments. Importantly, exogenous miRNAs presented two-fold lower inter-sample variability than the widely used endogenous miR-16-5p reflecting that the latter is subject to both biological and technical variability. Although Caenorhabditis elegans miRNAs isolation yields were heterogeneous, they correlated to each other and to their geometrical mean across samples. The normalization based on the geometrical mean of three exogenous miRNAs increased the correlation up-to 0.97 between the microarrays and individual RT-qPCR steps of circulating miRNAs expression. Overall, this new strategy open new avenue to identify reliable circulating miRNA signatures for translation into clinical practice. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

Plemons, R.E.; Hopwood, W.H. Jr.; Hamilton, J.H.

For a number of years the Oak Ridge Y-12 Plant Laboratory has been analyzing coal predominately for the utilities department of the Y-12 Plant. All laboratory procedures, except a Leco sulfur method which used the Leco Instruction Manual as a reference, were written based on the ASTM coal analyses. Sulfur is analyzed at the present time by two methods, gravimetric and Leco. The laboratory has two major endeavors for monitoring the quality of its coal analyses. (1) A control program by the Plant Statistical Quality Control Department. Quality Control submits one sample for every nine samples submitted by the utilitiesmore » departments and the laboratory analyzes a control sample along with the utilities samples. (2) An exchange program with the DOE Coal Analysis Laboratory in Bruceton, Pennsylvania. The Y-12 Laboratory submits to the DOE Coal Laboratory, on even numbered months, a sample that Y-12 has analyzed. The DOE Coal Laboratory submits, on odd numbered months, one of their analyzed samples to the Y-12 Plant Laboratory to be analyzed. The results of these control and exchange programs are monitored not only by laboratory personnel, but also by Statistical Quality Control personnel who provide statistical evaluations. After analysis and reporting of results, all utilities samples are retained by the laboratory until the coal contracts have been settled. The utilities departments have responsibility for the initiation and preparation of the coal samples. The samples normally received by the laboratory have been ground to 4-mesh, reduced to 0.5-gallon quantities, and sealed in air-tight containers. Sample identification numbers and a Request for Analysis are generated by the utilities departments.« less

Comparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls

PubMed Central

Alizadeh, Anahita; Mehrpour, Omid; Nikkhah, Karim; Bayat, Golnaz; Espandani, Mahsa; Golzari, Alireza; Jarahi, Lida; Foroughipour, Mohsen

2016-01-01

Introduction Multiple Sclerosis (MS) is defined as one of the inflammatory autoimmune disorders and is common. Its exact etiology is unclear. There are some evidences on the role of environmental factors in susceptible genetics. The aim of this study is to evaluate the possible role of Selenium, Zinc, Copper, Lead and Magnesium metals in Multiple Sclerosis patients. Methods In the present analytical cross-sectional study, 56 individuals including 26 patients and 30 healthy controls were enrolled in the evaluation. The serum level of Se, Zn, Cu, Pb were quantified in graphite furnace conditions and flame conditions by utilizing an atomic absorption Perkin Elmer spectrophotometer 3030. The serum levels of Mg were measured by auto analyzer 1500 BT. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls by using independent-samples t-test for normal distribution and Mann-Whitney U test as a non-parametric test. All statistical analyses were carried out using SPSS 11.0. Results As well as the Zn, Cu, and Se, there was no significant difference between MS patients and healthy individuals in Pb concentrations (p-value = 0.11, 0.14, 0.32, 0.20 respectively) but the level of Mg was significantly different (p= 0.001). Conclusion All serum concentrations of Zn, Pb, Se, Cu in both groups were in normal ranges and there was no difference in MS patients compared with the healthy group who were matched in genetics. Blood level of Mg was significantly lower in MS patients. But it should be noted that even with the low level of serum magnesium in MS patients, this value is still in the normal range. PMID:27757186

Interaction of attentional and motor control processes in handwriting.

PubMed

Brown, T L; Donnenwirth, E E

1990-01-01

The interaction between attentional capacity, motor control processes, and strategic adaptations to changing task demands was investigated in handwriting, a continuous (rather than discrete) skilled performance. Twenty-four subjects completed 12 two-minute handwriting samples under instructions stressing speeded handwriting, normal handwriting, or highly legible handwriting. For half of the writing samples, a concurrent auditory monitoring task was imposed. Subjects copied either familiar (English) or unfamiliar (Latin) passages. Writing speed, legibility ratings, errors in writing and in the secondary auditory task, and a derived measure of the average number of characters held in short-term memory during each sample ("planning unit size") were the dependent variables. The results indicated that the ability to adapt to instructions stressing speed or legibility was substantially constrained by the concurrent listening task and by text familiarity. Interactions between instructions, task concurrence, and text familiarity in the legibility ratings, combined with further analyses of planning unit size, indicated that information throughput from temporary storage mechanisms to motor processes mediated the loss of flexibility effect. Overall, the results suggest that strategic adaptations of a skilled performance to changing task circumstances are sensitive to concurrent attentional demands and that departures from "normal" or "modal" performance require attention.

Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions.

PubMed

Saigal, Sonal; Bhargava, Ankur; Mehra, S K; Dakwala, Falguni

2011-07-01

The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia.

Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions

PubMed Central

Saigal, Sonal; Bhargava, Ankur; Mehra, S. K.; Dakwala, Falguni

2011-01-01

Background and Objective: The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. Materials and Methods: Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. Results: In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. Conclusion: The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia. PMID:22090762

Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients

PubMed Central

Habib, Samy L

2009-01-01

Background The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. Results Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phopho-tuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. Conclusion These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients. PMID:19265534

[The expression and significance of RORγT in periapical granulomas and radicular cysts].

PubMed

Lang, Xiao-ying; Li, Song

2014-08-01

To identify retinoic acid-related orphan nuclear receptor-γT (RORγT), the specific markers of T helper 17 (Th17) cells by immunohistochemical analysis to confirm the presence of Th17 cells in periapical lesions. Eighteen radicular cysts (RCs) and 22 periapical granulomas (PGs) were collected in the Department of Oral Pathology after periapical surgery as the experimental samples. Five alveolar bone samples were obtained from a group of impacted third molars recommended for extraction as the control samples. The protein expression of RORγT was measured by immunohistochemical analysis for all samples. In addition, the protein expression of IL-17 was measured at the same time. Statistical analysis was performed using SPSS 17.0 software package to evaluate the differences of expression of RORγT and IL-17 according to type of lesion (PG vs. RC vs. control group) and intensity of the inflammatory infiltration (mild vs. moderate vs. severe vs. control group). RORγT+ cells were detected in all periapical lesions tissues, and the expression of RORγT was significantly higher in periapical lesions than in normal tissues which had no expression of RORγT (P<0.05). Significant differences in the expression of RORγT were observed among healthy tissues, lesions with mild inflammation, moderate inflammation and severe inflammation (P<0.05), respectively. Positive correlations between RORγT and IL-17 protein levels were observed in PGs (r=0.935,P<0.05) and RCs (r=0.803,P<0.05), respectively. The results demonstrates a significant increase in the expression of RORγT in patients suffering from periapical lesions in comparison with normal control subjects, indicating that Th17 cells are more likely to exist in periapical lesions.

Perceived health status and cardiometabolic risk among a sample of youth in Mexico

PubMed Central

Flores, Yvonne N.; Shaibi, Gabriel Q.; Morales, Leo S.; Salmerón, Jorge; Skalicky, Anne M.; Edwards, Todd C.; Gallegos-Carrillo, Katia; Patrick, Donald L.

2015-01-01

Purpose To examine differences in self-reported perceived mental and physical health status (PHS), as well as known cardiometabolic risk factors in a sample of normal weight, overweight, and obese Mexican youths. Methods Cross-sectional analysis of 164 youths aged 11-18 years recruited in Cuernavaca, Mexico. Participants completed a self-administered questionnaire that included measures of generic and weight-specific quality of life (QoL), perceived health, physical function, depressive symptoms, and body shape satisfaction. Height, weight and waist circumference were measured and body mass index (BMI) was determined. Fasting blood samples from participants yielded levels of glucose, triglycerides, and cholesterol (total, HDL and LDL). Results Nearly 50% of participants were female, 21% had a normal BMI, 39% were overweight, and 40% were obese. Obese youths reported significantly lower measures of PHS and showed an increase in cardiometabolic risk, compared to normal weight youths. Physical functioning, generic and weight-specific QoL were inversely associated with BMI, waist circumference and glucose. Depressive symptoms were positively correlated with BMI, waist circumference, glucose levels and HDL cholesterol. No correlation was found between PHS and cardiometabolic risk measures after controlling for BMI. Conclusions In this sample of Mexican youths, obesity was associated with a significantly lower PHS and increased cardiometabolic risk. PMID:25648756

Apparatus for Measuring Total Emissivity of Small, Low-Emissivity Samples

NASA Technical Reports Server (NTRS)

Tuttle, James; DiPirro, Michael J.

2011-01-01

An apparatus was developed for measuring total emissivity of small, lightweight, low-emissivity samples at low temperatures. The entire apparatus fits inside a small laboratory cryostat. Sample installation and removal are relatively quick, allowing for faster testing. The small chamber surrounding the sample is lined with black-painted aluminum honeycomb, which simplifies data analysis. This results in the sample viewing a very high-emissivity surface on all sides, an effect which would normally require a much larger chamber volume. The sample and chamber temperatures are individually controlled using off-the-shelf PID (proportional integral derivative) controllers, allowing flexibility in the test conditions. The chamber can be controlled at a higher temperature than the sample, allowing a direct absorptivity measurement. The lightweight sample is suspended by its heater and thermometer leads from an isothermal bar external to the chamber. The wires run out of the chamber through small holes in its corners, and the wires do not contact the chamber itself. During a steady-state measurement, the thermometer and bar are individually controlled at the same temperature, so there is zero heat flow through the wires. Thus, all of sample-temperature-control heater power is radiated to the chamber. Double-aluminized Kapton (DAK) emissivity was studied down to 10 K, which was about 25 K colder than any previously reported measurements. This verified a minimum in the emissivity at about 35 K and a rise as the temperature dropped to lower values.

Effects of Hyperbaric Oxygen Treatment on Renal System.

PubMed

Tezcan, Orhan; Caliskan, Ahmet; Demirtas, Sinan; Yavuz, Celal; Kuyumcu, Mahir; Nergiz, Yusuf; Guzel, Abdulmenap; Karahan, Oguz; Ari, Seyhmus; Soker, Sevda; Yalinkilic, Ibrahim; Turkdogan, Kenan Ahmet

2017-01-01

Hyperbaric oxygen (HBO) treatment is steadily increasing as a therapeutic modality for various types of diseases. Although good clinical outcomes were reported with HBO treatment for various diseases, the multisystemic effects of this modality are still unclear. This study aimed to investigate the renal effects of HBO experimentally. Fourteen New Zealand White rabbits were divided into 2 groups randomly as the control group and the study group. The study group received HBO treatment for 28 days (100% oxygen at 2.5 atmospheres for 90 minutes daily) and the control group was used to obtain normal renal tissue of the animal genus. After the intervention period, venous blood samples were obtained, and renal tissue samples were harvested for comparisons. Normal histological morphology was determined with Masson trichrome staining and periodic acid-Schiff staining in the control group. Atrophic glomerular structures, vacuolated tubule cells, and degeneration were detected in the renal samples of the study group with Masson trichrome staining. Additionally, flattening was observed on the brush borders of the proximal tubules, and tubular dilatation was visualized with periodic acid-Schiff staining. The histopathologic disruption of renal morphology was verified with detection of significantly elevated kidney function laboratory biomarkers in the study group. Our findings suggests that HBO has adverse effects on renal glomerulus and proximal tubules. However, the functional effects of this alteration should be investigated with further studies.

A survey of FRAXE allele sizes in three populations

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

Zhong, N.; Ju, W.; Curley, D.

1996-08-09

FRAXE is a fragile site located at Xq27-8, which contains polymorphic triplet GCC repeats associated with a CpG island. Similar to FRAXA, expansion of the GCC repeats results in an abnormal methylation of the CpG island and is associated with a mild mental retardation syndrome (FRAXE-MR). We surveyed the GCC repeat alleles of FRAXE from 3 populations. A total of 665 X chromosomes including 416 from a New York Euro-American sample (259 normal and 157 with FRAXA mutations), 157 from a Chinese sample (144 normal and 13 FRAXA), and 92 from a Finnish sample (56 normal and 36 FRAXA) weremore » analyzed by polymerase chain reaction. Twenty-seven alleles, ranging from 4 to 39 GCC repeats, were observed. The modal repeat number was 16 in the New York and Finnish samples and accounted for 24% of all the chromosomes tested (162/665). The modal repeat number in the Chinese sample was 18. A founder effect for FRAXA was suggested among the Finnish FRAXA samples in that 75% had the FRAXE 16 repeat allele versus only 30% of controls. Sequencing of the FRAXE region showed no imperfections within the GCC repeat region, such as those commonly seen in FRAXA. The smaller size and limited range of repeats and the lack of imperfections suggests the molecular mechanisms underlying FRAXE triplet mutations may be different from those underlying FRAXA. 27 refs., 4 figs., 1 tab.« less

OP17MICRORNA PROFILING USING SMALL RNA-SEQ IN PAEDIATRIC LOW GRADE GLIOMAS

PubMed Central

Jeyapalan, Jennie N.; Jones, Tania A.; Tatevossian, Ruth G.; Qaddoumi, Ibrahim; Ellison, David W.; Sheer, Denise

2014-01-01

INTRODUCTION: MicroRNAs regulate gene expression by targeting mRNAs for translational repression or degradation at the post-transcriptional level. In paediatric low-grade gliomas a few key genetic mutations have been identified, including BRAF fusions, FGFR1 duplications and MYB rearrangements. Our aim in the current study is to profile aberrant microRNA expression in paediatric low-grade gliomas and determine the role of epigenetic changes in the aetiology and behaviour of these tumours. METHOD: MicroRNA profiling of tumour samples (6 pilocytic, 2 diffuse, 2 pilomyxoid astrocytomas) and normal brain controls (4 adult normal brain samples and a primary glial progenitor cell-line) was performed using small RNA sequencing. Bioinformatic analysis included sequence alignment, analysis of the number of reads (CPM, counts per million) and differential expression. RESULTS: Sequence alignment identified 695 microRNAs, whose expression was compared in tumours v. normal brain. PCA and hierarchical clustering showed separate groups for tumours and normal brain. Computational analysis identified approximately 400 differentially expressed microRNAs in the tumours compared to matched location controls. Our findings will then be validated and integrated with extensive genetic and epigenetic information we have previously obtained for the full tumour cohort. CONCLUSION: We have identified microRNAs that are differentially expressed in paediatric low-grade gliomas. As microRNAs are known to target genes involved in the initiation and progression of cancer, they provide critical information on tumour pathogenesis and are an important class of biomarkers.

Short- and Long-Term Sleep Stability in Insomniacs and Healthy Controls.

PubMed

Gaines, Jordan; Vgontzas, Alexandros N; Fernandez-Mendoza, Julio; Basta, Maria; Pejovic, Slobodanka; He, Fan; Bixler, Edward O

2015-11-01

Assess the short- and long-term stability of sleep duration in patients with insomnia and normal-sleeping controls. Observational short-term and prospective studies. Sleep laboratory. Patients with insomnia (n = 150) and controls (n = 151) were recruited from the local community or sleep disorders clinic. A subsample of 95 men from the Penn State Adult Cohort (PSAC) were followed up 2.6 y after their initial visit. Participants underwent a physical examination and 8-h polysomnography (PSG) recording for 3 consecutive nights (controls and insomniacs), or 2 single nights separated by several years (PSAC). Intraclass correlation coefficients (ICCs) assessed the stability of the variables total sleep time (TST), sleep onset latency (SOL), and wake after sleep onset (WASO). We also examined persistence of the first-night classification of "short" versus "normal" sleep duration on subsequent nights. Stability of TST, SOL, and WASO based on 1 night were slight to moderate in both patients with insomnia (ICC = 0.37-0.57) and controls (ICC = 0.39-0.59), and became substantial to almost perfect when based on the average of 3 nights (ICC = 0.64-0.81). We observed similar degrees of stability for TST and WASO in the longitudinal sample, with moderate stability based on a single night and substantial stability based on both nights. In examining the persistence of "short" and "normal" sleep duration, 71.4% (controls), 74.7% (patients with insomnia), and 72.6% (longitudinal sample) of participants retained their first-night classifications over subsequent nights. Sleep duration variables, particularly total sleep time based on 3 consecutive nights in both patients with insomnia and controls or two single-night recordings separated by several years, are stable and reflect a person's habitual sleep. Furthermore, a single night in the laboratory may be useful for reliably classifying one's sleep duration. © 2015 Associated Professional Sleep Societies, LLC.

Structural and functional correlates in color vision deficiency

PubMed Central

Gupta, A; Laxmi, G; Nittala, M G; Raman, R

2011-01-01

Purpose The aim of this study is to assess the photoreceptor integrity, using spectral domain optical coherence tomography (SD-OCT), and to measure the retinal sensitivity of patients with congenital red–green color vision deficiency (CVD). Methods In all, 14 eyes from 7 patients with congenital red–green CVD (diagnosed by Farnsworth Munsell 100 hue test), and 14 eyes from 7 control subjects were examined by SD-OCT and microperimetry. Radial scans (7-mm) were taken of the macula. The center of the fovea was defined. The thickness of different retinal layers, at the foveal center, and at multiple defined points along all six radial scans, was measured. The median readings were compared between the two groups using Mann–Whitney U-test. Results SD-OCT demonstrated normal total retinal thickness, normal thickness of the photoreceptor layer, normal thickness of the outer nuclear layer, normal vertical thickness of the outer segments (OSs), and normal vertical thickness of the inner segments. OS horizontal diameter was less in left eye in cases with CVD when compared with controls. The mean retinal and foveal sensitivity was similar between cases and controls. Conclusions In subjects with congenital red–green CVD, there are no discernible anatomical abnormalities seen on SD-OCT in various retinal layers, except for a narrower foveal pit. However, further studies with larger sample size are required. PMID:21494280

Immune responses to Epstein-Barr virus in individuals with systemic and organ specific autoimmune disorders.

PubMed

Kannangai, R; Sachithanandham, J; Kandathil, A J; Ebenezer, D L; Danda, D; Vasuki, Z; Thomas, N; Vasan, S K; Sridharan, G

2010-01-01

Autoimmune diseases usually manifest in genetically predisposed individuals following an environmental trigger. There are several viral infections including Epstein-Barr virus (EBV) implicated in the pathogenesis of autoimmune disorders. The aim of this study was to look at the antibody pattern to EBV proteins in the plasma of both systemic and organ specific autoimmune disorders, estimate pro-inflammatory plasma cytokines (IL-8 and TNF-alpha) among these autoimmune patients and compare the observations with those in normal healthy controls. Samples from 44 rheumatoid arthritis patients, 25 Hashimoto's thyroiditis patients, appropriately age and sex matched healthy controls were tested for EBV IgM antibodies by an immunoblot assay and two cytokines (IL-8 and TNF-alpha) by commercial assays. Among the rheumatoid arthritis patients, 23 (52%) were positive for EBNA1 antibody, while 13 (52%) of the Hashimoto's thyroiditis patients and 12 (30%) of the healthy controls showed similar bands. The intensity of the bands was high in the autoimmune patients when compared to the bands seen in control samples. The difference in the EBNA1 reactivity between rheumatoid arthritis patients and controls were significant (P = 0.038). There was a significant difference in the IgM reactivity to VCAp19 protein between patients and controls (P = 0.011). Our study showed an increased EBV activation among the autoimmune patient groups compared to the normal healthy controls. Further studies are required to delineate the association between the aetiology of autoimmune disorders and EBV.

Normal-inverse bimodule operation Hadamard transform ion mobility spectrometry.

PubMed

Hong, Yan; Huang, Chaoqun; Liu, Sheng; Xia, Lei; Shen, Chengyin; Chu, Yannan

2018-10-31

In order to suppress or eliminate the spurious peaks and improve signal-to-noise ratio (SNR) of Hadamard transform ion mobility spectrometry (HT-IMS), a normal-inverse bimodule operation Hadamard transform - ion mobility spectrometry (NIBOHT-IMS) technique was developed. In this novel technique, a normal and inverse pseudo random binary sequence (PRBS) was produced in sequential order by an ion gate controller and utilized to control the ion gate of IMS, and then the normal HT-IMS mobility spectrum and the inverse HT-IMS mobility spectrum were obtained. A NIBOHT-IMS mobility spectrum was gained by subtracting the inverse HT-IMS mobility spectrum from normal HT-IMS mobility spectrum. Experimental results demonstrate that the NIBOHT-IMS technique can significantly suppress or eliminate the spurious peaks, and enhance the SNR by measuring the reactant ions. Furthermore, the gas CHCl 3 and CH 2 Br 2 were measured for evaluating the capability of detecting real sample. The results show that the NIBOHT-IMS technique is able to eliminate the spurious peaks and improve the SNR notably not only for the detection of larger ion signals but also for the detection of small ion signals. Copyright © 2018 Elsevier B.V. All rights reserved.

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel.

PubMed

Fernandez-Rozadilla, Ceres; Kartsonaki, Christiana; Woolley, Connor; McClellan, Michael; Whittington, Deb; Horgan, Gareth; Leedham, Simon; Kriaucionis, Skirmantas; East, James; Tomlinson, Ian

2018-03-06

Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors. We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms. Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations. PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.

Plasma-derived microparticles in polycythaemia vera.

PubMed

Ahadon, M; Abdul Aziz, S; Wong, C L; Leong, C F

2018-04-01

Microparticles are membrane bound vesicles, measuring less than 1.0 um, which are released during cellular activation or during apoptosis. Studies have shown that these circulating microparticles play a role in coagulation, cell signaling and cellular interactions. Increased levels of circulating microparticles have been observed in a number of conditions where there is vascular dysfunction, thrombosis and inflammation. The objective of this study was to determine the various plasma-derived microparticles in patients with polycythaemia vera (PV) in Universiti Kebangsaan Malaysia Medical Centre and to compare them with normal control. A total of 15 patients with PV and 15 healthy volunteers were included in this cross-sectional descriptive study. Plasma samples from both patients and healthy volunteers were prepared and further processed for isolation of microparticles. Flow cytometry analyses were then carried out in all samples to determine the cellular origin of the microparticles. Full blood count parameters for both groups were also collected. Data collected were analyzed using SPSS version 12.0. Patients with PV had a significantly higher percentage of platelet derived microparticles compared to healthy controls (P <0.05). The control group had a higher level of endothelial derived microparticles but the differences were not statistically significant (P > 0.05). The median percentage of positive events for platelet derived microparticles was higher in patients with PV compared to normal healthy controls.

Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy.

PubMed

Sleeper, Meg M; Rosato, Bradley P; Bansal, Seema; Avadhani, Narayan G

2012-11-01

To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy. Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy). Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs. Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy. Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

Purification of Bone Marrow Clonal Cells from Patients with Myelodysplastic Syndrome via IGF-IR

PubMed Central

He, Qi; Chang, Chun-Kang; Xu, Feng; Zhang, Qing-Xia; Shi, Wen-Hui; Li, Xiao

2015-01-01

Malignant clonal cells purification can greatly benefit basic and clinical studies in myelodysplastic syndrome (MDS). In this study, we investigated the potential of using type 1 insulin-like growth factor receptor (IGF-IR) as a marker for purification of malignant bone marrow clonal cells from patients with MDS. The average percentage of IGF-IR expression in CD34+ bone marrow cells among 15 normal controls was 4.5%, 70% of which also express the erythroid lineage marker CD235a. This indicates that IGF-IR mainly express in erythropoiesis. The expression of IGF-IR in CD34+ cells of 55 MDS patients was significantly higher than that of cells from the normal controls (54.0 vs. 4.5%). Based on the pattern of IGF-IR expression in MDS patients and normal controls, sorting of IGF-IR-positive and removal of CD235a-positive erythroid lineage cells with combination of FISH detection were performed on MDS samples with chromosomal abnormalities. The percentage of malignant clonal cells significantly increased after sorting. The enrichment effect was more significant in clonal cells with a previous percentage lower than 50%. This enrichment effect was present in samples from patients with +8, 5q-/-5, 20q-/-20 or 7q-/-7 chromosomal abnormalities. These data suggest that IGF-IR can be used as a marker for MDS bone marrow clonal cells and using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells. PMID:26469401

Induction of chromosome aberrations in cultured human lymphocytes treated with sand dust storm fine particles (PM2.5).

PubMed

Wei, Aili; Meng, Ziqiang

2006-09-30

The clastogenic activity of airborne air fine particulate matter (PM2.5, particulates with an aerodynamic diameter < or =2.5 microm) has already been demonstrated. However little is known about the health risks associated with sand dust storm PM2.5 and its extract. In order to investigate the clastogenic activity of sand dust storm PM2.5 (include its organic and inorganic extract) on human lymphocytes, the normal PM2.5 and sand dust storm PM2.5 samples were collected in Wuwei city (Gansu Province) and Baotou city (Inner Mongolia), China. The chromosomal aberration (CA) test was employed and the cells were treated with 0, 33, 100, 300 microg ml(-1) sand dust storm or normal ambient air PM2.5 suspension (physiological saline as solvent control), or inorganic extract (0, 75, 150, 300 microg ml(-1), physiological saline as solvent control) or organic extract (0, 20, 40, 80 microg ml(-1), DMSO as solvent control) at the beginning of the cell culture. The results indicated that sand dust storm PM2.5 and its extract as well as normal samples can induce increase in CA frequency. With the increase of treatment concentrations the CA frequency increased and the mitotic index (MI) values declined in a dose-response manner. In the same concentrates, the CA frequency of normal ambient air PM2.5 and its extract were significant higher than those of sand dust storm PM2.5 (P<0.05 or 0.01) except the treatment of Wuwei sample at higher doses (100, 300 microg ml(-1)), the treatment of inorganic extract of PM2.5 at the highest dose (300 microg ml(-1)) and the treatment of organic extract of PM2.5 at the higher dose (40 and 80 microg ml(-1)) either in Baotou or in Wuwei (P>0.05). The toxicity of sand dust storm PM2.5 and its extract at high dose is very potent. CA frequency of normal PM2.5 (include its organic extract) from Baotou were higher than those of Wuwei especially in low and middle dose (P<0.05), but the treatment results of sand dust storm PM2.5 (include its all extract) was not significant different between the cities (P>0.05).

Methotrexate Reduces DNA Integrity in Sperm From Men With Inflammatory Bowel Disease.

PubMed

Ley, Dana; Jones, Jeffrey; Parrish, John; Salih, Sana; Caldera, Freddy; Tirado, Edna; Leader, Benjamin; Saha, Sumona

2018-06-01

There are few data on the effects of methotrexate on reproductive capacity in men with inflammatory bowel diseases (IBDs). We performed a case-control study to determine the effects of methotrexate on sperm quality and genetic integrity. We compared sperm samples from 7 men with IBD who had been exposed to methotrexate for at least 3 months with sperm samples collected from 1912 age-matched men at fertility centers (controls) where sperm parameters would be expected to be worse than those of the general population. Sperm were evaluated by basic semen analysis and advanced sperm integrity testing. In samples from men with IBD, all basic semen analysis parameters were within normal limits. However, these samples had reduced sperm integrity, based on significant increases in levels of DNA fragmentation and damage from oxidative stress compared with controls. Our findings indicate that methotrexate can reduce DNA integrity in sperm and cause damage via oxidative stress. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Economic consequences of improved temperature forecasts: An experiment with the Florida citrus growers (control group results). [weather forecasting

NASA Technical Reports Server (NTRS)

1977-01-01

A demonstration experiment is being planned to show that frost and freeze prediction improvements are possible utilizing timely Synchronous Meteorological Satellite temperature measurements and that this information can affect Florida citrus grower operations and decisions. An economic experiment was carried out which will monitor citrus growers' decisions, actions, costs and losses, and meteorological forecasts and actual weather events and will establish the economic benefits of improved temperature forecasts. A summary is given of the economic experiment, the results obtained to date, and the work which still remains to be done. Specifically, the experiment design is described in detail as are the developed data collection methodology and procedures, sampling plan, data reduction techniques, cost and loss models, establishment of frost severity measures, data obtained from citrus growers, National Weather Service, and Federal Crop Insurance Corp., resulting protection costs and crop losses for the control group sample, extrapolation of results of control group to the Florida citrus industry and the method for normalization of these results to a normal or average frost season so that results may be compared with anticipated similar results from test group measurements.

The effectivenes of science domain-based science learning integrated with local potency

NASA Astrophysics Data System (ADS)

Kurniawati, Arifah Putri; Prasetyo, Zuhdan Kun; Wilujeng, Insih; Suryadarma, I. Gusti Putu

2017-08-01

This research aimed to determine the significant effect of science domain-based science learning integrated with local potency toward science process skills. The research method used was a quasi-experimental design with nonequivalent control group design. The population of this research was all students of class VII SMP Negeri 1 Muntilan. The sample of this research was selected through cluster random sampling, namely class VII B as an experiment class (24 students) and class VII C as a control class (24 students). This research used a test instrument that was adapted from Agus Dwianto's research. The aspect of science process skills in this research was observation, classification, interpretation and communication. The analysis of data used the one factor anova at 0,05 significance level and normalized gain score. The significance level result of science process skills with one factor anova is 0,000. It shows that the significance level < alpha (0,05). It means that there was significant effect of science domain-based science learning integrated with local potency toward science learning process skills. The results of analysis show that the normalized gain score are 0,29 (low category) in control class and 0,67 (medium category) in experiment class.

[Aberrant topological properties of whole-brain functional network in chronic right-sided sensorineural hearing loss: a resting-state functional MRI study].

PubMed

Zhang, Lingling; Liu, Bin; Xu, Yangwen; Yang, Ming; Feng, Yuan; Huang, Yaqing; Huan, Zhichun; Hou, Zhaorui

2015-02-03

To investigate the topological properties of the functional brain network in unilateral sensorineural hearing loss patients. In this study, we acquired resting-state BOLD- fMRI data from 19 right-sided SNHL patients and 31 healthy controls with normal hearing and constructed their whole brain functional networks. Two-sample two-tailed t-tests were performed to investigate group differences in topological parameters between the USNHL patients and the controls. Partial correlation analysis was conducted to determine the relationships between the network metrics and USNHL-related variables. Both USNHL patients and controls exhibited small-word architecture in their brain functional networks within the range 0. 1 - 0. 2 of sparsity. Compared to the controls, USNHL patients showed significant increase in characteristic path length and normalized characteristic path length, but significant decrease in global efficiency. Clustering coefficient, local efficiency and normalized clustering coefficient demonstrated no significant difference. Furthermore, USNHL patients exhibited no significant association between the altered network metrics and the duration of USNHL or the severity of hearing loss. Our results indicated the altered topological properties of whole brain functional networks in USNHL patients, which may help us to understand pathophysiologic mechanism of USNHL patients.

Parallel factor ChIP provides essential internal control for quantitative differential ChIP-seq.

PubMed

Guertin, Michael J; Cullen, Amy E; Markowetz, Florian; Holding, Andrew N

2018-04-17

A key challenge in quantitative ChIP combined with high-throughput sequencing (ChIP-seq) is the normalization of data in the presence of genome-wide changes in occupancy. Analysis-based normalization methods were developed for transcriptomic data and these are dependent on the underlying assumption that total transcription does not change between conditions. For genome-wide changes in transcription factor (TF) binding, these assumptions do not hold true. The challenges in normalization are confounded by experimental variability during sample preparation, processing and recovery. We present a novel normalization strategy utilizing an internal standard of unchanged peaks for reference. Our method can be readily applied to monitor genome-wide changes by ChIP-seq that are otherwise lost or misrepresented through analytical normalization. We compare our approach to normalization by total read depth and two alternative methods that utilize external experimental controls to study TF binding. We successfully resolve the key challenges in quantitative ChIP-seq analysis and demonstrate its application by monitoring the loss of Estrogen Receptor-alpha (ER) binding upon fulvestrant treatment, ER binding in response to estrodiol, ER mediated change in H4K12 acetylation and profiling ER binding in patient-derived xenographs. This is supported by an adaptable pipeline to normalize and quantify differential TF binding genome-wide and generate metrics for differential binding at individual sites.

Depersonalization: physiological or pathological in adolescents?

PubMed

Fagioli, Francesca; Dell'Erba, Alice; Migliorini, Vanina; Stanghellini, Giovanni

2015-05-01

This study analyzed the presence of DP symptoms in a sample of both psychiatric patients and normal subjects, addressing the issue of DP symptoms in adolescence. A total of 267 subjects (149 patients and 118 healthy controls) aged between 14 and 65 years, were assessed by means of CDS, the SCID-I and the K-SADS. The sample was then divided into two subsamples with a cut-off age of 21 years. As expected CDS score was significantly higher in the patient group compared to the healthy control group. As for the age issue, among patients no statistical difference was found comparing subjects over and under 21 years, whereas in the sample of healthy controls, subjects under 21 years reported CDS scores significantly higher. While in adults DP symptoms are frequently associated with mental disorders, in adolescents they could be considered as a quasi-physiological phenomenon. Copyright © 2015 Elsevier Inc. All rights reserved.

Difference in normal values of median nerve cross-sectional area between Dutch and Indian subjects.

PubMed

Burg, Ellen Walhout-van; Bathala, Lokesh; Visser, Leo H

2014-07-01

Ultrasound (US) measurement of the median nerve cross-sectional area (CSA) at the wrist is a useful diagnostic test for carpal tunnel syndrome (CTS). We compared median nerve normal values between samples of Indian and Dutch populations. The median nerve was examined by US at the wrist in 100 healthy volunteers in India and 137 volunteers in The Netherlands using the same protocol. Median nerve CSA at the wrist (7.0 ± 1.1 mm(2)) in the Indian cohort was lower in comparison to the Dutch cohort (8.3 ± 1.9 mm(2) ; P < 0.05). This difference was still present after controlling for age, height, and weight (P = 0.001). CSA normal values for the median nerve were different between the examined population samples even after correcting for age, height, and weight. This enforces the idea that laboratories around the world should obtain their own normative data. Copyright © 2013 Wiley Periodicals, Inc.

Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles.

PubMed

Giangarra, Jenna E; Barry, Sabrina L; Dahlgren, Linda A; Lanz, Otto I; Benitez, Marian E; Werre, Stephen R

2018-04-25

To identify if synovial fluid prostaglandin E 2 increases in response to a single intra-articular dose of bupivacaine in the normal canine stifle. There were no significant differences in synovial fluid prostaglandin E 2 (PGE 2 ) concentrations between treatment groups or over time within bupivacaine or saline groups. Samples requiring ≥ 3 arthrocentesis attempts had significantly higher PGE 2 concentrations compared to samples requiring 1 or 2 attempts. Following correction for number of arthrocentesis attempts, PGE 2 concentrations were significantly higher than baseline at 24 and 48 h in the bupivacaine group; however there were no significant differences between the bupivacaine and saline groups. In normal dogs, a single bupivacaine injection did not cause significant synovial inflammation, as measured by PGE 2 concentrations, compared to saline controls. Future research should minimize aspiration attempts and include evaluation of the synovial response to bupivacaine in clinical cases with joint disease.

Neuropsychological Assessment of Adult Offenders

ERIC Educational Resources Information Center

Marceau, Roger; Meghani, Rehana; Reddon, John R.

2008-01-01

This report is primarily concerned with reporting on the normative results obtained on a large sample of serious adult offenders. An expanded Halstead-Reitan Neuropsychological Test Battery was administered to 584 adult offenders (OF), 132 normal controls (NC), and 494 acute psychiatric patients (PP). Subjects were between 18 and 44 years of age.…

Personality correlates of criminals: A comparative study between normal controls and criminals

PubMed Central

Sinha, Sudhinta

2016-01-01

Background: Personality is a major factor in many kinds of behavior, one of which is criminal behavior. To determine what makes a criminal “a criminal,” we must understand his/her personality. This study tries to identify different personality traits which link criminals to their personality. Materials and Methods: In the present study, 37 male criminals of district jail of Dhanbad (Jharkhand) and 36 normal controls were included on a purposive sampling basis. Each criminal was given a personal datasheet and Cattel's 16 personality factors (PFs) scale for assessing their sociodemographic variables and different personality traits. Objective: The objective of this study was to examine the relation between personality traits and criminal behavior, and to determine whether such factors are predictive of future recidivism. Results: Results indicated high scores on intelligence, impulsiveness, suspicion, self-sufficient, spontaneity, self-concept control factors, and very low scores on emotionally less stable on Cattel's 16 PFs scale in criminals as compared with normal. Conclusion: Criminals differ from general population or non criminals in terms of personality traits. PMID:28163407

Brain cholinesterase activity of apparently normal wild birds

USGS Publications Warehouse

Hill, E.F.

1988-01-01

Organophosphorus and carbamate pesticides are potent anticholinesterase substances that have killed large numbers of wild birds of various species. Cause of death is diagnosed by demonstration of depressed brain cholinesterase (ChE) activity in combination with chemical detection of anticholinesterase residue in the affected specimen. ChE depression is determined by comparison of the affected specimen to normal ChE activity for a sample of control specimens of the same species, but timely procurement of controls is not always possible. Therefore, a reference file of normal whole brain ChE activity is provided for 48 species of wild birds from North America representing 11 orders and 23 families for use as emergency substitutes in diagnosis of anticholinesterase poisoning. The ChE values, based on 83 sets of wild control specimens from across the United States, are reproducible provided the described procedures are duplicated. Overall, whole brain ChE activity varied nearly three-fold among the 48 species represented, but it was usually similar for closely related species. However, some species were statistically separable in most families and some species of the same genus differed as much as 50%.

Body mass index, immune status, and virological control in HIV-infected men who have sex with men.

PubMed

Blashill, Aaron J; Mayer, Kenneth H; Crane, Heidi M; Grasso, Chris; Safren, Steven A

2013-01-01

Prior cross-sectional studies have found inconsistent relationships between body mass index (BMI) and disease progression in HIV-infected individuals. Cross-sectional and longitudinal analyses were conducted on data from a sample of 864 HIV-infected men who have sex with men (MSM) obtained from a large, nationally distributed HIV clinical cohort. Of the 864 HIV-infected MSM, 394 (46%) were of normal weight, 363 (42%) were overweight, and 107 (12%) were obese at baseline. The baseline CD4 count was 493 (standard error [SE] = 9), with viral load (log10) = 2.4 (SE = .04), and 561 (65%) were virologically suppressed. Over time, controlling for viral load, highly active antiretroviral therapy (HAART) adherence, age, and race/ethnicity, overweight and obese HIV-infected men possessed higher CD4 counts than that of normal weight HIV-infected men. Further, overweight and obese men possessed lower viral loads than that of normal weight HIV-infected men. For HIV-infected MSM, in this longitudinal cohort study, possessing a heavier than normal BMI is longitudinally associated with improved immunological health.

Epigenetic Silencing of the MLH1 Promoter in Relation to the Development of Gastric Cancer and its use as a Biomarker for Patients with Microsatellite Instability: a Systematic Analysis.

PubMed

Hu, Guimei; Qin, Lijun; Zhang, Xinjun; Ye, Guoliang; Huang, Tao

2018-01-01

Human mutL homolog 1 (MLH1) promoter methylation was reported in gastric cancer (GC). This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. The combined odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area under the curve (AUC) were analyzed. A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis. MLH1 promoter methylation was significantly higher in GC samples than in gastric adenomas, chronic gastritis, adjacent tissues, normal gastric mucosa, and normal healthy blood samples, but it exhibited a similar frequency in GC vs. intestinal metaplasia and dysplasia samples. MLH1 promoter methylation correlated with age and microsatellite instability (MSI), but it was not associated with gender, H. pylori infection, smoking, drinking behaviors, pathological histology, tumor differentiation, clinical stage, lymph node status, distant metastasis, or overall survival of GC. MLH1 promoter methylation exhibited a poor sensitivity value (< 0.5) in patients with GC compared with adjacent tissues, gastric adenomas, chronic gastritis, normal gastric mucosa, and normal healthy blood samples. The pooled sensitivity, specificity, and AUC of MLH1 promoter methylation in GC with MSI vs. GC with microsatellite stability (MSS) samples were 0.64, 0.96, and 0.90, respectively. Our results suggest that the detection of MLH1 promoter methylation may be a potential prognostic biomarker for GC patients with MSI. © 2018 The Author(s). Published by S. Karger AG, Basel.

Validation of reference genes aiming accurate normalization of qRT-PCR data in Dendrocalamus latiflorus Munro.

PubMed

Liu, Mingying; Jiang, Jing; Han, Xiaojiao; Qiao, Guirong; Zhuo, Renying

2014-01-01

Dendrocalamus latiflorus Munro distributes widely in subtropical areas and plays vital roles as valuable natural resources. The transcriptome sequencing for D. latiflorus Munro has been performed and numerous genes especially those predicted to be unique to D. latiflorus Munro were revealed. qRT-PCR has become a feasible approach to uncover gene expression profiling, and the accuracy and reliability of the results obtained depends upon the proper selection of stable reference genes for accurate normalization. Therefore, a set of suitable internal controls should be validated for D. latiflorus Munro. In this report, twelve candidate reference genes were selected and the assessment of gene expression stability was performed in ten tissue samples and four leaf samples from seedlings and anther-regenerated plants of different ploidy. The PCR amplification efficiency was estimated, and the candidate genes were ranked according to their expression stability using three software packages: geNorm, NormFinder and Bestkeeper. GAPDH and EF1α were characterized to be the most stable genes among different tissues or in all the sample pools, while CYP showed low expression stability. RPL3 had the optimal performance among four leaf samples. The application of verified reference genes was illustrated by analyzing ferritin and laccase expression profiles among different experimental sets. The analysis revealed the biological variation in ferritin and laccase transcript expression among the tissues studied and the individual plants. geNorm, NormFinder, and BestKeeper analyses recommended different suitable reference gene(s) for normalization according to the experimental sets. GAPDH and EF1α had the highest expression stability across different tissues and RPL3 for the other sample set. This study emphasizes the importance of validating superior reference genes for qRT-PCR analysis to accurately normalize gene expression of D. latiflorus Munro.

Reduced lymphoid response to skin allotransplants in cows with hepatic lipidosis.

PubMed

Wentink, G H; van den Ingh, T S; Rutten, V P; Müller, K E; Wensing, T

1999-04-01

The immune responsiveness of cows with hepatic lipidosis (fatty liver) in comparison to control cows with a normal liver fat content was tested by applying skin allotransplants to the skin of the back of cows on day 3 after parturition. Immunoreactivity was determined by semiquantitative counting of the number of infiltrating lymphocytes in the recipient skin adjacent to the allotransplants during a period of 21 days. There were more invading lymphocytes in samples from control cows than there were in samples from cows with hepatic lipidosis. It was concluded that cows with hepatic lipidosis have a reduced lymphoid response to skin allotransplants.

[Preparation of freeze - drying control materials of IgG antibody against Schistosoma japonicum for immunodetection kits].

PubMed

Jin, Huang; Chun-Lian, Tang; Zu-Wu, Tu; Li, Tang; Ke-Hui, Zhang; Qian, Li; Jun, Ye

2018-04-18

To prepare freeze-drying control materials of IgG antibody against Schistosoma japonicum for detection kits. The serum samples of schistosomiasis patients from endemic areas and normal people without history of schistosome infection or contact with infested water in Hubei Province were collected. All the sera were detected by the method approved by China Food and Drug Administration and selected for preparation of quality control samples. Totally twelve positive quality control materials, ten negative quality control materials, and one sensitive and one precision quality control materials were screened. According to the positive serum level, the positive degrees of quality control materials were divided into strong, medium and weak levels. The stability could be valid for one year. The freeze-drying quality control materials of IgG antibody against S. japonicum for detection kits are prepared. They are easy to use and have good stability, and therefore, they may meet the requirement of quality control for the detection of schistosomiasis diagnostics kits.

Influences of Normalization Method on Biomarker Discovery in Gas Chromatography-Mass Spectrometry-Based Untargeted Metabolomics: What Should Be Considered?

PubMed

Chen, Jiaqing; Zhang, Pei; Lv, Mengying; Guo, Huimin; Huang, Yin; Zhang, Zunjian; Xu, Fengguo

2017-05-16

Data reduction techniques in gas chromatography-mass spectrometry-based untargeted metabolomics has made the following workflow of data analysis more lucid. However, the normalization process still perplexes researchers, and its effects are always ignored. In order to reveal the influences of normalization method, five representative normalization methods (mass spectrometry total useful signal, median, probabilistic quotient normalization, remove unwanted variation-random, and systematic ratio normalization) were compared in three real data sets with different types. First, data reduction techniques were used to refine the original data. Then, quality control samples and relative log abundance plots were utilized to evaluate the unwanted variations and the efficiencies of normalization process. Furthermore, the potential biomarkers which were screened out by the Mann-Whitney U test, receiver operating characteristic curve analysis, random forest, and feature selection algorithm Boruta in different normalized data sets were compared. The results indicated the determination of the normalization method was difficult because the commonly accepted rules were easy to fulfill but different normalization methods had unforeseen influences on both the kind and number of potential biomarkers. Lastly, an integrated strategy for normalization method selection was recommended.

Continuous human cell lines and method of making same

DOEpatents

Stampfer, Martha R.

1989-01-01

Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo[a]pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors.

Personality dimensions in bulimia nervosa, binge eating disorder, and obesity.

PubMed

Peterson, Carol B; Thuras, Paul; Ackard, Diann M; Mitchell, James E; Berg, Kelly; Sandager, Nora; Wonderlich, Stephen A; Pederson, Melissa W; Crow, Scott J

2010-01-01

The purpose of this investigation was to examine differences in personality dimensions among individuals with bulimia nervosa, binge eating disorder, non-binge eating obesity, and a normal-weight comparison group as well as to determine the extent to which these differences were independent of self-reported depressive symptoms. Personality dimensions were assessed using the Multidimensional Personality Questionnaire in 36 patients with bulimia nervosa, 54 patients with binge eating disorder, 30 obese individuals who did not binge eat, and 77 normal-weight comparison participants. Participants with bulimia nervosa reported higher scores on measures of stress reaction and negative emotionality compared to the other 3 groups and lower well-being scores compared to the normal-weight comparison and the obese samples. Patients with binge eating disorder scored lower on well-being and higher on harm avoidance than the normal-weight comparison group. In addition, the bulimia nervosa and binge eating disorder groups scored lower than the normal-weight group on positive emotionality. When personality dimensions were reanalyzed using depression as a covariate, only stress reaction remained higher in the bulimia nervosa group compared to the other 3 groups and harm avoidance remained higher in the binge eating disorder than the normal-weight comparison group. The higher levels of stress reaction in the bulimia nervosa sample and harm avoidance in the binge eating disorder sample after controlling for depression indicate that these personality dimensions are potentially important in the etiology, maintenance, and treatment of these eating disorders. Although the extent to which observed group differences in well-being, positive emotionality, and negative emotionality reflect personality traits, mood disorders, or both, is unclear, these features clearly warrant further examination in understanding and treating bulimia nervosa and binge eating disorder.

The mechanical and physical properties of concrete containing polystyrene beads as aggregate and palm oil fuel ash as cement replacement material

NASA Astrophysics Data System (ADS)

Adnan, Suraya Hani; Abadalla, Musab Alfatih Salim; Jamellodin, Zalipah

2017-10-01

One of the disadvantages of normal concrete is the high self-weight of the concrete. Density of the normal concrete is in the range of 2200 kg/m3 to 2600 kg/ m3. This heavy self-weight make it as an uneconomical structural material. Advantages of expended polystyrene beads in lightweight concrete is its low in density which can reduce the dead load (self-weight) Improper disposal of the large quantity of palm oil fuel ash which has been produced may contribute to environmental problem in future. In this study, an alternative of using palm oil fuel ash as a cement replacement material is to improve the properties of lightweight concrete. The tests conducted in this study were slump test, compression strength, splitting tensile and water absorption test. These samples were cured under water curing condition for 7, 28 and 56 days before testing. Eight types of mixtures were cast based on percentage (25%, 50%) of polystyrene beads replacement for control samples and (25%, 50%) of polystyrene beads by different ratio 10%, 15%, and 20% replacement of palm oil fuel ash, respectively. Samples with 25% polystyrene beads and 10% palm oil fuel ash obtained the highest compressive strength which is 16.8 MPa, and the splitting tensile strength is 1.57 MPa. The water absorption for samples 25%, 50% polystyrene and 20% palm oil fuel ash is 3.89% and 4.67%, respectively which is lower compared to control samples.

Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the endometrium of patients with repeated implantation failure after in vitro fertilization.

PubMed

Turgut, A; Goruk, N Y; Tunc, S Y; Agaçayak, E; Alabalik, U; Yalinkaya, A; Gül, T

2014-01-01

To compare the immunohistochemical expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in repeated implantation failure (RIF) patients with normal fertile controls. The study group consisted of primary infertile patients with RIF and normal fertile controls between January 2011 and February 2013. Endometrial samples received at the luteal phase were exposed to immunohistochemical staining for EMMPRIN antibodies. EMMPRIN expression of endometrial glandular epithelial cells, stromal cells and vascular endothelial cells were evaluated. The main outcome measure was defined as immunohistochemical score with regard to the severity and extent of staining. The study group consisted of 26 primary infertile patients, whereas the control group consisted of 40 normal fertile controls. The fertile group was found to have stronger expression of EMMPRIN than the study group when endometrial glandular epithelial cells, stromal cells and vascular endothelial cells were evaluated with regards to the severity of staining (p < 0.001), the extent of staining (p < 0.001) and total staining score (p < 0.001). This is the first study showing low expression of EMMPRIN in the endometrial cells of the patients with RIF compared with fertile healthy controls. We suggest that reduced EMMPRIN expression in the human endometrium may lead to poor endometrial receptivity.

Variation of Ultrasound Findings in the First Trimester Examination of Recurrent Cases With Trisomy 21

PubMed Central

Daniilidis, Aggelos; Balaouras, Dimitrios; Chitzios, Dimitrios; Balaouras, Georgios; Capilna, Mihai; Asimakopoulos, Efstratios

2015-01-01

Increased nuchal translucency (NT) is present in about 50% of cases with trisomy 21. Very often the nuchal edema evolves in hydrops fetalis until the second trimester. Furthermore, a small amount of cases with a normal NT and trisomy 21 exhibit anatomical anomalies. We present a case of a 21-year-old woman, nulliparous, with a history of one termination of pregnancy and a smoking quitter. The prenatal control was negative for TORCH. During the first trimester scan on the 13th week, the NT was found 2.7 mm, the ductus venosus Doppler was normal, and the nasal bone was present. Hydrops fetalis was present though, and the parents were advised for chorionic villus sampling (CVS), but they opted for termination of pregnancy. The molecular control by QF-PCR showed normal karyotype for 13 and 18, a male fetus, but non-dysjunction trisomy 21 was present. Parental karyotype was advised, but they refused to perform it. One year later, the couple had another pregnancy. On the 12th week scan, the NT was found 1.0 mm, the ductus venosus Doppler was normal, and the nasal bone was present, but encephalocele was also found, and the parents consented again for termination of pregnancy. The new molecular control showed the same results. This time parental karyotype was performed. The father had a normal one, whereas the mother showed reversed p11 and q13 zones in chromosome 2. Genetical consulting and prenatal cytological control was advised in before next pregnancy. PMID:25883716

Power of tests of normality for detecting contaminated normal samples

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

Thode, H.C. Jr.; Smith, L.A.; Finch, S.J.

1981-01-01

Seventeen tests of normality or goodness of fit were evaluated for power at detecting a contaminated normal sample. This study used 1000 replications each of samples of size 12, 17, 25, 33, 50, and 100 from six different contaminated normal distributions. The kurtosis test was the most powerful over all sample sizes and contaminations. The Hogg and weighted Kolmogorov-Smirnov tests were second. The Kolmogorov-Smirnov, chi-squared, Anderson-Darling, and Cramer-von-Mises tests had very low power at detecting contaminated normal random variables. Tables of the power of the tests and the power curves of certain tests are given.

Human Papillomavirus Type 16 Viral Load Is Higher in Human Immunodeficiency Virus-Seropositive Women with High-Grade Squamous Intraepithelial Lesions Than in Those with Normal Cytology Smears

PubMed Central

Lefevre, Jonas; Hankins, Catherine; Money, Deborah; Rachlis, Anita; Pourreaux, Karina; Coutlée, François

2004-01-01

Human papillomavirus type 16 (HPV-16) viral load in cervicovaginal lavage samples collected from 66 human immunodeficiency virus-seropositive women was inversely correlated with blood CD4 count (P = 0.002). HPV-16 viral load was 81-fold higher in women with cervical smears suggestive of high-grade lesions (median, 4,425,883 copies/μg of DNA) than in women with normal smears (median, 54,576), controlling for age (P = 0.006). PMID:15131192

A comparative proteomic analysis of bile for biomarkers of cholangiocarcinoma.

PubMed

Laohaviroj, Marut; Potriquet, Jeremy; Jia, Xinying; Suttiprapa, Sutas; Chamgramol, Yaovalux; Pairojkul, Chawalit; Sithithaworn, Paiboon; Mulvenna, Jason; Sripa, Banchob

2017-06-01

Cholangiocarcinoma is a primary malignant tumor of the bile duct epithelium. Cholangiocarcinoma is usually detected at an advanced stage when successful treatment is no longer possible. As the tumor originates from the bile duct epithelium, bile is an ideal source of tumor biomarkers for cholangiocarcinoma. In this study, we used a quantitative proteomics approach to identify potential tumor-associated proteins in the bile fluid of six cholangiocarcinoma patients. Three different gross-appearance tumor types were used in the analysis: mass-forming type ( n = 2), periductal infiltrating type ( n = 2), and intraductal growth type ( n = 2). Two bile samples from non-cancerous patients were used as controls. Isobaric labeling, coupled with Tandem mass spectrometry, was used to quantify protein levels in the bile of cholangiocarcinoma and control patients. In all, 63 proteins were significantly increased in cholangiocarcinoma bile compared to normal bile. Alpha-1-antitrypsin was one of the overexpressed proteins that increased in cholangiocarcinoma bile samples. Immunohistochemical analysis revealed that alpha-1-antitrypsin was detected in 177 (50%) of 354 cholangiocarcinoma tissues from our Tissue Bank. Immunoblotting of 54 cholangiocarcinoma bile samples showed that alpha-1-antitrypsin was positive in 38 (70%) samples. Fecal enzyme-linked immunosorbent assay showed that alpha-1-antitrypsin level was able to distinguish cholangiocarcinoma patients from normal individuals. In conclusion, alpha-1-antitrypsin is a potential marker for early diagnosis of cholangiocarcinoma.

Elevated interleukin-1β in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis.

PubMed

Sun, Li; Zhang, Xiaoxu; Dai, Fang; Shen, Jijia; Ren, Cuiping; Zuo, Chunlin; Zhang, Qiu

2016-08-01

To explore the relationship between IL-1β expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1β in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. Although no significant differences in IL-1β levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1β mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1β mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1β levels with the pathogenesis of HT. Our study suggests that IL-1β may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.

Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs.

PubMed

Saunders, Christopher T; Wong, Wendy S W; Swamy, Sajani; Becq, Jennifer; Murray, Lisa J; Cheetham, R Keira

2012-07-15

Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity. We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. We demonstrate that the method has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests. The Strelka workflow source code is available at ftp://strelka@ftp.illumina.com/. csaunders@illumina.com

Beta Human Papillomavirus Infection Is Prevalent in Elephantiasis and Exhibits a Productive Phenotype: A Case-Control Study.

PubMed

Carlson, John Andrew; Rady, Peter; Kadam, Pooja; He, Qin; Simonette, Rebecca; Tyring, Stephen

2017-06-01

Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0-9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis.

Effect on long-term average spectrum of pop singers' vocal warm-up with vocal function exercises.

PubMed

Guzman, Marco; Angulo, Mabel; Muñoz, Daniel; Mayerhoff, Ross

2013-04-01

Abstract This case-control study aimed to investigate if there is any change on the spectral slope declination immediately after vocal function exercises (VFE) vs traditional vocal warm-up exercises in normal singers. Thirty-eight pop singers with perceptually normal voices were divided into two groups: an experimental group (n = 20) and a control group (n = 18). One single session with VFE for the experimental group and traditional singing warm-up exercises for the control group was applied. Voice was recorded before and after the exercises. The recorded tasks were to read a phonetically balanced text and to sing a song. Long-term average spectrum (LTAS) analysis included alpha ratio, L1-L0 ratio, and singing power ratio (SPR). Acoustic parameters of voice samples pre- and post-training were compared. Comparison between VFE and control group was also performed. Significant changes after treatment included the alpha ratio and singing power ratio in speaking voice, and SPR in the singing voice for VFE group. The traditional vocal warm-up of the control group also showed pre-post changes. Significant differences between VFE group and control group for alpha ratio and SPR were found in speaking voice samples. This study demonstrates that VFE have an immediate effect on the spectrum of the voice, specifically a decrease on the spectral slope declination. The results of this study provide support for the advantageous effect of VFE as vocal warm-up on voice quality.

Carbohydrate availability of arroz caldo with lambda-carrageenan.

PubMed

Dumelod, B D; Ramirez, R P; Tiangson, C L; Barrios, E B; Panlasigui, L N

1999-07-01

Total available carbohydrate (sugars and starches) and total dietary fiber (soluble and insoluble) make up the total carbohydrate content of a food. Soluble fiber decreases the availability of glucose by delaying its absorption in the proximal small intestine, thus reducing the postprandial glucose levels (Jenkins et al., 1978; Schneeman, 1987a). Carrageenan, a seaweed extract, is a good source of soluble fiber (Montaño et al., 1985). This study aimed to determine the effect of carrageenan incorporation into arroz caldo on carbohydrate availability by monitoring the postprandial blood glucose levels of normal subjects. Control and experimental arroz caldo samples were prepared and subjected to proximate analysis and feeding studies. The total dietary fiber (TDF) content of the experimental (2.03%) was about thrice that of the control (0.68%). Using randomized crossover design, preweighed 55 g available carbohydrate serving portions of control and experimental arroz caldo samples, with 3.45 and 14.84 g TDF, respectively, were fed to ten fasting normal subjects then their postprandial blood glucose levels were determined at 15, 30, 45, 60 and 90 min intervals. Results of the short-term in vivo study showed that the mean postprandial glycaemic responses of subjects after consuming the experimental sample were significantly lower than the levels after consuming the control at 15, 45, and 90 min (P < or = 0.05) and at 30 min (P < or = 0.001). Likewise, the mean glucose area under the curve was significantly lower (P < or = 0.01) after consumption of experimental (69.22 +/- 32.94) arroz caldo than control (147.29 +/- 53.34). The hypoglycaemic effect of carrageenan may prove useful in the prevention and management of metabolic conditions such as diabetes.

The effect of chronic prostatitis on zinc concentration of prostatic fluid and seminal plasma: a systematic review and meta-analysis.

PubMed

Cui, Dong; Han, GuangWei; Shang, YongGang; Mu, LiJun; Long, QingZhi; Du, YueFeng

2015-01-01

Prostatitis is a common disease in urology departments. Prostatic zinc accumulation is connected with the secretory function of the prostate, and zinc concentrations present in prostatic diseases differ greatly from the normal level. Studies have investigated the effect of chronic prostatitis on zinc concentration of prostatic fluid and seminal plasma, but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the effect of chronic prostatitis on the zinc concentration of prostatic fluid and seminal plasma. Systematic literature searches were conducted with PubMed, Embase, Science Direct/Elsevier, CNKI and the Cochrane Library up to March 2015 for case-control studies that involved the relationship between chronic prostatitis and zinc concentration of prostatic fluid and seminal plasma. Meta-analysis was performed with Review Manager and Stata software. Standard mean differences (SMDs) of zinc concentration were identified with 95% confidence intervals (95% CIs) in a random- or fixed-effects model. Our results illustrated that the zinc concentrations in prostatic fluid and seminal plasma from chronic prostatitis patients were significantly lower than normal controls (SMD [95% CI] -246.71 [-347.97, -145.44], -20.74 [-35.11, -6.37], respectively). The sample size of each study was relatively small, and a total of 731 chronic prostatitis patients and 574 normal controls were investigated in all fourteen studies. Several studies related to the subject were excluded due to lack of control data or means and standard deviations. The present study illustrates that there was a significant negative effect of chronic prostatitis on zinc concentrations of prostatic fluid and seminal plasma. Further studies with larger sample sizes are needed to better illuminate the negative impact of chronic prostatitis on zinc concentrations.

Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.

PubMed

Chen, Y K; Huang, Anderson H C; Chan, Anthony W S; Lin, L M

2016-06-01

Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Stone former urine proteome demonstrates a cationic shift in protein distribution compared to normal.

PubMed

Kolbach-Mandel, Ann M; Mandel, Neil S; Hoffmann, Brian R; Kleinman, Jack G; Wesson, Jeffrey A

2017-08-01

Many urine proteins are found in calcium oxalate stones, yet decades of research have failed to define the role of urine proteins in stone formation. This urine proteomic study compares the relative amounts of abundant urine proteins between idiopathic calcium oxalate stone forming and non-stone forming (normal) cohorts to identify differences that might correlate with disease. Random mid-morning urine samples were collected following informed consent from 25 stone formers and 14 normal individuals. Proteins were isolated from urine using ultrafiltration. Urine proteomes for each sample were characterized using label-free spectral counting mass spectrometry, so that urine protein relative abundances could be compared between the two populations. A total of 407 unique proteins were identified with the 38 predominant proteins accounting for >82% of all sample spectral counts. The most highly abundant proteins were equivalent in stone formers and normals, though significant differences were observed in a few moderate abundance proteins (immunoglobulins, transferrin, and epidermal growth factor), accounting for 13 and 10% of the spectral counts, respectively. These proteins contributed to a cationic shift in protein distribution in stone formers compared to normals (22% vs. 18%, p = 0.04). Our data showing only small differences in moderate abundance proteins suggest that no single protein controls stone formation. Observed increases in immunoglobulins and transferrin suggest increased inflammatory activity in stone formers, but cannot distinguish cause from effect in stone formation. The observed cationic shift in protein distribution would diminish protein charge stabilization, which could lead to protein aggregation and increased risk for crystal aggregation.

Identification of appropriate reference genes for normalizing transcript expression by quantitative real-time PCR in Litsea cubeba.

PubMed

Lin, Liyuan; Han, Xiaojiao; Chen, Yicun; Wu, Qingke; Wang, Yangdong

2013-12-01

Quantitative real-time PCR has emerged as a highly sensitive and widely used method for detection of gene expression profiles, via which accurate detection depends on reliable normalization. Since no single control is appropriate for all experimental treatments, it is generally advocated to select suitable internal controls prior to use for normalization. This study reported the evaluation of the expression stability of twelve potential reference genes in different tissue/organs and six fruit developmental stages of Litsea cubeba in order to screen the superior internal reference genes for data normalization. Two softwares-geNorm, and NormFinder-were used to identify stability of these candidate genes. The cycle threshold difference and coefficient of variance were also calculated to evaluate the expression stability of candidate genes. F-BOX, EF1α, UBC, and TUA were selected as the most stable reference genes across 11 sample pools. F-BOX, EF1α, and EIF4α exhibited the highest expression stability in different tissue/organs and different fruit developmental stages. Besides, a combination of two stable reference genes would be sufficient for gene expression normalization in different fruit developmental stages. In addition, the relative expression profiles of DXS and DXR were evaluated by EF1α, UBC, and SAMDC. The results further validated the reliability of stable reference genes and also highlighted the importance of selecting suitable internal controls for L. cubeba. These reference genes will be of great importance for transcript normalization in future gene expression studies on L. cubeba.

Retinal cell imaging in myopic chickens using adaptive optics multiphoton microscopy.

PubMed

Bueno, Juan M; Palacios, Raquel; Giakoumaki, Anastasia; Gualda, Emilio J; Schaeffel, Frank; Artal, Pablo

2014-03-01

Abnormal eye growth induced by visual deprivation can modify the structure and density of the retinal cells. We have used an adaptive optics multiphoton microscope to image photoreceptors (PRs) and ganglion cells (GCs) at different retinal locations in unstained retinas of chicken eyes with about 10D of myopia and their normal-sighted fellow eyes. In all samples, the local averaged inter-PR distance increased with eccentricity. No significant differences in PR density were found between control and myopic eyes. GC density declined in myopic eyes compared to control eyes and the inter-cell distance increased. In normal eyes, the size of the GC cell bodies increased approximately two-fold between the area centralis and the peripheral retina. In myopic eyes, this trend was preserved but the GC bodies were larger at each retinal location, compared to control eyes. Obviously, GC morphology is changing when the retinal area is enlarged in myopic eyes.

Retinal cell imaging in myopic chickens using adaptive optics multiphoton microscopy

PubMed Central

Bueno, Juan M.; Palacios, Raquel; Giakoumaki, Anastasia; Gualda, Emilio J.; Schaeffel, Frank; Artal, Pablo

2014-01-01

Abnormal eye growth induced by visual deprivation can modify the structure and density of the retinal cells. We have used an adaptive optics multiphoton microscope to image photoreceptors (PRs) and ganglion cells (GCs) at different retinal locations in unstained retinas of chicken eyes with about 10D of myopia and their normal-sighted fellow eyes. In all samples, the local averaged inter-PR distance increased with eccentricity. No significant differences in PR density were found between control and myopic eyes. GC density declined in myopic eyes compared to control eyes and the inter-cell distance increased. In normal eyes, the size of the GC cell bodies increased approximately two-fold between the area centralis and the peripheral retina. In myopic eyes, this trend was preserved but the GC bodies were larger at each retinal location, compared to control eyes. Obviously, GC morphology is changing when the retinal area is enlarged in myopic eyes. PMID:24688804

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

Jones, David Robert; Fensin, Saryu Jindal; Dippo, Olivia

Here, we present a study on the spall strength of additive manufactured (AM) Ti-6Al-4V. Samples were obtained from two pieces of selective laser melted (SLM, a powder bed fusion technique) Ti-6Al-4V such that the response to dynamic tensile loading could be investigated as a function of the orientation between the build layers and the loading direction. A sample of wrought bar-stock Ti-6Al-4V was also tested to act as a baseline representing the traditionally manufactured material response. A single-stage light gas-gun was used to launch a thin flyer plate into the samples, generating a region of intense tensile stress on amore » plane normal to the impact direction. The rear free surface velocity time history of each sample was recorded with laser-based velocimetry to allow the spall strength to be calculated. The samples were also soft recovered to enable post-mortem characterization of the spall damage evolution. Results showed that when the tensile load was applied normal to the interfaces between the build layers caused by the SLM fabrication process the spall strength was drastically reduced, dropping to 60% of that of the wrought material. However, when loaded parallel to the AM build layer interfaces the spall strength was found to remain at 95% of the wrought control, suggesting that when loading normal to the AM layer interfaces, void nucleation is facilitated more readily due to weaknesses along these boundaries. Quasi-static testing of the same sample orientations revealed a much lower degree of anisotropy, demonstrating the importance of rate-dependent studies for damage evolution in AM materials.« less

Indentation stiffness does not discriminate between normal and degraded articular cartilage.

PubMed

Brown, Cameron P; Crawford, Ross W; Oloyede, Adekunle

2007-08-01

Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage samples that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress-strain and stiffness characteristics. While our results demonstrated a 25% depreciation in the stiffness of individual samples after proteoglycan depletion, they also showed that when compared to the stiffness of normal samples only 17% lie outside the range of the stress-strain behaviour of normal samples. We conclude that the extent of the variability in the properties of normal samples, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage samples with consequences for the application of this mechanical process in the clinical environment.

Relation between Outcomes on a Continuous Performance Test and ADHD Symptoms over Time

ERIC Educational Resources Information Center

Vaughn, Aaron J.; Epstein, Jeffery N.; Rausch, Joseph; Altaye, Mekibib; Langberg, Joshua; Newcorn, Jeffrey H.; Hinshaw, Stephen P.; Hechtman, Lily; Arnold, L. Eugene; Swanson, James M.; Wigal, Timothy

2011-01-01

This study examined the relationship between the developmental trajectories of neuropsychological functioning and ADHD symptomatology in a longitudinal sample of children ages 9 to 14. Participants and measures were derived from the Multimodal Treatment Study for ADHD including 534MTA participants and 254 normal controls. Despite improvement over…

Automatic classification of schizophrenia using resting-state functional language network via an adaptive learning algorithm

NASA Astrophysics Data System (ADS)

Zhu, Maohu; Jie, Nanfeng; Jiang, Tianzi

2014-03-01

A reliable and precise classification of schizophrenia is significant for its diagnosis and treatment of schizophrenia. Functional magnetic resonance imaging (fMRI) is a novel tool increasingly used in schizophrenia research. Recent advances in statistical learning theory have led to applying pattern classification algorithms to access the diagnostic value of functional brain networks, discovered from resting state fMRI data. The aim of this study was to propose an adaptive learning algorithm to distinguish schizophrenia patients from normal controls using resting-state functional language network. Furthermore, here the classification of schizophrenia was regarded as a sample selection problem where a sparse subset of samples was chosen from the labeled training set. Using these selected samples, which we call informative vectors, a classifier for the clinic diagnosis of schizophrenia was established. We experimentally demonstrated that the proposed algorithm incorporating resting-state functional language network achieved 83.6% leaveone- out accuracy on resting-state fMRI data of 27 schizophrenia patients and 28 normal controls. In contrast with KNearest- Neighbor (KNN), Support Vector Machine (SVM) and l1-norm, our method yielded better classification performance. Moreover, our results suggested that a dysfunction of resting-state functional language network plays an important role in the clinic diagnosis of schizophrenia.

Best-Matched Internal Standard Normalization in Liquid Chromatography-Mass Spectrometry Metabolomics Applied to Environmental Samples.

PubMed

Boysen, Angela K; Heal, Katherine R; Carlson, Laura T; Ingalls, Anitra E

2018-01-16

The goal of metabolomics is to measure the entire range of small organic molecules in biological samples. In liquid chromatography-mass spectrometry-based metabolomics, formidable analytical challenges remain in removing the nonbiological factors that affect chromatographic peak areas. These factors include sample matrix-induced ion suppression, chromatographic quality, and analytical drift. The combination of these factors is referred to as obscuring variation. Some metabolomics samples can exhibit intense obscuring variation due to matrix-induced ion suppression, rendering large amounts of data unreliable and difficult to interpret. Existing normalization techniques have limited applicability to these sample types. Here we present a data normalization method to minimize the effects of obscuring variation. We normalize peak areas using a batch-specific normalization process, which matches measured metabolites with isotope-labeled internal standards that behave similarly during the analysis. This method, called best-matched internal standard (B-MIS) normalization, can be applied to targeted or untargeted metabolomics data sets and yields relative concentrations. We evaluate and demonstrate the utility of B-MIS normalization using marine environmental samples and laboratory grown cultures of phytoplankton. In untargeted analyses, B-MIS normalization allowed for inclusion of mass features in downstream analyses that would have been considered unreliable without normalization due to obscuring variation. B-MIS normalization for targeted or untargeted metabolomics is freely available at https://github.com/IngallsLabUW/B-MIS-normalization .

Are children of moderately low birth weight at increased risk for poor health? A new look at an old question.

PubMed

Stein, Ruth E K; Siegel, Michele J; Bauman, Laurie J

2006-07-01

The goal was to examine whether moderately low birth weight children were at greater risk for health problems than normal birth weight children in a nationally representative sample of US children. Data were analyzed for 7817 children, 0 to 12 years of age, from the sample child file of the 2002 National Health Interview Survey. Logistic regressions were estimated to examine whether morbidity rates were higher among moderately low birth weight children than among normal birth weight children and to control for covariates. Health was measured as having a special health care need, having a chronic condition, being hospitalized in the past year, having a learning disability, attention-deficit disorder/attention-deficit/hyperactivity disorder, or other behavioral disorders, having minor health conditions, and having acute illnesses. With control for other confounders, moderately low birth weight children were significantly more likely than normal birth weight children to be identified as having a special health care need, having a chronic condition, having a learning disability, and having attention-deficit disorder or attention-deficit/hyperactivity disorder. They were not more likely to have a hospitalization in the past year, other behavioral disorders, or minor health conditions or acute illnesses. This population-based study of rates of current morbidity shows that moderately low birth weight children born since 1990 are vulnerable to a wide range of health, learning, and behavioral problems, compared with normal birth weight children. This suggests the need for continued focus on ways to reduce morbidity rates for moderately low birth weight children.

Management of bacterial corneal ulcers.

PubMed Central

Maske, R; Hill, J C; Oliver, S P

1986-01-01

A prospective microbiological study of 48 patients with corneal ulcers due to bacterial infection was performed. Positive cultures of corneal ulcer samples were obtained in 60% of all patients; about half of these patients had received antimicrobial treatment prior to sampling. A relatively high incidence of Staphylococcus epidermidis was isolated from ulcer patients (27%) compared with normal controls (10%). Gram stains of ulcer samples were positive for organisms in only 27% of all patients and were not considered useful in determining initial therapy in this series. We concluded that treatment should be started with a broad combination of antibiotics while awaiting the culture results. PMID:3082352

Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users

PubMed Central

Edelman, Alison B; Cherala, Ganesh; Munar, Myrna Y.; DuBois, Barent; McInnis, Martha; Stanczyk, Frank Z.; Jensen, Jeffrey T

2014-01-01

Background Pharmacokinetic (PK) parameters based on short sampling times (48 h or less) may contain inaccuracies due to their dependency on extrapolated values. This study was designed to measure PK parameters with greater accuracy in obese users of a low-dose oral contraceptive (OC), and to correlate drug levels with assessments of end-organ activity. Study design Obese (BMI ≥30 kg/m2), ovulatory, otherwise healthy, women (n = 32) received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) for two cycles. EE and LNG PK parameters were characterized for 168 h at the end of Cycle 1. During Cycle 2, biweekly outpatient visits were performed to assess cervical mucus, monitor ovarian activity with transvaginal ultrasound, and obtain serum samples to measure EE, LNG, estradiol (E2), and progesterone (P) levels. PK parameters were calculated and correlated with end-organ activity and compared against control samples obtained from normal and obese women sampled up to 48 h in a previous study. Standard determination of PK accuracy was performed; defined by the dependency on extrapolated values (‘excess’ area under the curve of 25% or less). Results The mean BMI was 39.4 kg/m2 (SD 6.6) with a range of 30–64 kg/m2. Key LNG PK parameters were as follows: clearance 0.52 L/h (SD 0.24), half-life 65 h (SD 40), AUC 232 h*ng/mL (SD 102) and time to reach steady-state 13.6 days (SD 8.4). The majority of subjects had increased ovarian activity with diameter of follicles ≥8 mm (n = 25) but only seven women had follicles ≥10 mm plus cervical mucus scores ≥5. Evidence of poor end-organ suppression did not correlate with the severity of the alterations in PK. As compared to historical normal and obese controls (48 h PK sampling), clearance, half-life, area under the curve (AUC) and time to reach steady-state were found to be significantly different (p ≤ 0.05) in obese women undergoing a longer duration of PK sampling (168 h). Longer sampling also improved PK accuracy for obese women (excess AUC 20%) as compared to both normal and obese controls undergoing shorter sampling times (48 h) with excess AUCs of 25% and 50%, respectively. Conclusions Obesity results in significant alterations in OC steroid PK parameters but the severity of these alterations did not correlate with end-organ suppression. A longer PK sampling interval (168 h vs. 48 h) improved the accuracy of PK testing. PMID:23153898

Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users.

PubMed

Edelman, Alison B; Cherala, Ganesh; Munar, Myrna Y; Dubois, Barent; McInnis, Martha; Stanczyk, Frank Z; Jensen, Jeffrey T

2013-02-01

Pharmacokinetic (PK) parameters based on short sampling times (48 h or less) may contain inaccuracies due to their dependency on extrapolated values. This study was designed to measure PK parameters with greater accuracy in obese users of a low-dose oral contraceptive (OC) and to correlate drug levels with assessments of end-organ activity. Obese [body mass index (BMI) ≥30 kg/m2], ovulatory, otherwise healthy women (n=32) received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) for two cycles. EE and LNG PK parameters were characterized for 168 h at the end of Cycle 1. During cycle 2, biweekly outpatient visits were performed to assess cervical mucus, monitor ovarian activity with transvaginal ultrasound and obtain serum samples to measure EE, LNG, estradiol and progesterone levels. PK parameters were calculated and correlated with end-organ activity and compared against control samples obtained from normal and obese women sampled up to 48 h in a previous study. Standard determination of PK accuracy was performed, defined by the dependency on extrapolated values ('excess' area under the curve of 25% or less). The mean BMI was 39.4 kg/m2 (SD 6.6) with a range of 30-64 kg/m2. Key LNG PK parameters were as follows: clearance, 0.52 L/h (SD 0.24); half-life, 65 h (SD 40); area under the curve (AUC), 232 h*ng/mL (SD 102); and time to reach steady state, 13.6 days (SD 8.4). The majority of subjects had increased ovarian activity with diameter of follicles ≥8 mm (n=25), but only seven women had follicles ≥10 mm plus cervical mucus scores ≥5. Evidence of poor end-organ suppression did not correlate with the severity of the alterations in PK. As compared to historical normal and obese controls (48-h PK sampling), clearance, half-life, AUC and time to reach steady state were found to be significantly different (p≤.05) in obese women undergoing a longer duration of PK sampling (168 h). Longer sampling also improved PK accuracy for obese women (excess AUC 20%) as compared to both normal and obese controls undergoing shorter sampling times (48 h) with excess AUCs of 25% and 50%, respectively. Obesity results in significant alterations in OC steroid PK parameters, but the severity of these alterations did not correlate with end-organ suppression. A longer PK sampling interval (168 h vs. 48 h) improved the accuracy of PK testing. Copyright © 2013 Elsevier Inc. All rights reserved.

Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major.

PubMed

Ma, Jing; Liu, Fei; Du, Xin; Ma, Duan; Xiong, Likuan

2017-03-01

β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 (8 × 60 K, Arraystar) was used to detect changes in long non-coding RNAs (lncRNAs) and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups. Compared with normal controls, 1424 and 2045 lncRNAs were up- and downregulated, respectively, in β-thalassemia major patients, whereas 623 and 349 lncRNAs were up- and downregulated, respectively, in β-thalassemia minor patients. Compared with β-thalassemia minor group, 1367 and 2356 lncRNAs were up- and downregulated, respectively, in β-thalassemia major group. We selected five lncRNAs that displayed altered expressions (DQ583499, X-inactive specific transcript (Xist), lincRNA-TPM1, MRFS16P, and lincRNA-RUNX2-2) and confirmed their expression levels in all samples using real-time polymerase chain reaction. Based on coding-noncoding gene co-expression network and gene ontology biological process analyses, several signaling pathways were associated with three common organ systems exhibiting β-thalassemia phenotypes: hematologic, skeletal, and hepatic systems. This study implicates that abnormal expression levels of lncRNAs and mRNA in β-thalassemia cases may be correlated with its various clinical phenotypes.

[Spectral analysis of Heart Rate Variability in psychiatric patients: autonomic nervous system evaluation in psychotic, anxiety and depressive disorders].

PubMed

Lo Turco, Giovanni; Grimaldi Di Terresena, Liria

2012-01-01

The aim of this study was to test the primary hypothesis of altered Heart Rate Variability (HRV) and heart rate in a sample of patients with mental disorders and the secondary hypothesis of normalization of HRV values as a result of clinical improvement. The study was conducted on a sample of 90 patients with psychotic, anxiety and mood disorders. Each patient was subjected to detection of HRV and heart rate via a photoplethysmographic sensor and evaluated with rating scales based on the specific disorder. The parameters detected in the sample were compared with a control group of healthy subjects. There were no significant differences of cardiac autonomic modulation between the group of patients in whom is possible exclude the drug influence and the control group; significantly lower values of HRV parameters in the group of patients with drug influence, and especially in subgroup of psychotic patients, compared to controls, are, instead, detected. The study also shows a significant increase in heart rate as a common feature in mental disorders, regardless of treatment. Clinical improvement appears to promote the normalization of the variability in patients with high DS of tachogram. The study suggests a potential increased risk of cardiovascular mortality in patients, as evidenced by the increased values of heart rate, regardless of drug treatment. This risk is even more pronounced in psychotic patients in drug treatment because of the simultaneous significant reduction of HRV parameters.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique

NASA Astrophysics Data System (ADS)

Bellotti, Mariela I.; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J.

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique.

PubMed

Bellotti, Mariela I; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

Combustion of solid carbon rods in zero and normal gravity. Ph.D. Thesis - Toledo Univ., Ohio

NASA Technical Reports Server (NTRS)

Spuckler, C. M.

1981-01-01

In order to investigate the mechanism of carbon combustion and to assess the importance of gravitational induced convection on the process, zero and normal gravity experiments were conducted in which spectroscopic carbon rods were resistance ignitied and burned in dry oxygen environments. In the zero-gravity drop tower tests, a blue flame surrounded the rod, showing that a gas phase reaction in which carbon monoxide was oxidized to carbon dioxide was taking place. The ratio of flame diameter to rod diameter was obtained as a function of time. It was found that this ratio was inversely proportional to both the oxygen pressure and the rod diameter. In the normal gravity tests, direct mass spectrometric sampling was used to measure gas phase concentrations. The gas sampling probe was positioned near the circumference of a horizontally mounted 0.615 cm diameter carbon rod, either at the top or at angles of 45 deg to 90 deg from the top, and yielded concentration profiles of CO2, CO, and O2 as a function of distance from the surface. The mechanism controlling the combustion process was found to change from chemical process control at the 90 deg and 45 deg probe positions to mass transfer control at the 0 deg probe position at the top of the rod. Under the experimental conditions used, carbon combustion was characterized by two surface reactions, 2C + O2 yields 2CO and CO2 + C yields 2CO, and a gas phase reaction, 2CO + O2 yields 2CO2.

Longitudinal plasma metanephrines preceding pheochromocytoma diagnosis: a retrospective case-control serum repository study.

PubMed

Olson, S W; Yoon, S; Baker, T; Prince, L K; Oliver, D; Abbott, K C

2016-03-01

Plasma metanephrines (PMN) are highly sensitive for diagnosis of pheochromocytoma, but the natural history of PMN before pheochromocytoma diagnosis has not been previously described. The aim of the study was to compare the progression of PMN before pheochromocytoma diagnosis to matched healthy and essential hypertension disease controls. A retrospective case-control Department of Defense Serum Repository (DoDSR) study. We performed a DoDSR study that compared three longitudinal pre-diagnostic PMN for 30 biopsy-proven pheochromocytoma cases to three longitudinal PMN for age, sex, race, and age of serum sample matched healthy and essential hypertension disease controls. Predominant metanephrine (MN) or normetanephrine (NMN) production was identified for each case and converted to a percentage of the upper limit of normal to allow analysis of all cases together. PMN were measured by Quest Diagnostics. The predominant plasma metanephrine (PPM) was >100 and 300% of the upper limit of normal a median of 6.6 and 4.1 years before diagnosis respectively. A greater percentage of pheochromocytoma patients had a PPM >100 and >300% of the upper limit of normal compared with combined healthy and essential hypertension disease controls <2, 2-8, and >8 years prior to diagnosis. For patients with a baseline PPM 90-300% of the upper limit of normal, a 25% rate of rise per year was 100% specific for pheochromocytoma. PPMs elevate years before diagnosis which suggests that delayed diagnoses are common. For mild PMN elevations, follow-up longitudinal PMN trends may provide a highly specific and economical diagnostic tool. © 2016 European Society of Endocrinology.

Assessment of variations in thermal cycle life data of thermal barrier coated rods

NASA Astrophysics Data System (ADS)

Hendricks, R. C.; McDonald, G.

An analysis of thermal cycle life data for 22 thermal barrier coated (TBC) specimens was conducted. The Zr02-8Y203/NiCrAlY plasma spray coated Rene 41 rods were tested in a Mach 0.3 Jet A/air burner flame. All specimens were subjected to the same coating and subsequent test procedures in an effort to control three parametric groups; material properties, geometry and heat flux. Statistically, the data sample space had a mean of 1330 cycles with a standard deviation of 520 cycles. The data were described by normal or log-normal distributions, but other models could also apply; the sample size must be increased to clearly delineate a statistical failure model. The statistical methods were also applied to adhesive/cohesive strength data for 20 TBC discs of the same composition, with similar results. The sample space had a mean of 9 MPa with a standard deviation of 4.2 MPa.

Assessment of variations in thermal cycle life data of thermal barrier coated rods

NASA Technical Reports Server (NTRS)

Hendricks, R. C.; Mcdonald, G.

1981-01-01

An analysis of thermal cycle life data for 22 thermal barrier coated (TBC) specimens was conducted. The Zr02-8Y203/NiCrAlY plasma spray coated Rene 41 rods were tested in a Mach 0.3 Jet A/air burner flame. All specimens were subjected to the same coating and subsequent test procedures in an effort to control three parametric groups; material properties, geometry and heat flux. Statistically, the data sample space had a mean of 1330 cycles with a standard deviation of 520 cycles. The data were described by normal or log-normal distributions, but other models could also apply; the sample size must be increased to clearly delineate a statistical failure model. The statistical methods were also applied to adhesive/cohesive strength data for 20 TBC discs of the same composition, with similar results. The sample space had a mean of 9 MPa with a standard deviation of 4.2 MPa.

COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples

PubMed Central

Yamagata, Koichi; Yamanishi, Ayako; Kokubu, Chikara; Takeda, Junji; Sese, Jun

2016-01-01

An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis. PMID:26833260

Stress does not affect ghrelin secretion in obese and normal weight women.

PubMed

Kiessl, Gundula R R; Laessle, Reinhold G

2017-03-01

Stress has been supposed to increase appetite. The biological basis of this phenomenon may be a stress-induced alteration of the secretion of GUT peptides such as ghrelin. Stress-induced changes in ghrelin secretion could be a biological basis of overeating and a factor contributing to the development of obesity. Aim of the study was to analyze the effect of acute psychosocial stress on ghrelin secretion in obese and normal weight women. We compared pre- and postprandial plasma ghrelin secretion of 42 obese and 43 normal weight women in a randomized crossover design. Ghrelin and cortisol concentrations were measured and ratings of stress were also recorded in response to a psychological stressor (Trier Social Stress Test, TSST). Ghrelin samples were collected in the fasting state one time before participating in the TSST and one time before a control session. After the TSST, respectively, control session participants had a standardized ad libitum meal. 30 and 60 min after the TSST, respectively, control session preprandial ghrelin was measured again. Obese women showed lower pre- and postprandial release of ghrelin than normal weight controls. Moreover, obese women showed inhibited postprandial decrease of ghrelin secretion. Stress did not affect postprandial ghrelin secretion, but inhibited food intake in all subjects. The present data provide further evidence of altered ghrelin release in obesity. Acute stress did not affect postprandial ghrelin secretion, but inhibited food intake in all subjects. Results are discussed with regard to biological and psychological regulation of hunger and satiety in obesity.

Further improvement of hydrostatic pressure sample injection for microchip electrophoresis.

PubMed

Luo, Yong; Zhang, Qingquan; Qin, Jianhua; Lin, Bingcheng

2007-12-01

Hydrostatic pressure sample injection method is able to minimize the number of electrodes needed for a microchip electrophoresis process; however, it neither can be applied for electrophoretic DNA sizing, nor can be implemented on the widely used single-cross microchip. This paper presents an injector design that makes the hydrostatic pressure sample injection method suitable for DNA sizing. By introducing an assistant channel into the normal double-cross injector, a rugged DNA sample plug suitable for sizing can be successfully formed within the cross area during the sample loading. This paper also demonstrates that the hydrostatic pressure sample injection can be performed in the single-cross microchip by controlling the radial position of the detection point in the separation channel. Rhodamine 123 and its derivative as model sample were successfully separated.

Perceived interpersonal mistreatment among obese Americans: do race, class, and gender matter?

PubMed

Carr, Deborah; Jaffe, Karen J; Friedman, Michael A

2008-11-01

We examine the extent to which body weight affects three types of perceived interpersonal mistreatment, and evaluate whether these patterns vary by race, social class, and gender in a large sample of American men and women. We use data from the first wave (1995) of the Midlife Development in the United States (N = 3,511), a survey of persons aged 25-74, to contrast underweight, normal weight, overweight, obese I, and obese II/III persons' reports of three types of perceived interpersonal mistreatment: disrespectful treatment; harassment/teasing; and being treated as if one has a character flaw. We assess whether these relationships are contingent upon one's gender, race, and occupational status. We control for possible confounding influences, including physical and mental health. In the total sample, obese I and obese II/III persons report significantly higher levels of all three types of perceived mistreatment (compared to normal weight persons), even when demographic, socioeconomic status, and health characteristics are controlled. Among black men, however, obese II/III persons report significantly lower levels of all three types of perceived mistreatment, compared to their normal weight peers. Among both men and women, obese professional workers report significantly more perceived interpersonal mistreatment, compared to obese persons of lower socioeconomic status. These findings reveal the ways that intersecting social identities may shape obese Americans' perceptions of stigmatizing interpersonal encounters.

Perceived Interpersonal Mistreatment Among Obese Americans: Do Race, Class, and Gender Matter?

PubMed Central

Carr, Deborah; Jaffe, Karen J.; Friedman, Michael A.

2010-01-01

Objective: We examine the extent to which body weight affects three types of perceived interpersonal mistreatment, and evaluate whether these patterns vary by race, social class, and gender in a large sample of American men and women. Methods and Procedures: We use data from the first wave (1995) of the Midlife Development in the United States (N = 3,511), a survey of persons aged 25–74, to contrast underweight, normal weight, overweight, obese I, and obese II/III persons' reports of three types of perceived interpersonal mistreatment: disrespectful treatment; harassment/teasing; and being treated as if one has a character flaw. We assess whether these relationships are contingent upon one's gender, race, and occupational status. We control for possible confounding influences, including physical and mental health. Results: In the total sample, obese I and obese II/III persons report significantly higher levels of all three types of perceived mistreatment (compared to normal weight persons), even when demographic, socioeconomic status, and health characteristics are controlled. Among black men, however, obese II/III persons report significantly lower levels of all three types of perceived mistreatment, compared to their normal weight peers. Among both men and women, obese professional workers report significantly more perceived interpersonal mistreatment, compared to obese persons of lower socioeconomic status. Discussion: These findings reveal the ways that intersecting social identities may shape obese Americans' perceptions of stigmatizing interpersonal encounters. PMID:18978765

Continuous human cell lines and method of making same

DOEpatents

Stampfer, M.R.

1985-07-01

Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo(a)pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors. 2 tabs.

Normal and reverse flow injection–spectrophotometric determination of thiamine hydrochloride in pharmaceutical preparations using diazotized metoclopramide

PubMed Central

Al Abachi, Mouayed Q.; Hadi, Hind

2012-01-01

Simple and sensitive normal and reverse flow injection methods for spectrophotometric determination of thiamine hydrochloride (THC) at the microgram level were proposed and optimized. Both methods are based on the reaction between THC and diazotized metoclopramide in alkaline medium. Beer’s law was obeyed over the range of 10–300 and 2–90 μg/mL, the limits of detection were 2.118 and 0.839 μg/mL and the sampling rates were 80 and 95 injections per hour for normal and reverse flow injection methods respectively. The application of both methods to commercially available pharmaceuticals produced acceptable results. The flow system is suitable for application in quality control processes. PMID:29403765

On estimation of linear transformation models with nested case–control sampling

PubMed Central

Liu, Mengling

2011-01-01

Nested case–control (NCC) sampling is widely used in large epidemiological cohort studies for its cost effectiveness, but its data analysis primarily relies on the Cox proportional hazards model. In this paper, we consider a family of linear transformation models for analyzing NCC data and propose an inverse selection probability weighted estimating equation method for inference. Consistency and asymptotic normality of our estimators for regression coefficients are established. We show that the asymptotic variance has a closed analytic form and can be easily estimated. Numerical studies are conducted to support the theory and an application to the Wilms’ Tumor Study is also given to illustrate the methodology. PMID:21912975

On designing a new cumulative sum Wilcoxon signed rank chart for monitoring process location

PubMed Central

Nazir, Hafiz Zafar; Tahir, Muhammad; Riaz, Muhammad

2018-01-01

In this paper, ranked set sampling is used for developing a non-parametric location chart which is developed on the basis of Wilcoxon signed rank statistic. The average run length and some other characteristics of run length are used as the measures to assess the performance of the proposed scheme. Some selective distributions including Laplace (or double exponential), logistic, normal, contaminated normal and student’s t-distributions are considered to examine the performance of the proposed Wilcoxon signed rank control chart. It has been observed that the proposed scheme shows superior shift detection ability than some of the competing counterpart schemes covered in this study. Moreover, the proposed control chart is also implemented and illustrated with a real data set. PMID:29664919

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

PubMed

Abend, M; Pfeiffer, R M; Ruf, C; Hatch, M; Bogdanova, T I; Tronko, M D; Hartmann, J; Meineke, V; Mabuchi, K; Brenner, A V

2013-10-15

A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

Vacuum/compression valving (VCV) using parrafin-wax on a centrifugal microfluidic CD platform.

PubMed

Al-Faqheri, Wisam; Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Moebius, Jacob; Joseph, Karunan; Arof, Hamzah; Madou, Marc

2013-01-01

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control.

Vacuum/Compression Valving (VCV) Using Parrafin-Wax on a Centrifugal Microfluidic CD Platform

PubMed Central

Al-Faqheri, Wisam; Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Moebius, Jacob; Joseph, Karunan; Arof, Hamzah; Madou, Marc

2013-01-01

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control. PMID:23505528

Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo.

PubMed

Vaiphei, S Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Chaubey, R C; Kma, L; Sharan, R N

2015-01-01

In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving (60)Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of (60)Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min(-1) at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

SELDI-TOF-MS proteomic profiling of serum, urine, and amniotic fluid in neural tube defects.

PubMed

Liu, Zhenjiang; Yuan, Zhengwei; Zhao, Qun

2014-01-01

Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection.

Enhanced Cumulative Sum Charts for Monitoring Process Dispersion

PubMed Central

Abujiya, Mu’azu Ramat; Riaz, Muhammad; Lee, Muhammad Hisyam

2015-01-01

The cumulative sum (CUSUM) control chart is widely used in industry for the detection of small and moderate shifts in process location and dispersion. For efficient monitoring of process variability, we present several CUSUM control charts for monitoring changes in standard deviation of a normal process. The newly developed control charts based on well-structured sampling techniques - extreme ranked set sampling, extreme double ranked set sampling and double extreme ranked set sampling, have significantly enhanced CUSUM chart ability to detect a wide range of shifts in process variability. The relative performances of the proposed CUSUM scale charts are evaluated in terms of the average run length (ARL) and standard deviation of run length, for point shift in variability. Moreover, for overall performance, we implore the use of the average ratio ARL and average extra quadratic loss. A comparison of the proposed CUSUM control charts with the classical CUSUM R chart, the classical CUSUM S chart, the fast initial response (FIR) CUSUM R chart, the FIR CUSUM S chart, the ranked set sampling (RSS) based CUSUM R chart and the RSS based CUSUM S chart, among others, are presented. An illustrative example using real dataset is given to demonstrate the practicability of the application of the proposed schemes. PMID:25901356

Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones

PubMed Central

Zisman, Anna L.; Asplin, John R.; Worcester, Elaine M.; Coe, Fredric L.

2011-01-01

Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range. PMID:21123489

Stress inhibits PYY secretion in obese and normal weight women.

PubMed

Kiessl, Gundula R R; Laessle, Reinhold G

2016-06-01

The impact of stress on circulating levels of appetite-regulating hormones remains largely unknown. The aim of this study was to analyze the effect of acute psychosocial stress on the gut hormone peptide YY (PYY) secretion in obese and normal weight women. Therefore, we compared pre- and post-prandial plasma PYY secretion of 42 obese and 43 normal weight women in a repeated measure randomized controlled laboratory experiment. PYY and cortisol concentrations were measured and ratings of stress and satiety were also recorded in response to a psychological stressor (Trier Social Stress Test, TSST). PYY samples were collected in the fasting state both before participating in the TSST and before a control session. Participants had a standardized meal after the TSST and control session, respectively. PYY was measured both 30 and 60 min after the TSST and control session, respectively. Stress inhibited PYY secretion as well as food intake in all women, but did not influence subjective satiety perception. The present data indicate that despite of lower PYY levels the subjects' requirement to overeat was not increased. From an evolutionary perspective this finding is adaptive. After stress the organism is prepared for fight or flight reaction, whereas not primarily necessary functions are inhibited. Therefore, increased food intake during stress would be dysfunctional.

Adenoviral receptor expression of normal bladder and transitional cell carcinoma of the bladder.

PubMed

Buscarini, Maurizio; Quek, Marcus L; Gilliam-Hegarich, Susan; Kasahara, Nori; Bochner, Bernard

2007-01-01

The insertion of absent or underexpressed genes into cancer cells to alter their malignant phenotype is an important potential application of available gene therapy technology. One of the more common viral vector systems that has been extensively studied for this purpose are the replication-deficient adenoviruses (Ad). Adenoviral infection of cells is mediated through a complex pathway, initiated following viral-cell attachment. Adenoviral-cell attachment occurs following interactions with a 46-kDa transmembrane protein with high affinity for both the Coxsackie and adenovirus, designated the CAR (Coxsackie and adenoviral receptor). Additional important cell-viral interactions that occur involve the alpha(v)-based integrins, specifically alpha(v)beta3 and alpha(v)beta5. The purpose of the present study was to determine the extent of expression and localization of the known Ad receptor proteins (CAR, alpha(v)beta3, and alpha(v)beta5) in normal and cancerous human bladders. Frozen tissue samples of normal bladder and invasive transitional cell cancers of the bladder were evaluated. Tissue blocks containing muscle-invasive transitional cell carcinoma (TCC) were obtained following radical cystectomy, which were performed at our institution. Thirty-two invasive transitional cell bladder tumors were evaluated, each with a matched sample of histologically normal-appearing bladder used as a control. Four additional samples of normal bladder were obtained from patients with no evidence of disease of the bladder and served as further controls. Three additional cases of invasive bladder cancer with no matching normal tissue were also evaluated. Identification of the CAR receptor was performed using the anti-CAR mouse monoclonal antibody designated RmBC. The integrins alpha(v)beta3 and alpha(v)beta5 were identified using the mouse monoclonal antibodies designated LM609 and P1F6 respectively. All slides were evaluated by two of the authors (M.B., B.B.) without knowledge of the clinical and pathological data. Normal bladder: Normal bladder mucosa demonstrated a marked positivity for CAR in 29/35 (82.8%) cases. In contrast, normal transitional epithelial cells were uniformly negative when tested for the integrins alpha(v)beta3 and alpha(v)beta5. Subepithelial tissues, specifically the connective tissue components of the lamina propria and deep muscle wall of the bladder, were positive for alpha(v)beta3 and for alpha(v)beta5 in 61 and 75% of samples, respectively. Endothelial cells associated with the various layers throughout the bladder uniformly expressed both integrins and served as a consistent internal control for both antibodies. An almost identical staining pattern of the endothelium was observed using LM609 and P1F6 in all samples tested. Bladder transitional cell carcinoma: CAR immunoreactivity against TCC cells was uniformly decreased compared to normal transitional cells. Nine tumors exhibited a weak positivity for CAR while the remaining samples were negative. In some cases, the absence of CAR positivity was associated with histological evidence of carcinoma in situ. In 6 cases, it led to the identification of small regions of carcinoma in situ that were not noted on primary pathological evaluation. Peritumoral connective tissue expressed both integrins in the majority of cases, similar to the pattern described above for normal bladder. Transitional cell cancers demonstrated a similar pattern of expression of alpha(v)beta5, in which all tumor cells exhibited minimal or no staining. The success of all viral-mediated gene therapy strategies relies on the ability of the vector to efficiently deliver its genetic material to a target cell population. In the current study, we demonstrate that the bladder epithelial layer consistently expresses high levels of CAR. Deeper layers of the epithelium also express CAR, including the basal layer cells. A decrease in the expression of CAR appears as an early event in bladder carcinogenesis. We observed that both alpha(v)beta3 and alpha(v)beta5 are strongly expressed in muscle cells surrounding the neoplastic cells, as well as within the peritumoral connective tissue. In cases of invasive bladder cancer that have lost CAR expression, an adenoviral vector may still be utilized through the less efficient interactions with the integrins. Bladder tumor tissue may be less susceptible to an adenoviral-mediated gene therapy approach in which a significant percentage of tumor cells require transduction. Adenoviral uptake by tumor or peritumoral cells with subsequent gene transfer could be predicted by the level of CAR and alpha(v)-based integrin expression. This would enhance our ability to identify those patients whose tumors would be more susceptible to Ad-mediated gene delivery as part of an antitumor treatment. 2007 S. Karger AG, Basel

XYLITOL IMPROVES ANTI-OXIDATIVE DEFENSE SYSTEM IN SERUM, LIVER, HEART, KIDNEY AND PANCREAS OF NORMAL AND TYPE 2 DIABETES MODEL OF RATS.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Shahidul

2017-05-01

The present study investigated the anti-oxidative effects of xylitol both in vitro and in vivo in normal and type 2 diabetes (T2D) rat model. Free radical scavenging and ferric reducing potentials of different concentrations of xylitol were investigated in vitro. For in vivo study, six weeks old male Sprague-Dawley rats were divided into four groups, namely: Normal Control (NC), Diabetic Control (DBC), Normal Xylitol (NXYL) and Diabetic Xylitol (DXYL). T2D was induced in the DBC and DXYL groups. After the confirmation of diabetes, a 10% xylitol solution was supplied instead of drinking water to NXYL and DXYL, while normal drinking water was supplied to NC and DBC ad libitum. After five weeks intervention period, the animals were sacri- ficed and thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) concentrations as well as superoxide dismutase, catalase glutathione reductase and glutathione peroxidase activities were determined in the liver, heart, kidney, pancreatic tissues and serum samples. Xylitol exhibited significant (p < 0.05) in vitro nitric oxide and hydroxyl radical scavenging and ferric reducing activities. In vivo study revealed significant (p < 0.05) reduction in TBARS concentrations in the xylitol consuming groups compared to their respective controls. Significant (p < 0.05) increase in GSH levels and antioxidant enzyme activities were observed in analyzed tissues and serum of xylitol-fed animals compared to their respective controls. Results of this study indicate that xylitol has strong anti-oxidative potential against T2D-associated oxidative stress. Hence, xylitol can be used as a potential supplement in diabetic foods and food products.

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

PubMed Central

Treit, Sarah; Zhou, Dongming; Chudley, Albert E.; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M.; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level. PMID:26928125

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

PubMed

Treit, Sarah; Zhou, Dongming; Chudley, Albert E; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.

Improved Discovery of Molecular Interactions in Genome-Scale Data with Adaptive Model-Based Normalization

PubMed Central

Brown, Patrick O.

2013-01-01

Background High throughput molecular-interaction studies using immunoprecipitations (IP) or affinity purifications are powerful and widely used in biology research. One of many important applications of this method is to identify the set of RNAs that interact with a particular RNA-binding protein (RBP). Here, the unique statistical challenge presented is to delineate a specific set of RNAs that are enriched in one sample relative to another, typically a specific IP compared to a non-specific control to model background. The choice of normalization procedure critically impacts the number of RNAs that will be identified as interacting with an RBP at a given significance threshold – yet existing normalization methods make assumptions that are often fundamentally inaccurate when applied to IP enrichment data. Methods In this paper, we present a new normalization methodology that is specifically designed for identifying enriched RNA or DNA sequences in an IP. The normalization (called adaptive or AD normalization) uses a basic model of the IP experiment and is not a variant of mean, quantile, or other methodology previously proposed. The approach is evaluated statistically and tested with simulated and empirical data. Results and Conclusions The adaptive (AD) normalization method results in a greatly increased range in the number of enriched RNAs identified, fewer false positives, and overall better concordance with independent biological evidence, for the RBPs we analyzed, compared to median normalization. The approach is also applicable to the study of pairwise RNA, DNA and protein interactions such as the analysis of transcription factors via chromatin immunoprecipitation (ChIP) or any other experiments where samples from two conditions, one of which contains an enriched subset of the other, are studied. PMID:23349766

Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples

PubMed Central

Hecht, Elizabeth S.; Scholl, Elizabeth H.; Walker, S. Hunter; Taylor, Amber D.; Cliby, William A.; Motsinger-Reif, Alison A.; Muddiman, David C.

2016-01-01

An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I–IV, respectively. For relatve quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). For all N-glycans, the vectors of the effects from stages II–IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. PMID:26347193

Prostate cancer antigen 3 gene expression in peripheral blood and urine sediments from prostate cancer and benign prostatic hyperplasia patients versus healthy individuals.

PubMed

Moradi Sardareh, Hemen; Goodarzi, Mohammad Taghi; Yadegar-Azari, Reza; Poorolajal, Jalal; Mousavi-Bahar, Seyed Habibollah; Saidijam, Massoud

2014-11-30

To determine the expression of prostate cancer antigen 3 (PCA3) gene in peripheral blood and urine sediments from patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and normal subjects. A total number of 48 patients [24 with biopsy proven prostate cancer (PCa) and 24 with benign prostate hyperplasia (BPH)] were studied. Twenty-four healthy individuals were also recruited as control group. After blood and urine sampling, total RNA was extracted and cDNA was synthesized. Expression of PCA3 gene was assessed by quantitative reverse transcription polymerase chain reaction. Comparison of PCA3 gene expression between control and BPH groups indicated no statistically significant differences in both urine and blood samples. Patients with PCa demonstrated an increased PCA3 gene expression rate compared to control and BPH groups (10.64 and 7.17 folds, respectively). The rate of fold increased PCA3 gene expression in urine was 20.90, 20.90, and 20.35 in patients with PCa, BPH and normal subjects, respectively. Evaluation of PCA3 gene expression can be considered as a reliable marker for detection of PCa. Increased level of this marker in urine sediments is more sensitive than blood for distinguishing between cancerous and non-cancerous groups. 

Wireless connection of continuous glucose monitoring system to the electronic patient record

NASA Astrophysics Data System (ADS)

Murakami, Alexandre; Gutierrez, Marco A.; Lage, Silvia G.; Rebelo, Marina S.; Granja, Luiz A. R.; Ramires, Jose A. F.

2005-04-01

The control of blood sugar level (BSL) at near-normal levels has been documented to reduce both acute and chronic complications of diabetes mellitus. Recent studies suggested, the reduction of mortality in a surgical intensive care unit (ICU), when the BSL are maintained at normal levels. Despite of the benefits appointed by these and others clinical studies, the strict BSL control in critically ill patients suffers from some difficulties: a) medical staff need to measure and control the patient"s BSL using blood sample at least every hour. This is a complex and time consuming task; b) the inaccuracy of standard capillary glucose monitoring (fingerstick) in hypotensive patients and, if frequently used to sample arterial or venous blood, may lead to excess phlebotomy; c) there is no validated procedure for continuously monitoring of BSL levels. This study used the MiniMed CGMS in ill patients at ICU to send, in real-time, BSL values to a Web-Based Electronic Patient Record. The BSL values are parsed and delivered through a wireless network as an HL7 message. The HL7 messages with BSL values are collected, stored into the Electronic Patient Record and presented into a bed-side monitor at the ICU together with other relevant patient information.

Formation and removal of PCDD/Fs in a municipal waste incinerator during different operating periods.

PubMed

Wang, Hou Chuan; Hwang, Jyh Feng; Chi, Kai Hsien; Chang, Moo Been

2007-04-01

The PCDD/F concentrations and removal efficiencies achieved with air pollution control devices (APCDs) during different operating periods (start-up, normal operation, and shut-down) at an existing municipal waste incinerator (MWI) in Taiwan are evaluated via stack sampling and analysis. The MWI investigated is equipped with electrostatic precipitators (EP), wet scrubbers (WS), and selective catalytic reduction system (SCR) as APCDs. The sampling results indicate that the PCDD/F concentrations at the EP inlet during start-up period were 15 times higher than that measured during normal operation period. The PCDD/F concentration observed at shut-down period was close to that measured at normal operation period. The CO concentration was between 400 and 1000 ppm during start-up period, which was about 50 times higher compared with the normal operation. Hence, combustion condition significantly affected the PCDD/F formation concentration during the waste incineration process. In addition, the distributions of the PCDD/F congeners were similar at different operating periods. During the normal operation and shut-down periods, the EP decreases the PCDD/F concentration (based on TEQ) by 18.4-48.6%, while the removal efficiency of PCDD/Fs achieved with SCR system reaches 99.3-99.6%. Nevertheless, the PCDD/F removal efficiency achieved with SCR was only 42% during the 19-h start-up period due to the low SCR operating temperature (195 degrees C).

Peroxisome proliferator-activated receptor (PPAR)gamma is highly expressed in normal human pituitary gland.

PubMed

Bogazzi, F; Russo, D; Locci, M T; Chifenti, B; Ultimieri, F; Raggi, F; Viacava, P; Cecchetti, D; Cosci, C; Sardella, C; Acerbi, G; Gasperi, M; Martino, E

2005-11-01

Expression of peroxisome proliferator-activated receptor (PPAR)gamma in normal pituitary seems to be restricted to ACTH-secreting cells. The aim of the study was to evaluate the expression of PPARgamma in normal human pituitary tissue and to study its localization in the pituitary secreting cells. Normal pituitary tissue samples were obtained form 11 patients with non-secreting adenoma who underwent surgical excision of the tumor. Expression of PPARgamma was evaluated by immunostaining and western blotting; localization of PPARgamma in each pituitary secreting cell lineage was evaluated by double immunofluorescence using confocal microscopy. Pituitary non-functioning adenomas served as Controls. PPARgamma was highly expressed in all pituitary samples with a (mean +/- SD) 81 +/- 6.5% of stained cells; expression of PPARgamma was confirmed by western blotting. Non-functioning pituitary adenomas had 74 +/- 11% PPARgamma positive cells. Expression of PPARy was either in cytoplasm or nuclei. In addition, treatment of GH3 cells, with a PPARgamma ligand was associated with traslocation of the receptor from cytoplasm into the nucleus. Double immunostaining revealed that every pituitary secreting cell (GH, TSH, LH, FSH, PRL and ACTH) had PPARgamma expressed. The present study demonstrated that PPARgamma is highly expressed in every normal pituitary secreting cell lineage. It can translocate into the nucleus by ligand binding; however, its role in pituitary hormone regulation remains to be elucidated.

Introduction of a rapid, simple radioimmunoassay and quality control scheme for thyroxine.

PubMed Central

Nye, L; Hassan, M; Willmott, E; Landon, J

1976-01-01

A simple radioimmunoassay has been developed for service purposes to determine serum total thyroxine levels. Only three additions are required, of standard or sample, labelled thyroxine and antibody in polyethylene glycol. After 2 hours' incubation at room temperature the antibody-bound and free fractions are separated by centrifugation. Serum total thyroxine levels were measured in 195 euthyroid subjects and it was established that normal values lay within the range 57 to 155 nmol/1. Serial blood samples taken over a 24-hour period, from 11 subjects, indicated that there was no circadian rhythm so that samples for total thyroxine assay can be taken at any time of the day. Similar results were obtained using serum or plasma. Satisfactory results were obtained for three quality control sera when measured by seven different laboratories using this method. PMID:932232

Cardiac morphology after conditions of microgravity during Cosmos 2044

NASA Technical Reports Server (NTRS)

Goldstein, Margaret A.; Edwards, Robert J.; Schroeter, John P.

1992-01-01

Light- and electron-microscopic studies were performed on cardiac muscle from rats flown on Cosmos 2044 and from four control groups. Average cross-sectional area of myofibers was measured by video analysis of the light-microscopic images of papillary and ventricular muscle samples from all animals. This cross-sectional area was significantly decreased in flight rats (P = 0.03) compared with synchronous controls. Additional findings at the electron microscopic level consistent with this atrophy were obtained by stereological analysis and optical diffraction analysis of papillary muscle samples. Slightly higher mitochondrial volume density values and mitochondria-to-myofibril ratios as well as normal A-band spacings (d1,0) and Z-band spacings of myofibrils were observed in the tail-suspension and flight groups. General morphological features similar to those in ventricular samples from the previous Cosmos 1887 flight were observed.

Vitamin A values of wild-caught Cuban tree frogs (Osteopilus septentrionalis) and marine toads (Rhinella marina) in whole body, liver, and serum.

PubMed

Sullivan, Kathleen E; Fleming, Greg; Terrell, Scott; Smith, Dustin; Ridgley, Frank; Valdes, Eduardo V

2014-12-01

Recent issues surrounding captive amphibians are often nutritionally related problems, such as hypovitaminosis A. Although supplementation of frogs with vitamin A is a topic of investigation, the underlying issue is understanding vitamin A metabolism in amphibian species. To develop a range of "normal" vitamin A concentrations for captive amphibians, baseline vitamin A concentrations must be established in wild amphibian species. In this study, two species, Cuban tree frogs (Osteopilus septentrionalis; n = 59) and marine toads (Rhinella marina; n = 20) were collected from the wild as part of an invasive species control program at Zoo Miami, Miami, Florida. Serum, liver, and whole body samples were analyzed for vitamin A content. The Cuban tree frogs showed higher concentrations on average of vitamin A in serum (82.8 ppb), liver (248.3 IU/g), and whole body (5474.7 IU/kg) samples compared with marine toads (60.1 ppb; 105.3 IU/g; 940.7 IU/kg, respectively), but differences were not significant (P = 0.22). What can be considered "normal" values of vitamin A concentrations across different amphibian species requires further investigation. Although all amphibians collected in this study appeared healthy, a larger sample size of animals, with known health histories and diets, may provide stronger evidence of normal expectations.

Gene Expression Profile Analysis is Directly Affected by the Selected Reference Gene: The Case of Leaf-Cutting Atta Sexdens

PubMed Central

Máximo, Wesley P. F.; Zanetti, Ronald; Paiva, Luciano V.

2018-01-01

Although several ant species are important targets for the development of molecular control strategies, only a few studies focus on identifying and validating reference genes for quantitative reverse transcription polymerase chain reaction (RT-qPCR) data normalization. We provide here an extensive study to identify and validate suitable reference genes for gene expression analysis in the ant Atta sexdens, a threatening agricultural pest in South America. The optimal number of reference genes varies according to each sample and the result generated by RefFinder differed about which is the most suitable reference gene. Results suggest that the RPS16, NADH and SDHB genes were the best reference genes in the sample pool according to stability values. The SNF7 gene expression pattern was stable in all evaluated sample set. In contrast, when using less stable reference genes for normalization a large variability in SNF7 gene expression was recorded. There is no universal reference gene suitable for all conditions under analysis, since these genes can also participate in different cellular functions, thus requiring a systematic validation of possible reference genes for each specific condition. The choice of reference genes on SNF7 gene normalization confirmed that unstable reference genes might drastically change the expression profile analysis of target candidate genes. PMID:29419794

Human longevity and common variations in the LMNA gene: a meta-analysis

PubMed Central

Conneely, Karen N.; Capell, Brian C.; Erdos, Michael R.; Sebastiani, Paola; Solovieff, Nadia; Swift, Amy J.; Baldwin, Clinton T.; Budagov, Temuri; Barzilai, Nir; Atzmon, Gil; Puca, Annibale A.; Perls, Thomas T.; Geesaman, Bard J.; Boehnke, Michael; Collins, Francis S.

2012-01-01

Summary A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4 kb of the LMNA gene on a sample of long-lived individuals (US Caucasians with age ≥95 years, N=873) and genetically matched younger controls (N=443). We tested all common non-redundant haplotypes (frequency ≥ 0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on 4 SNPs, remained significant after adjustment for multiple testing (OR = 1.56, P=2.5×10−5, multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3448 subjects from four independent samples of long-lived individuals and control subjects from 1) the New England Centenarian Study (NECS) (N=738), 2) the Southern Italian Centenarian Study (SICS) (N=905), 3) France (N=1103), and 4) the Einstein Ashkenazi Longevity Study (N=702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR = 1.60, P=0.0023), but not in the other three samples (P>.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR = 1.18, P=7.5×10−4, multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. PMID:22340368

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

PubMed

Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

2017-11-01

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor-somatosensory cortex was associated with increased Expanded Disability Status Scale scores in surface-based general linear modelling (P < 0.05). Microstructural pathology was frequent in early multiple sclerosis, and present mainly focally in cortical lesions, whereas more diffusely in white matter. These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cerebrospinal Fluid Amyloid-β 42, Total Tau and Phosphorylated Tau are Low in Patients with Normal Pressure Hydrocephalus: Analogies and Differences with Alzheimer's Disease.

PubMed

Santangelo, Roberto; Cecchetti, Giordano; Bernasconi, Maria Paola; Cardamone, Rosalinda; Barbieri, Alessandra; Pinto, Patrizia; Passerini, Gabriella; Scomazzoni, Francesco; Comi, Giancarlo; Magnani, Giuseppe

2017-01-01

Co-existence of Alzheimer's disease (AD) in normal pressure hydrocephalus (NPH) is a frequent finding, thus a common pathophysiological basis between AD and NPH has been postulated. We measured CSF amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) concentrations in a sample of 294 patients with different types of dementia and 32 subjects without dementia. We then compared scores on neuropsychological tests of NPH patients with pathological and normal CSF Aβ42 values. Aβ42 levels were significantly lower in NPH than in control patients, with no significant differences between AD and NPH. On the contrary, t-tau and p-tau levels were significantly lower in NPH than in AD, with no differences between NPH and controls. NPH patients with pathological Aβ42 levels did not perform worse than NPH patients with normal Aβ42 levels in any cognitive domains. Our data seem to support the hypothesis of amyloid accumulation in brains of NPH patients. Nevertheless, amyloid does not seem to play a pathogenetic role in the development of cognitive deficits in NPH.

Static posturography with dynamic tests. Usefulness of biomechanical parameters in assessing vestibular patients.

PubMed

Balaguer García, Ramón; Pitarch Corresa, Salvador; Baydal Bertomeu, José María; Morales Suárez-Varela, María M

2012-01-01

Posturography allows evaluating postural control. This study showed the posturographic parameters that were useful for assessing the functional ability to maintain balance in our sample of vestibular patients. Of a total of 89 patients, 59 were healthy subjects and 30 had a peripheral vestibular disorder. The subjects were studied using the posturographic NedSVE/IBV system, combining static (Romberg) and dynamic (stability limits and rhythmic weight shifts) tests. We then compared the measurements found in the groups. Normal subjects showed significantly lower oscillations than our patients in all of the posturographic parameters studied (except the displacement angle). In testing the limits of stability, although normal subjects achieved maximum displacements greater than the subjects with the disorder, the differences found were not significant. In rhythmic weight shift tests, normal subjects showed more favourable results than did the vestibular patients, with significant differences in 3 of the 4 parameters studied: 1) anteroposterior ability, 2) mediolateral ability, and 3) anteroposterior control and efficiency. Rhythmic weight shift tests and the static posturography test parameters used were useful in discriminating among the normal and pathological subjects in this study. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Capillary whole blood testing by a new portable monitor. Comparison with standard determination of the international normalized ratio.

PubMed

de Miguel, Dunia; Burgaleta, Carmen; Reyes, Eduardo; Pascual, Teresa

2003-07-01

We evaluated a new portable monitor (AvoSure PT PRO, Menarini Diagnostics, Firenze, Italy) developed to test the prothrombin time in capillary blood and plasma by comparing it with the standard laboratory determination. We studied 62 patients receiving acenocoumarol therapy. The international normalized ratio (INR) in capillary blood was analyzed by 2 methods: AvoSure PT PRO and Thrombotrack Nycomed Analyzer (Axis-Shield, Dundee, Scotland). Parallel studies were performed in plasma samples by a reference method using the Behring Coagulation Timer (Behring Diagnostics, Marburg, Germany). Plasma samples also were tested with the AvoSure PT PRO. Correlation was good for INR values for capillary blood and plasma samples by AvoSure PT PRO and our reference method (R2 = 0.8596) and for capillary blood samples tested by the AvoSure PT PRO and Thrombotrack Nycomed Analyzer (R2 = 0.8875). The correlation for INR in capillary blood and plasma samples by AvoSure PT PRO was 0.6939 (P < .0004). Capillary blood determinations are rapid and effective for monitoring oral anticoagulation therapy and have a high correlation to plasma determinations. AvoSure PT PRO is accurate for controlling INR in plasma and capillary blood samples, may be used in outpatient clinics, and has advantages over previous portable monitors.

Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

PubMed

Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

2016-01-01

The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast Cancer.

PubMed

Park, Kihan; Chen, Wenjin; Chekmareva, Marina A; Foran, David J; Desai, Jaydev P

2018-01-01

This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25-45 temperature range. While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences ( 0.0039) between the two groups. The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple parameters of breast tissue allowing for practical application.

Persistent HyperCKemia in Athletes

PubMed Central

Brancaccio, Paola; Maffulli, Nicola; Politano, Luisa; Lippi, Giuseppe; Limongelli, Francesco Mario

2011-01-01

Summary We compared the effects of exercise on serum levels of creatin kinase (CK) in athletes with persistent hyperCKemia at rest (CK group) and in healthy athletes (control group). Prospective controlled study. Eighteen male Caucasian athletes with high serum CK levels at rest (CK between 80 and 150 U/L) and 25 male Caucasian athletes with normal serum CK levels at rest (CK between 10 and 80 U/L) Main Outcome Measures Blood samples were collected at rest, 30 minutes, 6 hours, 24 hours, 48 hours and 72 hours after a progressive cycloergometer test to exhaustion. The levels of serum CK and its isoenzymes were measured. In the control group, serum CK values at rest were normal (48.18 ± 14.14 U/L). After exercise, they increased slightly, though they always remained <80 U/L, decreasing to the rest level after 48 hours. The CK group had serum CK levels at rest higher than normal (116.56 ± 33.30 U/L). Serum CK levels were still outwith the normal range after 48 hours (130.11 ± 46.95 U/L) and 72 hours (116.55 ± 24.84 U/L). Serum CK levels were significantly different in both groups both before and after progressive cycloergometer test to exhaustion. In athletes with high serum CK levels at rest, serum CK levels remained elevated and had a different kinetics after exercise when compared with healthy athletes. PMID:23738242

Psychological aspects of sexual functioning among cleric and noncleric alleged sex offenders.

PubMed

Haywood, T W; Kravitz, H M; Grossman, L S; Wasyliw, O E; Hardy, D W

1996-06-01

Cleric sexual misconduct with minors is a problem receiving increased attention from the media, victims groups, and church authorities. Mental health professionals are increasingly being asked to assist church and civil authorities to help better understand the problem of cleric sexual misconduct with minors. In the current study we compared self-reported sexual functioning among cleric alleged child molesters, noncleric alleged child molesters, and normal control subjects. We hypothesized clerics would differ from nonclerics and normals in reported sexual functioning. Our sample included 30 Roman Catholic clerics and 39 nonclerics who were alleged to have engaged in sexual misconduct with minors, and 38 normal control subjects, all of whom took the Derogatis Sexual Functioning Inventory (DSFI) as part of their forensic psychiatric evaluation. Our results indicated clerics were more likely to report fewer victims, older victims, and victims of male gender than noncleric alleged child molesters. Clerics differed from nonclerics and normal control subjects on several dimensions of self-reported sexual functioning. Lower offense rate histories among clerics suggest that, as a group, clerics may be less seriously psychologically disordered than noncleric child molesters. Low DSFI scores among Roman Catholic clerics may be accounted for in part by their unique training and socialization process. Future studies should attempt to study the influence of social desirability on DSFI scores. Normative data from nonoffending celibate clergy are needed.

Investigations of the microbial transformation of cortisol to prednisolone in urine samples.

PubMed

Bredehöft, Michael; Baginski, Rainer; Parr, Maria-Kristina; Thevis, Mario; Schänzer, Wilhelm

2012-03-01

Doping control samples are normally collected under non-sterile conditions and sometimes, storage and transportation are influenced by parameters such as the temperature. Therefore, microbial contamination and subsequent alteration of a sample's composition are possible. Studies regarding sample collection in cattle breeding have already shown enzymatic transformation of endogenous testosterone to boldenone causing false-positive findings. The aim of the present study was to investigate whether positive doping cases with the synthetic corticosteroids prednisolone and prednisone may result from microbial transformation of the endogenous corticosteroids cortisol and cortisone, respectively. A method comprising parameters such as pH values and screening results for synthetic glucocorticosteroids as well as incubation experiments followed by liquid chromatographic and mass spectrometric analysis was employed to test for contaminating germs with Δ(1)-dehydrogenase activity. Over 700 urine samples comprising inpatient and doping control specimens were investigated. In none of them, 1,2-dehydrogenating activity was confirmed. These findings are in accordance with other studies. However, the problem of microbial alteration of doping control specimens with special respect to 1,2-dehydrogenation must not be underestimated. Article from a special issue on steroids and microorganisms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Variance in total levels of phospholipase C zeta (PLC-ζ) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability.

PubMed

Kashir, Junaid; Jones, Celine; Mounce, Ginny; Ramadan, Walaa M; Lemmon, Bernadette; Heindryckx, Bjorn; de Sutter, Petra; Parrington, John; Turner, Karen; Child, Tim; McVeigh, Enda; Coward, Kevin

2013-01-01

To examine whether similar levels of phospholipase C zeta (PLC-ζ) protein are present in sperm from men whose ejaculates resulted in normal oocyte activation, and to examine whether a predominant pattern of PLC-ζ localization is linked to normal oocyte activation ability. Laboratory study. University laboratory. Control subjects (men with proven oocyte activation capacity; n = 16) and men whose sperm resulted in recurrent intracytoplasmic sperm injection failure (oocyte activation deficient [OAD]; n = 5). Quantitative immunofluorescent analysis of PLC-ζ protein in human sperm. Total levels of PLC-ζ fluorescence, proportions of sperm exhibiting PLC-ζ immunoreactivity, and proportions of PLC-ζ localization patterns in sperm from control and OAD men. Sperm from control subjects presented a significantly higher proportion of sperm exhibiting PLC-ζ immunofluorescence compared with infertile men diagnosed with OAD (82.6% and 27.4%, respectively). Total levels of PLC-ζ in sperm from individual control and OAD patients exhibited significant variance, with sperm from 10 out of 16 (62.5%) exhibiting levels similar to OAD samples. Predominant PLC-ζ localization patterns varied between control and OAD samples with no predictable or consistent pattern. The results indicate that sperm from control men exhibited significant variance in total levels of PLC-ζ protein, as well as significant variance in the predominant localization pattern. Such variance may hinder the diagnostic application of quantitative PLC-ζ immunofluorescent analysis. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Minimally-invasive biomarker studies in eosinophilic esophagitis: a systematic review.

PubMed

Hines, Brittany T; Rank, Matthew A; Wright, Benjamin L; Marks, Lisa A; Hagan, John B; Straumann, Alex; Greenhawt, Matthew; Dellon, Evan S

2018-05-10

Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus which currently requires repeated endoscopic biopsies for diagnosis and monitoring as no reliable non-invasive markers have been identified. To identify promising minimally-invasive EoE biomarkers and remaining gaps in biomarker validation. We performed a systematic review of EMBASE, Ovid Medline, PubMed, and Web of Science from inception to June 6, 2017. Studies were included if subjects met the 2007 consensus criteria for EoE diagnosis, a minimally-invasive biomarker was assessed, and the study included at least 1 control for comparison. The search identified 2094 studies, with 234 reviewed at full text level, and 49 included in the analysis (20 adult, 19 pediatric, 7 pediatric and adult, and 3 not stated). The majority (26 of 49) were published after 2014. Thirty-five studies included normal controls, 9 analyzed atopic controls, and 29 compared samples from subjects with active and inactive EoE. Minimally-invasive biomarkers were obtained from peripheral blood (n=41 studies), sponge/string samples (3), oral/throat swab secretions (2), breath condensate (2), stool (2), and urine (2). The most commonly reported biomarkers were peripheral blood eosinophils (16), blood and string eosinophil granule proteins (14), and eosinophil surface or intracellular markers (12). EoE biomarkers distinguished active EoE from normal controls in 23 studies, atopic controls in 2 studies, and inactive EoE controls in 20 studies. Several promising minimally-invasive biomarkers for EoE have emerged; however, few are able to differentiate EoE from other atopic diseases. Copyright © 2018. Published by Elsevier Inc.

CYP2D6*4 polymorphism is associated with statin-induced muscle effects.

PubMed

Frudakis, Tony N; Thomas, Matthew J; Ginjupalli, Siva N; Handelin, Barbara; Gabriel, Richard; Gomez, Hector J

2007-09-01

Statin use is associated with a variety of overtly related muscle symptoms including muscle pain, myalgia, creatine kinase elevations without pain with myolysis and myositis (rhabdomyolysis), a potentially fatal side effect that led to the withdrawal of cerivastatin in 2001. Unintended drug response phenotypes have an impact on patient compliance and sometimes patient health and the assessment of risk on an individual basis could enhance therapeutic benefit. We therefore investigated whether common single nucleotide polymorphisms were associated with the expression of broadly grouped atorvastatin-induced muscle events in a case-control study (n=263 samples, n=388 SNPs). Of a number of associations identified in a discovery sample (51 atorvastatin-induced muscle and 55 normal) only those corresponding to the CYP2D6*4 allele were significantly associated in the sample (24 atorvastatin-induced muscle and 133 normal) (Discovery P=0.004, odds ratio=3.6; Validation P=0.036, odds ratio=2.7; total P=0.001, odds ratio=2.5). The frequency of the CYP2D6*4 allele was about 50% in atorvastatin-induced muscle patients but only 28% in controls, similar to that of other patient types (28.5%). The association was independent of various demographic variables and not explained by gross demographic, clinical or population-structure differences among cases and controls. Surprisingly, the CYP2D6*4 allele appeared similarly distributed among controls and patients expressing simvastatin-induced muscle events (n=169, frequency in case participants=49.2%, P=0.067, odds ratio=1.7). Our results suggest that the CYP2D6*4 allele is associated with broadly related muscle events caused by at least two structurally dissimilar HMG-CoA reductase inhibitors, and as such, may have implications for a better understanding of this statin-wide phenomena.

Classification of Electrophotonic Images of Yogic Practice of Mudra through Neural Networks.

PubMed

Kumar, Kotikalapudi Shiva; Srinivasan, T M; Ilavarasu, Judu; Mondal, Biplob; Nagendra, H R

2018-01-01

Mudras signify a gesture with hands, eyes, and the body. Different configurations of the joining of fingertips are also termed mudra and are used by yoga practitioners for energy manipulation and for therapeutic applications. Electrophotonic imaging (EPI) captures the coronal discharge around the fingers as a result of electron capture from the ten fingers. The coronal discharge around each fingertip is studied to understand the effect of mudra on EPI parameters. The participants were from Swami Vivekananda Yoga Anusandhana Samsthana and Sushrutha Ayurvedic Medical College, in Bengaluru, India. There were 29 volunteers in the mudra group and 32 in the control group. There were two designs: one was a pre-post design with control the other was pre-post with repeated measures with 18 individuals practicing mudra for 3 days. The duration of intervention for the pre-post design was 10 min on the 1 st day, 15 min on the 2 nd day, and 20 min on the 3 rd day. A neural network classifier was used for classifying mudra and control samples. The EPI parameters, normalized area and average intensity, passed the test of normality Shapiro-Wilk. The Cohen's d , effect size was 0.988 and 0.974 for the mudra and control groups, respectively. Neural network-based analysis showed the classification accuracy of the post-intervention samples for mudra and control varied from 85% to 100% while the classification accuracy varied from 55% to 70% for the pre-intervention samples. The result of the mudra intervention showed statistically significant changes in the mean values on the 3 rd day compared to the 1 st day. The effect size of the variations in mudra was more than that of the control group. Mudra practice of a longer duration showed statistically significant change in the EPI parameter, average intensity in comparison to the practice on the 1 st day.

The childhood executive function inventory: confirmatory factor analyses and cross-cultural clinical validity in a sample of 8- to 11-year-old children.

PubMed

Catale, Corinne; Meulemans, Thierry; Thorell, Lisa B

2015-06-01

The aim was to investigate the psychometric characteristics of the French adaptation of the Childhood Executive Functioning Inventory (CHEXI) in children and to explore the cross-cultural validity of the CHEXI in discriminating between children with ADHD and controls in two culturally different samples (Belgian and Swedish). Study I included normally developing children (n = 242), whereas Study II included both children diagnosed with ADHD (n = 87) and controls (n = 87). CHEXI ratings were collected from parents. Confirmatory factor analyses replicated the two-factor solution, referred to as inhibition and working memory, which had been identified previously. Both subscales had good psychometric properties. Furthermore, the CHEXI was found to discriminate, with high sensitivity and specificity, between children with ADHD and controls in both cultural samples. The CHEXI can be considered as a valuable screening measure for ADHD in children, but the cross-cultural clinical implications of ratings have to be considered. © 2013 SAGE Publications.

Automatic Method of Pause Measurement for Normal and Dysarthric Speech

ERIC Educational Resources Information Center

Rosen, Kristin; Murdoch, Bruce; Folker, Joanne; Vogel, Adam; Cahill, Louise; Delatycki, Martin; Corben, Louise

2010-01-01

This study proposes an automatic method for the detection of pauses and identification of pause types in conversational speech for the purpose of measuring the effects of Friedreich's Ataxia (FRDA) on speech. Speech samples of [approximately] 3 minutes were recorded from 13 speakers with FRDA and 18 healthy controls. Pauses were measured from the…

Use of Spectral/Cepstral Analyses for Differentiating Normal from Hypofunctional Voices in Sustained Vowel and Continuous Speech Contexts

ERIC Educational Resources Information Center

Watts, Christopher R.; Awan, Shaheen N.

2011-01-01

Purpose: In this study, the authors evaluated the diagnostic value of spectral/cepstral measures to differentiate dysphonic from nondysphonic voices using sustained vowels and continuous speech samples. Methodology: Thirty-two age- and gender-matched individuals (16 participants with dysphonia and 16 controls) were recorded reading a standard…

Whole exome sequencing identifies driver mutations in asymptomatic computed tomography-detected lung cancers with normal karyotype.

PubMed

Belloni, Elena; Veronesi, Giulia; Rotta, Luca; Volorio, Sara; Sardella, Domenico; Bernard, Loris; Pece, Salvatore; Di Fiore, Pier Paolo; Fumagalli, Caterina; Barberis, Massimo; Spaggiari, Lorenzo; Pelicci, Pier Giuseppe; Riva, Laura

2015-04-01

The efficacy of curative surgery for lung cancer could be largely improved by non-invasive screening programs, which can detect the disease at early stages. We previously showed that 18% of screening-identified lung cancers demonstrate a normal karyotype and, following high-density genome scanning, can be subdivided into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole exome sequencing was applied to the two normal karyotype, screening-detected lung cancers, constituting group 2, as well as normal controls. We identified mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other. The two normal karyotype screening-detected lung tumors displayed a typical lung cancer mutational profile that only next generation sequencing could reveal, which offered an additional contribution to the over-diagnosis bias concept hypothesized within lung cancer screening programs. Copyright © 2015 Elsevier Inc. All rights reserved.

Compulsive sexual behavior inventory: a preliminary study of reliability and validity.

PubMed

Coleman, E; Miner, M; Ohlerking, F; Raymond, N

2001-01-01

This preliminary study was designed to develop empirically a scale of compulsive sexual behavior (CSB) and to test its reliability and validity in a sample of individuals with nonparaphilic CSB (N = 15), in a sample of pedophiles (N = 35) in treatment for sexual offending, and in a sample of normal controls (N = 42). Following a factor analysis and a varimax rotation, those items with factor loadings on the rotated factors of greater than .60 were retained. Three factors were identified, which appeared to measure control, abuse, and violence. Cronbach's alphas indicated that the subscales have good reliability. The 28-item scale was then tested for validity by a linear discriminant function analysis. The scale successfully discriminated the nonparaphilic CSB sample and the pedophiles from controls. Further analysis indicated that this scale is a valid measure of CSB in that there were significant differences between the three groups on the control subscale. Pedophiles scored significantly lower than the other two groups on the abuse subscale, with the other two groups not scoring significantly differently from one another. This indicated that pedophiles were more abusive than the nonparaphilic CSB individuals or the controls. Pedophiles scored significantly lower than controls on the violence subscale. Nonparaphilic individuals with compulsive sexual behavior scored slightly lower on the violence subscale, although not significantly different. As a preliminary study, there are several limitations to this study, which should be addressed, in further studies with larger sample sizes.

Legionnaires' Disease Bacteria in power plant cooling systems: downtime report. Final report

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

Tyndall, R.L.; Solomon, J.A.; Christensen, S.W.

1985-04-01

Legionnaires' Disease Bacteria (Legionella) are a normal part of the aquatic community that, when aerosolized, can be pathogenic to man. The downtime study was designed to determine the degree to which Legionella populations are aerosolized during cleaning and maintenance operations in a closed-cycle steam-electric power plant. Both high-volume and impinger air samples were collected prior to and during downtime operations. Emphasis was placed on sampling inside or adjacent to water boxes, condensers, and cooling towers. Control air samples were taken upwind from the plant site. Water and sludge samples were also collected at various locations. In the laboratory, the concentrationsmore » of Groups A, B, and C Legionella were determined using the direct fluorescent antibody method. All positive air samples, and other selected air samples, were injected into guinea pigs to detect infectious Legionella. Legionella could be detected in only 12 of the 126 air samples collected. These were predominantly Group A Legionella (L. pneumophila, serogroups 1 to 6). All 12 positive samples had been collected in the vicinity of water boxes, condensers, detention ponds, and cooling towers during downtime operations where aerosolization of Legionella populations would be expected. None of the air samples yielded infectious Legionella when injected into guinea pigs. Detection of Legionella in air samples taken during downtime was significantly more likely than detection during normal operating conditions (p <0.01). 13 refs., 4 figs., 10 tabs.« less

Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

NASA Astrophysics Data System (ADS)

Sakhnini, Lama

2003-05-01

In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

Sensitivity and specificity of normality tests and consequences on reference interval accuracy at small sample size: a computer-simulation study.

PubMed

Le Boedec, Kevin

2016-12-01

According to international guidelines, parametric methods must be chosen for RI construction when the sample size is small and the distribution is Gaussian. However, normality tests may not be accurate at small sample size. The purpose of the study was to evaluate normality test performance to properly identify samples extracted from a Gaussian population at small sample sizes, and assess the consequences on RI accuracy of applying parametric methods to samples that falsely identified the parent population as Gaussian. Samples of n = 60 and n = 30 values were randomly selected 100 times from simulated Gaussian, lognormal, and asymmetric populations of 10,000 values. The sensitivity and specificity of 4 normality tests were compared. Reference intervals were calculated using 6 different statistical methods from samples that falsely identified the parent population as Gaussian, and their accuracy was compared. Shapiro-Wilk and D'Agostino-Pearson tests were the best performing normality tests. However, their specificity was poor at sample size n = 30 (specificity for P < .05: .51 and .50, respectively). The best significance levels identified when n = 30 were 0.19 for Shapiro-Wilk test and 0.18 for D'Agostino-Pearson test. Using parametric methods on samples extracted from a lognormal population but falsely identified as Gaussian led to clinically relevant inaccuracies. At small sample size, normality tests may lead to erroneous use of parametric methods to build RI. Using nonparametric methods (or alternatively Box-Cox transformation) on all samples regardless of their distribution or adjusting, the significance level of normality tests depending on sample size would limit the risk of constructing inaccurate RI. © 2016 American Society for Veterinary Clinical Pathology.

A microplate reader-based method to quantify NADH-cytochrome b5 reductase activity for diagnosis of recessive congenital methaemoglobinemia.

PubMed

Kedar, Prabhakar; Desai, Anand; Warang, Prashant; Colah, Roshan

2017-05-01

Congenital methemoglobinemia due to NADH-cytochrome b5 reductase 3 (CYB5R3) deficiencies is an autosomal recessive disorder that occurs sporadically worldwide, A sensitive, accurate, and rapid analysis of NADH-CYB5R enzyme concentrations is necessary for the diagnosis of RCM. Here we present an alternative microplate method that is based on a standard 96-well microplate format and microplate reader that simplify the quantification of NADH-CYB5R activity. TECAN (Infinite 200 PRO series) microplate reader with Tecan's proven Magellan™ software measured the NADH-CYB5R enzyme activity in 250 normal controls and previously diagnosed 25 cases of RCM due to NADH-CYB5R deficiency in the Indian population using 96-well microplates using 200 μl of total reaction mixture and also compared with standard spectrophotometric assay. We have also studied stability of the hemolysate stored at 4 and -20°C temperature. Enzyme activity in all 25 samples ranged from 6.09 to 10.07 IU/g Hb (mean ± SD: 8.08 ± 1.99 IU/g Hb) where as normal control ranged (n = 250) between 13.42 and 21.58 IU/g Hb) (mean ± SD: 17.5 ± 4.08 IU/g of Hb). Data obtained from the microplate reader were compared with standard spectrophotometer method and found 100% concordance using both methods. Microplate method allows differentiating between normal, deficient and intermediate enzyme activity. It was observed that samples had significant loss of activity when stored at 4°C and retained stable activity at -20°C for 1 week time. Our new method, incorporating a whole process of enzyme assay into a microplate format is readily applicable and allows rapid monitoring of enzyme assay. It is readily applicable to quantitative assay on pediatric sample as well as large number of samples for population screening.

Biological indicators of exposure to total and respirable aluminium dust fractions in a primary aluminium smelter.

PubMed Central

Röllin, H B; Theodorou, P; Cantrell, A C

1996-01-01

OBJECTIVES: The study attempts to define biological indicators of aluminium uptake and excretion in workers exposed to airborne aluminium compounds in a primary aluminium smelter. Also, this study defines the total and respirable aluminium dust fractions in two different potrooms, and correlates their concentrations with biological indicators in this group of workers. METHODS: Air was sampled at defined work sites. Non-destructive and conventional techniques were used to find total and respirable aluminium content of the dust. Blood and urine was collected from 84 volunteers employed at various work stations throughout the smelter and from two different cohorts of controls matched for sex, age, and socioeconomic status. Aluminium in serum samples and urine specimens was measured by flameless atomic absorption with a PE 4100 ZL spectrometer. RESULTS: The correlation of aluminium concentrations in serum and urine samples with the degree of exposure was assessed for three arbitrary exposure categories; low (0.036 mg Al/m3), medium (0.35 mg Al/m3) and high (1.47 mg Al/m3) as found in different areas of the smelter. At medium and high exposure, the ratio of respirable to total aluminium in the dust samples varied significantly. At high exposure, serum aluminium, although significantly raised, was still within the normal range of an unexposed population. The workers with low exposure excreted aluminium in urine at levels significantly higher than the controls, but still within the normal range of the population. However, potroom workers with medium and high exposure had significantly higher urinary aluminium than the normal range. CONCLUSIONS: It is concluded that only urinary aluminium constitutes a practical index of occupational exposure at or above 0.35 mg Al/m3, and that the respirable fraction of the dust may play a major role in the biological response to exposure to aluminium in a smelter environment. PMID:8758038

Human papillomavirus type-16 variants in Quechua aboriginals from Argentina.

PubMed

Picconi, María Alejandra; Alonio, Lidia Virginia; Sichero, Laura; Mbayed, Viviana; Villa, Luisa Lina; Gronda, Jorge; Campos, Rodolfo; Teyssié, Angélica

2003-04-01

Cervical carcinoma is the leading cause of cancer death in Quechua indians from Jujuy (northwestern Argentina). To determine the prevalence of HPV-16 variants, 106 HPV-16 positive cervical samples were studied, including 33 low-grade squamous intraepithelial lesions (LSIL), 28 high-grade squamous intraepithelial lesions (HSIL), 9 invasive cervical cancer (ICC), and 36 samples from women with normal colposcopy and cytology. HPV genome variability was examined in the L1 and E6 genes by PCR-hybridization. In a subset of 20 samples, a LCR fragment was also analyzed by PCR-sequencing. Most variants belonged to the European branch with subtle differences that depended on the viral gene fragment studied. Only about 10% of the specimens had non-European variants, including eight Asian-American, two Asian, and one North-American-1. E6 gene analysis revealed that 43% of the samples were identical to HPV-16 prototype, while 57% corresponded to variants. Interestingly, the majority (87%) of normal smears had HPV-16 prototype, whereas variants were detected mainly in SIL and ICC. LCR sequencing yielded 80% of variants, including 69% of European, 19% Asian-American, and 12% Asian. We identified a new variant, the Argentine Quechua-51 (AQ-51), similar to B-14 plus two additional changes: G7842-->A and A7837-->C; phylogenetic inference allocated it in the Asian-American branch. The high proportion of European variants may reflect Spanish colonial influence on these native Inca descendants. The predominance of HPV-16 variants in pathologic samples when compared to normal controls could have implications for the natural history of cervical lesions. Copyright 2003 Wiley-Liss, Inc.

Associations of body weight perception and weight control behaviors with problematic internet use among Korean adolescents.

PubMed

Park, Subin; Lee, Yeeun

2017-05-01

We examined the association of body mass index (BMI), body weight perception, and weight control behaviors with problematic Internet use in a nationwide sample of Korean adolescents. Cross-sectional data from the 2010 Korean Youth Risk Behavior Web-based Survey collected from 37,041 boys and 33,655 girls in middle- and high- schools (grades 7-12) were analyzed. Participants were classified into groups based on BMI (underweight, normal weight, overweight, and obese), body weight perception (underweight, normal weight, and overweight), and weight control behavior (no weight control behavior, appropriate weight control behavior, inappropriate weight control behavior). The risk of problematic Internet use was assessed with the Korean Internet Addiction Proneness Scale for Youth-Short Form. Both boys and girls with inappropriate weight control behavior were more likely to have problematic Internet use. Underweight, overweight, and obese boys and girls were more likely to have problematic Internet use. For both boys and girls, subjective perception of underweight and overweight were positively associated with problematic Internet use. Given the negative effect of inappropriate weight control behavior, special attention needs to be given to adolescents' inappropriate weight control behavior, and an educational intervention for adolescents to control their weight in healthy ways is needed. Copyright © 2017. Published by Elsevier B.V.

Spall fracture in additive manufactured Ti-6Al-4V

DOE PAGES

Jones, David Robert; Fensin, Saryu Jindal; Dippo, Olivia; ...

2016-10-07

Here, we present a study on the spall strength of additive manufactured (AM) Ti-6Al-4V. Samples were obtained from two pieces of selective laser melted (SLM, a powder bed fusion technique) Ti-6Al-4V such that the response to dynamic tensile loading could be investigated as a function of the orientation between the build layers and the loading direction. A sample of wrought bar-stock Ti-6Al-4V was also tested to act as a baseline representing the traditionally manufactured material response. A single-stage light gas-gun was used to launch a thin flyer plate into the samples, generating a region of intense tensile stress on amore » plane normal to the impact direction. The rear free surface velocity time history of each sample was recorded with laser-based velocimetry to allow the spall strength to be calculated. The samples were also soft recovered to enable post-mortem characterization of the spall damage evolution. Results showed that when the tensile load was applied normal to the interfaces between the build layers caused by the SLM fabrication process the spall strength was drastically reduced, dropping to 60% of that of the wrought material. However, when loaded parallel to the AM build layer interfaces the spall strength was found to remain at 95% of the wrought control, suggesting that when loading normal to the AM layer interfaces, void nucleation is facilitated more readily due to weaknesses along these boundaries. Quasi-static testing of the same sample orientations revealed a much lower degree of anisotropy, demonstrating the importance of rate-dependent studies for damage evolution in AM materials.« less

Spall fracture in additive manufactured Ti-6Al-4V

NASA Astrophysics Data System (ADS)

Jones, D. R.; Fensin, S. J.; Dippo, O.; Beal, R. A.; Livescu, V.; Martinez, D. T.; Trujillo, C. P.; Florando, J. N.; Kumar, M.; Gray, G. T.

2016-10-01

We present a study on the spall strength of additive manufactured (AM) Ti-6Al-4V. Samples were obtained from two pieces of selective laser melted (SLM, a powder bed fusion technique) Ti-6Al-4V such that the response to dynamic tensile loading could be investigated as a function of the orientation between the build layers and the loading direction. A sample of wrought bar-stock Ti-6Al-4V was also tested to act as a baseline representing the traditionally manufactured material response. A single-stage light gas-gun was used to launch a thin flyer plate into the samples, generating a region of intense tensile stress on a plane normal to the impact direction. The rear free surface velocity time history of each sample was recorded with laser-based velocimetry to allow the spall strength to be calculated. The samples were also soft recovered to enable post-mortem characterization of the spall damage evolution. Results showed that when the tensile load was applied normal to the interfaces between the build layers caused by the SLM fabrication process the spall strength was drastically reduced, dropping to 60% of that of the wrought material. However, when loaded parallel to the AM build layer interfaces the spall strength was found to remain at 95% of the wrought control, suggesting that when loading normal to the AM layer interfaces, void nucleation is facilitated more readily due to weaknesses along these boundaries. Quasi-static testing of the same sample orientations revealed a much lower degree of anisotropy, demonstrating the importance of rate-dependent studies for damage evolution in AM materials.

Association between oral lichen planus and Epstein–Barr virus in Iranian patients

PubMed Central

Shariati, Matin; Mokhtari, Mojgan; Masoudifar, Aria

2018-01-01

Background: Oral lichen planus (OLP) is a common mucocutaneous disease with malignant transformation potential. Several etiologies such as humoral, autoimmunity, and viral infections might play a role, but still there is no definite etiology for this disease. The aim of this study was to investigate the presence of Epstein–Barr virus (EBV) genome in Iranian patients with OLP as compared to people with normal mucosa. Materials and Methods: The study was carried out on a case group including 38 tissue specimens of patients with histopathological confirmation of OLP and a control group including 38 samples of healthy mucosa. All samples were examined by nested polymerase chain reaction (PCR) method to determine the DNA of EBV. Results: Twenty-two (57.9%) female samples and 16 (42.1%) male samples with OLP were randomly selected as the case group, and 20 (52.6%) female samples and 18 (47.4%) male samples with healthy mucosa as the control group. There was a statistically significant difference in the percentage of EBV positivity between the case (15.8%) and the control groups (P < 0.05); in the case group, three female samples (13.6%) and three male samples (18.8%) were infected with EBV; the difference between the genders was not statistically significant (P = 0.50). Conclusion: Results emphasized that EBV genome was significantly higher among Iranian patients with OLP so antiviral therapy might be helpful. PMID:29692821

Association between oral lichen planus and Epstein-Barr virus in Iranian patients.

PubMed

Shariati, Matin; Mokhtari, Mojgan; Masoudifar, Aria

2018-01-01

Oral lichen planus (OLP) is a common mucocutaneous disease with malignant transformation potential. Several etiologies such as humoral, autoimmunity, and viral infections might play a role, but still there is no definite etiology for this disease. The aim of this study was to investigate the presence of Epstein-Barr virus (EBV) genome in Iranian patients with OLP as compared to people with normal mucosa. The study was carried out on a case group including 38 tissue specimens of patients with histopathological confirmation of OLP and a control group including 38 samples of healthy mucosa. All samples were examined by nested polymerase chain reaction (PCR) method to determine the DNA of EBV. Twenty-two (57.9%) female samples and 16 (42.1%) male samples with OLP were randomly selected as the case group, and 20 (52.6%) female samples and 18 (47.4%) male samples with healthy mucosa as the control group. There was a statistically significant difference in the percentage of EBV positivity between the case (15.8%) and the control groups ( P < 0.05); in the case group, three female samples (13.6%) and three male samples (18.8%) were infected with EBV; the difference between the genders was not statistically significant ( P = 0.50). Results emphasized that EBV genome was significantly higher among Iranian patients with OLP so antiviral therapy might be helpful.

Rushed, unhappy, and drained: an experience sampling study of relations between time pressure, perceived control, mood, and emotional exhaustion in a group of accountants.

PubMed

Teuchmann, K; Totterdell, P; Parker, S K

1999-01-01

Experience sampling methodology was used to examine how work demands translate into acute changes in affective response and thence into chronic response. Seven accountants reported their reactions 3 times a day for 4 weeks on pocket computers. Aggregated analysis showed that mood and emotional exhaustion fluctuated in parallel with time pressure over time. Disaggregated time-series analysis confirmed the direct impact of high-demand periods on the perception of control, time pressure, and mood and the indirect impact on emotional exhaustion. A curvilinear relationship between time pressure and emotional exhaustion was shown. The relationships between work demands and emotional exhaustion changed between high-demand periods and normal working periods. The results suggest that enhancing perceived control may alleviate the negative effects of time pressure.

Coherent Raman Scattering Microscopy for Evaluation of Head and Neck Carcinoma.

PubMed

Hoesli, Rebecca C; Orringer, Daniel A; McHugh, Jonathan B; Spector, Matthew E

2017-09-01

Objective We aim to describe a novel, label-free, real-time imaging technique, coherent Raman scattering (CRS) microscopy, for histopathological evaluation of head and neck cancer. We evaluated the ability of CRS microscopy to delineate between tumor and nonneoplastic tissue in tissue samples from patients with head and neck cancer. Study Design Prospective case series. Setting Tertiary care medical center. Subjects and Methods Patients eligible were surgical candidates with biopsy-proven, previously untreated head and neck carcinoma and were consented preoperatively for participation in this study. Tissue was collected from 50 patients, and after confirmation of tumor and normal specimens by hematoxylin and eosin (H&E), there were 42 tumor samples and 42 normal adjacent controls. Results There were 42 confirmed carcinoma specimens on H&E, and CRS microscopy identified 37 as carcinoma. Of the 42 normal specimens, CRS microscopy identified 40 as normal. This resulted in a sensitivity of 88.1% and specificity of 95.2% in distinguishing between neoplastic and nonneoplastic images. Conclusion CRS microscopy is a unique label-free imaging technique that can provide rapid, high-resolution images and can accurately determine the presence of head and neck carcinoma. This holds potential for implementation into standard practice, allowing frozen margin evaluation even at institutions without a histopathology laboratory.

Evaluation of Normalization Methods to Pave the Way Towards Large-Scale LC-MS-Based Metabolomics Profiling Experiments

PubMed Central

Valkenborg, Dirk; Baggerman, Geert; Vanaerschot, Manu; Witters, Erwin; Dujardin, Jean-Claude; Burzykowski, Tomasz; Berg, Maya

2013-01-01

Abstract Combining liquid chromatography-mass spectrometry (LC-MS)-based metabolomics experiments that were collected over a long period of time remains problematic due to systematic variability between LC-MS measurements. Until now, most normalization methods for LC-MS data are model-driven, based on internal standards or intermediate quality control runs, where an external model is extrapolated to the dataset of interest. In the first part of this article, we evaluate several existing data-driven normalization approaches on LC-MS metabolomics experiments, which do not require the use of internal standards. According to variability measures, each normalization method performs relatively well, showing that the use of any normalization method will greatly improve data-analysis originating from multiple experimental runs. In the second part, we apply cyclic-Loess normalization to a Leishmania sample. This normalization method allows the removal of systematic variability between two measurement blocks over time and maintains the differential metabolites. In conclusion, normalization allows for pooling datasets from different measurement blocks over time and increases the statistical power of the analysis, hence paving the way to increase the scale of LC-MS metabolomics experiments. From our investigation, we recommend data-driven normalization methods over model-driven normalization methods, if only a few internal standards were used. Moreover, data-driven normalization methods are the best option to normalize datasets from untargeted LC-MS experiments. PMID:23808607

Skeletal maturation in obese patients.

PubMed

Giuca, Maria Rita; Pasini, Marco; Tecco, Simona; Marchetti, Enrico; Giannotti, Laura; Marzo, Giuseppe

2012-12-01

The objective of this study was to compare skeletal maturation in obese patients and in subjects of normal weight to evaluate the best timing for orthopedic and orthodontic treatment. The null hypothesis was that obese and normal-weight patients show similar degrees of skeletal maturation. The sample for this retrospective study consisted of 50 white patients (28 boys, 22 girls) whose x-rays (hand-wrist and lateral cephalometric radiographs) were already available. The test group included 25 obese patients (11 girls, 14 boys; average age, 9.8 ± 2.11 years), and the control group included 25 subjects of normal weight (11 girls, 14 boys; average age, 9.9 ± 2.5 years). Skeletal maturation was determined by using the carpal analysis method and the cervical vertebral maturation method. According to the carpal analysis, there was a significant difference between skeletal and chronologic ages between the test group (11.8 ± 11.4 months) and the control group (-2.9 ± 3.1 months). Furthermore, the obese subjects exhibited a significantly higher mean cervical vertebral maturation score (2.8 ± 0.7) than did the control subjects (2 ± 0.6) (P <0.05). Compared with the normal-weight subjects, the obese subjects showed a higher mean discrepancy between skeletal and chronologic ages according to the carpal analysis and had a significantly higher cervical vertebral maturation score. Thus, to account for the growth in obese patients with skeletal discrepancies, it might be necessary to perform examinations and dentofacial and orthopedic treatments earlier than in normal-weight subjects. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

New Noble Gas Studies on Popping Rocks from the Mid-Atlantic Ridge near 14°N

NASA Astrophysics Data System (ADS)

Kurz, M. D.; Curtice, J.; Jones, M.; Péron, S.; Wanless, V. D.; Mittelstaedt, E. L.; Soule, S. A.; Klein, F.; Fornari, D. J.

2017-12-01

New Popping Rocks were recovered in situ on the Mid-Atlantic Ridge (MAR) near 13.77° N, using HOV Alvin on cruise AT33-03 in 2016 on RV Atlantis. We report new helium, neon, argon, and CO2 step-crushing measurements on a subset of the glass samples, with a focus on a new procedure to collect seafloor samples with minimal exposure to air. Glassy seafloor basalts were collected in sealed containers using the Alvin mechanical arm and transported to the surface without atmospheric exposure. On the ship, the seawater was drained, the volcanic glass was transferred to stainless steel ultra-high-vacuum containers (in an oxygen-free glove box), which were then evacuated using a turbo-molecular pump and sealed for transport under vacuum. All processing was carried out under a nitrogen atmosphere. A control sample was collected from each pillow outcrop and processed normally in air. The preliminary step-crushing measurements show that the anaerobically collected samples have systematically higher 20Ne/22Ne, 21Ne/22Ne and 40Ar/36Ar than the control samples. Helium abundances and isotopes are consistent between anaerobically collected samples and control samples. These results suggest that minimizing atmospheric exposure during sample processing can significantly reduce air contamination for heavy noble gases, providing a new option for seafloor sampling. Higher vesicle abundances appear to yield a greater difference in neon and argon isotopes between the anaerobic and control samples, suggesting that atmospheric contamination is related to vesicle abundance, possibly through micro-fractures. The new data show variability in the maximum mantle neon and argon isotopic compositions, and abundance ratios, suggesting that the samples experienced variable outgassing prior to eruption, and may represent different phases of a single eruption, or multiple eruptions.

Normalization and microbial differential abundance strategies depend upon data characteristics.

PubMed

Weiss, Sophie; Xu, Zhenjiang Zech; Peddada, Shyamal; Amir, Amnon; Bittinger, Kyle; Gonzalez, Antonio; Lozupone, Catherine; Zaneveld, Jesse R; Vázquez-Baeza, Yoshiki; Birmingham, Amanda; Hyde, Embriette R; Knight, Rob

2017-03-03

Data from 16S ribosomal RNA (rRNA) amplicon sequencing present challenges to ecological and statistical interpretation. In particular, library sizes often vary over several ranges of magnitude, and the data contains many zeros. Although we are typically interested in comparing relative abundance of taxa in the ecosystem of two or more groups, we can only measure the taxon relative abundance in specimens obtained from the ecosystems. Because the comparison of taxon relative abundance in the specimen is not equivalent to the comparison of taxon relative abundance in the ecosystems, this presents a special challenge. Second, because the relative abundance of taxa in the specimen (as well as in the ecosystem) sum to 1, these are compositional data. Because the compositional data are constrained by the simplex (sum to 1) and are not unconstrained in the Euclidean space, many standard methods of analysis are not applicable. Here, we evaluate how these challenges impact the performance of existing normalization methods and differential abundance analyses. Effects on normalization: Most normalization methods enable successful clustering of samples according to biological origin when the groups differ substantially in their overall microbial composition. Rarefying more clearly clusters samples according to biological origin than other normalization techniques do for ordination metrics based on presence or absence. Alternate normalization measures are potentially vulnerable to artifacts due to library size. Effects on differential abundance testing: We build on a previous work to evaluate seven proposed statistical methods using rarefied as well as raw data. Our simulation studies suggest that the false discovery rates of many differential abundance-testing methods are not increased by rarefying itself, although of course rarefying results in a loss of sensitivity due to elimination of a portion of available data. For groups with large (~10×) differences in the average library size, rarefying lowers the false discovery rate. DESeq2, without addition of a constant, increased sensitivity on smaller datasets (<20 samples per group) but tends towards a higher false discovery rate with more samples, very uneven (~10×) library sizes, and/or compositional effects. For drawing inferences regarding taxon abundance in the ecosystem, analysis of composition of microbiomes (ANCOM) is not only very sensitive (for >20 samples per group) but also critically the only method tested that has a good control of false discovery rate. These findings guide which normalization and differential abundance techniques to use based on the data characteristics of a given study.

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

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

Lindsay, WD; Oncora Medical, LLC, Philadelphia, PA; Berlind, CG

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013more » was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced machine learning methodologies need be consider in the future.« less

Multidimensional Normalization to Minimize Plate Effects of Suspension Bead Array Data.

PubMed

Hong, Mun-Gwan; Lee, Woojoo; Nilsson, Peter; Pawitan, Yudi; Schwenk, Jochen M

2016-10-07

Enhanced by the growing number of biobanks, biomarker studies can now be performed with reasonable statistical power by using large sets of samples. Antibody-based proteomics by means of suspension bead arrays offers one attractive approach to analyze serum, plasma, or CSF samples for such studies in microtiter plates. To expand measurements beyond single batches, with either 96 or 384 samples per plate, suitable normalization methods are required to minimize the variation between plates. Here we propose two normalization approaches utilizing MA coordinates. The multidimensional MA (multi-MA) and MA-loess both consider all samples of a microtiter plate per suspension bead array assay and thus do not require any external reference samples. We demonstrate the performance of the two MA normalization methods with data obtained from the analysis of 384 samples including both serum and plasma. Samples were randomized across 96-well sample plates, processed, and analyzed in assay plates, respectively. Using principal component analysis (PCA), we could show that plate-wise clusters found in the first two components were eliminated by multi-MA normalization as compared with other normalization methods. Furthermore, we studied the correlation profiles between random pairs of antibodies and found that both MA normalization methods substantially reduced the inflated correlation introduced by plate effects. Normalization approaches using multi-MA and MA-loess minimized batch effects arising from the analysis of several assay plates with antibody suspension bead arrays. In a simulated biomarker study, multi-MA restored associations lost due to plate effects. Our normalization approaches, which are available as R package MDimNormn, could also be useful in studies using other types of high-throughput assay data.

[Gene polymorphisms in patients with Down's syndrome].

PubMed

Kuz'mina, N S; Ushenkova, L I; Shagirova, Zh M; Sheĭkhaev, G O; Mikhaĭlov, V F; Kurbatova, L A; Mazurik, V K; Rubanovich, A V; Zasukhina, G D

2009-01-01

Polymorphisms of glutation-S-transferase (GSTM1, GSTT1 GSTP1) and methylentetrahydrofolate reductase (MTHFR) genes have been studied in DNA from blood lymphocytes of 18 patients with Down's syndrome and 61 controls. Frequencies of normal alleles of GST genotypes were lower in patients as compared to the controls. A DNA analysis of 11 patients and 17 controls revealed the presence of mutations in region 246-250 of exon 7 of the p53 gene in 4 patients. Mutations were not found in the control group. Due to the small sample size, the results of this study should be interpreted with caution and need replication in larger studies.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Control chart pattern recognition using RBF neural network with new training algorithm and practical features.

PubMed

Addeh, Abdoljalil; Khormali, Aminollah; Golilarz, Noorbakhsh Amiri

2018-05-04

The control chart patterns are the most commonly used statistical process control (SPC) tools to monitor process changes. When a control chart produces an out-of-control signal, this means that the process has been changed. In this study, a new method based on optimized radial basis function neural network (RBFNN) is proposed for control chart patterns (CCPs) recognition. The proposed method consists of four main modules: feature extraction, feature selection, classification and learning algorithm. In the feature extraction module, shape and statistical features are used. Recently, various shape and statistical features have been presented for the CCPs recognition. In the feature selection module, the association rules (AR) method has been employed to select the best set of the shape and statistical features. In the classifier section, RBFNN is used and finally, in RBFNN, learning algorithm has a high impact on the network performance. Therefore, a new learning algorithm based on the bees algorithm has been used in the learning module. Most studies have considered only six patterns: Normal, Cyclic, Increasing Trend, Decreasing Trend, Upward Shift and Downward Shift. Since three patterns namely Normal, Stratification, and Systematic are very similar to each other and distinguishing them is very difficult, in most studies Stratification and Systematic have not been considered. Regarding to the continuous monitoring and control over the production process and the exact type detection of the problem encountered during the production process, eight patterns have been investigated in this study. The proposed method is tested on a dataset containing 1600 samples (200 samples from each pattern) and the results showed that the proposed method has a very good performance. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Comparison of folic acid levels in schizophrenic patients and control groups

NASA Astrophysics Data System (ADS)

Arthy, C. C.; Amin, M. M.; Effendy, E.

2018-03-01

Folic acid deficiency is a risk factor for schizophrenia through epidemiology, biochemistry and gene-related studies. Compared with healthy people, schizophrenic patients may have high homocysteine plasma values and homocysteine or low levels of folic acid, which seems to correlate with extrapyramidal motor symptoms caused by neuroleptic therapy and with symptoms of schizophrenia. In this present study, we focus on the difference of folic acid level between schizophrenic patient and control group. The study sample consisted of schizophrenic patients and 14 people in the control group and performed blood sampling to obtain the results of folic acid levels. The folic acid level in both groups was within normal range, but the schizophrenic patient group had lower mean folic acid values of 5.00 ng/ml (sb 1.66), compared with the control group with mean folic acid values of 10.75 ng/ml (sb 4.33). there was the group of the control group had a higher value of folic acid than the schizophrenic group.

Immune Modulation in Normal Human Peripheral Blood Mononuclear Cells (PBMCs) (Lymphocytes) in Response to Benzofuran-2-Carboxylic Acid Derivative KMEG during Spaceflight

NASA Astrophysics Data System (ADS)

Okoro, Elvis; Mann, Vivek; Ellis, Ivory; Mansoor, Elvedina; Olamigoke, Loretta; Marriott, Karla Sue; Denkins, Pamela; Williams, Willie; Sundaresan, Alamelu

2017-08-01

Microgravity and radiation exposure during space flight have been widely reported to induce the suppression of normal immune system function, and increase the risk of cancer development in humans. These findings pose a serious risk to manned space missions. Interestingly, recent studies have shown that benzofuran-2-carboxylic acid derivatives can inhibit the progression of some of these devastating effects on earth and in modeled microgravity. However, these studies had not assessed the impacts of benzofuran-2- carboxylic acid and its derivatives on global gene expression under spaceflight conditions. In this study, the ability of a specific benzofuran-2-carboxylic acid derivative (KMEG) to confer protection from radiation and restore normal immune function was investigated following exposure to space flight conditions on the ISS. Normal human peripheral blood mononuclear cells (lymphocytes) treated with 10 µ g/ml of KMEG together with untreated control samples were flown on Nanoracks hardware on Spacex-3 flight. The Samples were returned one month later and gene expression was analyzed. A 1g-ground control experiment was performed in parallel at the Kennedy spaceflight center. The first overall subtractive unrestricted analysis revealed 78 genes, which were differentially expressed in space flight KMEG, untreated lymphocytes as compared to the corresponding ground controls. However, in KMEG-treated space flight lymphocytes, there was an increased expression of a group of genes that mediate increased transcription, translation and innate immune system mediating functions of lymphocytes as compared to KMEG-untreated samples. Analysis of genes related to T cell proliferation in spaceflight KMEG-treated lymphocytes compared to 1g-ground KMEG- treated lymphocytes revealed six T cell proliferation and signaling genes to be significantly upregulated (p < 0.001) and five related genes were found to be significantly down-regulated. These genes play a significant role in promoting the proliferation of T-lymphocytes, the regulation of membrane trafficking, promote early response, mediating C-myc related proliferation, promote antiapoptotic activity and protects mitochondria from the accumulation of oxidatively damaged membrane proteins. Overall, our analysis indicates that KMEG promotes T- cell proliferation and has an anti-inflammatory effect, thereby increasing immunity and possible protection from chronic inflammation setting which is optimally required during long term space flights.

Generation Scotland: Donor DNA Databank; A control DNA resource.

PubMed

Kerr, Shona M; Liewald, David C M; Campbell, Archie; Taylor, Kerrie; Wild, Sarah H; Newby, David; Turner, Marc; Porteous, David J

2010-11-23

Many medical disorders of public health importance are complex diseases caused by multiple genetic, environmental and lifestyle factors. Recent technological advances have made it possible to analyse the genetic variants that predispose to complex diseases. Reliable detection of these variants requires genome-wide association studies in sufficiently large numbers of cases and controls. This approach is often hampered by difficulties in collecting appropriate control samples. The Generation Scotland: Donor DNA Databank (GS:3D) aims to help solve this problem by providing a resource of control DNA and plasma samples accessible for research. GS:3D participants were recruited from volunteer blood donors attending Scottish National Blood Transfusion Service (SNBTS) clinics across Scotland. All participants gave full written consent for GS:3D to take spare blood from their normal donation. Participants also supplied demographic data by completing a short questionnaire. Over five thousand complete sets of samples, data and consent forms were collected. DNA and plasma were extracted and stored. The data and samples were unlinked from their original SNBTS identifier number. The plasma, DNA and demographic data are available for research. New data obtained from analysis of the resource will be fed back to GS:3D and will be made available to other researchers as appropriate. Recruitment of blood donors is an efficient and cost-effective way of collecting thousands of control samples. Because the collection is large, subsets of controls can be selected, based on age range, gender, and ethnic or geographic origin. The GS:3D resource should reduce time and expense for investigators who would otherwise have had to recruit their own controls.

Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

NASA Technical Reports Server (NTRS)

Tietze, Karen J.

1990-01-01

Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

Approach bias for food cues in obese individuals.

PubMed

Kemps, Eva; Tiggemann, Marika

2015-01-01

This study aimed to investigate the existence of an approach bias for food cues in obese individuals. A community sample of 56 obese women and 56 normal weight controls completed an approach-avoidance variant of the implicit association task. The obese participants were faster to respond to trials that paired food words with approach words, and trials that paired non-food words with avoid words, than the converse pairings, thus, demonstrating an approach bias for food. This bias was evident for both high caloric and low caloric food words, and was not attributable to a state of deprivation or feelings of hunger. By contrast, the normal weight controls did not show any such bias. The results are consistent with recent neurocognitive perspectives of obesity. At a practical level, approach biases for food may present a potential target for modifying (excessive) food intake.

Water and Salt Stresses, Kinetin and Protein Synthesis in Tobacco Leaves 1

PubMed Central

Ben-Zioni, Aliza; Itai, C.; Vaadia, Y.

1967-01-01

The capacity of tobacco (Nicotiana rustica) leaf discs to incorporate l-leucine 14C into proteins was measured. Leaf discs were obtained from plants which experienced soil water depletion, or which were exposed to a saline or osmotic stress in the root medium. The stresses were brief of relatively short duration and water potential did not decrease below 4 bars in the root media. Leaf discs were sampled 2 hours after stress removal, achieved by reirrigation, or replacement of saline and osmotic solutions with normal nutrient solution. Plants were always turgid when leaves were sampled. All stressed tissues showed reduced capacity to incorporate l-leucine 14C into protein. The reduction was about 50% and could not be attributed either to reduced uptake into the discs, or to possible isotopic dilution. Incorporation decreased progressively with leaf age in control discs as well as in stressed leaf discs. At all ages tested, incorporation in stressed discs was lower than that of the control. Full recovery of incorporation capacity in stressed discs was obtained when discs were sampled 72 hours after stress removal but not earlier. Kinetin pretreatment prior to incubation with labelled leucine partially restored incorporation in stressed discs. The differences in response to kinetin of stressed and control discs suggest a lower endogenous level of cytokinins in the stressed discs. The results were qualitatively similar regardless of the kind of stress given to the plants during pretreatment. This supports the hypothesis that the normal supply of root cytokinins is important in shoot metabolism. PMID:16656515

Multielement extraction system for the determination of 18 trace elements in geochemical samples

USGS Publications Warehouse

Clark, J.R.; Viets, J.G.

1981-01-01

A Methyl isobutyl ketone-Amine synerGistic Iodide Complex (MAGIC) extraction system has been developed for use in geochemical exploration which separates a maximum number of trace elements from interfering matrices. Extraction curves for 18 of these trace elements are presented: Pd, Pt, Cu, Ag, Au, Zn, Cd, Hg, Ga, In, Tl, Sa, Pb, As, Sb, Bi, Se, and Te. The acid normality of the aqueous phase controls the extraction into the organic phase, and each of these 18 elements has a broad range of HCl normality over which H is quantitatively extracted, making H possible to determine all 18 trace elements from a single sample digestion or leach solution. The extract can be analyzed directly by flame atomic absorption or inductively coupled plasma emission spectroscopy. Most of these 18 elements can be determined by Nameless atomic absorption after special treatment of the organic extract.

Cardiovascular disease risk in women with migraine

PubMed Central

2013-01-01

Background Studies suggest a higher prevalence of unfavourable cardiovascular risk factors amongst migraineurs, but results have been conflicting. The aim of this study was to investigate traditional and newly recognized risk factors as well as other surrogate markers of cardiovascular risk in obese and normal weight women with migraine. Methods Fifty-nine adult female probands participated in this case–control study. The sample was divided into normal weight and obese migraineurs and age- and body mass index-matched control groups. The following cardiovascular risk factors were analyzed: serum levels of lipids, fasting glucose, and insulin; insulin resistance; blood pressure; smoking (categorized as current, past or never); Framingham 10-year risk of general cardiovascular disease score; C-reactive protein; family history of cardiovascular disease; physical activity; sleep disturbances; depression; and bioelectrical impedance phase angle. The means of continuous variables were compared using Student’s t-test for independent samples or the Mann–Whitney U-test (for 2 groups) and ANOVA or the Kruskal-Wallis test (for 4 groups) depending on the distribution of data. Results All migraineurs were sedentary irrespective of nutritional status. Migraineurs had higher depression scores and shorter sleep duration, and obese migraineurs, in particular, had worse sleep quality scores. Insulin resistance and insulinaemia were associated with obesity, and obese migraineurs had lower HDL-c than normal weight controls and migraineurs. Also, the Framingham risk score was higher in obese migraineurs. Conclusion These findings suggest that female migraineurs experience marked inactivity, depression, and some sleep disturbance, that higher insulin resistance and insulinaemia are related to obesity, and that obesity and migraine probably exert overlapping effects on HDL-c levels and Framingham 10-year cardiovascular risk. PMID:24011175

[Expression of proBNP and NT-proBNP in Sudden Death of Coronary Heart Disease].

PubMed

Zeng, Q; Sun, R F; Li, Z; Zhai, L Q; Liu, M Z; Guo, X J; Gao, C R

2017-10-01

To study the expression change of pro-brain natriuretic peptide （proBNP） and N-terminal pro-brain natriuretic peptide （NT-proBNP） in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis. Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group （20 cases in each group）. The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR （RT-PCR）. The content of NT-proBNP in plasma were detected by ELISA. Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group （ P <0.05）. The NT-proBNP content in plasma of sudden death of coronary atherosclerotic heart disease group was higher than that of single coronary stenosis group （ P <0.05）. In myocardial ischemia condition, the higher expression of proBNP in cardiac muscle cell shows that the detection of NT-proBNP in plasma can be useful to differentially diagnose the degree of coronary atherosclerotic heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine

[Relationship between breast milk composition and weight growth velocity of infants fed with exclusive breast milk].

PubMed

Huang, Li-Li; Xiong, Fei; Yang, Fan

2016-10-01

To study the effect of breast milk composition on weight growth velocity of infants fed with exclusive breast milk. One hundred and thirty-eight full-term singleton infants who received regular follow-up visits and fed with exclusive breast milk and their mothers were recruited. Body height, weight and head circumference of these infants were measured at regular visits. Z scores were used to evaluate growth velocity. The subjects were classified into a failure to thrive group (ΔZ scores≤-0.67), a poor growth group (-0.67<ΔZ scores<0) and a normal control group (ΔZ scores≥0). The samples of mature breast milk were collected for composition analysis. The differences in the levels of the protein, fats, energy, carbohydrates and minerals in breast milk were compared among the three groups. ΔZ scores for weight in the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). There was no significant difference in the levels of protein, fats and energy in breast milk among the failure to thrive, poor growth and normal control groups. However, the levels of carbohydrates and minerals in both the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). Weight growth velocity of infants can be affected by the composition of breast milk to a certain degree in a short period. In order to maintain a good weight growth velocity of infants, mothers should have a balanced diet to improve the quality of breast milk.

Assessment of vitamin K2 levels in osteoporotic patients: a case control study.

PubMed

Noori, Akram; Lashkari, Mahin; Oveisi, Sonia; Khair Khah, Mohamad Reza; Zargar, Ali

2014-07-14

The aim of this study was to measure the level of Vitamin K2 (Vit K2) in osteoporotic patients and individuals with normal bone density as controls. This case-control study was done in Outpatient Department of Rheumatology at Qazvin Boo-ali Sina Hospital in 2013. Participants were 50 patients with osteoporotic densitometry measured by DEXA (T score? -2.5) who were matched with 48 persons in control group with normal bone density (T score> -1). The level of Vit K2 in samples was measured using enzyme linked immunosorbent assay (ELISA). Data were analyzed by Mann-Whitney U test and Chi-square test. The level of Vit K2 in patients with osteoporosis was not significantly different from the control group (Median: 75.95 vs. 71.35 nmol/L, respectively; P-value: 0.709). The authors determined cut-offs 75 percentile of vitamin K2 in all participants that was 85 nmol/L and percentages of persons in two groups were similar. Although Vit K2 level in patients with osteoporosis was not significantly different from the control group, further studies are necessary to confirm the association of osteoporosis and Vit K2.

Internal associations and dynamic expression of c-kit and nanog genes in ventricular remodelling induced by adriamycin.

PubMed

Liu, Zhen; Li, Shuo; Liu, Lingling; Guo, Zhikun; Wang, Pengfei

2016-09-01

The present study aimed to investigate the dynamic expression of the c-kit and nanog genes in rats with left ventricular remodelling induced by adriamycin (ADR), and explore its internal association and mechanism of action. Sprague-Dawley male rats were randomly divided into a normal control group and a heart failure model group. Heart failure was induced by a single intraperitoneal injection of ADR (4 mg/kg) weekly for six weeks. The normal control group was given the same amount of saline. At the eighth week, rat cardiac function was examined to demonstrate the formation of heart failure. The rat hearts were harvested frozen and sectioned, and the expression levels of the nanog and c-kit genes in the myocardial tissue samples were detected using immunohistochemistry, immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Hematoxylin and eosin staining demonstrated various pathological changes in the myocardial cells in the heart failure model group, whereas myocardial infarction was not observed in the normal control group. Immunohistochemistry and immunofluorescence demonstrated that nanog-positive cells were predominantly expressed in the vascular endothelium, with a few myocardial cells and stem cells in normal myocardium. The expression levels of c-kit and nanog in the myocardium of the rats with heart failure decreased significantly. c-kit-positive cells clustered together in the epicardium and its vicinity, and c-kit expression significantly decreased in the myocardium of rats with heart failure, as compared with normal rats. In both groups, some cells co-expressed both the c-kit and nanog genes. The RT-PCR results demonstrated that the expression levels of the two genes in the heart failure model group were significantly lower compared with those in the normal control group (P<0.05). In conclusion, the c-kit- and nanog-positive stem cells decreased in the myocardium of the rats with left ventricular remodelling induced by ADR. Their abnormal expression was significantly correlated with left ventricular remodelling, thereby indicating an internal association (influences of two indexes in the experimental group and control group) between them.

The effect of flurbiprofen on the development of anencephaly in early stage chicken embryos.

PubMed

Özeren, Ersin; Er, Uygur; Güvenç, Yahya; Demirci, Adnan; Arıkök, Ata Türker; Şenveli, Engin; Ergün, Rüçhan Behzat

2015-04-01

The study investigated the effect of flurbiprofen on the development of anencephaly in early stage chicken embryos. We looked at four groups with a total of 36 embryos. There was a control group, a normal saline group, a normal-dose group and a high-dose group with ten, ten, eight and eight eggs with embryo respectively. Two embryos in the control group, studied with light microscopy at 48 h, were consistent with 28-29 hours' incubation in the Hamburger-Hamilton System. They had open neural tubes. The other embryos in this group were considered normal. One embryo in the normal saline group was on the occlusion stage at 48 h. One embryo showed an open neural tube. They were compatible with 28-29 hours' incubation in the Hamburger-Hamilton system. The remaining eight embryos showed normal development. In the normal dose group, one embryo showed underdevelopment of the embryonic disc and the embryo was dead. In four embryos, the neural tubes were open. One cranial malformation was found that was complicated with anencephaly in one embryo. In two embryos the neural tubes were closed, as they showed normal development, and they reached their expected stages according to the Hamburger-Hamilton classification. There was no malformation or growth retardation. Four experimental embryos were anencephalic in the high dose group, and three embryos had open neural tubes. One embryo exhibited both anencephaly and a neural tube closure defect. None of the embryos in this group showed normal development. Even the usual therapeutic doses of flurbiprofen increased the risk of neural tube defect. Flurbiprofen was found to significantly increase the risk of anencephaly. The provision of improved technical materials and studies with larger sample sizes will reveal the stage of morphological disruption during the development of embryos.

Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

PubMed

Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

2010-05-01

Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

Ex vivo characterization of normal and adenocarcinoma colon samples by Mueller matrix polarimetry.

PubMed

Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ashraf, Sumara; Ahmad, Shakil; Ikram, Masroor

2015-05-01

Mueller matrix polarimetry along with polar decomposition algorithm was employed for the characterization of ex vivo normal and adenocarcinoma human colon tissues by polarized light in the visible spectral range (425-725 nm). Six derived polarization metrics [total diattenuation (DT ), retardance (RT ), depolarization(ΔT ), linear diattenuation (DL), retardance (δ), and depolarization (ΔL)] were compared for normal and adenocarcinoma colon tissue samples. The results show that all six polarimetric properties for adenocarcinoma samples were significantly higher as compared to the normal samples for all wavelengths. The Wilcoxon rank sum test illustrated that total retardance is a good candidate for the discrimination of normal and adenocarcinoma colon samples. Support vector machine classification for normal and adenocarcinoma based on the four polarization properties spectra (ΔT , ΔL, RT ,and δ) yielded 100% accuracy, sensitivity, and specificity, while both DTa nd DL showed 66.6%, 33.3%, and 83.3% accuracy, sensitivity, and specificity, respectively. The combination of polarization analysis and given classification methods provides a framework to distinguish the normal and cancerous tissues.

Effects of land use and sample location on nitrate-stream flow hysteresis descriptors during storm events

USGS Publications Warehouse

Feinson, Lawrence S.; Gibs, Jacob; Imbrigiotta, Thomas E.; Garrett, Jessica D.

2016-01-01

The U.S. Geological Survey's New Jersey and Iowa Water Science Centers deployed ultraviolet-visible spectrophotometric sensors at water-quality monitoring sites on the Passaic and Pompton Rivers at Two Bridges, New Jersey, on Toms River at Toms River, New Jersey, and on the North Raccoon River near Jefferson, Iowa to continuously measure in-stream nitrate plus nitrite as nitrogen (NO3 + NO2) concentrations in conjunction with continuous stream flow measurements. Statistical analysis of NO3 + NO2 vs. stream discharge during storm events found statistically significant links between land use types and sampling site with the normalized area and rotational direction of NO3 + NO2-stream discharge (N-Q) hysteresis patterns. Statistically significant relations were also found between the normalized area of a hysteresis pattern and several flow parameters as well as the normalized area adjusted for rotational direction and minimum NO3 + NO2 concentrations. The mean normalized hysteresis area for forested land use was smaller than that of urban and agricultural land uses. The hysteresis rotational direction of the agricultural land use was opposite of that of the urban and undeveloped land uses. An r2 of 0.81 for the relation between the minimum normalized NO3 + NO2 concentration during a storm vs. the normalized NO3 + NO2 concentration at peak flow suggested that dilution was the dominant process controlling NO3 + NO2 concentrations over the course of most storm events.

Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

PubMed

Madsen, Karine; Hesby, Sara; Poulsen, Ingrid; Fuglsang, Stefan; Graff, Jesper; Larsen, Karen B; Kammersgaard, Lars P; Law, Ian; Siebner, Hartwig R

2017-11-01

Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [ 18 F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [ 18 F]FDG-PET scan and venous blood sampling. Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. Our study demonstrates that the analysis method of the [ 18 F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. We recommend supplementing a static [ 18 F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc. Copyright © 2017 Elsevier B.V. All rights reserved.

Total Antioxidant Status in Type 2 Diabetic Patients in Palestine.

PubMed

Kharroubi, Akram T; Darwish, Hisham M; Akkawi, Mutaz A; Ashareef, Abdelkareem A; Almasri, Zaher A; Bader, Khaldoun A; Khammash, Umaiyeh M

2015-01-01

The objective of this study was to compare the level of total antioxidant status (TAS) in type 2 diabetic and normal Palestinian subjects as well as the major factors influencing TAS levels. A sample of convenience composed of 212 type 2 diabetic and 208 normal subjects above the age of 40 were recruited. Only 9.8% of the subjects had normal body mass index (BMI) levels (<25), 29% were overweight (≥25 to <30), and 61.2% were obese (≥30). The mean levels of TAS were significantly higher in diabetic compared to control subjects (2.18 versus 1.84 mM Trolox, P = 0.001) and in hypertensive subjects compared to subjects with normal blood pressure (BP). Mean TAS levels were higher in obese compared to nonobese subjects (2.12 versus 1.85 mM Trolox, P = 0.001). Mean TAS levels were similarly higher in subjects with high fasting plasma glucose (FPG) compared to normal FPG (2.19 versus 1.90 mM Trolox) and high HbA1c (≥6.5%) compared to HbA1c < 6.5% (2.14 versus 1.91 mM Trolox). Multivariate analysis revealed that only diabetic status (P = 0.032) and the level of education (P = 0.036) were significantly associated with TAS. In conclusion diabetic patients had 18.5% increase in TAS levels compared to control subjects.

Nanomachining by rubbing at ultrasonic frequency under controlled shear force.

PubMed

Muraoka, Mikio

2011-03-01

This study proposes a new method of proximal-probe machining that uses a rubbing process by introducing concentrated-mass (CM) cantilevers. At the second resonance of the CM cantilever vibration, the tip site of the cantilever becomes a node of the standing deflection wave because of the sufficient inertia of the attached concentrated mass. The tip makes a cyclic motion that is tangential to the sample surface, not vertical to it, as in a tapping motion. This lateral tip motion that is selectively excited by CM cantilevers was effective for the material modification of a sample due to the friction between the tip and the sample. Imaging and nanomachining under controlled shear force were demonstrated by means of the modified cantilever and a normal atomic force microscope. We were able to write a micron-sized letter "Z" having a line width of 30-100 nm on a resin surface.

Collagen crosslinks in chondromalacia of the patella.

PubMed

Väätäinen, U; Kiviranta, I; Jaroma, H; Arokosi, J; Tammi, M; Kovanen, V

1998-02-01

The aim of the study was to determine collagen concentration and collagen crosslinks in cartilage samples from chondromalacia of the patella. To study the extracellular matrix alterations associated to chondromalacia, we determined the concentration of collagen (hydroxyproline) and its hydroxylysylpyridinoline and lysylpyridinoline crosslinks from chondromalacia foci of the patellae in 12 patients and 7 controls from apparently normal cadavers. The structure of the collagen network in 8 samples of grades II-IV chondromalacia was examined under polarized light microscopy. The full-thickness cartilage samples taken with a surgical knife from chondromalacia lesions did not show changes in collagen, hydroxylysylpyridinoline and lysylpyridinoline concentration as compared with the controls. Polarized light microscopy showed decreased birefringence in the superficial cartilage of chondromalacia lesions, indicating disorganization or disappearance of collagen fibers in this zone. It is concluded that the collagen network shows gradual disorganization with the severity of chondromalacia lesion of the patella without changes in the concentration or crosslinks of collagen.

Quantitative computed tomography determined regional lung mechanics in normal nonsmokers, normal smokers and metastatic sarcoma subjects.

PubMed

Choi, Jiwoong; Hoffman, Eric A; Lin, Ching-Long; Milhem, Mohammed M; Tessier, Jean; Newell, John D

2017-01-01

Extra-thoracic tumors send out pilot cells that attach to the pulmonary endothelium. We hypothesized that this could alter regional lung mechanics (tissue stiffening or accumulation of fluid and inflammatory cells) through interactions with host cells. We explored this with serial inspiratory computed tomography (CT) and image matching to assess regional changes in lung expansion. We retrospectively assessed 44 pairs of two serial CT scans on 21 sarcoma patients: 12 without lung metastases and 9 with lung metastases. For each subject, two or more serial inspiratory clinically-derived CT scans were retrospectively collected. Two research-derived control groups were included: 7 normal nonsmokers and 12 asymptomatic smokers with two inspiratory scans taken the same day or one year apart respectively. We performed image registration for local-to-local matching scans to baseline, and derived local expansion and density changes at an acinar scale. Welch two sample t test was used for comparison between groups. Statistical significance was determined with a p value < 0.05. Lung regions of metastatic sarcoma patients (but not the normal control group) demonstrated an increased proportion of normalized lung expansion between the first and second CT. These hyper-expanded regions were associated with, but not limited to, visible metastatic lung lesions. Compared with the normal control group, the percent of increased normalized hyper-expanded lung in sarcoma subjects was significantly increased (p < 0.05). There was also evidence of increased lung "tissue" volume (non-air components) in the hyper-expanded regions of the cancer subjects relative to non-hyper-expanded regions. "Tissue" volume increase was present in the hyper-expanded regions of metastatic and non-metastatic sarcoma subjects. This putatively could represent regional inflammation related to the presence of tumor pilot cell-host related interactions. This new quantitative CT (QCT) method for linking serial acquired inspiratory CT images may provide a diagnostic and prognostic means to objectively characterize regional responses in the lung following oncological treatment and monitoring for lung metastases.

The Corticostriatal Adenosine A2A Receptor Controls Maintenance and Retrieval of Spatial Working Memory.

PubMed

Li, Zhihui; Chen, Xingjun; Wang, Tao; Gao, Ying; Li, Fei; Chen, Long; Xue, Jin; He, Yan; Li, Yan; Guo, Wei; Zheng, Wu; Zhang, Liping; Ye, Fenfen; Ren, Xiangpeng; Feng, Yue; Chan, Piu; Chen, Jiang-Fan

2018-03-15

Working memory (WM) taps into multiple executive processes including encoding, maintenance, and retrieval of information, but the molecular and circuit modulation of these WM processes remains undefined due to the lack of methods to control G protein-coupled receptor signaling with temporal resolution of seconds. By coupling optogenetic control of the adenosine A 2A receptor (A 2A R) signaling, the Cre-loxP-mediated focal A 2A R knockdown with a delayed non-match-to-place (DNMTP) task, we investigated the effect of optogenetic activation and focal knockdown of A 2A Rs in the dorsomedial striatum (n = 8 to 14 per group) and medial prefrontal cortex (n = 16 to 22 per group) on distinct executive processes of spatial WM. We also evaluated the therapeutic effect of the A 2A R antagonist KW6002 on delayed match-to-sample/place tasks in 6 normal and 6 MPTP-treated cynomolgus monkeys. Optogenetic activation of striatopallidal A 2A Rs in the dorsomedial striatum selectively at the delay and choice (not sample) phases impaired DNMTP performance. Optogenetic activation of A 2A Rs in the medial prefrontal cortex selectively at the delay (not sample or choice) phase improved DNMTP performance. The corticostriatal A 2A R control of spatial WM was specific for a novel but not well-trained DNMTP task. Focal dorsomedial striatum A 2A R knockdown or KW6002 improved DNMTP performance in mice. Last, KW6002 improved spatial WM in delayed match-to-sample and delayed match-to-place tasks of normal and dopamine-depleted cynomolgus monkeys. The A 2A Rs in striatopallidal and medial prefrontal cortex neurons exert distinctive control of WM maintenance and retrieval to achieve cognitive stability and flexibility. The procognitive effect of KW6002 in nonhuman primates provides the preclinical data to translate A 2A R antagonists for improving cognitive impairments in Parkinson's disease. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Actinobacillus actinomycetemcomitans in Human Periodontal Disease: a Cross-Sectional Microbiological Investigation

PubMed Central

Slots, Jørgen; Reynolds, Homer S.; Genco, Robert J.

1980-01-01

Actinobacillus actinomycetemcomitans is a facultative gram-negative bacterium which has been associated with severe oral and nonoral infections. This study examined its occurrence in the oral cavities of 10 normal juveniles, 11 normal adults, 10 juvenile periodontitis patients, and 12 adult periodontitis patients. Four deep periodontal pockets and two normal periodontal sites were sampled in the diseased patients, and six normal periodontal sites were sampled in the healthy individuals. In all subjects samples were obtained from the cheek, tongue, and saliva. Samples from a total of 172 normal periodontal sites, 83 deep periodontal pockets, 42 cheek mucosae, 42 tongue dorsa, and 42 salivas were examined. Isolation was performed by using a medium for selective isolation of A. actinomycetemcomitans (Trypticase soy agar [BBL Microbiology Systems] supplemented with 10% serum and 75 μg of bacitracin per ml). The carrier rates were 20% for normal juveniles, 36% for normal adults, 50% for adult periodontitis patients, and 90% for juvenile periodontitis patients. A. actinomycetemcomitans was on average recovered in about fivefold-higher numbers from infected deep periodontal pockets than from infected normal subgingival areas. Samples of periodontal pockets generally contained 100-fold-more cells of A. actinomycetemcomitans than did samples of the cheek, tongue, and saliva. A. actinomycetemcomitans is commonly isolated from patients with juvenile periodontitis, often isolated from patients with adult periodontitis, and occasionally isolated from normal juveniles and adults. Its primary oral ecological niche appears to be dental plaque and periodontal pockets. PMID:6968718

Two modulator generalized ellipsometer for complete mueller matrix measurement

DOEpatents

Jellison, Jr., Gerald E.; Modine, Frank A.

1999-01-01

A two-modulator generalized ellipsometer (2-MGE) comprising two polarizer-photoelastic modulator (PEM) pairs, an optical light source, an optical detection system, and associated data processing and control electronics, where the PEMs are free-running. The input light passes through the first polarizer-PEM pair, reflects off the sample surface or passes through the sample, passes through the second PEM-polarizer pair, and is detected. Each PEM is free running and operates at a different resonant frequency, e.g., 50 and 60 kHz. The resulting time-dependent waveform of the light intensity is a complicated function of time, and depends upon the exact operating frequency and phase of each PEM, the sample, and the azimuthal angles of the polarizer-PEM pairs, but can be resolved into a dc component and eight periodic components. In one embodiment, the waveform is analyzed using a new spectral analysis technique that is similar to Fourier analysis to determine eight sample Mueller matrix elements (normalized to the m.sub.00 Mueller matrix element). The other seven normalized elements of the general 4.times.4 Mueller matrix can be determined by changing the azimuthal angles of the PEM-polarizer pairs with respect to the plane of incidence. Since this instrument can measure all elements of the sample Mueller matrix, it is much more powerful than standard ellipsometers.

Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platform.

PubMed

Sista, Ramakrishna S; Wang, Tong; Wu, Ning; Graham, Carrie; Eckhardt, Allen; Winger, Theodore; Srinivasan, Vijay; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2013-09-23

New therapies for lysosomal storage diseases (LSDs) have generated interest in screening newborns for these conditions. We present performance validation data on a digital microfluidic platform that performs multiplex enzymatic assays for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases. We developed an investigational disposable digital microfluidic cartridge that uses a single dried blood spot (DBS) punch for performing a 5-plex fluorometric enzymatic assay on up to 44 DBS samples. Precision and linearity of the assays were determined by analyzing quality control DBS samples; clinical performance was determined by analyzing 600 presumed normal and known affected samples (12 for Pompe, 7 for Fabry and 10 each for Hunter, Gaucher and Hurler). Overall coefficient of variation (CV) values between cartridges, days, instruments, and operators ranged from 2 to 21%; linearity correlation coefficients were ≥0.98 for all assays. The multiplex enzymatic assay performed from a single DBS punch was able to discriminate presumed normal from known affected samples for 5 LSDs. Digital microfluidic technology shows potential for rapid, high-throughput screening for 5 LSDs in a newborn screening laboratory environment. Sample preparation to enzymatic activity on each cartridge is less than 3h. Copyright © 2013 Elsevier B.V. All rights reserved.

Detection of micronuclei formation and nuclear anomalies in regenerative nodules of human cirrhotic livers and relationship to hepatocellular carcinoma.

PubMed

de Almeida, Terezinha M B; Leitão, Regina C; Andrade, Joyce D; Beçak, Willy; Carrilho, Flair J; Sonohara, Shigueko

2004-04-01

Human cirrhosis is considered an important factor in hepatocarcinogenesis. The lack of substantial genetics and cytogenetics data in human cirrhosis led us to investigate spontaneous micronuclei formation, as an indicator of chromosomal damage. The analysis was performed in hepatocytes of regenerative, macroregenerative, and tumoral nodules from 30 cases of cirrhosis (paraffin-embedded archival material), retrospectively selected: cryptogenic, hepatitis C virus, and hepatitis C virus associated with hepatocellular carcinoma (HCC). Thirteen control liver samples of healthy organ donors were included. Micronucleated hepatocytes were analyzed with Feulgen-fast-green dyeing techniques. The spontaneous frequency of micronucleated hepatocytes in both regenerative and macroregenerative nodules of all cirrhotic patients was significantly higher than for the normal control group. There was no significant difference in frequency of micronucleated hepatocytes in regenerative nodules compared with macroregenerative nodules for all cases analyzed, whereas a significantly higher frequency of micronucleated hepatocytes was detected in tumoral nodules, compared with cirrhotic regenerative nodules and normal parenchyma. A higher frequency of the nuclear anomalies termed broken-eggs was observed in hepatitis C virus-related samples. Chromatinic losses and genotoxicity already existed in the cirrhotic regenerative nodules, which might predispose to development of HCC.

Inheritance of Properties of Normal and Non-Normal Distributions after Transformation of Scores to Ranks

ERIC Educational Resources Information Center

Zimmerman, Donald W.

2011-01-01

This study investigated how population parameters representing heterogeneity of variance, skewness, kurtosis, bimodality, and outlier-proneness, drawn from normal and eleven non-normal distributions, also characterized the ranks corresponding to independent samples of scores. When the parameters of population distributions from which samples were…

CpG methylation of HPV 16 LCR at E2 binding site proximal to P97 is associated with cervical cancer in presence of intact E2.

PubMed

Bhattacharjee, Bornali; Sengupta, Sharmila

2006-10-25

Human papillomavirus type 16 (HPV-16) E2 protein negatively regulates transcription of the E6 and E7 genes. This study was done to test the hypothesis that methylation of the HPV 16 long control region (LCR) is overrepresented among cervical cancer (CaCx) cases compared to cytologically normal controls harboring intact E2 gene. Methylation of the E2 binding site (E2BS-I), proximal to the P97 promoter, was assessed by HpaII/ MspI restriction digestion while McrBC digestion was used to assess LCR-E6 (7289-540) for 57 CaCx samples and 15 normal controls. E2BS-I methylation was found to be significantly higher (56.14%) in cases compared to (20%) controls [OR(age-adjusted) (95% CI): 4.53 (1.05-19.43) p=0.042]. The difference between cases (54.39%) and controls (40%) with respect to LCR-E6 methylation status [OR(age-adjusted) (95% CI): 1.77(0.5-6.3); p=0.38] was not significant. Sequencing of a randomly selected set of 13 methylated malignant samples revealed absence or rare presence, of methylation at CpGs 7579, 7535, 7683 and 7862 respectively. Methylation was found to be more at CpGs within E2 binding sites proximal to the P97 promoter. These results indicate the involvement of E2 binding site methylation in presence of intact E2, leading to loss of E2 repressor activity in CaCx.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Downregulation of external death receptor genes FAS and DR5 in colorectal cancer samples positive for human papillomavirus infection.

PubMed

Karbasi, Ashraf; Borhani, Nasim; Daliri, Karim; Kazemi, Bahram; Manoochehri, Mehdi

2015-06-01

Human papillomaviruses (HPV) have frequently been detected in colorectal cancer tumor samples, and may play a role in the pathogenesis of colorectal cancer. This study was designed to investigate the presence of DNA and RNA for the high-risk HPV genotypes 16 and 18 in samples of colorectal cancer tumors and adjacent normal tissues. We also investigated the expression of proapoptotic genes in HPV-positive colorectal tumors compared to normal tissue samples. Samples of tumoral and adjacent normal tissues were fresh-frozen, and HPV DNA was identified by nested and semiquantitative PCR. Real time PCR was used to quantitatively compare the expression of HPV-18 E6 and nine proapoptotic genes in HPV-positive tumors and samples of adjacent normal tissue. HPV-16 DNA was found in 10.5% of the tumor samples, and HPV-18 DNA was found in 23.6% of the samples. Real time PCR results showed lower expression of the E6 gene in HPV-positive tumors than in adjacent normal tissue. The expression of two proapoptotic genes, FAS and DR5, was significantly lower in tumor samples than in adjacent normal tissues. HPV infection, especially HPV-18, may play a role in colorectal cancer tumorigenesis by downregulating death receptor genes and interfering with the extrinsic pathway of apoptosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

PubMed

Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

2016-12-01

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

Development and functional significance of private speech among attention-deficit hyperactivity disordered and normal boys.

PubMed

Berk, L E; Potts, M K

1991-06-01

We compared the development of spontaneous private speech and its relationship to self-controlled behavior in a sample of 6- to 12-year-olds with attention-deficit hyperactivity disorder (ADHD) and matched normal controls. Thirty-eight boys were observed in their classrooms while engaged in math seatwork. Results revealed that ADHD children were delayed in private speech development in that they engaged in more externalized, self-fuiding and less inaudible, internalized speech than normal youngsters. Several findings suggest that the developmental lag was a consequence of a highly unmanageable attentional system that prevents ADHD children's private speech from gaining efficient mastery over behavior. First, self-guiding speech was associated with greater attentional focus only among the least distractible ADHD boys. Second, the most mature, internalized speech forms were correlated with self-stimulating behavior for ADHD subjects but not for controls. Third, observations of ADHD children both on and off stimulant medication indicated that reducing their symptoms substantially increased the maturity of private speech and its association with motor quiescence and attention to task. Results suggest that the Vygotskian hypothesis of a unidirectional path of influence from private speech to self-controlled behavior should be expanded into a bidirectional model. These findings may also shed light on why treatment programs that train children with attentional deficits in speech-to-self have shown limited efficacy.

Measurement of central venous pressure and determination of hormones in blood serum during weightlessness

NASA Technical Reports Server (NTRS)

Kirsch, K.

1981-01-01

A Spacelab experiment is described which proposes to obtain data on the degree of engorgement of the cephalad circulation during weightlessness by recording central venous pressure. Of practical importance is the question of how close the astronauts are to pulmonary edema and whether the pressure falls toward normal during the time of the mission. Another experiment to investigate deviations from normal fluid and mineral metabolism, possibly initiated by the central engorgement of the low pressure system, is discussed. Hormones responsible for the control of water and mineral balance (vasopressin, catecholamines, renin, aldosterone, corticosteroids, and prostaglandin E1) will be analyzed from blood samples.

Sample normalization methods in quantitative metabolomics.

PubMed

Wu, Yiman; Li, Liang

2016-01-22

To reveal metabolomic changes caused by a biological event in quantitative metabolomics, it is critical to use an analytical tool that can perform accurate and precise quantification to examine the true concentration differences of individual metabolites found in different samples. A number of steps are involved in metabolomic analysis including pre-analytical work (e.g., sample collection and storage), analytical work (e.g., sample analysis) and data analysis (e.g., feature extraction and quantification). Each one of them can influence the quantitative results significantly and thus should be performed with great care. Among them, the total sample amount or concentration of metabolites can be significantly different from one sample to another. Thus, it is critical to reduce or eliminate the effect of total sample amount variation on quantification of individual metabolites. In this review, we describe the importance of sample normalization in the analytical workflow with a focus on mass spectrometry (MS)-based platforms, discuss a number of methods recently reported in the literature and comment on their applicability in real world metabolomics applications. Sample normalization has been sometimes ignored in metabolomics, partially due to the lack of a convenient means of performing sample normalization. We show that several methods are now available and sample normalization should be performed in quantitative metabolomics where the analyzed samples have significant variations in total sample amounts. Copyright © 2015 Elsevier B.V. All rights reserved.

Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study.

PubMed

Lidbury, Brett A; Kita, Badia; Lewis, Donald P; Hayward, Susan; Ludlow, Helen; Hedger, Mark P; de Kretser, David M

2017-03-16

Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available. A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted. Comparisons with a previously defined activin reference population were also performed. For the total study cohort the age range was 18-65 years with a female: male participant ratio of greater than 3:1. All participants were assessed via a primary care community clinic. Blood samples were collected for pathology testing after physical examination and orthostatic intolerance assessment. Cytokines, activin A, activin B and follistatin were also measured in sera from these samples. All data were compared between the CFS/ME and control cohorts, with the activins and follistatin also compared with previously defined reference intervals. Serum activin B levels for CFS/ME participants were significantly elevated when compared to the study controls, as well as the established reference interval. Serum activin A and follistatin were within their normal ranges. All routine and special pathology markers were within the normal laboratory reference intervals for the total study cohort, with no significant differences detected between CFS/ME and control groups. Also, no significant differences were detected for IL-2, IL-4, IL-6, IL-10, IL-17A, TNF or IFN-gamma. Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.

Microstructure control for high strength 9Cr ferritic-martensitic steels

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

Tan, Lizhen; Hoelzer, David T; Busby, Jeremy T

2012-01-01

Ferritic-martensitic (F-M) steels with 9 wt.%Cr are important structural materials for use in advanced nuclear reactors. Alloying composition adjustment, guided by computational thermodynamics, and thermomechanical treatment (TMT) were employed to develop high strength 9Cr F-M steels. Samples of four heats with controlled compositions were subjected to normalization and tempering (N&T) and TMT, respectively. Their mechanical properties were assessed by Vickers hardness and tensile testing. Ta-alloying showed significant strengthening effect. The TMT samples showed strength superior to the N&T samples with similar ductility. All the samples showed greater strength than NF616, which was either comparable to or greater than the literaturemore » data of the PM2000 oxide-dispersion-strengthened (ODS) steel at temperatures up to 650 C without noticeable reduction in ductility. A variety of microstructural analyses together with computational thermodynamics provided rational interpretations on the strength enhancement. Creep tests are being initiated because the increased yield strength of the TMT samples is not able to deduce their long-term creep behavior.« less

Telomerase activity as a marker for malignancy in feline tissues.

PubMed

Cadile, C D; Kitchell, B E; Biller, B J; Hetler, E R; Balkin, R G

2001-10-01

To establish the diagnostic significance of the telomeric repeat amplification protocol (TRAP) assay in detecting feline malignancies. Solid tissue specimens collected from 33 client-owned cats undergoing diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital between July 1997 and September 1999 and an additional 20 tissue samples were collected from 3 clinically normal control cats euthanatized at the conclusion of an unrelated study. The TRAP assay was used for detection of telomerase activity. Each result was compared to its respective histopathologic diagnosis. Twenty-nine of 31 malignant and 1 of 22 benign or normal tissue samples had telomerase activity, indicating 94% sensitivity and 95% specificity of the TRAP assay in our laboratory. The diagnostic significance of telomerase activity has been demonstrated in humans and recently in dogs by our laboratory. We tested feline samples to determine whether similar patterns of telomerase activity exist. On the basis of our results, the TRAP assay may be clinically useful in providing a rapid diagnosis of malignancy in cats. The telomerase enzyme may also serve as a therapeutic target in feline tumors.

COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.

PubMed

Yamagata, Koichi; Yamanishi, Ayako; Kokubu, Chikara; Takeda, Junji; Sese, Jun

2016-05-05

An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Short Polarity Albian Events in the Cretaceous Normal Superchron - Magnetostratigraphy of the Morelos and Tlayua Formations (Mexico)

NASA Astrophysics Data System (ADS)

Benammi, M.; Urrutia-Fucugauchi, J.

2007-12-01

Interest in the long period of normal polarity in the Cretaceous has continued to increase since the early study of Helsley and Steiner (1969), who suspected that it corresponded to vast stretches of relatively low amplitude behaviour in the sea-floor magnetic anomaly profiles known informally as the "Cretaceous quiet zone". Since these first studies, paleomagnetists have continued to explore what is now known as the Cretaceous Normal Superchron, an interval of prolonged normal polarity from 118 to 84 Ma. Paleomagnetic data from sediment cores from the DSDP Holes 369, 386, and 364, were interpreted as brief reverse intervals (Keating and Helsley, 1978, 1979). Relatively fewer studies have been reported for land-based sections of pelagic and platform limestones; reports include studies in northern and central Italy (Vandenberg et al., 1978; Tarduno et al., 1992; Tarduno, 1990; Cronin et al., 2001) and Mexico (Urrutia-Fucugauchi, 1988; Benammi et al., 2006). We present here new magnetostratigraphic data for limestone sequences in central and southern Mexico from the Cretaceous Morelos and Tlayua Formations, which record short intervals of reversed polarity during the K normal superchron. The Morelos Formation has been revisited in Guerrero, southern Mexico, where the sequence of platform limestones with almost horizontal thick beds is well-exposed. The magnetostratigraphy shows dominant normal polarity for the sampled sections, with the occurrence of three short reverse polarity intervals corresponding to the Albian, which have been re-sampled and studied in additional detail for magnetic mineralogy and remanent acquisition. The Tlayua Formation is sampled in Tepeji de Rodriguez area, which is known for its rich and well-preserved fossil contents. Age control has mainly been provided from studies on ammonites, belemnites and benthic foraminifera (Cantu, 1987; Seibertz and Buitron, 1987; Kashiyama et al., 2003). Nine polarity intervals are documented in the Tlayua Middle Member, which correlate with middle part of chron C34n (C34n.1n-C34n.2n, 100-105 Ma). Results give further evidence for occurrence of short polarity events within the K normal superchron, and provide additional documentation on the polarity events.

Marination and cooking performance of portioned broiler breast fillets with the wooden breast condition.

PubMed

Bowker, B C; Maxwell, A D; Zhuang, H; Adhikari, K

2018-05-11

The wooden breast (WB) condition in broiler breast meat negatively influences technological meat quality. However, it is unknown if the WB effects are uniform throughout the Pectoralis major. The objective of this study was to determine the effects of WB on the marination and cooking performance of the dorsal and ventral portions of broiler breast fillets. Sixty butterfly breast fillets were collected from the deboning line of a commercial plant and sorted into normal (no WB) and severe WB categories. Each fillet was horizontally portioned into dorsal and ventral halves. Portions from one side of each butterfly were used as non-marinated controls, while portions from the other side were vacuum-tumble marinated (16 rpm, -0.6 atm, 4°C, 20 min) with 20% (wt/wt) marinade to meat ratio. Marinade was formulated to target a final concentration of 0.75% salt and 0.45% sodium tripolyphosphate in the final product. Samples were cooked to 78°C in a combination oven. Marinade uptake and retention were lower (P < 0.001) in both the ventral and dorsal portions of the WB fillets. The dorsal portions had greater (P < 0.001) marinade uptake and retention than the ventral portions in both normal and WB fillets. For non-marinated samples, cook loss was greater (P < 0.05) in both the ventral and dorsal portions of WB fillets. In marinated samples, however, cook loss was similar between the dorsal portions of normal and WB fillets. Final cooked product yield was calculated based on pre-marination and post-cook weights. Non-marinated WB samples exhibited lower (P < 0.001) cooked product yields than normal samples in both portions. For marinated samples, cooked product yields were greater (P < 0.001) in the dorsal portions. Data demonstrated that the dorsal portion of the Pectoralis major more readily absorbs and retains marinade during vacuum tumbling and storage than the ventral portion. Although the WB condition negatively influenced marination and cooking performance in both fillet portions, the effects were less severe in the dorsal portion.

Low-power polling mode of the next-generation IMES2 implantable wireless EMG sensor.

PubMed

DeMichele, Glenn A; Hu, Zhe; Troyk, Philip R; Chen, Hongnan; Weir, Richard F ff

2014-01-01

The IMES1 Implantable MyoElectric Sensor device is currently in human clinical trials led by the Alfred Mann Foundation. The IMES is implanted in a residual limb and is powered wirelessly using a magnetic field. EMG signals resulting from the amputee's voluntary movement are amplified and transmitted wirelessly by the IMES to an external controller which controls movement of an external motorized prosthesis. Development of the IMES technology is on-going, producing the next-generation IMES2. Among various improvements, a new feature of the IMES2 is a low-power polling mode. In this low-power mode, the IMES2 power consumption can be dramatically reduced when the limb is inactive through the use of a polled sampling. With the onset of EMG activity, the IMES2 system can switch to the normal higher sample rate to allow the acquisition of high-fidelity EMG data for prosthesis control.

Low-Power Polling Mode of the Next-Generation IMES2 Implantable Wireless EMG Sensor

PubMed Central

DeMichele, Glenn A.; Hu, Zhe; Troyk, Philip R.; Chen, Hongnan; Weir, Richard F. ff.

2015-01-01

The IMES1 Implantable MyoElectric Sensor device is currently in human clinical trials led by the Alfred Mann Foundation. The IMES is implanted in a residual limb and is powered wirelessly using a magnetic field. EMG signals resulting from the amputee’s voluntary movement are amplified and transmitted wirelessly by the IMES to an external controller which controls movement of an external motorized prosthesis. Development of the IMES technology is on-going, producing the next-generation IMES2. Among various improvements, a new feature of the IMES2 is a lowpower polling mode. In this low-power mode, the IMES2 power consumption can be dramatically reduced when the limb is inactive through the use of a polled sampling. With the onset of EMG activity, the IMES2 system can switch to the normal higher sample rate to allow the acquisition of high-fidelity EMG data for prosthesis control. PMID:25570642

[Relationship between blood glucose levels and salivary pH and buffering capacity in type II diabetes patients].

PubMed

Elkafri, I H; Mashlah, A; Shaqifa, A

2014-03-13

This study was evaluated the relationship between blood glucose levels and salivary pH and buffering capacity in type II diabetic patients. The sample comprised 210 participants (age ranged 40-60 years). Based on fasting blood glucose levels the participants were divided into 3 groups: controls with normal blood glucose levels; diabetic patients with levels ≤ 200 mg/dL; and diabetic patients with levels > 200 mg/dL. Salivary pH and buffering capacity were determined in a sample of resting (non-stimulated) saliva taken from each participant. Salivary pH levels in diabetic patients with blood glucose levels > 200 mg/dL were lower than in the controls and diabetic patients with levels ≤ 200 mg/dL. Salivary pH levels were comparable in controls and diabetic patients with blood glucose levels ≤ 200 mg/dL. Salivary buffering capacity in the 3 groups was comparable.

High normal fasting blood glucose is associated with dementia in Chinese elders

PubMed Central

Mortimer, J.A.; Borenstein, A.R.; Ding, D.; DeCarli, C.; Zhao, Q.; Copenhaver, C.; Guo, Q.; Chu, S.; Galasko, D.; Salmon, D.P.; Dai, Q.; Wu, Y.; Petersen, R.; Hong, Z.

2010-01-01

Background Diabetes is a risk factor for MCI and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. Methods Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. Results Controlling for age, sex, education, body mass index, Hachinski Ischemic Score, MRI stroke, and normalized brain, hippocampal and white matter hyperintensity MRI volumes; higher FBG was associated with dementia vs. aMCI status (OR= 3.13; 95% CI:1.28–7.69). This association remained (OR= 7.75; 95% CI:1.10–55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, sex and education a significant association with FBG also was seen (OR=1.83; 95%CI:1.09–3.08), but the association was lost when vascular covariates were added to the model. FBG was not associated with aMCI status vs. NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B (p=0.003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (χ2=13.9, p<0.001). Conclusions Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia. PMID:21044774

Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets

PubMed Central

Pinto, Yishay; Buchumenski, Ilana

2018-01-01

Abstract A-to-I RNA editing is an important post-transcriptional modification, known to be altered in tumors. It targets dozens of sites within miRNAs, some of which impact miRNA biogenesis and function, as well as many miRNA recognition sites. However, the full extent of the effect of editing on regulation by miRNAs and its behavior in human cancers is still unknown. Here we systematically characterized miRNA editing in 10 593 human samples across 32 cancer types and normal controls. We find that the majority of previously reported sites show little to no evidence for editing in this dataset, compile a list of 58 reliable miRNA editing sites, and study them across normal and cancer samples. Edited miRNA versions tend to suppress expression of known oncogenes, and, consistently, we observe a clear global tendency for hypo-editing in tumors, in strike contrast to the behavior for mRNA editing, allowing an accurate classification of normal/tumor samples based on their miRNA editing profile. In many cancers this profile correlates with patients' survival. Finally, thousands of miRNA binding sites are differentially edited in cancer. Our study thus establishes the important effect of RNA editing on miRNA-regulation in the tumor cell, with prospects for diagnostic and prognostic applications. PMID:29165639

A brief report on the relationship between self-control, video game addiction and academic achievement in normal and ADHD students.

PubMed

Haghbin, Maryam; Shaterian, Fatemeh; Hosseinzadeh, Davood; Griffiths, Mark D

2013-12-01

Over the last two decades, research into video game addiction has grown increasingly. The present research aimed to examine the relationship between video game addiction, self-control, and academic achievement of normal and ADHD high school students. Based on previous research it was hypothesized that (i) there would be a relationship between video game addiction, self-control and academic achievement (ii) video game addiction, self-control and academic achievement would differ between male and female students, and (iii) the relationship between video game addiction, self-control and academic achievement would differ between normal students and ADHD students. The research population comprised first grade high school students of Khomeini-Shahr (a city in the central part of Iran). From this population, a sample group of 339 students participated in the study. The survey included the Game Addiction Scale (Lemmens, Valkenburg & Peter, 2009), the Self-Control Scale (Tangney, Baumeister & Boone, 2004) and the ADHD Diagnostic checklist (Kessler et al., 2007). In addition to questions relating to basic demographic information, students' Grade Point Average (GPA) for two terms was used for measuring their academic achievement. These hypotheses were examined using a regression analysis. Among Iranian students, the relationship between video game addiction, self-control, and academic achievement differed between male and female students. However, the relationship between video game addiction, self-control, academic achievement, and type of student was not statistically significant. Although the results cannot demonstrate a causal relationship between video game use, video game addiction, and academic achievement, they suggest that high involvement in playing video games leaves less time for engaging in academic work.

Viscoelastic and histologic properties in scarred rabbit vocal folds after mesenchymal stem cell injection.

PubMed

Hertegård, S; Cedervall, J; Svensson, B; Forsberg, K; Maurer, F H J; Vidovska, D; Olivius, P; Ahrlund-Richter, L; Le Blanc, K

2006-07-01

The aim of this study was to analyze the short-term viscoelastic and histologic properties of scarred rabbit vocal folds after injection of human mesenchymal stem cells (MSC) as well as the degree of MSC survival. Because MSCs are antiinflammatory and regenerate mesenchymal tissues, can MSC injection reduce vocal fold scarring after injury? Twelve vocal folds from 10 New Zealand rabbits were scarred by a localized resection and injected with human MSC or saline. Eight vocal folds were left as controls. After 4 weeks, 10 larynges were stained for histology and evaluation of the lamina propria thickness. Collagen type I content was analyzed from six rabbits. MSC survival was analyzed by fluorescent in situ hybridization staining from three rabbits. Viscoelasticity for 10 vocal folds was analyzed in a parallel-plate rheometer. The rheometry on fresh-frozen samples showed decreased dynamic viscosity and lower elastic modulus (P<.01) in the scarred samples injected with MSC as compared with the untreated scarred group. Normal controls had lower dynamic viscosity and elastic modulus as compared with the scarred untreated and treated vocal folds (P<.01). Histologic analysis showed a higher content of collagen type 1 in the scarred samples as compared with the normal vocal folds and with the scarred folds treated with MSC. MSCs remained in all samples analyzed. The treated scarred vocal folds showed persistent MSC. Injection of scarred rabbit vocal folds with MSC rendered improved viscoelastic parameters and less signs of scarring expressed as collagen content in comparison to the untreated scarred vocal folds.

Novel mutation of GATA4 gene in Kurdish population of Iran with nonsyndromic congenital heart septals defects.

PubMed

Soheili, Fariborz; Jalili, Zahra; Rahbar, Mahtab; Khatooni, Zahed; Mashayekhi, Amir; Jafari, Hossein

2018-03-01

The mutations in GATA4 gene induce inherited atrial and ventricular septation defects, which is the most frequent forms of congenital heart defects (CHDs) constituting about half of all cases. We have performed High resolution melting (HRM) mutation scanning of GATA4 coding exons of nonsyndrome 100 patients as a case group including 39 atrial septal defects (ASD), 57 ventricular septal defects (VSD) and four patients with both above defects and 50 healthy individuals as a control group. Our samples are categorized according to their HRM graph. The genome sequencing has been done for 15 control samples and 25 samples of patients whose HRM analysis were similar to healthy subjects for each exon. The PolyPhen-2 and MUpro have been used to determine the causative possibility and structural stability prediction of GATA4 sequence variation. The HRM curve analysis exhibit that 21 patients and 3 normal samples have deviated curves for GATA4 coding exons. Sequencing analysis has revealed 12 nonsynonymous mutations while all of them resulted in stability structure of protein 10 of them are pathogenic and 2 of them are benign. Also we found two nucleotide deletions which one of them was novel and one new indel mutation resulting in frame shift mutation, and 4 synonymous variations or polymorphism in 6 of patients and 3 of normal individuals. Six or about 50% of these nonsynonymous mutations have not been previously reported. Our results show that there is a spectrum of GATA4 mutations resulting in septal defects. © 2018 Wiley Periodicals, Inc.

[Cognitive markers to discriminate between mild cognitive impairment and normal ageing].

PubMed

Rodríguez Rodríguez, Nely; Juncos-Rabadán, Onésimo; Facal Mayo, David

2008-01-01

mild cognitive impairment (MCI) has been characterized as a transitional stage between normal ageing and dementia. The aim of the present study was to examine differences between normal ageing and MCI in the performance of several cognitive tests. These differences might serve as differential markers. we performed a longitudinal study (24 months) with two evaluations at 12-monthly intervals using the CAMCOG-R and a verbal learning test [test de aprendizaje verbal España-Complutense (TAVEC)]. The sample was composed of 25 persons aged more than 50 years old (five men and 20 women), distributed into two groups: the control group and the MCI group. To assign persons to either of the two groups, Petersen's MCI criteria were applied to Mini-Mental State Examination (MMSE) scores. repeated measures ANOVA (2 groups x 2 assessment) showed significant differences between the MCI and control group in the CAMCOG-R scores in orientation, language, memory, abstract thinking, executive function and global score and in the TAVEC scores for immediate recall and short- and long-term free and clued recall. No significant differences were found between the first and second assessment or in the interaction group assessment. the results of the present study confirm that the CAMCOG-R and the TAVEC effectively discriminate between normal ageing and MCI and can be used complementarily.

The impact of sample non-normality on ANOVA and alternative methods.

PubMed

Lantz, Björn

2013-05-01

In this journal, Zimmerman (2004, 2011) has discussed preliminary tests that researchers often use to choose an appropriate method for comparing locations when the assumption of normality is doubtful. The conceptual problem with this approach is that such a two-stage process makes both the power and the significance of the entire procedure uncertain, as type I and type II errors are possible at both stages. A type I error at the first stage, for example, will obviously increase the probability of a type II error at the second stage. Based on the idea of Schmider et al. (2010), which proposes that simulated sets of sample data be ranked with respect to their degree of normality, this paper investigates the relationship between population non-normality and sample non-normality with respect to the performance of the ANOVA, Brown-Forsythe test, Welch test, and Kruskal-Wallis test when used with different distributions, sample sizes, and effect sizes. The overall conclusion is that the Kruskal-Wallis test is considerably less sensitive to the degree of sample normality when populations are distinctly non-normal and should therefore be the primary tool used to compare locations when it is known that populations are not at least approximately normal. © 2012 The British Psychological Society.

Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery.

PubMed

Gizaw, Solomon T; Ohashi, Tetsu; Tanaka, Masakazu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2016-08-01

Understanding of the significance of posttranslational glycosylation in Alzheimer's disease (AD) is of growing importance for the investigation of the pathogenesis of AD as well as discovery research of the disease-specific serum biomarkers. We designed a standard protocol for the glycoblotting combined with MALDI-TOFMS to perform rapid and quantitative profiling of the glycan parts of glycoproteins (N-glycans) and glycosphingolipids (GSLs) using human AD's post-mortem samples such as brain tissues (dissected cerebral cortices such as frontal, parietal, occipital, and temporal domains), serum and cerebrospinal fluid (CSF). The structural profiles of the major N-glycans released from glycoproteins and the total expression levels of the glycans were found to be mostly similar between the brain tissues of the AD patients and those of the normal control group. In contrast, the expression levels of the serum and CSF protein N-glycans such as bisect-type and multiply branched glycoforms were increased significantly in AD patient group. In addition, the levels of some gangliosides such as GM1, GM2 and GM3 appeared to alter in the AD patient brain and serum samples when compared with the normal control groups. Alteration of the expression levels of major N- and GSL-glycans in human brain tissues, serum and CSF of AD patients can be monitored quantitatively by means of the glycoblotting-based standard protocols. The changes in the expression levels of the glycans derived from the human post-mortem samples uncovered by the standardized glycoblotting method provides potential serum biomarkers in central nervous system disorders and can contribute to the insight into the molecular mechanisms in the pathogenesis of neurodegenerative diseases and future drug discovery. Most importantly, the present preliminary trials using human post-mortem samples of AD patients suggest that large-scale serum glycomics cohort by means of various-types of human AD patients as well as the normal control sera can facilitate the discovery research of highly sensitive and reliable serum biomarkers for an early diagnosis of AD. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

Oral cancer screening: serum Raman spectroscopic approach

NASA Astrophysics Data System (ADS)

Sahu, Aditi K.; Dhoot, Suyash; Singh, Amandeep; Sawant, Sharada S.; Nandakumar, Nikhila; Talathi-Desai, Sneha; Garud, Mandavi; Pagare, Sandeep; Srivastava, Sanjeeva; Nair, Sudhir; Chaturvedi, Pankaj; Murali Krishna, C.

2015-11-01

Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80% these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer.

Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.

PubMed

Roy, Michael J; Costanzo, Michelle E; Blair, James R; Rizzo, Albert A

2014-01-01

Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD.

Differential effects of mental stress on plasma homovanillic acid in schizophrenia and normal controls.

PubMed

Sumiyoshi, T; Saitoh, O; Yotsutsuji, T; Itoh, H; Kurokawa, K; Kurachi, M

1999-04-01

We previously reported that mental stress by Kraepelin's arithmetic test decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal healthy human subjects. The present study was undertaken to determine whether this pattern of changes in pHVA concentrations resulting from mental stress is altered in patients with schizophrenia. Fourteen male patients with schizophrenia including those under ongoing neuroleptic treatment and 14 normal male volunteers participated in the study. Following overnight fast and restricted physical activity, the subjects performed Kraepelin's arithmetic test for 30 minutes. Plasma samples were collected immediately before and after the test for measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect was observed due to a decrease in pHVA levels by the Kraepelin test in control subjects but not in patients with schizophrenia. Changes in pHVA levels during the Kraepelin test positively correlated with pre-test pHVA levels in control subjects, while this correlation was not observed in patients with schizophrenia. These results may be further support for the presence of a dopamine-dependent restitutive system in the brain. The absence of response of pHVA levels to mental stress in patients with schizophrenia may indicate that the dopamine restitutive system in these patients is disrupted or already down-regulated, as previously predicted.

Analysis of Tank 13H (HTF-13-14-156, 157) Surface and Subsurface Supernatant Samples in Support of Enrichment Control, Corrosion Control and Sodium Aluminosilicate Formation Potential Programs

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

Oji, L. N.

2015-02-18

The 2H Evaporator system includes mainly Tank 43H (feed tank) and Tank 38H (drop tank) with Tank 22H acting as the DWPF recycle receipt tank. The Tank 13H is being characterized to ensure that it can be transferred to the 2H evaporator. This report provides the results of analyses on Tanks 13H surface and subsurface supernatant liquid samples to ensure compliance with the Enrichment Control Program (ECP), the Corrosion Control Program and Sodium Aluminosilicate Formation Potential in the Evaporator. The U-235 mass divided by the total uranium averaged 0.00799 (0.799 % uranium enrichment) for both the surface and subsurface Tankmore » 13H samples. This enrichment is slightly above the enrichment for Tanks 38H and 43H, where the enrichment normally ranges from 0.59 to 0.7 wt%. The U-235 concentration in Tank 13H samples ranged from 2.01E-02 to 2.63E-02 mg/L, while the U-238 concentration in Tank 13H ranged from 2.47E+00 to 3.21E+00 mg/L. Thus, the U-235/total uranium ratio is in line with the prior 2H-evaporator ECP samples. Measured sodium and silicon concentrations averaged, respectively, 2.46 M and 1.42E-04 M (3.98 mg/L) in the Tank 13H subsurface sample. The measured aluminum concentration in Tanks 13H subsurface samples averaged 2.01E-01 M.« less

A Case-control Study on the Relationship between Mycoplasma genitalium Infection in Women with Normal Pregnancy and Spontaneous Abortion using Polymerase Chain Reaction.

PubMed

Ramazanzadeh, Rashid; Khodabandehloo, Mazaher; Farhadifar, Fariba; Rouhi, Samaneh; Ahmadi, Amjad; Menbari, Shaho; Fallahi, Fariba; Mirnejad, Reza

2016-10-01

Mycoplasma genitalium infections are suggested as causes of a number of pathological outcomes in pregnant women. The aim of this study was to evaluate the frequency of M. genitalium infections among pregnant women and its association with spontaneous abortion. In this case-control study we included 109 women with spontaneous abortion with a gestational age of 10-20 weeks (patients), and 109 women with normal pregnancy with a gestational age of 20-37 weeks (controls) in Sanandaj, Iran. Using specific primers and extracted DNA from endocervical swabs, a polymerase chain reaction was conducted for the detection of M. genitalium infection in both groups. The frequency of M. genitalium infection in patient and control groups was one (0.91%) and three (2.75%), respectively. In both control and patient groups using Fisher test, no association between mycoplasma infection and spontaneous abortion was seen. M. genitalium may be positive in the genital tract of some pregnant women but was not associated with spontaneous abortion. Further powerful studies with larger sample sizes are needed for the determination of a possible role of M. genitalium in pregnancy outcomes and spontaneous abortion.

Simulation techniques for estimating error in the classification of normal patterns

NASA Technical Reports Server (NTRS)

Whitsitt, S. J.; Landgrebe, D. A.

1974-01-01

Methods of efficiently generating and classifying samples with specified multivariate normal distributions were discussed. Conservative confidence tables for sample sizes are given for selective sampling. Simulation results are compared with classified training data. Techniques for comparing error and separability measure for two normal patterns are investigated and used to display the relationship between the error and the Chernoff bound.

Investigation of orbitofrontal sulcogyral pattern in chronic schizophrenia.

PubMed

Cropley, Vanessa L; Bartholomeusz, Cali F; Wu, Peter; Wood, Stephen J; Proffitt, Tina; Brewer, Warrick J; Desmond, Patricia M; Velakoulis, Dennis; Pantelis, Christos

2015-11-30

Abnormalities of orbitofrontal cortex (OFC) pattern type distribution have been associated with schizophrenia-spectrum disorders. We investigated OFC pattern type in a large sample of chronic schizophrenia patients and healthy controls. We found an increased frequency of Type II but no difference in Type I or III folding pattern in the schizophrenia group in comparison to controls. Further large studies are required to investigate the diagnostic specificity of altered OFC pattern type and to confirm the distribution of pattern type in the normal population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Association of the hypertriglyceridemic waist phenotype and type 2 diabetes mellitus among adults in China.

PubMed

Ren, Yongcheng; Zhang, Ming; Zhao, Jingzhi; Wang, Chongjian; Luo, Xinping; Zhang, Jiatong; Zhu, Tian; Li, Xi; Yin, Lei; Pang, Chao; Feng, Tianping; Wang, Bingyuan; Zhang, Lu; Li, Linlin; Yang, Xiangyu; Zhang, Hongyan; Hu, Dongsheng

2016-09-01

To clarify the association of the hypertriglyceridemic waist phenotype and type 2 diabetes mellitus among adults in China. In the present case-control study, we included 1,685 patients with type 2 diabetes mellitus and 7,141 normal glucose-tolerant controls from the Henan Province of China in 2011. Elevated waist circumference (GW) was defined as ≥90 cm for men and ≥80 cm for women. Hypertriglyceridemia (HT) was defined as >1.7 m mol/L triglycerides (TG) level. The association of hypertriglyceridemic waist phenotype and type 2 diabetes mellitus was investigated by sex, body mass index, physical activity, and family history of diabetes. Cases and controls differed in age, waist circumference (WC), weight, TG level, fasting glucose, body mass index, smoking status, diabetic family history, physical activity and hypertriglyceridemic waist phenotype (P < 0.05), but not alcohol drinking (P = 0.63). In the overall sample, as compared with the phenotype of normal TG level and normal WC (NTNW), normal TG level/enlarged WC (NTGW), elevated TG level/normal WC (HTNW) and elevated TG level/enlarged WC (HTGW) were associated with type 2 diabetes mellitus (odds ratio 4.14, 2.42 and 6.23, respectively). Only HTGW was consistently associated with risk of type 2 diabetes mellitus, with or without adjustment. The strongest relationship between HTGW and type 2 diabetes mellitus was for subjects with body mass index <24.0 kg/m(2) (odds ratio 6.54, 95% confidence interval 4.22-10.14) after adjustment for cofounding variables. HTGW was stably and significantly associated with risk of type 2 diabetes mellitus in adult Chinese. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Combination of MRI hippocampal volumetry and arterial spin labeling MR perfusion at 3-Tesla improves the efficacy in discriminating Alzheimer's disease from cognitively normal elderly adults.

PubMed

Mak, Henry Ka-Fung; Qian, Wenshu; Ng, Kwok Sing; Chan, Queenie; Song, You-Qiang; Chu, Leung Wing; Yau, Kelvin Kai-Wing

2014-01-01

Structural magnetic resonance imaging has been employed for evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD). Arterial spin labeling (ASL) technique could detect cerebral perfusion abnormalities in AD. We hypothesized that combination of hippocampal volumetry and cerebral blood flow yield higher accuracy than either method alone in discriminating AD patients from cognitively normal elderly adults. 13 AD patients and 15 healthy controls were studied using a 3-tesla scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences were employed for cerebral volumetry and perfusion respectively. Manual Right and left hippocampal volumetry was performed manually by ANALYZE software, with total intracranial volume normalization. ASL data were analyzed by institutional specially-design software to calculate cerebral blood flow of region-of-interests placed at the middle and posterior cingulate gyri. Right and left hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows were significantly lower in the patients than in the controls (independent-samples t-tests, p < 0.05), and prediction accuracies of 89.3%, 82.1%, 75.0% and 71.4% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using corresponding optimized cut-off values, various combinations of these parameters were used to create the Receiver Operating Characteristic curves. The highest area under curve value was 0.944, by combining cerebral blood flow at the middle cingulate gyrus, normalized right and left hippocampal volumes. A 'one-stop-shop' magnetic resonance study of combined hippocampal volumetry and cerebral perfusion has improved efficacy in discriminating AD patients from cognitively normal elderly adults.

Escherichia coli growth under modeled reduced gravity

NASA Technical Reports Server (NTRS)

Baker, Paul W.; Meyer, Michelle L.; Leff, Laura G.

2004-01-01

Bacteria exhibit varying responses to modeled reduced gravity that can be simulated by clino-rotation. When Escherichia coli was subjected to different rotation speeds during clino-rotation, significant differences between modeled reduced gravity and normal gravity controls were observed only at higher speeds (30-50 rpm). There was no apparent affect of removing samples on the results obtained. When E. coli was grown in minimal medium (at 40 rpm), cell size was not affected by modeled reduced gravity and there were few differences in cell numbers. However, in higher nutrient conditions (i.e., dilute nutrient broth), total cell numbers were higher and cells were smaller under reduced gravity compared to normal gravity controls. Overall, the responses to modeled reduced gravity varied with nutrient conditions; larger surface to volume ratios may help compensate for the zone of nutrient depletion around the cells under modeled reduced gravity.

Sensitivity and specificity of univariate MRI analysis of experimentally degraded cartilage

PubMed Central

Lin, Ping-Chang; Reiter, David A.; Spencer, Richard G.

2010-01-01

MRI is increasingly used to evaluate cartilage in tissue constructs, explants, and animal and patient studies. However, while mean values of MR parameters, including T1, T2, magnetization transfer rate km, apparent diffusion coefficient ADC, and the dGEMRIC-derived fixed charge density, correlate with tissue status, the ability to classify tissue according to these parameters has not been explored. Therefore, the sensitivity and specificity with which each of these parameters was able to distinguish between normal and trypsin- degraded, and between normal and collagenase-degraded, cartilage explants were determined. Initial analysis was performed using a training set to determine simple group means to which parameters obtained from a validation set were compared. T1 and ADC showed the greatest ability to discriminate between normal and degraded cartilage. Further analysis with k-means clustering, which eliminates the need for a priori identification of sample status, generally performed comparably. Use of fuzzy c-means (FCM) clustering to define centroids likewise did not result in improvement in discrimination. Finally, a FCM clustering approach in which validation samples were assigned in a probabilistic fashion to control and degraded groups was implemented, reflecting the range of tissue characteristics seen with cartilage degradation. PMID:19705467

Commonly dysregulated genes in murine APL cells

PubMed Central

Yuan, Wenlin; Payton, Jacqueline E.; Holt, Matthew S.; Link, Daniel C.; Watson, Mark A.; DiPersio, John F.; Ley, Timothy J.

2007-01-01

To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial gene expression profiling studies were performed with primary murine hematopoietic progenitors that were induced to undergo myeloid maturation in vitro with G-CSF. Many genes were reproducibly expressed in restricted developmental “windows,” suggesting a structured hierarchy of expression that is relevant for the induction of developmental fates and/or differentiated cell functions. We compared the normal myeloid developmental transcriptome with that of APL cells derived from mice expressing PML-RARα under control of the murine cathepsin G locus. While many promyelocyte-specific genes were highly expressed in all APL samples, 116 genes were reproducibly dysregulated in many independent APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was expressed normally in preleukemic, early myeloid cells from the same mouse model, suggesting that dysregulation occurs as a “downstream” event during disease progression. These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis. PMID:17008535

Using partially labeled data for normal mixture identification with application to class definition

NASA Technical Reports Server (NTRS)

Shahshahani, Behzad M.; Landgrebe, David A.

1992-01-01

The problem of estimating the parameters of a normal mixture density when, in addition to the unlabeled samples, sets of partially labeled samples are available is addressed. The density of the multidimensional feature space is modeled with a normal mixture. It is assumed that the set of components of the mixture can be partitioned into several classes and that training samples are available from each class. Since for any training sample the class of origin is known but the exact component of origin within the corresponding class is unknown, the training samples as considered to be partially labeled. The EM iterative equations are derived for estimating the parameters of the normal mixture in the presence of partially labeled samples. These equations can be used to combine the supervised and nonsupervised learning processes.

A closer look at the effect of preliminary goodness-of-fit testing for normality for the one-sample t-test.

PubMed

Rochon, Justine; Kieser, Meinhard

2011-11-01

Student's one-sample t-test is a commonly used method when inference about the population mean is made. As advocated in textbooks and articles, the assumption of normality is often checked by a preliminary goodness-of-fit (GOF) test. In a paper recently published by Schucany and Ng it was shown that, for the uniform distribution, screening of samples by a pretest for normality leads to a more conservative conditional Type I error rate than application of the one-sample t-test without preliminary GOF test. In contrast, for the exponential distribution, the conditional level is even more elevated than the Type I error rate of the t-test without pretest. We examine the reasons behind these characteristics. In a simulation study, samples drawn from the exponential, lognormal, uniform, Student's t-distribution with 2 degrees of freedom (t(2) ) and the standard normal distribution that had passed normality screening, as well as the ingredients of the test statistics calculated from these samples, are investigated. For non-normal distributions, we found that preliminary testing for normality may change the distribution of means and standard deviations of the selected samples as well as the correlation between them (if the underlying distribution is non-symmetric), thus leading to altered distributions of the resulting test statistics. It is shown that for skewed distributions the excess in Type I error rate may be even more pronounced when testing one-sided hypotheses. ©2010 The British Psychological Society.

The 10:00-11:00 pm urine cortisol/creatinine ratio. An alternative to late-night salivary cortisol for the diagnosis of Cushing's syndrome.

PubMed

Bruno, Oscar D; Rossi, María A; Juárez-Allen, Lea; Serra, Héctor A; Albiero, María C

2015-01-01

The aim of this study was to investigate interchangeability of two tests to diagnose Cushing's syndrome. We compared 10:00-11:00 PM urinary free cortisol/creatinine ratio (UFC/Cr) with late night 11:00 PM salivary cortisol (LNSC) in normal and obese controls vs. patients with Cushing's syndrome. Mean UFC/Cr did not differ between 69 normal and 62 obese controls (9.9 ± 7.9 vs. 9.7 ± 9.3) whereas 116 Cushing's patients had significantly higher values (277.0 ± 318.0; z: -11.1 and -10.2, respectively; p < 0.001). LNSC was 1.9 ± 1.2 nmol/l in 44 normal and 2.5 ± 1.6 in 45 obese subjects with no differences between them, but was significantly higher in 47 Cushing's patients (24.8 ± 23.3; z: -7.22 and -6.96, respectively, p < 0.001). Comparison of UFC/Cr and LNSC in samples obtained simultaneously showed that UFC/Cr was 12.0 ± 8.7 ng cortisol/mg creatinine in 34 normal, 12.3 ± 8.9 in 40 obese and 319.5 ± 333.4 in 35 CS subjects (p < 0.001 vs. normal and obese), whereas LNSC was 1.8 ± 1.2 nmol/l in normal, 2.6 ± 1.7 in obese and 24.6 ± 17.4 in CS patients (p < 0.001 vs. normal and obese); ROC curves showed comparable high sensitivity and specificity figures for the diagnosis of CS. We concluded that UFC/Cr test is easy to perform, readily available in routine laboratories, has high sensitivity and specificity, and offers a valuable alternative to LNSC in the study of Cushing's syndrome.

Stable And Oscillating Acoustic Levitation

NASA Technical Reports Server (NTRS)

Barmatz, Martin B.; Garrett, Steven L.

1988-01-01

Sample stability or instability determined by levitating frequency. Degree of oscillation of acoustically levitated object along axis of levitation chamber controlled by varying frequency of acoustic driver for axis above or below frequency of corresponding chamber resonance. Stabilization/oscillation technique applied in normal Earth gravity, or in absence of gravity to bring object quickly to rest at nominal levitation position or make object oscillate in desired range about that position.

An explorative investigation of functional differences in plantar center of pressure of four foot types using sample entropy method.

PubMed

Mei, Zhanyong; Ivanov, Kamen; Zhao, Guoru; Li, Huihui; Wang, Lei

2017-04-01

In the study of biomechanics of different foot types, temporal or spatial parameters derived from plantar pressure are often used. However, there is no comparative study of complexity and regularity of the center of pressure (CoP) during the stance phase among pes valgus, pes cavus, hallux valgus and normal foot. We aim to analyze whether CoP sample entropy characteristics differ among these four foot types. In our experiment participated 40 subjects with normal feet, 40 with pes cavus, 19 with pes valgus and 36 with hallux valgus. A Footscan ® system was used to collect CoP data. We used sample entropy to quantify several parameters of the investigated four foot types. These are the displacement in medial-lateral (M/L) and anterior-posterior (A/P) directions, as well as the vertical ground reaction force of CoP during the stance phase. To fully examine the potential of the sample entropy method for quantification of CoP components, we provide results for two cases: calculating the sample entropy of normalized CoP components, as well as calculating it using the raw data of CoP components. We also explored what are the optimal values of parameters m (the matching length) and r (the tolerance range) when calculating the sample entropy of CoP data obtained during the stance phases. According to statistical results, some factors significantly influenced the sample entropy of CoP components. The sample entropies of non-normalized A/P values for the left foot, as well as for the right foot, were different between the normal foot and pes valgus, and between the normal foot and hallux valgus. The sample entropy of normalized M/L displacement of the right foot was different between the normal foot and pes cavus. The measured variable for A/P and M/L displacements could serve for the study of foot function.

Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region.

PubMed

Dąbrowski, Andrzej; Kwaśniewski, Wojciech; Skoczylas, Tomasz; Bednarek, Wiesława; Kuźma, Dorota; Goździcka-Józefiak, Anna

2012-10-28

To assess the prevalence of human papilloma virus (HPV) in esophageal squamous cell carcinoma (ESCC) in the south-eastern region of Poland. The study population consisted of 56 ESCC patients and 35 controls. The controls were patients referred to our department due to other non-esophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology. In the ESCC patients, samples were taken from normal mucosa (56 mucosa samples) and from the tumor (56 tumor samples). Tissue samples from the controls were taken from normal mucosa of the middle esophagus (35 control samples). Quantitative determination of DNA was carried out using a spectrophotometric method. Genomic DNA was isolated using the QIAamp DNA Midi Kit. HPV infection was identified following PCR amplification of the HPV gene sequence, using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV. The sequencing results were computationally analyzed using the basic local alignment search tool database. In tumor samples, HPV DNA was identified in 28 of 56 patients (50%). High risk HPV phenotypes (16 or/and 18) were found in 5 of 56 patients (8.9%), low risk in 19 of 56 patients (33.9%) and other types of HPV (37, 81, 97, CP6108) in 4 of 56 patients (7.1%). In mucosa samples, HPV DNA was isolated in 21 of 56 patients (37.5%). High risk HPV DNA was confirmed in 3 of 56 patients (5.3%), low risk HPV DNA in 12 of 56 patients (21.4%), and other types of HPV in 6 of 56 patients (10.7%). In control samples, HPV DNA was identified in 4 of 35 patients (11.4%) with no high risk HPV. The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56 (50%) vs 4 of 35 (11.4%), P < 0.001]. In esophageal cancer patients, both in tumor and mucosa samples, the predominant HPV phenotypes were low risk HPV, isolated 4 times more frequently than high risk phenotypes [19 of 56 (33.9%) vs 5 of 56 (8.9%), P < 0.001]. A higher prevalence of HPV was identified in female patients (71.4% vs 46.9%). Accordingly, the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7 (42.9%) vs 2 of 49 (4.1%), P < 0.05]. Of the pathological characteristics, only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27 (74.1%) vs 8 of 29 (27.6%) for ulcerative or protruding macroscopic type, P < 0.05]. The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation, phases in depth of tumor infiltration, grades of nodal involvement and stages of tumor progression. Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex, progressive, multifactorial and multistep esophageal carcinogenesis.

Speckle-type POZ (pox virus and zinc finger protein) protein gene deletion in ovarian cancer: Fluorescence in situ hybridization analysis of a tissue microarray.

PubMed

Hu, Xiaoyu; Yang, Zhu; Zeng, Manman; Liu, Y I; Yang, Xiaotao; Li, Yanan; Li, X U; Yu, Qiubo

2016-07-01

The aim of the present study was to investigate the status of speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) gene located on chromosome 17q21 in ovarian cancer (OC). The present study evaluated a tissue microarray, which contained 90 samples of ovarian cancer and 10 samples of normal ovarian tissue, using fluorescence in situ hybridization (FISH). FISH is a method where a SPOP-specific DNA red fluorescence probe was used for the experimental group and a centromere-specific DNA green fluorescence probe for chromosome 17 was used for the control group. The present study demonstrated that a deletion of the SPOP gene was observed in 52.27% (46/88) of the ovarian cancer tissues, but was not identified in normal ovarian tissues. Simultaneously, monosomy 17 was frequently identified in the ovarian cancer tissues, but not in the normal ovarian tissues. Furthermore, the present data revealed that the ovarian cancer histological subtype and grade were significantly associated with a deletion of the SPOP gene, which was assessed by the appearance of monosomy 17 in the ovarian cancer samples; the deletion of the SPOP gene was observed in a large proportion of serous epithelial ovarian cancer (41/61; 67.21%), particularly in grade 3 (31/37; 83.78%). In conclusion, deletion of the SPOP gene on chromosome 17 in ovarian cancer samples, which results from monosomy 17, indicates that the SPOP gene may serve as a tumor suppressor gene in ovarian cancer.

Effect of humic substance photodegradation on bacterial growth and respiration in lake water

USGS Publications Warehouse

Anesio, A.M.; Graneli, W.; Aiken, G.R.; Kieber, D.J.; Mopper, K.

2005-01-01

This study addresses how humic substance (HS) chemical composition and photoreactivity affect bacterial growth, respiration, and growth efficiency (BGE) in lake water. Aqueous solutions of HSs from diverse aquatic environments representing different dissolved organic matter sources (autochthonous and allochthonous) were exposed to artificial solar UV radiation. These solutions were added to lake water passed through a 0.7-??m-pore-size filter (containing grazer-free lake bacteria) followed by dark incubation for 5, 43, and 65 h. For the 5-h incubation, several irradiated HSs inhibited bacterial carbon production (BCP) and this inhibition was highly correlated with H 2O2 photoproduction. The H2O2 decayed in the dark, and after 43 h, nearly all irradiated HSs enhanced BCP (average 39% increase relative to nonirradiated controls, standard error = 7.5%, n = 16). UV exposure of HSs also increased bacterial respiration (by ???18%, standard error = 5%, n = 4), but less than BCP, resulting in an average increase in BGE of 32% (standard error = 10%, n = 4). Photoenhancement of BCP did not correlate to HS bulk properties (i.e., elemental and chemical composition). However, when the photoenhancement of BCP was normalized to absorbance, several trends with HS origin and extraction method emerged. Absorbance-normalized hydrophilic acid and humic acid samples showed greater enhancement of BCP than hydrophobic acid and fulvic acid samples. Furthermore, absorbance-normalized autochthonous samples showed ???10-fold greater enhancement of BCP than allochthonous-dominated samples, indicating that the former are more efficient photoproducers of biological substrates. Copyright ?? 2005, American Society for Microbiology. All Rights Reserved.

Antibody responses to bacteriophage phi X-174 in human subjects exposed to the antarctic winter-over model of spaceflight

NASA Technical Reports Server (NTRS)

Shearer, W. T.; Lugg, D. J.; Rosenblatt, H. M.; Nickolls, P. M.; Sharp, R. M.; Reuben, J. M.; Ochs, H. D.

2001-01-01

BACKGROUND: It has been proposed that exposure to long-term spaceflight conditions (stress, isolation, sleep disruption, containment, microbial contamination, and solar radiation) or to ground-based models of spaceflight will alter human immune responses, but specific antibody responses have not been fully evaluated. OBJECTIVE: We sought to determine whether exposure to the 8-month Antarctic winter-over model of spaceflight would alter human antibody responses. METHODS: During the 1999 Australian National Antarctic Research Expeditions, 11 adult study subjects at Casey, Antarctica, and 7 control subjects at Macquarie Island, sub-Antarctica, received primary and secondary immunizations with the T cell-dependent neoantigen bacteriophage phi X-174. Periodic plasma samples were analyzed for specific antibody function. RESULTS: All of the subjects from Casey, Antarctica, cleared bacteriophage phi X-174 normally by 1 week after primary immunization, and all had normal primary and secondary antibody responses, including immunologic memory amplification and switch from IgM to IgG antibody production. One subject showed a high normal pattern, and one subject had a low normal pattern. The control subjects from Macquarie Island also had normal immune responses to bacteriophage phi X-174. CONCLUSIONS: These data do not support the hypothesis that de novo specific antibody responses of subjects become defective during the conditions of the Antarctic winter-over. Because the Antarctic winter-over model of spaceflight lacks the important factors of microgravity and solar radiation, caution must be used in interpreting these data to anticipate normal antibody responses in long-term spaceflight.

Subcortical hyperintensity volumetrics in Alzheimer's disease and normal elderly in the Sunnybrook Dementia Study: correlations with atrophy, executive function, mental processing speed, and verbal memory.

PubMed

Ramirez, Joel; McNeely, Alicia A; Scott, Christopher Jm; Stuss, Donald T; Black, Sandra E

2014-01-01

Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature. Using the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study. Compared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD. These brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer's dementia.

Sample entropy predicts lifesaving interventions in trauma patients with normal vital signs.

PubMed

Naraghi, L; Mejaddam, A Y; Birkhan, O A; Chang, Y; Cropano, C M; Mesar, T; Larentzakis, A; Peev, M; Sideris, A C; Van der Wilden, G M; Imam, A M; Hwabejire, J O; Velmahos, G C; Fagenholz, P J; Yeh, D; de Moya, M A; King, D R

2015-08-01

Heart rate complexity, commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice is not yet widely adopted. We previously demonstrated the ability of this noninvasive technology to predict lifesaving interventions (LSIs) in trauma patients. This study was conducted to prospectively evaluate the utility of real-time, automated, noninvasive, instantaneous sample entropy (SampEn) analysis to predict the need for an LSI in a trauma alert population presenting with normal vital signs. Prospective enrollment of patients who met criteria for trauma team activation and presented with normal vital signs was conducted at a level I trauma center. High-fidelity electrocardiogram recording was used to calculate SampEn and SD of the normal-to-normal R-R interval (SDNN) continuously in real time for 2 hours with a portable, handheld device. Patients who received an LSI were compared to patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. Treating clinicians were blinded to results. Of 129 patients enrolled, 38 (29%) received 136 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. Lifesaving intervention patients had a lower Glasgow Coma Scale. The mean SampEn on presentation was 0.7 (0.4-1.2) in the LSI group compared to 1.5 (1.1-2.0) in the non-LSI group (P < .0001). The area under the curve with initial SampEn alone was 0.73 (95% confidence interval [CI], 0.64-0.81) and increased to 0.93 (95% CI, 0.89-0.98) after adding sedation to the model. Sample entropy of less than 0.8 yields sensitivity, specificity, negative predictive value, and positive predictive value of 58%, 86%, 82%, and 65%, respectively, with an overall accuracy of 76% for predicting an LSI. SD of the normal-to-normal R-R interval had no predictive value. In trauma patients with normal presenting vital signs, decreased SampEn is an independent predictor of the need for LSI. Real-time SampEn analysis may be a useful adjunct to standard vital signs monitoring. Adoption of real-time, instantaneous SampEn monitoring for trauma patients, especially in resource-constrained environments, should be considered. Copyright © 2015 Elsevier Inc. All rights reserved.

Terrestrial predator alarm vocalizations are a valid monitor of stress in captive brown capuchins (Cebus apella)

USGS Publications Warehouse

Boinski, S.; Gross, T.S.; Davis, J.K.

1999-01-01

The vocal behavior of captive animals is increasingly exploited as an index of well-being. Here we show that the terrestrial predator alarm (TPA) vocalization, a robust and acoustically distinctive anti-predation vocal response present in many mammal and bird species, offers useful information on the relative well-being and stress levels of captive animals. In a 16-week experiment evaluating the effects of varying levels of physical environmental enrichment (control < toys < foraging box < foraging box and toys) in the cages of eight singly housed adult male brown capuchins, we quantified the 1) emission rate of TPAs, 2) proportions of normal and abnormal behavior sample intervals, and 3) fecal and plasma cortisol levels. Variation in TPA emission across the experimental conditions was significant. We found significant reductions in the mean TPA production rate by the group in the enriched (toys, foraging box, and foraging box and toys) compared to the control condition; pre-and post-experimental conditions, however, did not differ from the control condition. Mean TPA production by the group was also significantly positively correlated to mean group levels of fecal cortisol and proportion of abnormal behavior sample intervals, and significantly negatively correlated to the average proportion of normal behavior sample intervals in the group. Based on group means, plasma cortisol levels were positively, but not significantly, related to increasing TPA rate. At the level of the responses of an individual subject, however, the covariation between the vocal and non-vocal behavioral measures and the cortisol assays seldom attained significance. Nevertheless, the direction of the relationships among these parameters within individual subjects typically mirrored those correlations based on group means. At both the group mean and individual levels, our results are consistent with the.

Systemic hyperfibrinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma.

PubMed

Banerjee, Anirban; Silliman, Christopher C; Moore, Ernest E; Dzieciatkowska, Monika; Kelher, Marguerite; Sauaia, Angela; Jones, Kenneth; Chapman, Michael P; Gonzalez, Eduardo; Moore, Hunter B; D'Alessandro, Angelo; Peltz, Erik; Huebner, Benjamin E; Einerson, Peter; Chandler, James; Ghasabayan, Arsen; Hansen, Kirk

2018-06-01

Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. Blood samples were collected in the field or at emergency department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), "eufibrinolytic" (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins. HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 and fold change of concentrations of 0.75-1.3). HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times, or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs. Prognostic, level III.

The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours.

PubMed

Räsänen, J V; Sihvo, E I T; Ahotupa, M O; Färkkilä, M A; Salo, J A

2007-12-01

The most common marker of oxidative DNA damage is 8-hydroxydeoxyguanosine (8-OHdG), which is linked with several malignancies. In the present study we investigated whether DNA damage linked to oxidative stress (as 8-OHdG) is present in Barrett's mucosa with or without associated adenocarcinoma or high-grade dysplasia and in normal controls' squamous mucosa. We measured 8-OHdG in 51 patients (13 Barrett's metaplasia, six Barrett's oesophagus with high-grade dysplasia, 18 adenocarcinoma of the distal oesophagus/oesophagogastric junction and 14 normal controls). The amount of DNA damage was determined by high-performance liquid chromatography in oesophagus samples obtained either from endoscopy or as samples from surgery. The median 8-OHdG concentration was expressed as the ratio of 8-OHdG per 10(5) deoxyguanosine. Analysis revealed that 8-OHdG was present in both Barrett's metaplasia with and without dysplasia as well as in adenocarcinoma of the oesophagus/oesophagogastric junction. Although the study group was small the amount of 8-OHdG was significantly increased in the distal oesophagus both in Barrett's epithelium 1.26 (0.08-29.47) and in high-grade dysplasia 1.35 (1.04-1.65) as well as in adenocarcinoma of oesophagus/oesophagogastric junction 1.08 (0.59-1.94) compared to controls 0.06 (0-4.08) (p=0.002, p=0.012, p=0.001, respectively). Barrett's patients had no significant difference in 8-OHdG levels between their distal and proximal oesophageal samples. Our results show the presence of oxidative DNA damage in the distal oesophagus of patients with Barrett's oesophagus and adenocarcinoma of the oesophagus/oesophagogastric junction. This may have a connection to carcinogenesis in Barrett's oesophagus.

Study design and data analysis considerations for the discovery of prognostic molecular biomarkers: a case study of progression free survival in advanced serous ovarian cancer.

PubMed

Qin, Li-Xuan; Levine, Douglas A

2016-06-10

Accurate discovery of molecular biomarkers that are prognostic of a clinical outcome is an important yet challenging task, partly due to the combination of the typically weak genomic signal for a clinical outcome and the frequently strong noise due to microarray handling effects. Effective strategies to resolve this challenge are in dire need. We set out to assess the use of careful study design and data normalization for the discovery of prognostic molecular biomarkers. Taking progression free survival in advanced serous ovarian cancer as an example, we conducted empirical analysis on two sets of microRNA arrays for the same set of tumor samples: arrays in one set were collected using careful study design (that is, uniform handling and randomized array-to-sample assignment) and arrays in the other set were not. We found that (1) handling effects can confound the clinical outcome under study as a result of chance even with randomization, (2) the level of confounding handling effects can be reduced by data normalization, and (3) good study design cannot be replaced by post-hoc normalization. In addition, we provided a practical approach to define positive and negative control markers for detecting handling effects and assessing the performance of a normalization method. Our work showcased the difficulty of finding prognostic biomarkers for a clinical outcome of weak genomic signals, illustrated the benefits of careful study design and data normalization, and provided a practical approach to identify handling effects and select a beneficial normalization method. Our work calls for careful study design and data analysis for the discovery of robust and translatable molecular biomarkers.

Lipid regulatory genes polymorphism in children with and without obesity and cardiometabolic risk factors: The CASPIAN-III study

PubMed Central

Hovsepian, Silva; Javanmard, Shaghayegh Haghjooy; Mansourian, Marjan; Hashemipour, Mahin; Tajadini, Mohamadhasan; Kelishadi, Roya

2018-01-01

Background: Genetically, predisposed children are considered as at-risk individuals for cardiovascular disease. In this study, we aimed to compare the frequency of four-lipid regulatory polymorphism in obese and normal-weight children with and without cardiometabolic risk factors. Materials and Methods: In this nested case–control study, 600 samples of four groups of participants consisted of those with normal weight with and without cardiometabolic risk factors and obese with and without cardiometabolic risk factors. Allelic and genotypic frequencies of GCKR (rs780094), GCKR (rs1260333), MLXIPL (rs3812316), and FADS (rs174547) polymorphisms were compared in the four studied groups. Results: Data of 528 samples were complete and included in this study. The mean (standard deviation) age of participants was 15.01 (2.21) years. Frequency of tt allele (minor allele) of GCKR (rs1260333) polymorphism was significantly lower in normal weight metabolically healthy participants than metabolically unhealthy normal weight (MUHNW) and obese children with and without cardiometabolic risk factor (P = 0.01). Frequency of ga allele of GCKR (rs780094) polymorphism was significantly higher in normal weight children with cardiometabolic risk factor than in their obese counterparts with cardiometabolic risk factor (P = 0.04). Frequency of cg and gg alleles (minor type) of MLXIPL (rs3812316) polymorphism in normal weight metabolically healthy participants was significantly higher than MUHNW (P = 0.04) and metabolically healthy obese children (P = 0.04). Conclusion: The findings of our study indicated that the minor allele of GCKR (rs1260333) single nucleotide polymorphisms (SNPs) could have pathogenic effect for obesity and cardiometabolic risk factors. Ga allele of GCKR (rs780094) SNPs had a protective effect on obesity. Minor alleles of MLXIPL (rs3812316) could have a protective effect for obesity and cardiometabolic risk factors. PMID:29531563

Fluorescent Cell Barcoding for Multiplex Flow Cytometry

PubMed Central

Krutzik, Peter O.; Clutter, Matthew R.; Trejo, Angelica; Nolan, Garry P.

2011-01-01

Fluorescent Cell Barcoding (FCB) enables high throughput, i.e. high content flow cytometry by multiplexing samples prior to staining and acquisition on the cytometer. Individual cell samples are barcoded, or labeled, with unique signatures of fluorescent dyes so that they can be mixed together, stained, and analyzed as a single sample. By mixing samples prior to staining, antibody consumption is typically reduced 10 to 100-fold. In addition, data robustness is increased through the combination of control and treated samples, which minimizes pipetting error, staining variation, and the need for normalization. Finally, speed of acquisition is enhanced, enabling large profiling experiments to be run with standard cytometer hardware. In this unit, we outline the steps necessary to apply the FCB method to cell lines as well as primary peripheral blood samples. Important technical considerations such as choice of barcoding dyes, concentrations, labeling buffers, compensation, and software analysis are discussed. PMID:21207359

Breast Reference Set Application: Chris Li-FHCRC (2014) — EDRN Public Portal

Cancer.gov

This application proposes to use Reference Set #1. We request access to serum samples collected at the time of breast biopsy from subjects with IC (n=30) or benign disease without atypia (n=30). Statistical power: With 30 BC cases and 30 normal controls, a 25% difference in mean metabolite levels can be detected between groups with 80% power and α=0.05, assuming coefficients of variation of 30%, consistent with our past studies. These sample sizes appear sufficient to enable detection of changes similar in magnitude to those previously reported in pre-clinical (BC recurrence) specimens (20).

Selection of appropriate reference genes for RT-qPCR analysis in a streptozotocin-induced Alzheimer's disease model of cynomolgus monkeys (Macaca fascicularis).

PubMed

Park, Sang-Je; Kim, Young-Hyun; Lee, Youngjeon; Kim, Kyoung-Min; Kim, Heui-Soo; Lee, Sang-Rae; Kim, Sun-Uk; Kim, Sang-Hyun; Kim, Ji-Su; Jeong, Kang-Jin; Lee, Kyoung-Min; Huh, Jae-Won; Chang, Kyu-Tae

2013-01-01

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) has been widely used to quantify relative gene expression because of the specificity, sensitivity, and accuracy of this technique. In order to obtain reliable gene expression data from RT-qPCR experiments, it is important to utilize optimal reference genes for the normalization of target gene expression under varied experimental conditions. Previously, we developed and validated a novel icv-STZ cynomolgus monkey model for Alzheimer's disease (AD) research. However, in order to enhance the reliability of this disease model, appropriate reference genes must be selected to allow meaningful analysis of the gene expression levels in the icv-STZ cynomolgus monkey brain. In this study, we assessed the expression stability of 9 candidate reference genes in 2 matched-pair brain samples (5 regions) of control cynomolgus monkeys and those who had received intracerebroventricular injection of streptozotocin (icv-STZ). Three well-known analytical programs geNorm, NormFinder, and BestKeeper were used to choose the suitable reference genes from the total sample group, control group, and icv-STZ group. Combination analysis of the 3 different programs clearly indicated that the ideal reference genes are RPS19 and YWHAZ in the total sample group, GAPDH and RPS19 in the control group, and ACTB and GAPDH in the icv-STZ group. Additionally, we validated the normalization accuracy of the most appropriate reference genes (RPS19 and YWHAZ) by comparison with the least stable gene (TBP) using quantification of the APP and MAPT genes in the total sample group. To the best of our knowledge, this research is the first study to identify and validate the appropriate reference genes in cynomolgus monkey brains. These findings provide useful information for future studies involving the expression of target genes in the cynomolgus monkey.

Patterns of brain structural connectivity differentiate normal weight from overweight subjects

PubMed Central

Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Van Horn, John D.; Woodworth, Davis; Ellingson, Benjamin M.; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S.

2015-01-01

Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69% accuracy in discriminating overweight from normal weight. In both brain signatures regions of the reward, salience, executive control and emotional arousal networks were associated with lower morphological values in overweight individuals compared to normal weight individuals, while the opposite pattern was seen for regions of the somatosensory network. Conclusions 1. An increased BMI (i.e., overweight subjects) is associated with distinct changes in gray-matter and fiber density of the brain. 2. Classification algorithms based on white-matter connectivity involving regions of the reward and associated networks can identify specific targets for mechanistic studies and future drug development aimed at abnormal ingestive behavior and in overweight/obesity. PMID:25737959

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

PubMed

Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

2008-05-01

In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Serum Levels of Angiopoietin-Like Protein 2 and Obestatin in Iranian Women with Polycystic Ovary Syndrome and Normal Body Mass Index.

PubMed

Rahmani, Elham; Akbarzadeh, Samad; Broomand, Ainaz; Torabi, Fatemeh; Motamed, Niloofar; Zohrabi, Marzieh

2018-06-22

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of reproduction age and a major cause of anovulatory infertility. Insulin resistance plays an important role in the development and durability of this disorder. ANGPTL2 is known as an inflammatory mediator derived from adipose tissue that links obesity to systemic insulin resistance, and obestatin has been identified as a hormone associated with insulin resistance that suppresses food reabsorption, inhibits gastric emptying and decreases weight gain. The aim of this study was to evaluate serum levels of ANGPTL2 and obestatin in PCOS women with normal body mass index (BMI). In this case-control study, 26 PCOS women based on the Rotterdam 2003 diagnostic criteria as the case group and 26 women with normal menstrual cycles as the control group were enrolled. Serum levels of ANGPTL2, obestatin, insulin and other hormone factors related with PCOS were measured by ELISA method and biochemical parameters were measured by an autoanalyzer. Data were analyzed by independent samples- T test, Chi Square, Correlation and a single sample Kolmogrov⁻Smirnov test using SPSS software, version 16. There were no significant variations in the amount of ANGPTL2, obestatin, cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein, cholesterol, creatinine and dehydroepiandrosterone-sulfate between the two groups. There were significant increases in serum levels of fasting blood sugar ( p = 0.01), insulin ( p = 0.04), homeostasis model assessments of insulin resistance ( p = 0.04), testosterone ( p = 0.02), luteinizing hormone ( p = 0.004), luteinizing hormone/follicle stimulating hormone ( p = 0.006) and prolactin ( p = 0.04) in case group compared to the control group. A significant positive correlation was observed between ANGPTL2 and insulin ( p = 0.02), HOMA-IR ( p = 0.01) and, on the other hand, a significant negative correlation was observed between obestatin and insulin ( p = 0.01), HOMA-IR ( p = 0.008) in PCOS group. In this study, no significant variations were observed in serum levels of ANGPTL2 and obestatin in PCOS women with normal BMI.

In vitro test of external Qigong

PubMed Central

Yount, Garret; Solfvin, Jerry; Moore, Dan; Schlitz, Marilyn; Reading, Melissa; Aldape, Ken; Qian, Yifang

2004-01-01

Background Practitioners of the alternative medical practice 'external Qigong' generally claim the ability to emit or direct "healing energy" to treat patients. We investigated the ability of experienced Qigong practitioners to enhance the healthy growth of cultured human cells in a series of studies, each following a rigorously designed protocol with randomization, blinding and controls for variability. Methods Qigong practitioners directed healing intentionality toward normal brain cell cultures in a basic science laboratory. Qigong treatments were delivered for 20 minutes from a minimum distance of 10 centimeters. Cell proliferation was measured by a standard colony-forming efficiency (CFE) assay and a CFE ratio (CFE for treated samples/CFE for sham samples) was the dependent measure for each experiment. Results During a pilot study (8 experiments), a trend of increased cell proliferation in Qigong-treated samples (CFE Qigong/sham ratios > 1.0) was observed (P = 0.162). In a formal study (28 experiments), a similar trend was observed, with Qigong-treated samples showing on average more colony formation than sham samples (P = 0.036). In a replication study (60 experiments), no significant difference between Qigong-treated samples and sham samples was observed (P = 0.465). Conclusion We observed an apparent increase in the proliferation of cultured cells following external Qigong treatment by practitioners under strictly controlled conditions, but we did not observe this effect in a replication study. These results suggest the need for more controlled and thorough investigation of external Qigong before scientific validation is claimed. PMID:15102336

Effect of diesel leakage in circulating cooling water system on preponderant bacteria diversity and bactericidal effect of biocides.

PubMed

Zhong, Huiyun; Liu, Fang; Lu, Jinjin; Yang, Wei; Zhao, Chaocheng

2015-01-01

Petroleum products leakage results in adverse effect on the normal operation of a circulating cooling water system. However, relatively little research has been done to explore the effect of petroleum products leakage on circulating cooling water quality and biofilm preponderant bacteria diversity. Also, normal biocides application modes cannot fulfil the need for biofilm control. In this study, diesel oil was used as the experimental subject representing leaking petroleum products; the effect of diesel addition on biofilm preponderant bacteria diversity and the bactericidal effect of chlorine dioxide and tetradecyl dimethyl benzyl ammonium chloride (1427) was investigated. Bacterial community structures were examined by PCR-denaturing gradient gel electrophoresis and PCR cloning of 16S rDNA genes. Except for 100 mg/L diesel, increasing diesel concentration enhanced the biofilm detachment ratio compared with the control test. The microstructure of biofilm samples with 0, 300 and 900 mg/L diesel addition was observed. The species of preponderant bacteria in the biofilm sample with 300 mg/L diesel addition were more and the bacterial distribution was more uniform than those in the biofilm sample with 900 mg/L diesel addition. With ClO2 and 1427 addition, chemical oxygen demand increased, lipid phosphorus and bacterial count first decreased and then remained stable, and the bactericidal ratio first increased and then remained stable. Diesel addition variation has more obvious effect on ClO2 than 1427.

Prevalence and Predictors of Bullying Behavior among Overweight and Obese Youth in a Nationally Representative Sample.

PubMed

Odar Stough, Cathleen; Merianos, Ashley; Nabors, Laura; Peugh, James

2016-08-01

Child and adolescent overweight and obesity are independent risk factors for poor social outcomes. Whether children who are overweight display greater bullying behaviors than normal weight peers, controlling for demographic and other social-ecological factors, was examined. The influence of child (e.g., mental health), family (e.g., income, parent mental health, and exposure to domestic violence), and community (e.g., exposure to neighborhood violence, unfair treatment based on race or ethnic group) factors on bullying risk in the subset of children who are overweight and obese was explored. We conducted a secondary data analysis of the 2011-2012 National Survey of Children's Health, a cross-sectional study providing a nationally representative sample of participants, using a series of multinomial logistic regressions in Mplus software (Muthén & Muthén, Los Angeles, CA). Participants were 41,361 youth ages 10-17 years. Despite statistically significant differences in unadjusted analyses, no differences were found in bullying behavior by weight status once controlling for other factors. Child, family, and neighborhood factors predicted bullying behavior in both the overall sample and the subset of overweight and obese youth. However, some risk factors were unique to children who were overweight or obese. Children who are overweight or obese are not at greater risk for engaging in bullying behavior than normal weight peers. Health professionals targeting bullying behavior should be aware of the impact child, family, and neighborhood factors have on bullying by overweight and obese children and adolescents.

DNA methylation profiling identifies global methylation differences and markers of adrenocortical tumors.

PubMed

Rechache, Nesrin S; Wang, Yonghong; Stevenson, Holly S; Killian, J Keith; Edelman, Daniel C; Merino, Maria; Zhang, Lisa; Nilubol, Naris; Stratakis, Constantine A; Meltzer, Paul S; Kebebew, Electron

2012-06-01

It is not known whether there are any DNA methylation alterations in adrenocortical tumors. The objective of the study was to determine the methylation profile of normal adrenal cortex and benign and malignant adrenocortical tumors. Genome-wide methylation status of CpG regions were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8), and metastatic malignant (n = 12) adrenocortical tissue samples. An integrated analysis of genome-wide methylation and mRNA expression in benign vs. malignant adrenocortical tissue samples was also performed. Methylation profiling revealed the following: 1) that methylation patterns were distinctly different and could distinguish normal, benign, primary malignant, and metastatic tissue samples; 2) that malignant samples have global hypomethylation; and 3) that the methylation of CpG regions are different in benign adrenocortical tumors by functional status. Normal compared with benign samples had the least amount of methylation differences, whereas normal compared with primary and metastatic adrenocortical carcinoma samples had the greatest variability in methylation (adjusted P ≤ 0.01). Of 215 down-regulated genes (≥2-fold, adjusted P ≤ 0.05) in malignant primary adrenocortical tumor samples, 52 of these genes were also hypermethylated. Malignant adrenocortical tumors are globally hypomethylated as compared with normal and benign tumors. Methylation profile differences may accurately distinguish between primary benign and malignant adrenocortical tumors. Several differentially methylated sites are associated with genes known to be dysregulated in malignant adrenocortical tumors.

Subtelomeric multiplex ligation-dependent probe amplification as a supplement for rapid prenatal detection of fetal chromosomal aberrations.

PubMed

Chen, Xiangnan; Li, Huanzheng; Mao, Yijian; Xu, Xueqin; Lv, Jiaojiao; Zhou, Lili; Lin, Xiaoling; Tang, Shaohua

2014-01-01

Pregnant women with high-risk indications are highly suspected of fetal chromosomal aberrations. To determine whether Multiplex Ligation-dependent Probe Amplification (MLPA) using subtelomeric probe mixes (P036-E2 and P070-B2) is a reliable method for rapid detection of fetal chromosomal aberrations. The subtelomeric MLPA probe mixes were used to evaluate 50 blood samples from healthy individuals. 168 amniocytes and 182 umbilical cord blood samples from high-risk fetuses were analyzed using the same subtelomeric MLPA probe sets. Karyotyping was also performed in all cases of high-risk pregnancies, and single nucleotide polymorphism array analysis was used to confirm submicroscopic and ambiguous results from MLPA/karyotyping. Subtelomeric MLPA analysis of normal samples showed normal result in all cases by use of P036-E2 probe mix, while P070-B2 probe mix gave normal results for all but one case. In one normal control case P070-B2 produced a duplicated signal of probe for 13q34. In the high-risk group, totally 44 chromosomal abnormalities were found by karyotyping and MLPA, including 23 aneuploidies and 21 rearrangements or mosaics. MLPA detected all 23 aneuploidies, 12 rearrangements and 1 mosaic. Importantly, MLPA revealed 4 chromosomal translocations, 2 small supernumerary marker chromosomes (sSMCs), and 3 subtelomeric imbalances that were not well characterized or not detectable by karyotyping. However, MLPA showed negetive results for the remaining 8 rearrangements or mosaics, including 3 low mosaic aneuploidies, 1 inherited sSMC, and 4 paracentric inversions. Results suggest that combined use of subtelomeric MLPA and karyotyping may be an alternative method for using karyotype analyses alone in rapid detection of aneuploidies, rearrangements, and sSMCs.

Semen of spinal cord injured men freezes reliably.

PubMed

Padron, O F; Brackett, N L; Weizman, M S; Lynne, C M

1994-01-01

The objectives of the present study were to: 1) determine the effect of cryopreservation on the percent and the grade of motility of sperm from spinal cord injured (SCI) men and 2) determine which method of freezing yields the best post-thaw motility in sperm from SCI men. Antegrade semen samples were obtained from 9 SCI subjects and 10 age-matched healthy control subjects. Motility in fresh samples was determined and cryopreservative medium was added to each sample. Aliquots of each sample were frozen according to three methods: 1) liquid nitrogen vapor only (V); 2) vapor for 12 minutes followed by submersion into liquid nitrogen (V+N2); and 3) direct submersion into liquid nitrogen (N2). Samples were frozen for 1 week, then thawed. The post-thaw percent and grade of motility was determined. The mean percent motility of fresh samples for SCI subjects (21.0%) was significantly lower than for control subjects (55.7%). After thawing, the mean percent drop in motility for V, V+N2, and N2 for controls was 65.2%, 73.5%, and 79.4%, respectively, and for SCI subjects, it was 64.7%, 74.5%, and 81.6%, respectively. There was no statistically significant difference between control and SCI subjects by method of freezing. Vapor only as a freezing method was superior to all other methods for retention of sperm motility in both control and SCI subjects. We conclude that the semen of SCI men may be frozen reliably and that their sperm retain motility similar to that of normal men. Vapor only, being the most gentle method used, gives the best recovery of sperm motility in either group.

Expression signature as a biomarker for prenatal diagnosis of trisomy 21.

PubMed

Volk, Marija; Maver, Aleš; Lovrečić, Luca; Juvan, Peter; Peterlin, Borut

2013-01-01

A universal biomarker panel with the potential to predict high-risk pregnancies or adverse pregnancy outcome does not exist. Transcriptome analysis is a powerful tool to capture differentially expressed genes (DEG), which can be used as biomarker-diagnostic-predictive tool for various conditions in prenatal setting. In search of biomarker set for predicting high-risk pregnancies, we performed global expression profiling to find DEG in Ts21. Subsequently, we performed targeted validation and diagnostic performance evaluation on a larger group of case and control samples. Initially, transcriptomic profiles of 10 cultivated amniocyte samples with Ts21 and 9 with normal euploid constitution were determined using expression microarrays. Datasets from Ts21 transcriptomic studies from GEO repository were incorporated. DEG were discovered using linear regression modelling and validated using RT-PCR quantification on an independent sample of 16 cases with Ts21 and 32 controls. The classification performance of Ts21 status based on expression profiling was performed using supervised machine learning algorithm and evaluated using a leave-one-out cross validation approach. Global gene expression profiling has revealed significant expression changes between normal and Ts21 samples, which in combination with data from previously performed Ts21 transcriptomic studies, were used to generate a multi-gene biomarker for Ts21, comprising of 9 gene expression profiles. In addition to biomarker's high performance in discriminating samples from global expression profiling, we were also able to show its discriminatory performance on a larger sample set 2, validated using RT-PCR experiment (AUC=0.97), while its performance on data from previously published studies reached discriminatory AUC values of 1.00. Our results show that transcriptomic changes might potentially be used to discriminate trisomy of chromosome 21 in the prenatal setting. As expressional alterations reflect both, causal and reactive cellular mechanisms, transcriptomic changes may thus have future potential in the diagnosis of a wide array of heterogeneous diseases that result from genetic disturbances.

Laser-induced differential normalized fluorescence method for cancer diagnosis

DOEpatents

Vo-Dinh, Tuan; Panjehpour, Masoud; Overholt, Bergein F.

1996-01-01

An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample.

Laser-induced differential normalized fluorescence method for cancer diagnosis

DOEpatents

Vo-Dinh, T.; Panjehpour, M.; Overholt, B.F.

1996-12-03

An apparatus and method for cancer diagnosis are disclosed. The diagnostic method includes the steps of irradiating a tissue sample with monochromatic excitation light, producing a laser-induced fluorescence spectrum from emission radiation generated by interaction of the excitation light with the tissue sample, and dividing the intensity at each wavelength of the laser-induced fluorescence spectrum by the integrated area under the laser-induced fluorescence spectrum to produce a normalized spectrum. A mathematical difference between the normalized spectrum and an average value of a reference set of normalized spectra which correspond to normal tissues is calculated, which provides for amplifying small changes in weak signals from malignant tissues for improved analysis. The calculated differential normalized spectrum is correlated to a specific condition of a tissue sample. 5 figs.

Intravenous cannulation of adolescents does not affect the modulation of autonomic tone assessed by heart rate and blood pressure variability.

PubMed

Stewart, J M

2000-02-01

Invasive arterial monitoring alters autonomic tone. The effects of intravenous (i.v.) insertion are less clear. The author assessed the effects of i.v. insertion on autonomic activity in patients aged 11 to 19 years prior to head-up tilt by measuring heart rate, blood pressure, heart rate variability, blood pressure variability, and baroreceptor gain before and after i.v. insertion with continuous electrocardiography and arterial tonometry in patients with orthostatic tachycardia syndrome (OTS, N = 21), in patients who experienced simple fainting (N = 14), and in normal control subjects (N = 6). Five-minute samples were collected after 30 minutes supine. Fifteen minutes after i.v. insertion, data were collected again. These 5-minute samples were also collected in a separate control population without i.v. insertion after 30 minutes supine and again 30 minutes later. This population included 12 patients with OTS, 13 patients who experienced simple fainting, and 6 normal control subjects. Heart rate variability included the mean RR, the standard deviation of the RR interval (SDNN), and the root mean square of successive RR differences (RMSSD). Autoregressive spectral modeling was used. Low-frequency power (LFP, 0.04-0.15 Hz), high-frequency power (HFP, 0.15-0.40 Hz), and total power (TP, 0.01-0.40 Hz) were compared. Blood pressure variability included standard deviation of systolic blood pressure, LFP, and HFP. Baroreceptor gain at low frequency and high frequency was calculated from cross-spectral transfer function magnitudes when coherence was greater than 0.5. In patients with OTS, RR (790 +/- 50 msec), SDNN (54 +/- 6 msec), RMSSD (55 +/- 5 msec), LFP (422 +/- 200 ms2/Hz), HFP (846 +/- 400 ms2/Hz), and TP (1550 +/- 320 ms2/Hz) were less than in patients who experienced simple fainting (RR, 940 +/- 50 msec; SDNN, 84 +/- 10 msec; RMSSD, 91 +/- 7 msec; LFP, 880 +/- 342 ms2/Hz; HFP, 1720 +/- 210 ms2/Hz; and TP, 3228 +/- 490 ms2/Hz) or normal control subjects (RR, 920 +/- 30 msec; SDNN, 110 +/- 29 msec; RMSSD, 120 +/- 16 msec; LFP, 1600 +/- 331 ms2/Hz; HFP, 2700 +/- 526 ms2/Hz; and TP, 5400 +/- 1017 ms2/Hz). Blood pressure and blood pressure variability were not different in any group. Standard deviation, LFP, and HFP were, respectively, 5.24 +/- 0.8 mm Hg, 1.2 +/- 0.2, and 1.5 +/- 0.3 for patients with OTS; 4.6 +/- 0.4 mm Hg, 1.2 +/- 0.2, and 1.4 +/- 0.3 for patients who experienced simple fainting; and 5.55 +/- 1.0 mm Hg, 1.4 +/- 0.2, and 1.6 +/- 0.3 for normal control subjects. Baroreceptor gain at low frequency and high frequency in patients with OTS (16 +/- 4 msec/mm Hg, 17 +/- 5) was comparable to that in patients who experienced simple fainting (33 +/- 4, 32 +/- 3) and that in normal control subjects (31 +/- 8, 37 +/- 9). Heart rate variability differed between patients with OTS and patients who experienced simple fainting or normal control subjects, and blood pressure and blood pressure variability were not different, but no parameter changed after i.v. insertion. There were no differences from the groups that did not receive i.v. insertions. Data suggest, at most, a limited effect of i.v. insertion on autonomic function in adolescents.

Predicting Sensitivity of Breast Tumors to Src-targeted Therapies Through Assessment of Cas/Src/BCAR3 Activity

DTIC Science & Technology

2017-10-01

expression is elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and DCIS... compared to IDC. (2) BCAR3 is significantly upregulated in triple negative breast cancer and normal tissue; (3) BCAR3 expression shows a modest...expression was seen to be elevated in DCIS samples compared to normal mammary tissue, invasive ductal carcinoma (IDC) compared to normal mammary tissue, and

Adrenocorticotrophic Hormone Levels in Ground Based Studies

NASA Technical Reports Server (NTRS)

Campbell, B. O.

1972-01-01

Baseline values of immunoreactive ACTH were established in the normal healthy adult. Normal levels of ACTH secretion were determined for both the male and the female in circulating plasma and serum. The data obtained in these studies are particularly significant in that the sampling was carefully controlled; only healthy employed individuals of both sexes were tested in a routine work situation that would not be considered conducive to stress. It has been found that alterations in the classically described circadian rhythm of ACTH secretion can occur when activities (such as work/rest cycles) are imposed on the individual studied. These changes can be demonstrated even when there is no appreciable change noted in the rhythm of hydrocortisone secretion.

A study to promote breast feeding in the Helsinki Metropolitan area in Finland.

PubMed

Hannula, Leena S; Kaunonen, Marja E; Puukka, Pauli J

2014-06-01

the aim of this study was to assess the impact of providing intensified support for breast feeding during the perinatal period. a quasi-experimental design with non-equivalent control group. three public maternity hospitals (two study, one control) in the Helsinki Metropolitan area in Finland. a convenience sample of 705 mothers (431 in the intervention group, 274 in the control group). in this study, families in the intervention group had access to intensified breast feeding support from midpregnancy, whereas those in the control group had access to normal care. Intensified support included lectures and workshops to health professionals, and families in the intervention group had access to more intensive support and counselling for breast feeding and a breast feeding outpatient clinic. Additionally, an internet-based intervention was only used in the intervention group, but not in the control group. Mothers in the control group received normal care from the midwifery and nursing professionals who were to continue their work normally. The data were analysed statistically. altogether 705 women participated in the study. In the intervention group (n=431), 76% of the women breast fed exclusively throughout the hospital stay, compared to 66% of the mothers in the control group (n=274). In multivariate analysis, the likelihood of exclusive breast feeding at the time of responding (at hospital discharge or after that at home) was increased by the mother not being treated for an underlying illness or medical problem during pregnancy, being in the intervention group, having normal vaginal childbirth, high breast feeding confidence, positive attitude towards breast feeding, good coping with breast feeding, and 24-hour presence of the infant's father in the ward. the low exclusive breast feeding rates of newborns could be increased by using intensified breast feeding support. Mothers' health problems during pregnancy can decrease exclusive breast feeding. Mothers with health problems or other than normal childbirth should receive extra breast feeding support, and the presence of fathers in the ward should be encouraged. Intensified breast feeding counselling and support helps mothers to breast feed exclusively. This support should be available in a variety of forms, so that mothers can choose the type of support they need. As breast feeding counselling and support is intensified, more mothers succeed with exclusive breast feeding. © 2013 Published by Elsevier Ltd.

Mediterranean diet adherence in individuals with prediabetes and unknown diabetes: the Di@bet.es Study.

PubMed

Ortega, E; Franch, J; Castell, C; Goday, A; Ribas-Barba, L; Soriguer, F; Vendrell, J; Casamitjana, R; Bosch-Comas, A; Bordiú, E; Calle-Pascual, A; Carmena, R; Castaño, L; Catalá, M; Delgado, E; Gaztambide, S; Girbés, J; López-Alba, A; Martínez-Larrad, M T; Menéndez, E; Mora-Peces, I; Pascual-Manich, G; Rojo-Martínez, G; Serrano-Rios, M; Urrutía, I; Valdés, S; Vázquez, J A; Gomis, R

2013-01-01

Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL). This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects. We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group. In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies. Copyright © 2013 S. Karger AG, Basel.

Dietary exposure to aflatoxin in human male infertility in Benin City, Nigeria.

PubMed

Ibeh, I N; Uraih, N; Ogonar, J I

1994-01-01

To discover the relationship between aflatoxin levels, if any, in serum of infertile men in comparison with random controls from the community. In a parallel experiment, adult male rats were given an aflatoxin-contaminated diet. 100 adult males, yielding 50 semen samples, from men attending Infertility Clinics at a university teaching hospital and 50 normal men in the same community. The staple foods of the men were assayed for aflatoxin content. The rats were given the aflatoxin-rich diet, and their spermatozoa were examined and their ability to reproduce assessed. A random sampling of semen from 100 adult males comprising 50 samples drawn from infertile men and 50 drawn from normal individuals within the same community revealed the presence of aflatoxins in 20 semen samples from the infertile group (40.0%) and four samples from the fertile group (8.0%). The mean aflatoxin concentrations were 1.660 +/- 0.04 micrograms/mL (infertile men) and 1.041 +/- 0.01 micrograms/mL (fertile men). Infertile men with aflatoxin in their semen showed a higher percentage of spermatozoal abnormality (50.0%) than the fertile men (10.0-15.0%). Dietary exposure of adult male Albino rats to aflatoxin (8.5 micrograms AF1/g of Guinea growers feed for 14 days) produced deleterious effects on the spermatozoa of the affected rats, producing features that resemble those seen in semen of infertile men exposed to aflatoxin.

Thermoluminescence of contaminating minerals for the detection of radiation treatment of dried fruits

NASA Astrophysics Data System (ADS)

Khan, H. M.; Bhatti, Ijaz A.; Delincée, Henry

2002-03-01

Several types of dry fruits (pistachio nut, dried apricot, almond and raisins) have been investigated for detection of their radiation treatment by gamma rays or electron beam using thermoluminescence (TL) measurements. These samples were irradiated to 1.0-3.0 kGy (gamma rays) or 0.75-3.9 kGy (10 MeV electron beam). Thermoluminescence glow curves for the contaminating minerals separated from the dry fruits were recorded between the temperature range of 50°C and 500°C. In all the cases, the intensity of TL signal for the irradiated dry fruits was 1-3 orders of magnitudes higher than the TL intensity of the corresponding unirradiated control samples allowing clear distinction between the irradiated and unirradiated samples. These results were normalized by re-irradiating the mineral grains with a gamma-ray dose of 1.0 kGy, and a second glow curve was recorded. The ratio of intensity of the first glow curve (TL 1) to that after the normalization dose (TL 2), i.e. (TL 1/TL 2) was determined and compared with the recommended threshold values. These parameters, together with comparison of the shape of the first glow curve, gave unequivocal results about the radiation treatment of the dry fruit samples.

Delivery route determines the presence of immune complexes on umbilical cord erythrocytes.

PubMed

de Lima, Andrés; Franco, Luis C; Sarmiento, Andrés; González, John M

2017-11-01

Umbilical cord blood offers a unique opportunity to study the basal level of immunoglobulin complexes. This study aims to determine the presence of immune complexes and complement deposition on erythrocytes from umbilical cord blood from normal, full-term pregnancies. In vitro pre-formed IgA, IgG, and IgM complexes were used as positive control for flow cytometry detection, and for C3d deposition. Blood samples (34) of umbilical cord blood taken from vaginal and cesarean deliveries were tested for the presence of immunoglobulin complexes. Fourteen samples from vaginal deliveries and 20 samples from cesarean deliveries were assessed. IgG and IgM complexes were detected on erythrocytes, whereas no IgA complexes or complement deposition was observed. Interestingly, the percentage of IgG complexes was higher on erythrocytes from vaginal delivery samples compared to those from cesarean deliveries. No other associations between immune complexes and other maternal or newborn variables were found. IgG and IgM complexes seem to be normally present on umbilical cord erythrocytes. Erythrocytes from vaginal deliveries have a higher percentage of IgG complexes present compared to that from cesarean deliveries. Since no C3d activity was detected, these complexes are non-pathological and should be part of the newborn's initial innate immune response.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

PubMed

Costa, Nádia Lago; Gonçalves, Andréia Souza; Martins, Allisson Filipe Lopes; Arantes, Diego Antônio Costa; Silva, Tarcília Aparecida; Batista, Aline Carvalho

2016-07-01

There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcription profiling using RNA-Seq demonstrates expression differences in the body walls of juvenile albino and normal sea cucumbers Apostichopus japonicus

NASA Astrophysics Data System (ADS)

Ma, Deyou; Yang, Hongsheng; Sun, Lina; Chen, Muyan

2014-01-01

Sea cucumbers Apostichopus japonicus are one of the most important aquaculture species in China. Their normal body color is black to fit their surroundings. Wild albinos are rare and hard to breed. To understand the differences between albino and normal (control) sea cucumbers at the transcriptional level, we sequenced the transcriptomes in their body-wall tissues using RNA-Seq high-throughput sequencing. Approximately 4.876 million (M) and 4.884 M 200-nucleotide-long cDNA reads were produced in the cDNA libraries derived from the body walls of albino and control samples, respectively. A total of 9 561 (46.89%) putative genes were identified from among the RNA-Seq reads in both libraries. After filtering, 837 significantly differentially regulated genes were identified in the albino library compared with in the control library, and 3.6% of the differentially expressed genes (DEGs) were found to have changed those more than five-fold. The expression levels of 10 DEGs were checked by real-time PCR and the results were in full accord with the RNA-Seq expression trends, although the amplitude of the differences in expression levels was lower in all cases. A series of pathways were significantly enriched for the DEGs. These pathways were closely related to phagocytosis, the complement and coagulation cascades, apoptosis-related diseases, cytokine-cytokine receptor interaction, and cell adhesion. The differences in gene expression and enriched pathways between the albino and control sea cucumbers offer control targets for cultivating excellent albino A. japonicus strains in the future.

Seropositivity for the human heat shock protein (Hsp)60 accompanying seropositivity for Chlamydia trachomatis is less prevalent among tubal ectopic pregnancy cases than individuals with normal reproductive history.

PubMed

Ozyurek, Eser S; Karacan, Tolga; Ozdalgicoglu, Cenk; Yilmaz, Salih; Isik, Salman; San, Mevlide; Kaya, Erdal

2018-04-01

To investigate the role of anti-human heat shock protein 60 (hHsp60) antibody positivity in the pathogenesis of ectopic pregnancy, following Chlamydia trachomatis (CT) infection. In a case-control study, serological tests for anti-hHsp60 were performed in ectopic pregnancies (study group) and parturients with normal reproductive histories (control group). All participants in both groups were CT IgG(+). hHsp60 IgG(+) prevalences were compared between the two groups, by semiquantitative ELISA. Data were evaluated using nonparametric and parametric tests and multivariable regression. After an initial pilot study, two groups were formed: 63 ectopic gestations (study group) and 95 normal parturients (control group), all CT IgG(+). Blood samples from all cases were tested for anti-hHsp60 IgG. Age, gravidity, and practising contraception were higher in the control group, while a history of pelvic infections were more common in the study group. Hsp60 IgG(+) was found to be significantly higher in the control group (63/95, 66.3%) compared to study group (30/63, 47.6%). Regression analysis revealed anti-hHsp60 positivity was an independent factor delineating the two groups. Immunity to hHsp60 is less common in CT IgG(+) ectopic pregnancies than CT IgG(+) fertile subjects without a history of ectopic pregnancies. Hence, our findings suggest that hHsp60 seropositivity may decrease the probability of an ectopic gestation in subjects with previous CT infections. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of acidification, lipid removal and mathematical normalization on carbon and nitrogen stable isotope compositions in beaked whale (Ziphiidae) bone.

PubMed

Tatsch, Ana Carolina C; Secchi, Eduardo R; Botta, Silvina

2016-02-15

The analysis of stable isotopes in tissues such as teeth and bones has been used to study long-term trophic ecology and habitat use in marine mammals. However, carbon isotope ratios (δ(13) C values) can be altered by the presence of (12) C-rich lipids and carbonates. Lipid extraction and acidification are common treatments used to remove these compounds. The impact of lipids and carbonates on carbon and nitrogen isotope ratios (δ(15) N values), however, varies among tissues and/or species, requiring taxon-specific protocols to be developed. The effects of lipid extraction and acidification and their interaction on carbon and nitrogen isotope values were studied for beaked whale (Ziphiidae) bone samples. δ(13) C and δ(15) N values were determined in quadruplicate samples: control, lipid-extracted, acidified and lipid-extracted followed by acidification. Samples were analyzed by means of elemental analysis isotope ratio mass spectrometry. Furthermore, the efficiency of five mathematical models developed for estimating lipid-normalized δ(13) C values from untreated δ(13) C values was tested. Significant increases in δ(13) C values were observed after lipid extraction. No significant changes in δ(13) C values were found in acidified samples. An interaction between both treatments was demonstrated for δ(13) C but not for δ(15) N values. No change was observed in δ(15) N values for lipid-extracted and/or acidified samples. Although all tested models presented good predictive power to estimate lipid-free δ(13) C values, linear models performed best. Given the observed changes in δ(13) C values after lipid extraction, we recommend a priori lipid extraction or a posteriori lipid normalization, through simple linear models, for beaked whale bones. Furthermore, acidification seems to be an unnecessary step before stable isotope analysis, at least for bone samples of ziphiids. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Power/Sample Size Calculations for Assessing Correlates of Risk in Clinical Efficacy Trials

PubMed Central

Gilbert, Peter B.; Janes, Holly E.; Huang, Yunda

2016-01-01

In a randomized controlled clinical trial that assesses treatment efficacy, a common objective is to assess the association of a measured biomarker response endpoint with the primary study endpoint in the active treatment group, using a case-cohort, case-control, or two-phase sampling design. Methods for power and sample size calculations for such biomarker association analyses typically do not account for the level of treatment efficacy, precluding interpretation of the biomarker association results in terms of biomarker effect modification of treatment efficacy, with detriment that the power calculations may tacitly and inadvertently assume that the treatment harms some study participants. We develop power and sample size methods accounting for this issue, and the methods also account for inter-individual variability of the biomarker that is not biologically relevant (e.g., due to technical measurement error). We focus on a binary study endpoint and on a biomarker subject to measurement error that is normally distributed or categorical with two or three levels. We illustrate the methods with preventive HIV vaccine efficacy trials, and include an R package implementing the methods. PMID:27037797

Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency.

PubMed

Turcu, Adina F; Nanba, Aya T; Chomic, Robert; Upadhyay, Sunil K; Giordano, Thomas J; Shields, James J; Merke, Deborah P; Rainey, William E; Auchus, Richard J

2016-05-01

To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation. Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies. We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess. © 2016 European Society of Endocrinology.

The Study of Pentoxifylline Drug Effects on Renal Apoptosis and BCL-2 Gene Expression Changes Following Ischemic Reperfusion Injury in Rat

PubMed Central

Hashemi, Mehrdad

2014-01-01

Ischemia Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. In this study, the effect of pentoxyfylline on BCL-2 gene expression changes and cell injury in kidney of rat following Ischemia Reperfusion were evaluated. In this experimental study, 20 male wistar rats with average weight of 250-300 g were selected and then were accidently divided them on two tenth group of control and treatment groups. In the control group, celiotomy was performed by ventral midline incision. The left kidney was isolated, and then both the renal artery and vein were obstructed. After 60 minutes of warm ischemia, vessel obstruction resolved and the right kidney was removed. 72 hours after reperfusion, tissue samples were taken from left kidney for Tunel assay. We used quantitative real time PCR for detection of BCL-2 gene expression in treated groups and then compared them to control samples. In the treatment group, the cell death changes, showed lower level than the control group. The results also showed the BCL-2 gene expression was declined in ischemia group as campared to PNT drug group. The pentoxyfylline might have a role in control of apoptosis result from Ischemia- reperfusion and quantitative real-time PCR can be used as a direct method for detection BCL-2 gene expression in tested samples and normal samples. PMID:24734070

Fish Oil Supplementation and Urinary Oxalate Excretion in Normal Subjects on a Low-oxalate Diet

PubMed Central

Lange, Jessica N.; Mufarrij, Patrick W.; Easter, Linda; Knight, John; Holmes, Ross P.; Assimos, Dean G.

2014-01-01

OBJECTIVE To determine if fish oil supplementation reduces endogenous oxalate synthesis in healthy subjects. MATERIALS AND METHODS Fifteen healthy non–stone-forming adults participated in this study. Subjects first abstained from using vitamins, medications, or foods enriched in omega-3 fatty acids for 30 days. Next, they collected two 24-hour urine specimens while consuming a self-selected diet. Subjects consumed an extremely low-oxalate and normal-calcium diet for 5 days and collected 24-hour urine specimens on the last 3 days of this diet. Next, the subjects took 2 fish oil capsules containing 650-mg eicosapentaenoic acid and 450-mg docosahexaenoic acid twice daily for 30 days. They consumed a self-selected diet on days 1–25 and the controlled diet on days 26–30. Twenty-four-hour urine samples were collected on days 28–30. Excretion levels of urinary analytes including oxalate and glycolate were analyzed. RESULTS Although there was a significant reduction in urinary oxalate, magnesium, and potassium excretions and an increase in uric acid excretion during the controlled dietary phases compared with the self-selected diet, there were no significant differences in their excretion during controlled diet phases with and without fish oil supplementation. CONCLUSION These results suggest that fish oil supplementation does not reduce endogenous oxalate synthesis or urinary oxalate excretion in normal adults during periods of extremely low oxalate intake. However, these results do not challenge the previously described reduction in urinary oxalate excretion demonstrated in normal subjects consuming a moderate amount of oxalate in conjunction with fish oil. PMID:25102784

Amniotic fluid inhibin-A in chromosomally normal and Down's syndrome pregnancies.

PubMed

Wallace, E M; Crossley, J A; Groome, N P; Aitken, D A

1997-01-01

Recently, inhibin-A has been shown to be a useful new prenatal marker of Down's syndrome, significantly increasing detection rates. While the placenta is believed to be the major source of inhibin in pregnancy, there are actually very limited data available on specific inhibin dimers in pregnancy. Using a sensitive and specific ELISA we have measured the inhibin-A content of amniotic fluid (AF) to investigate further the biology of inhibin-A in chromosomally normal and abnormal pregnancies. AF from 51 Down's syndrome and 161 chromosomally normal pregnancies between 16 and 19 weeks of gestation were analysed, blinded as to whether the sample was from a Down's syndrome or normal pregnancy. There were no sex differences in inhibin-A content in either the control or Down's syndrome pregnancies. The median (10-90th percentiles) inhibin-A level in the control pregnancies increased from 339.6 (175.2-649.1) pg/ml at 16 weeks to 592.9 (256.4-1027.3) pg/ml at 19 weeks of gestation. The median (95% confidence interval) inhibin-A in the Down's syndrome pregnancies, expressed as multiples of the median (MoM) to correct for gestation, was 0.77 (0.68-0.89) MoM, significantly lower than the controls (P < 0.001, Mann-Whitney U test). We believe that these data are compatible with more than one source of inhibin-A in pregnancy and suggest that the fetal membranes may be contributing significantly to AF inhibin-A content. Further, our data would suggest that the endocrine function of the placenta and the other inhibin source(s) are differentially regulated.

The scent fingerprint of hepatocarcinoma: in-vitro metastasis prediction with volatile organic compounds (VOCs)

PubMed Central

Amal, Haitham; Ding, Lu; Liu, Bin-bin; Tisch, Ulrike; Xu, Zhen-qin; Shi, Da-you; Zhao, Yan; Chen, Jie; Sun, Rui-xia; Liu, Hu; Ye, Sheng-Long; Tang, Zhao-you; Haick, Hossam

2012-01-01

Background: Hepatocellular carcinoma (HCC) is a common and aggressive form of cancer. Due to a high rate of postoperative recurrence, the prognosis for HCC is poor. Subclinical metastasis is the major cause of tumor recurrence and patient mortality. Currently, there is no reliable prognostic method of invasion. Aim: To investigate the feasibility of fingerprints of volatile organic compounds (VOCs) for the in-vitro prediction of metastasis. Methods: Headspace gases were collected from 36 cell cultures (HCC with high and low metastatic potential and normal cells) and analyzed using nanomaterial-based sensors. Predictive models were built by employing discriminant factor analysis pattern recognition, and the classification success was determined using leave-one-out cross-validation. The chemical composition of each headspace sample was studied using gas chromatography coupled with mass spectrometry (GC-MS). Results: Excellent discrimination was achieved using the nanomaterial-based sensors between (i) all HCC and normal controls; (ii) low metastatic HCC and normal controls; (iii) high metastatic HCC and normal controls; and (iv) high and low HCC. Several HCC-related VOCs that could be associated with biochemical cellular processes were identified through GC-MS analysis. Conclusion: The presented results constitute a proof-of-concept for the in-vitro prediction of the metastatic potential of HCC from VOC fingerprints using nanotechnology. Further studies on a larger number of more diverse cell cultures are needed to evaluate the robustness of the VOC patterns. These findings could benefit the development of a fast and potentially inexpensive laboratory test for subclinical HCC metastasis. PMID:22888249

Differences in the Prevalence, Severity and Symptom Profiles of Depression in Boys and Adolescents with an Autism Spectrum Disorder versus Normally Developing Controls

ERIC Educational Resources Information Center

Bitsika, Vicki; Sharpley, Christopher F.

2015-01-01

The prevalence, severity and symptom profiles for major depressive disorder (MDD) were compared in samples of boys and adolescents with and without an autism spectrum disorder (ASD). Self-reports were obtained on the Depression subscale of the Child and Adolescent Symptoms Inventory (CASI-D) with 70 ASD and 50 non-ASD male participants between the…

Studies of Current Induced Magnetization reversal and generation of GHz radiation in magnetic nanopillars

NASA Astrophysics Data System (ADS)

Alhajdarwish, Mustafa Yousef

This thesis describes studies of two phenomena: Current-Induced Magnetization Switching (CIMS), and Current-Induced Generation of GHz Radiation. The CIMS part contains results of measurements of current-perpendicular-to-plane (CPP) magnetoresistance (MR) and CIMS behavior on Ferromagnetic/Nonmetal/Ferromagnetic (F1/N/F2) nanopillars. Judicious combinations of F1 and F2 metals with different bulk scattering asymmetries, and with F1/N and N/F2 interfaces having different interfacial scattering asymmetries, are shown to be able to controllably, and independently, 'invert' both the CPP-MR and the CIMS. In 'normal' CPP-MR, R(AP) > R(P), where R(AP) and R(P) are the nanopillar resistances for the anti-parallel (AP) and parallel (P) orientations of the Fi and F2 magnetic moments. In 'inverse' CPP-MR, R(P) > R(AP). In 'normal' CIMS, positive current switches the nanopillar from the P to the AP state. In 'inverse' CIMS, positive current switches the nanopillar from AP to P. All four possible combinations of CPP-MR and CIMS---(a) 'normal'-'normal', (b) 'normal'- 'inverse', 'inverse'-'normal', and (d) 'inverse'-'inverse' are shown and explained. These results rule out the self-Oersted field as the switching source, since the direction of that field is independent of the bulk or interfacial scattering asymmetries. Successful use of impurities to reverse the bulk scattering asymmetry shows the importance of scattering off of impurities within the bulk F1 and F2 metals---i.e. that the transport must be treated as 'diffusive' rather than 'ballistic'. The GHz studies consist of five parts: (1) designing a sample geometry that allows reliable measurements; (2) making nanopillar samples with this geometry; (3) constructing a system for measuring frequencies up to 12 GHz and measuring current-driven GHz radiation data with it; (4) showing 'scaling' behavior of GHz data with the critical fields and currents for nominally identical (but actually slightly different) samples, and justifying such scaling; and (5) designing and constructing a system for frequency domain studies up to 40 GHz and for time domain studies.

Potential of non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Huang, Shaohua; Wang, Lan; Chen, Weisheng; Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Li, Buhong; Chen, Rong

2014-11-01

Non-invasive esophagus cancer detection based on urine surface-enhanced Raman spectroscopy (SERS) analysis was presented. Urine SERS spectra were measured on esophagus cancer patients (n = 56) and healthy volunteers (n = 36) for control analysis. Tentative assignments of the urine SERS spectra indicated some interesting esophagus cancer-specific biomolecular changes, including a decrease in the relative content of urea and an increase in the percentage of uric acid in the urine of esophagus cancer patients compared to that of healthy subjects. Principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to analyze and differentiate the SERS spectra between normal and esophagus cancer urine. The diagnostic algorithms utilizing a multivariate analysis method achieved a diagnostic sensitivity of 89.3% and specificity of 83.3% for separating esophagus cancer samples from normal urine samples. These results from the explorative work suggested that silver nano particle-based urine SERS analysis coupled with PCA-LDA multivariate analysis has potential for non-invasive detection of esophagus cancer.

The alternative complement pathway control protein H binds to immune complexes and serves their detection

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

Nydegger, U.E.; Corvetta, A.; Spaeth, P.J.

1983-01-01

During solubilization of immune complexes C3b becomes fixed to the immunoglobulin part and serves as a receptor for the alternative complement pathway control protein H. The H-C3b immune complex interaction can be made detectable using 4% polyethyleneglycol to separate free from bound /sup 125/I-H. Tetanus toxoid (Te)/anti-Te complexes kept soluble with fresh serum and containing 125 IU of specific antibody bound 18% of /sup 125/I-H; when fresh serum was chelated with 10 mM EDTA, /sup 125/I-H binding was only 5%. On sucrose density gradients, the H-binding material sedimented in the range of 12 to 30 S. In 36 serum samplesmore » from rheumatoid arthritis (RA) patients and in 12 serum samples from patients with systemic lupus erythematosus (SLE), /sup 125/I-H binding was significantly elevated to 9.5 +/- 4.7% (mean +/- 1 SD) and 13.3 +/- 5.6%, respectively, while /sup 125/I-H binding by 36 normal human sera was 4 +/- 2%. RA samples (17/36, 47%) and SLE samples (9/12, 75%) had H-binding values increased by more than 2 SD above the normal mean. The serum samples were also assessed for conglutinin- and C1q-binding activities; a significant correlation between H and C1q binding was observed (P less than 0.001); there was no correlation between H and conglutinin binding. Although binding to immune complexes through its interaction with C3b, H clearly detects a population of complexes other than conglutinin, thus expanding the possibilities of further characterizing pathological complexes.« less

Identification of genetic aberrations on chromosome 22 outside the NF2 locus in schwannomatosis and neurofibromatosis type 2.

PubMed

Buckley, Patrick G; Mantripragada, Kiran K; Díaz de Ståhl, Teresita; Piotrowski, Arkadiusz; Hansson, Caisa M; Kiss, Hajnalka; Vetrie, David; Ernberg, Ingemar T; Nordenskjöld, Magnus; Bolund, Lars; Sainio, Markku; Rouleau, Guy A; Niimura, Michihito; Wallace, Andrew J; Evans, D Gareth R; Grigelionis, Gintautas; Menzel, Uwe; Dumanski, Jan P

2005-12-01

Schwannomatosis is characterized by multiple peripheral and cranial nerve schwannomas that occur in the absence of bilateral 8th cranial nerve schwannomas. The latter is the main diagnostic criterion of neurofibromatosis type 2 (NF2), which is a related but distinct disorder. The genetic factors underlying the differences between schwannomatosis and NF2 are poorly understood, although available evidence implicates chromosome 22 as the primary location of the gene(s) of interest. To investigate this, we comprehensively profiled the DNA copy number in samples from sporadic and familial schwannomatosis, NF2, and a large cohort of normal controls. Using a tiling-path chromosome 22 genomic array, we identified two candidate regions of copy number variation, which were further characterized by a PCR-based array with higher resolution. The latter approach allows the detection of minute alterations in total genomic DNA, with as little as 1.5 kb per measurement point of nonredundant sequence on the array. In DNA derived from peripheral blood from a schwannomatosis patient and a sporadic schwannoma sample, we detected rearrangements of the immunoglobulin lambda (IGL) locus, which is unlikely to be due to a B-cell specific somatic recombination of IGL. Analysis of normal controls indicated that these IGL rearrangements were restricted to schwannomatosis/schwannoma samples. In the second candidate region spanning GSTT1 and CABIN1 genes, we observed a frequent copy number polymorphism at the GSTT1 locus. We further describe missense mutations in the CABIN1 gene that are specific to samples from schwannomatosis and NF2 and make this gene a plausible candidate for contributing to the pathogenesis of these disorders. Copyright 2005 Wiley-Liss, Inc.

Linking inter-individual differences in the conflict adaptation effect to spontaneous brain activity.

PubMed

Wang, Ting; Chen, Zhencai; Zhao, Guang; Hitchman, Glenn; Liu, Congcong; Zhao, Xiaoyue; Liu, Yijun; Chen, Antao

2014-04-15

Conflict adaptation has been widely researched in normal and clinical populations. There are large individual differences in conflict adaptation, and it has been linked to the schizotypal trait. However, no study to date has examined how individual differences in spontaneous brain activity are related to behavioral conflict adaptation (performance). Resting-state functional magnetic resonance imaging (RS-fMRI) is a promising tool to investigate this issue. The present study evaluated the regional homogeneity (ReHo) of RS-fMRI signals in order to explore the neural basis of individual differences in conflict adaptation across two independent samples comprising a total of 67 normal subjects. A partial correlation analysis was carried out to examine the relationship between ReHo and behavioral conflict adaptation, while controlling for reaction time, standard deviation and flanker interference effects. This analysis was conducted on 39 subjects' data (sample 1); the results showed significant positive correlations in the left dorsolateral prefrontal cortex (DLPFC) and left ventrolateral prefrontal cortex. We then conducted a test-validation procedure on the remaining 28 subjects' data (sample 2) to examine the reliability of the results. Regions of interest were defined based on the correlation results. Regression analysis showed that variability in ReHo values in the DLPFC accounted for 48% of the individual differences in the conflict adaptation effect in sample 2. The present findings provide further support for the importance of the DLPFC in the conflict adaptation process. More importantly, we demonstrated that ReHo of RS-fMRI signals in the DLPFC can predict behavioral performance in conflict adaptation, which provides potential biomarkers for the early detection of cognitive control deterioration. Copyright © 2013 Elsevier Inc. All rights reserved.

Cytogenetic analysis of somatic and germinal cells from 38,XX/38,XY phenotypically normal boars.

PubMed

Barasc, Harmonie; Ferchaud, Stéphane; Mary, Nicolas; Cucchi, Marie Adélaïde; Lucena, Amalia Naranjo; Letron, Isabelle Raymond; Calgaro, Anne; Bonnet, Nathalie; Dudez, Anne Marie; Yerle, Martine; Ducos, Alain; Pinton, Alain

2014-01-15

Many chromosomal abnormalities have been reported to date in pigs. Most of them have been balanced structural rearrangements, especially reciprocal translocations. A few cases of XY/XX chimerism have also been diagnosed within the national systematic chromosomal control program of young purebred boars carried out in France. Until now, this kind of chromosomal abnormality has been mainly reported in intersex individuals. We investigated 38,XY/38,XX boars presenting apparently normal phenotypes to evaluate the potential effects of this particular chromosomal constitution on their reproductive performance. To do this, we analyzed (1) the chromosomal constitution of cells from different organs in one boar; (2) the aneuploidy rates for chromosomes X, Y, and 13 in sperm nuclei sampled from seven XY/XX boars. 2n = 38,XX cells were identified in different nonhematopoietic tissues including testis (frequency, <8%). Similar aneuploidy rates were observed in the sperm nuclei of XY/XX and normal individuals (controls). Altogether, these results suggest that the presence of XX cells had no or only a very limited effect on the reproduction abilities of the analyzed boars. Copyright © 2014 Elsevier Inc. All rights reserved.

Whole-Blood Nested-PCR Amplification of M. leprae-Specific DNA for Early Diagnosis of Leprosy

PubMed Central

Wen, Yan; Xing, Yan; Yuan, Lian-Chao; Liu, Jian; Zhang, Ying; Li, Huan-Ying

2013-01-01

We evaluated the sensitivity and specificity of a nested-polymerase chain reaction (PCR) method for detection of Mycobacterium leprae DNA from whole blood. Whole-blood specimens were subjected to nested-PCR amplification of M. leprae repeat DNA sequences in 49 multibacillary (MB) and 30 paucibacillary (PB) leprosy patients, 96 household contacts (HHCs), 18 tuberculosis (TB) patients, and 35 normal healthy individuals. M. leprae DNA was detected in 95.92% (47/49) of MB, 70% (21/30) of PB, and 6.25% (6/96) of HHC, but it was not detected in 18 TB or 35 normal controls. The sensitivities of the anti-bovine serum albumin (ND-O-BSA) immunoglobulin M (IgM) and antifusion protein of ML0405-ML2331 IgG for MB were 97.96% and 89.8%, and these values for PB were 70% and 53.33%. However, the ND-O-BSA enzyme-linked immunosorbent assay (ELISA) had lower specificity, with relatively high false-positive results for TB patients (16.67%) and normal healthy controls (10%). Based on these promising findings, we propose the use of nested PCR of whole-blood samples along with ELISA test for early detection of leprosy cases. PMID:23478578

A role for GPx3 in activity of normal and leukemia stem cells

PubMed Central

Herault, Olivier; Hope, Kristin J.; Deneault, Eric; Mayotte, Nadine; Chagraoui, Jalila; Wilhelm, Brian T.; Cellot, Sonia; Sauvageau, Martin; Andrade-Navarro, Miguel A.; Hébert, Josée

2012-01-01

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs. PMID:22508837

Expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) in human cholesteatoma.

PubMed

Lee, No Hee; Chang, Ji-Won; Choi, June; Jung, Hak Hyun; Im, Gi Jung

2013-02-01

Ras-related C3 botulinum toxin substrate 1 (RAC1) is a 21-kDa signaling G protein that functions as a pleiotropic regulator of many cellular processes including epithelial differentiation. RAC1 activates the nicotinamide adenine dinucleotide phosphate oxidase complex which promotes formation of reactive oxygen species and degradation enzymes. RAC1 has been associated with rapid epithelial differentiation and invasive properties in human cholesteatoma. This study aimed to identify the presence of RAC1 in human cholesteatoma and analyze its functional role as a regulator of proteolysis and overgrowth. Tissue samples from human cholesteatoma and normal postaural skin were obtained from patients during otologic surgery for cholesteatoma. The expression of RAC1 mRNA was quantified by real-time RT-PCR, and localization of RAC1 expression was confirmed using immunohistochemical staining. Expression of RAC1 mRNA in the epithelium of cholesteatoma was significantly elevated 2.94 fold on average, compared with normal control skin. RAC1 expression in the suprabasal and basal layer of cholesteatoma epithelium was stronger than normal control skin. Our results suggest that RAC1 can be associated with rapid epithelial differentiation and invasive properties of human cholesteatoma.

[An experimental study on the implantation of a biomaterial with electro-activity for replacement of hard tissue in bone].

PubMed

Chen, L; Chen, Z; Zhang, M

2001-12-01

To assess the effects of a piezoelectric biological ceramic on osteogenesis. Hydroxyapatite (HA) and piezoelectric biological ceramics (hydroxyapatite and barium titanate, HABT) were implanted in the jawbones of 5 dogs, and for sample collection, the dogs were killed separately at 1 week, 2 weeks, 1 month, 2 months and 3 months after implantation. The samples from a rhesus monkey and a blank control were collected 34 months after implantation. The implanted samples and surrounding tissues were subjected to histological observations using light microscopy (LM) and scanning electronmicroscopy (SEM) were made. Compared with the control groups, the HABTs promoted osteogenesis significantly. One week after implantation, new bone tissues were found on the surface vertical to the longitudinal direction of HABT; more bone tissues were found after 2 weeks. HABTs induced the bone tissues to arrange orderly. After two years and ten months of implantation, the piezoelectric bioceramic and bone became monolithic, and the structure of bone was normal. HABTs could promote osteogenesis.

Experimental investigation of the tip based micro/nano machining

NASA Astrophysics Data System (ADS)

Guo, Z.; Tian, Y.; Liu, X.; Wang, F.; Zhou, C.; Zhang, D.

2017-12-01

Based on the self-developed three dimensional micro/nano machining system, the effects of machining parameters and sample material on micro/nano machining are investigated. The micro/nano machining system is mainly composed of the probe system and micro/nano positioning stage. The former is applied to control the normal load and the latter is utilized to realize high precision motion in the xy plane. A sample examination method is firstly introduced to estimate whether the sample is placed horizontally. The machining parameters include scratching direction, speed, cycles, normal load and feed. According to the experimental results, the scratching depth is significantly affected by the normal load in all four defined scratching directions but is rarely influenced by the scratching speed. The increase of scratching cycle number can increase the scratching depth as well as smooth the groove wall. In addition, the scratching tests of silicon and copper attest that the harder material is easier to be removed. In the scratching with different feed amount, the machining results indicate that the machined depth increases as the feed reduces. Further, a cubic polynomial is used to fit the experimental results to predict the scratching depth. With the selected machining parameters of scratching direction d3/d4, scratching speed 5 μm/s and feed 0.06 μm, some more micro structures including stair, sinusoidal groove, Chinese character '田', 'TJU' and Chinese panda have been fabricated on the silicon substrate.

Evaluation of an ATP Assay to Quantify Bacterial Attachment to Surfaces in Reduced Gravity

NASA Technical Reports Server (NTRS)

Birmele, Michele N.; Roberson, Luke B.; Roberts, Michael S.

2010-01-01

Aim: To develop an assay to quantify the biomass of attached cells and biofilm formed on wetted surfaces in variable-gravity environments. Methods and Results: Liquid cultures of Pseudomonas aeruginosa were exposed to 30-35 brief cycles of hypergravity (< 2-g) followed by free fall (i.e., reduced gravity) equivalent to either lunar-g (i.e., 0.17 normal Earth gravity) or micro-g (i.e., < 0.001 normal Earth gravity) in an aircraft flying a series of parabolas. Over the course of two days of parabolic flight testing, 504 polymer or metal coupons were exposed to a stationary-phase population of P. aeruginosa strain ERC1 at a concentration of 1.0 x 10(exp 5) cells per milliliter. After the final parabola on each flight test day, half of the material coupon samples were treated with either 400 micro-g/L ionic silver fluoride (microgravity-exposed cultures) or 1% formalin (lunar-gravity-exposed cultures). The remaining sample coupons from each flight test day were not treated with a fixative. All samples were returned to the laboratory for analysis within 2 hours of landing, and all biochemical assays were completed within 8 hours of exposure to variable gravity. The intracellular ATP luminescent assay accurately reflected cell physiology compared to both cultivation-based and direct-count microscopy analyses. Cells exposed to variable gravity had more than twice as much intracellular ATP as control cells exposed only to normal Earth gravity.

Factors modulating expression of Renilla luciferase from control plasmids used in luciferase reporter gene assays1

PubMed Central

Shifera, Amde Selassie; Hardin, John A.

2009-01-01

The Renilla luciferase gene is commonly used as an internal control in luciferase-based reporter gene assays to normalize the values of the experimental reporter gene for variations that could be caused by transfection efficiency and sample handling. Various plasmids encoding Renilla luciferase under different promoter constructs are commercially available. The validity of the use of Renilla luciferase as an internal control is based on the assumption that it is constitutively expressed in transfected cells and that its constitutive expression is not modulated by experimental factors that could result in either the upregulation or the downregulation of the amounts of the enzyme produced. During the past ten years, a number of reports have appeared that identified a variety of conditions that could alter the basal constitutive expression of Renilla luciferase. The use of Renilla luciferase in those circumstances would not be valid and an alternative way of normalization would be necessary. This review covers the factors that have been reported thus far as modulating the expression of Renilla luciferase from plasmid constructs. PMID:19788887

Intelligent tuning method of PID parameters based on iterative learning control for atomic force microscopy.

PubMed

Liu, Hui; Li, Yingzi; Zhang, Yingxu; Chen, Yifu; Song, Zihang; Wang, Zhenyu; Zhang, Suoxin; Qian, Jianqiang

2018-01-01

Proportional-integral-derivative (PID) parameters play a vital role in the imaging process of an atomic force microscope (AFM). Traditional parameter tuning methods require a lot of manpower and it is difficult to set PID parameters in unattended working environments. In this manuscript, an intelligent tuning method of PID parameters based on iterative learning control is proposed to self-adjust PID parameters of the AFM according to the sample topography. This method gets enough information about the output signals of PID controller and tracking error, which will be used to calculate the proper PID parameters, by repeated line scanning until convergence before normal scanning to learn the topography. Subsequently, the appropriate PID parameters are obtained by fitting method and then applied to the normal scanning process. The feasibility of the method is demonstrated by the convergence analysis. Simulations and experimental results indicate that the proposed method can intelligently tune PID parameters of the AFM for imaging different topographies and thus achieve good tracking performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Magnetic and electric control of multiferroic properties in monodomain crystals of BiFeO3

NASA Astrophysics Data System (ADS)

Tokunaga, Masashi

One of the important goals for multiferroics is to develop the non-volatile magnetic memories that can be controlled by electric fields with low power consumption. Among numbers of multiferroic materials, BiFeO3 has been the most extensively studied because of its substantial ferroelectric polarization and magnetic order up to above room temperature. Recent high field experiments on monodomain crystals of BiFeO3 revealed the existence of additional electric polarization normal to the three-fold rotational axis. This transverse component is coupled with the cycloidal magnetic domain, and hence, can be controlled by external magnetic fields. Application of electric fields normal to the trigonal axis modifies volume fraction of these multiferroic domains, which involves change in resistance of the sample, namely exhibits the bipolar resistive memory effect. In this talk, I will introduce the effects of magnetic and electric fields on magnetoelectric and structural properties observed in monodomain crystals of BiFeO3. This work was supported by JSPS Grant Number 16K05413 and by a research Grant from The Murata Science Foundation.

Statistical transformation and the interpretation of inpatient glucose control data from the intensive care unit.

PubMed

Saulnier, George E; Castro, Janna C; Cook, Curtiss B

2014-05-01

Glucose control can be problematic in critically ill patients. We evaluated the impact of statistical transformation on interpretation of intensive care unit inpatient glucose control data. Point-of-care blood glucose (POC-BG) data derived from patients in the intensive care unit for 2011 was obtained. Box-Cox transformation of POC-BG measurements was performed, and distribution of data was determined before and after transformation. Different data subsets were used to establish statistical upper and lower control limits. Exponentially weighted moving average (EWMA) control charts constructed from April, October, and November data determined whether out-of-control events could be identified differently in transformed versus nontransformed data. A total of 8679 POC-BG values were analyzed. POC-BG distributions in nontransformed data were skewed but approached normality after transformation. EWMA control charts revealed differences in projected detection of out-of-control events. In April, an out-of-control process resulting in the lower control limit being exceeded was identified at sample 116 in nontransformed data but not in transformed data. October transformed data detected an out-of-control process exceeding the upper control limit at sample 27 that was not detected in nontransformed data. Nontransformed November results remained in control, but transformation identified an out-of-control event less than 10 samples into the observation period. Using statistical methods to assess population-based glucose control in the intensive care unit could alter conclusions about the effectiveness of care processes for managing hyperglycemia. Further study is required to determine whether transformed versus nontransformed data change clinical decisions about the interpretation of care or intervention results. © 2014 Diabetes Technology Society.

Statistical Transformation and the Interpretation of Inpatient Glucose Control Data From the Intensive Care Unit

PubMed Central

Saulnier, George E.; Castro, Janna C.

2014-01-01

Glucose control can be problematic in critically ill patients. We evaluated the impact of statistical transformation on interpretation of intensive care unit inpatient glucose control data. Point-of-care blood glucose (POC-BG) data derived from patients in the intensive care unit for 2011 was obtained. Box–Cox transformation of POC-BG measurements was performed, and distribution of data was determined before and after transformation. Different data subsets were used to establish statistical upper and lower control limits. Exponentially weighted moving average (EWMA) control charts constructed from April, October, and November data determined whether out-of-control events could be identified differently in transformed versus nontransformed data. A total of 8679 POC-BG values were analyzed. POC-BG distributions in nontransformed data were skewed but approached normality after transformation. EWMA control charts revealed differences in projected detection of out-of-control events. In April, an out-of-control process resulting in the lower control limit being exceeded was identified at sample 116 in nontransformed data but not in transformed data. October transformed data detected an out-of-control process exceeding the upper control limit at sample 27 that was not detected in nontransformed data. Nontransformed November results remained in control, but transformation identified an out-of-control event less than 10 samples into the observation period. Using statistical methods to assess population-based glucose control in the intensive care unit could alter conclusions about the effectiveness of care processes for managing hyperglycemia. Further study is required to determine whether transformed versus nontransformed data change clinical decisions about the interpretation of care or intervention results. PMID:24876620

Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence.

PubMed

Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L; Liao, Duanping; Bixler, Edward O

2016-05-01

To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15-35Hz) range during sleep in an adolescent general population sample. A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. © 2016 Associated Professional Sleep Societies, LLC.

Effect of nebulized eucalyptus on contamination of microbial plaque of endotracheal tube in ventilated patients

PubMed Central

Amini, Nazanin; Rezaei, Korosh; Yazdannik, Ahmadreza

2016-01-01

Background: Formation of biofilm and bacterial colonization within the endotracheal tube (ETT) are significant sources of airway contamination and play a role in the development of ventilator-associated pneumonia (VAP). This study was conducted to examine the effect of nebulized eucalyptus (NE) on bacterial colonization of ETT biofilm. Materials and Methods: We performed a randomized clinical trial in three intensive care units (ICUs) of an educational hospital. Seventy intubated patients were selected and randomly divided into intervention (n = 35) and control (n = 35) groups. The intervention group received 4 ml (5%) of eucalyptus in 6 ml normal saline every 8 h. The placebo group received only 10 ml of normal saline in the same way. On extubation, the interior of the tube was immediately sampled using a sterile swab for standard microbiological analysis. Chi-square and Fisher's exact tests were used for statistical analysis in SPSS. P values less than 0.05 were considered statistically significant. Results: In both samples, Klebsiella pneumoniae and Acinetobacter baumannii were the most frequently isolated bacteria. In the control group, heavy colonization was greater than in the intervention group (P = 0.002). The frequency of isolation of K. pneumoniae in the intervention group was lower than in the control group (P < 0.001). However, there was no difference between the two groups in other isolated bacteria. Conclusions: NE can reduce microbial contamination of the endotracheal tube biofilm in ventilated patients. Moreover, K. pneumoniae was the most sensitive to NE. PMID:27095990

Personality assessment of children with attention deficit hyperactivity disorder.

PubMed

Lufi, D; Parish-Plass, J

1995-01-01

The present research was designed to assess several potentially important factors in the personality structure of a sample of children with attention deficit hyperactive disorder (ADHD) as compared to normal control children. Three questionnaires were administered to a group of 28 ADHD boys and to a control group of 83 boys: (1) The Locus of Control Scale for Children; (2) The Revised Children's Manifest Anxiety Scale; and (3) The Persistence Scale for Children. Results showed that the ADHD children had significantly higher external locus of control, were significantly less persistent, and reported an elevated level of "concentration/social worry" (an anxiety subscale). Such findings can help to clarify both the personality structure and the coping styles of the ADHD child.

Modeling of human operator dynamics in simple manual control utilizing time series analysis. [tracking (position)

NASA Technical Reports Server (NTRS)

Agarwal, G. C.; Osafo-Charles, F.; Oneill, W. D.; Gottlieb, G. L.

1982-01-01

Time series analysis is applied to model human operator dynamics in pursuit and compensatory tracking modes. The normalized residual criterion is used as a one-step analytical tool to encompass the processes of identification, estimation, and diagnostic checking. A parameter constraining technique is introduced to develop more reliable models of human operator dynamics. The human operator is adequately modeled by a second order dynamic system both in pursuit and compensatory tracking modes. In comparing the data sampling rates, 100 msec between samples is adequate and is shown to provide better results than 200 msec sampling. The residual power spectrum and eigenvalue analysis show that the human operator is not a generator of periodic characteristics.

Correlation between Na/K ratio and electron densities in blood samples of breast cancer patients.

PubMed

Topdağı, Ömer; Toker, Ozan; Bakırdere, Sezgin; Bursalıoğlu, Ertuğrul Osman; Öz, Ersoy; Eyecioğlu, Önder; Demir, Mustafa; İçelli, Orhan

2018-05-31

The main purpose of this study was to investigate the relationship between the electron densities and Na/K ratio which has important role in breast cancer disease. Determinations of sodium and potassium concentrations in blood samples performed with inductive coupled plasma-atomic emission spectrometry. Electron density values of blood samples were determined via ZXCOM. Statistical analyses were performed for electron densities and Na/K ratio including Kolmogorov-Smirnov normality tests, Spearman's rank correlation test and Mann-Whitney U test. It was found that the electron densities significantly differ between control and breast cancer groups. In addition, statistically significant positive correlation was found between the electron density and Na/K ratios in breast cancer group.

Presence of Bacteria in Spontaneous Achilles Tendon Ruptures.

PubMed

Rolf, Christer G; Fu, Sai-Chuen; Hopkins, Chelsea; Luan, Ju; Ip, Margaret; Yung, Shu-Hang; Friman, Göran; Qin, Ling; Chan, Kai-Ming

2017-07-01

The structural pathology of Achilles tendon (AT) ruptures resembles tendinopathy, but the causes remain unknown. Recently, a number of diseases were found to be attributed to bacterial infections, resulting in low-grade inflammation and progressive matrix disturbance. The authors speculate that spontaneous AT ruptures may also be influenced by the presence of bacteria. Bacteria are present in ruptured ATs but not in healthy tendons. Cross-sectional study; Level of evidence, 3. Patients with spontaneous AT ruptures and patients undergoing anterior cruciate ligament (ACL) reconstruction were recruited for this study. During AT surgical repair, excised tendinopathic tissue was collected, and healthy tendon samples were obtained as controls from hamstring tendon grafts used in ACL reconstruction. Half of every sample was reserved for DNA extraction and the other half for histology. Polymerase chain reaction (PCR) was conducted using 16S rRNA gene universal primers, and the PCR products were sequenced for the identification of bacterial species. A histological examination was performed to compare tendinopathic changes in the case and control samples. Five of 20 AT rupture samples were positive for the presence of bacterial DNA, while none of the 23 hamstring tendon samples were positive. Sterile operating and experimental conditions and tests on samples, controlling for harvesting and processing procedures, ruled out the chance of postoperative bacterial contamination. The species identified predominantly belonged to the Staphylococcus genus. AT rupture samples exhibited histopathological features characteristic of tendinopathy, and most healthy hamstring tendon samples displayed normal tendon features. There were no apparent differences in histopathology between the bacterial DNA-positive and bacterial DNA-negative AT rupture samples. The authors have demonstrated the presence of bacterial DNA in ruptured AT samples. It may suggest the potential involvement of bacteria in spontaneous AT ruptures.

Incubation temperature effects on physical characteristics of normal, dark, firm and dry, and halothane-carrier pork longissimus.

PubMed

McCaw, J; Ellis, M; Brewer, M S; McKeith, F K

1997-06-01

Pigs (n = 18) were selected to represent three different muscle conditions (six pigs per condition): normal: dark, firm, and dry; and halothane carrier. A 45-cm-long longissimus section was excised from each side of the carcass at 30 min postmortem and cut into six sections. Right side sections were assigned to the intermediate temperature incubation (23 degrees C), and left side sections were designated high temperature incubation (40 degrees C). Sections were randomly assigned to incubation times (0, 1, 2, 4, 6, or 8 h). The 0 h section from each incubation treatment was designated as a control and was placed directly into a 4 degree C cooler. Temperature and pH were evaluated on the control section and for each loin section a the end of the incubation time. Color (L*, a*, and b* values), percentage of purge loss, water-holding capacity, and drip loss were determined. Incubation treatment did not alter pH decline in dark, firm, and dry muscle; however, high temperature increased pH decline in normal and halothane carrier samples. Results suggest that there is a strong interaction between pH and temperature that affects pork quality attributes. High incubation temperature had a negative effect on most quality variables; however, muscle condition (normal or halothane carrier) had limited effects on muscle quality.

Treatment with Huisheng oral solution inhibits the development of pulmonary thromboembolism and metastasis in mice with Lewis lung carcinoma

PubMed Central

WANG, WEI; WANG, HONG; WANG, CHUN-MEI; GOU, SI; CHEN, ZHONG-HUA; GUO, JIE

2014-01-01

The aim of this study was to investigate whether Huisheng oral solution (HSOS) has an inhibitory effect on the development of pulmonary thrombosis and metastasis in mice with Lewis lung carcinoma (LLC), and to explore the possible mechanisms involved. A mouse model of LLC was developed, and model mice were divided into either a treatment group or a control group to undergo treatment with HSOS or normal saline. Normal mice treated with saline were used as normal controls. On day 25 after treatment, blood samples were drawn from the eyes of half the mice in each group to determine blood cell counts and plasma levels of D-Dimer and vascular endothelial growth factor (VEGF), while heart blood samples were collected from the remaining mice to measure the rate of thrombin-induced platelet aggregation. For all mice, pathological analyses of the cerebrum, lung, mesentery, femoral vein, external iliac vein and spleen were performed. Tumors were weighed to assess the impact of HSOS treatment on tumor growth, and the number of thrombi, metastatic nodules and neovessels in the tumor tissue were counted. In addition, 24 normal New Zealand rabbits were divided into two groups and treated with either HSOS or normal saline to determine the rates of ADP-, collagen- or thrombin-induced platelet aggregation. Compared with the model group, HSOS treatment decreased the incidence of pulmonary thromboembolism and metastasis, the number of metastatic nodules, the plasma levels of D-dimer and VEGF, the rate of collagen-induced platelet aggregation in rabbits and the numbers of leukocytes and tumor neovessels (P<0.05 for all). It increased the thymus and spleen coefficients and the number of platelets (P<0.05 for all), but had no significant effect on thrombin-induced platelet aggregation in mice and rabbits, ADP-induced platelet aggregation in rabbits, or the number of red blood cells. The reduced rate of tumor growth was 9.7% in mice treated with HSOS. HSOS treatment effectively reduced the development of pulmonary thromboembolism and metastasis in mice bearing LLC via mechanisms possibly associated with ameliorating a blood hypercoagulable state, decreasing tumor angiogenesis and enhancing immunity. PMID:24348827

Distinct expression patterns of the E3 ligase SIAH-1 and its partner Kid/KIF22 in normal tissues and in the breast tumoral processes.

PubMed

Bruzzoni-Giovanelli, Heriberto; Fernandez, Plinio; Veiga, Lucía; Podgorniak, Marie-Pierre; Powell, Darren J; Candeias, Marco M; Mourah, Samia; Calvo, Fabien; Marín, Mónica

2010-02-09

SIAH proteins are the human members of an highly conserved family of E3 ubiquitin ligases. Several data suggest that SIAH proteins may have a role in tumor suppression and apoptosis. Previously, we reported that SIAH-1 induces the degradation of Kid (KIF22), a chromokinesin protein implicated in the normal progression of mitosis and meiosis, by the ubiquitin proteasome pathway. In human breast cancer cells stably transfected with SIAH-1, Kid/KIF22 protein level was markedly reduced whereas, the Kid/KIF22 mRNA level was increased. This interaction has been further elucidated through analyzing SIAH and Kid/KIF22 expression in both paired normal and tumor tissues and cell lines. It was observed that SIAH-1 protein is widely expressed in different normal tissues, and in cells lines but showing some differences in western blotting profiles. Immunofluorescence microscopy shows that the intracellular distribution of SIAH-1 and Kid/KIF22 appears to be modified in human tumor tissues compared to normal controls. When mRNA expression of SIAH-1 and Kid/KIF22 was analyzed by real-time PCR in normal and cancer breast tissues from the same patient, a large variation in the number of mRNA copies was detected between the different samples. In most cases, SIAH-1 mRNA is decreased in tumor tissues compared to their normal counterparts. Interestingly, in all breast tumor tissues analyzed, variations in the Kid/KIF22 mRNA levels mirrored those seen with SIAH-1 mRNAs. This concerted variation of SIAH-1 and Kid/KIF22 messengers suggests the existence of an additional level of control than the previously described protein-protein interaction and protein stability regulation. Our observations also underline the need to re-evaluate the results of gene expression obtained by qRT-PCR and relate it to the protein expression and cellular localization when matched normal and tumoral tissues are analyzed.

Porosity dependence of terahertz emission of porous silicon investigated using reflection geometry terahertz time-domain spectroscopy

NASA Astrophysics Data System (ADS)

Mabilangan, Arvin I.; Lopez, Lorenzo P.; Faustino, Maria Angela B.; Muldera, Joselito E.; Cabello, Neil Irvin F.; Estacio, Elmer S.; Salvador, Arnel A.; Somintac, Armando S.

2016-12-01

Porosity dependent terahertz emission of porous silicon (PSi) was studied. The PSi samples were fabricated via electrochemical etching of boron-doped (100) silicon in a solution containing 48% hydrofluoric acid, deionized water and absolute ethanol in a 1:3:4 volumetric ratio. The porosity was controlled by varying the supplied anodic current for each sample. The samples were then optically characterized via normal incidence reflectance spectroscopy to obtain values for their respective refractive indices and porosities. Absorbance of each sample was also computed using the data from its respective reflectance spectrum. Terahertz emission of each sample was acquired through terahertz - time domain spectroscopy. A decreasing trend in the THz signal power was observed as the porosity of each PSi was increased. This was caused by the decrease in the absorption strength as the silicon crystallite size in the PSi was minimized.

Further search for selectivity of positron annihilation in the skin and cancerous systems

NASA Astrophysics Data System (ADS)

Liu, Guang; Chen, Hongmin; Chakka, Lakshmi; Cheng, Mei-Ling; Gadzia, Joseph E.; Suzuki, R.; Ohdaira, T.; Oshima, N.; Jean, Y. C.

2008-10-01

Positronium annihilation lifetime (PAL) spectroscopy and Doppler broadening energy spectra (DBES) have been used to search for selectivity and sensitivity for cancerous skin samples with and without cancer. This study is to further explore the melanoma cancerous system and other different types of skin samples. We found that the S parameter in melanoma skin samples cut at 0.39 mm depth from the same patient's skin is smaller than near the skin surface. However in 10 melanoma samples from different patients, the S parameters vary significantly. Similarly, among 10 normal skin samples without cancer, the S parameters also vary largely among different patients. To understand the sensitivity of PAS as a tool to detect cancer formation at the early stage, we propose a controlled and systematic study of in vivo experiments using UV-induced cancer skin from living animals.

New S control chart using skewness correction method for monitoring process dispersion of skewed distributions

NASA Astrophysics Data System (ADS)

Atta, Abdu; Yahaya, Sharipah; Zain, Zakiyah; Ahmed, Zalikha

2017-11-01

Control chart is established as one of the most powerful tools in Statistical Process Control (SPC) and is widely used in industries. The conventional control charts rely on normality assumption, which is not always the case for industrial data. This paper proposes a new S control chart for monitoring process dispersion using skewness correction method for skewed distributions, named as SC-S control chart. Its performance in terms of false alarm rate is compared with various existing control charts for monitoring process dispersion, such as scaled weighted variance S chart (SWV-S); skewness correction R chart (SC-R); weighted variance R chart (WV-R); weighted variance S chart (WV-S); and standard S chart (STD-S). Comparison with exact S control chart with regards to the probability of out-of-control detections is also accomplished. The Weibull and gamma distributions adopted in this study are assessed along with the normal distribution. Simulation study shows that the proposed SC-S control chart provides good performance of in-control probabilities (Type I error) in almost all the skewness levels and sample sizes, n. In the case of probability of detection shift the proposed SC-S chart is closer to the exact S control chart than the existing charts for skewed distributions, except for the SC-R control chart. In general, the performance of the proposed SC-S control chart is better than all the existing control charts for monitoring process dispersion in the cases of Type I error and probability of detection shift.

Longitudinal Urinary Protein Variability in Participants of the Space Flight Simulation Program.

PubMed

Khristenko, Nina A; Larina, Irina M; Domon, Bruno

2016-01-04

Urine is a valuable material for the diagnosis of renal pathologies and to investigate the effects of their treatment. However, the variability in protein abundance in the context of normal homeostasis remains a major challenge in urinary proteomics. In this study, the analysis of urine samples collected from healthy individuals, rigorously selected to take part in the MARS-500 spaceflight simulation program, provided a unique opportunity to estimate normal concentration ranges for an extended set of urinary proteins. In order to systematically identify and reliably quantify peptides/proteins across a large sample cohort, a targeted mass spectrometry method was developed. The performance of parallel reaction monitoring (PRM) analyses was improved by implementing tight control of the monitoring windows during LC-MS/MS runs, using an on-the-fly correction routine. Matching the experimentally obtained MS/MS spectra with reference fragmentation patterns allowed dependable peptide identifications to be made. Following optimization and evaluation, the targeted method was applied to investigate protein abundance variability in 56 urine samples, collected from six volunteers participating in the MARS-500 program. The intrapersonal protein concentration ranges were determined for each individual and showed unexpectedly high abundance variation, with an average difference of 1 order of magnitude.

Phenotypic regional fMRI activation patterns during memory encoding in MCI and AD

PubMed Central

Browndyke, Jeffrey N.; Giovanello, Kelly; Petrella, Jeffrey; Hayden, Kathleen; Chiba-Falek, Ornit; Tucker, Karen A.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2014-01-01

Background Reliable blood-oxygen-level-dependent (BOLD) fMRI phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. Methods A series of random-effects, activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based upon a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. Results ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal controls across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe (MTL), specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal controls. Conclusions ALE consistencies broadly support the presence of frontal compensatory activity, MTL activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective pre-disease condition. Taken together these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD. PMID:22841497

Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma.

PubMed

Wang, Ting; Liu, Mei; Zheng, Su-Jun; Bian, Dan-Dan; Zhang, Jin-Yan; Yao, Jia; Zheng, Qing-Fen; Shi, A-Meng; Li, Wen-Han; Li, Lu; Chen, Yu; Wang, Jin-Hai; Duan, Zhong-Ping; Dong, Lei

2017-05-21

To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls ( P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.

Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma

PubMed Central

Wang, Ting; Liu, Mei; Zheng, Su-Jun; Bian, Dan-Dan; Zhang, Jin-Yan; Yao, Jia; Zheng, Qing-Fen; Shi, A-Meng; Li, Wen-Han; Li, Lu; Chen, Yu; Wang, Jin-Hai; Duan, Zhong-Ping; Dong, Lei

2017-01-01

AIM To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). METHODS Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. RESULTS The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls (P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. CONCLUSION Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC. PMID:28596685

A sliding plate microgap rheometer for the simultaneous measurement of shear stress and first normal stress difference

NASA Astrophysics Data System (ADS)

Baik, Seung Jae; Moldenaers, Paula; Clasen, Christian

2011-03-01

A new generation of the "flexure-based microgap rheometer" (the N-FMR) has been developed which is also capable of measuring, in addition to the shear stress, the first normal stress difference of micrometer thin fluid films. This microgap rheometer with a translation system based on compound spring flexures measures the rheological properties of microliter samples of complex fluids confined in a plane couette configuration with gap distances of h = 1-400 μm up to shear rates of dot γ = 3000 s-1. Feed back loop controlled precise positioning of the shearing surfaces with response times <1 ms enables to control the parallelism within 1.5 μrad and to maintain the gap distance within 20 nm. This precise gap control minimizes squeeze flow effects and allows therefore to measure the first normal stress difference N1 of the thin film down to a micrometer gap distance, with a lower limit of {{N_1 }/{dot γ }} = 9.375 × 10^{ - 11} {η/{h^2 }} that depends on the shear viscosity η and the squared inverse gap. Structural development of complex fluids in the confinement can be visualized by using a beam splitter on the shearing surface and a long working distance microscope. In summary, this new instrument allows to investigate the confinement dependent rheological and morphological evolution of micrometer thin films.

Raman spectroscopy analysis of differences in composition of spent culture media of in vitro cultured preimplantation embryos isolated from normal and fat mice dams.

PubMed

Fabian, Dušan; Kačmarová, Martina; Kubandová, Janka; Čikoš, Štefan; Koppel, Juraj

2016-06-01

The aim of the present study was to compare overall patterns of metabolic activity of in vitro cultured preimplantation embryos isolated from normal and fat mice dams by means of non-invasive profiling of spent culture media using Raman spectroscopy. To produce females with two different types of body condition (normal and fat), a previously established two-generation model was used, based on overfeeding of experimental mice during prenatal and early postnatal development. Embryos were isolated from spontaneously ovulating and naturally fertilized dams at the 2-cell stage of development and cultured to the blastocyst stage in synthetic oviductal medium KSOMaa. Embryos from fat mice (displaying significantly elevated body weight and fat) showed similar developmental capabilities in vitro as embryos isolated from normal control dams (displaying physiological body weight and fat). The results show that alterations in the composition of culture medium caused by the presence of developing mouse preimplantation embryos can be detected using Raman spectroscopy. Metabolic activity of embryos was reflected in evident changes in numerous band intensities in the 1620-1690cm(-1) (amide I) region and in the 1020-1140cm(-1) region of the Raman spectrum for KSOMaa. Moreover, multivariate analysis of spectral data proved that the composition of proteins and other organic compounds in spent samples obtained after the culture of embryos isolated from fat dams was different from that in spent samples obtained after the culture of embryos from control dams. This study demonstrates that metabolic activity of cultured preimplantation embryos might depend on the body condition of their donors. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Long term imaging of living brain cancer cells

NASA Astrophysics Data System (ADS)

Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

2018-02-01

QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

Selection of housekeeping genes for gene expression studies in the adult rat submandibular gland under normal, inflamed, atrophic and regenerative states

PubMed Central

Silver, Nicholas; Cotroneo, Emanuele; Proctor, Gordon; Osailan, Samira; Paterson, Katherine L; Carpenter, Guy H

2008-01-01

Background Real-time PCR is a reliable tool with which to measure mRNA transcripts, and provides valuable information on gene expression profiles. Endogenous controls such as housekeeping genes are used to normalise mRNA levels between samples for sensitive comparisons of mRNA transcription. Selection of the most stable control gene(s) is therefore critical for the reliable interpretation of gene expression data. For the purpose of this study, 7 commonly used housekeeping genes were investigated in salivary submandibular glands under normal, inflamed, atrophic and regenerative states. Results The program NormFinder identified the suitability of HPRT to use as a single gene for normalisation within the normal, inflamed and regenerative states, and GAPDH in the atrophic state. For normalisation to multiple housekeeping genes, for each individual state, the optimal number of housekeeping genes as given by geNorm was: ACTB/UBC in the normal, ACTB/YWHAZ in the inflamed, ACTB/HPRT in the atrophic and ACTB/GAPDH in the regenerative state. The most stable housekeeping gene identified between states (compared to normal) was UBC. However, ACTB, identified as one of the most stably expressed genes within states, was found to be one of the most variable between states. Furthermore we demonstrated that normalising between states to ACTB, rather than UBC, introduced an approximately 3 fold magnitude of error. Conclusion Using NormFinder, our studies demonstrated the suitability of HPRT to use as a single gene for normalisation within the normal, inflamed and regenerative groups and GAPDH in the atrophic group. However, if normalising to multiple housekeeping genes, we recommend normalising to those identified by geNorm. For normalisation across the physiological states, we recommend the use of UBC. PMID:18637167

Sample size determination for logistic regression on a logit-normal distribution.

PubMed

Kim, Seongho; Heath, Elisabeth; Heilbrun, Lance

2017-06-01

Although the sample size for simple logistic regression can be readily determined using currently available methods, the sample size calculation for multiple logistic regression requires some additional information, such as the coefficient of determination ([Formula: see text]) of a covariate of interest with other covariates, which is often unavailable in practice. The response variable of logistic regression follows a logit-normal distribution which can be generated from a logistic transformation of a normal distribution. Using this property of logistic regression, we propose new methods of determining the sample size for simple and multiple logistic regressions using a normal transformation of outcome measures. Simulation studies and a motivating example show several advantages of the proposed methods over the existing methods: (i) no need for [Formula: see text] for multiple logistic regression, (ii) available interim or group-sequential designs, and (iii) much smaller required sample size.

The classification of secondary colorectal liver cancer in human biopsy samples using angular dispersive x-ray diffraction and multivariate analysis

NASA Astrophysics Data System (ADS)

Theodorakou, Chrysoula; Farquharson, Michael J.

2009-08-01

The motivation behind this study is to assess whether angular dispersive x-ray diffraction (ADXRD) data, processed using multivariate analysis techniques, can be used for classifying secondary colorectal liver cancer tissue and normal surrounding liver tissue in human liver biopsy samples. The ADXRD profiles from a total of 60 samples of normal liver tissue and colorectal liver metastases were measured using a synchrotron radiation source. The data were analysed for 56 samples using nonlinear peak-fitting software. Four peaks were fitted to all of the ADXRD profiles, and the amplitude, area, amplitude and area ratios for three of the four peaks were calculated and used for the statistical and multivariate analysis. The statistical analysis showed that there are significant differences between all the peak-fitting parameters and ratios between the normal and the diseased tissue groups. The technique of soft independent modelling of class analogy (SIMCA) was used to classify normal liver tissue and colorectal liver metastases resulting in 67% of the normal tissue samples and 60% of the secondary colorectal liver tissue samples being classified correctly. This study has shown that the ADXRD data of normal and secondary colorectal liver cancer are statistically different and x-ray diffraction data analysed using multivariate analysis have the potential to be used as a method of tissue classification.

Urinary mRNA for the Diagnosis of Renal Allograft Rejection: The Issue of Normalization.

PubMed

Galichon, P; Amrouche, L; Hertig, A; Brocheriou, I; Rabant, M; Xu-Dubois, Y-C; Ouali, N; Dahan, K; Morin, L; Terzi, F; Rondeau, E; Anglicheau, D

2016-10-01

Urinary messenger RNA (mRNA) quantification is a promising method for noninvasive diagnosis of renal allograft rejection (AR), but the quantification of mRNAs in urine remains challenging due to degradation. RNA normalization may be warranted to overcome these issues, but the strategies of gene normalization have been poorly evaluated. Herein, we address this issue in a case-control study of 108 urine samples collected at time of allograft biopsy in kidney recipients with (n = 52) or without (n = 56) AR by comparing the diagnostic value of IP-10 and CD3ε mRNAs-two biomarkers of AR-after normalization by the total amount of RNA, normalization by one of the three widely used reference RNAs-18S, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Hypoxanthine-guanine phosphoribosyltransferase (HPRT)-or normalization using uroplakin 1A (UPK) mRNA as a possible urine-specific reference mRNA. Our results show that normalization based on the total quantity of RNA is not substantially improved by additional normalization and may even be worsened with some classical reference genes that are overexpressed during rejection. However, considering that normalization by a reference gene is necessary to ensure polymerase chain reaction (PCR) quality and reproducibility and to suppress the effect of RNA degradation, we suggest that GAPDH and UPK1A are preferable to 18S or HPRT RNA. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Interactions of speaking condition and auditory feedback on vowel production in postlingually deaf adults with cochlear implants.

PubMed

Ménard, Lucie; Polak, Marek; Denny, Margaret; Burton, Ellen; Lane, Harlan; Matthies, Melanie L; Marrone, Nicole; Perkell, Joseph S; Tiede, Mark; Vick, Jennell

2007-06-01

This study investigates the effects of speaking condition and auditory feedback on vowel production by postlingually deafened adults. Thirteen cochlear implant users produced repetitions of nine American English vowels prior to implantation, and at one month and one year after implantation. There were three speaking conditions (clear, normal, and fast), and two feedback conditions after implantation (implant processor turned on and off). Ten normal-hearing controls were also recorded once. Vowel contrasts in the formant space (expressed in mels) were larger in the clear than in the fast condition, both for controls and for implant users at all three time samples. Implant users also produced differences in duration between clear and fast conditions that were in the range of those obtained from the controls. In agreement with prior work, the implant users had contrast values lower than did the controls. The implant users' contrasts were larger with hearing on than off and improved from one month to one year postimplant. Because the controls and implant users responded similarly to a change in speaking condition, it is inferred that auditory feedback, although demonstrably important for maintaining normative values of vowel contrasts, is not needed to maintain the distinctiveness of those contrasts in different speaking conditions.

Certified Normal: Alzheimer’s Disease Biomarkers and Normative Estimates of Cognitive Functioning

PubMed Central

Hassenstab, Jason; Chasse, Rachel; Grabow, Perri; Benzinger, Tammie L.S.; Fagan, Anne M.; Xiong, Chengjie; Jasielec, Mateusz; Grant, Elizabeth; Morris, John C.

2016-01-01

Normative samples drawn from older populations may unintentionally include individuals with preclinical Alzheimer’s disease (AD) pathology, resulting in reduced means, increased variability, and overestimation of age-effects on cognitive performance. 264 cognitively normal (CDR=0) older adults were classified as biomarker-negative (“Robust Normal,” n=177) or biomarker-positive (“Preclinical Alzheimer’s Disease” (PCAD), n=87) based on amyloid imaging, cerebrospinal fluid biomarkers, and hippocampal volumes. PCAD participants performed worse than Robust Normals on nearly all cognitive measures. Removing PCAD participants from the normative sample yielded higher means and less variability on episodic memory, visuospatial ability, and executive functioning measures. These results were more pronounced in participants aged 75 and older. Notably, removing PCAD participants from the sample significantly reduced age effects across all cognitive domains. Applying norms from the Robust Normal sample to a separate cohort did not improve CDR classification when using standard deviation cutoff scores. Overall, removing individuals with biomarker evidence of preclinical AD improves normative sample quality and substantially reduces age-effects on cognitive performance, but provides no substantive benefit for diagnostic classifications. PMID:27255812

Development and validation of a UPLC-MS/MS method for the simultaneous determination of paritaprevir and ritonavir in rat liver.

PubMed

Ocque, Andrew J; Hagler, Colleen E; Difrancesco, Robin; Woolwine-Cunningham, Yvonne; Bednasz, Cindy J; Morse, Gene D; Talal, Andrew H

2016-07-01

Determination of paritaprevir and ritonavir in rat liver tissue samples. We successfully validated a UPLC-MS/MS method to measure paritaprevir and ritonavir in rat liver using deuterated internal standards (d8-paritapervir and d6-ritonavir). The method is linear from 20 to 20,000 and 5 to 10,000 pg on column for paritaprevir and ritonavir, respectively, and is normalized per milligram tissue. Interday and intraday variability ranged from 0.591 to 5.33% and accuracy ranged from -6.68 to 10.1% for quality control samples. The method was then applied to the measurement of paritaprevir and ritonavir in rat liver tissue samples from a pilot study. The validated method is suitable for measurement of paritaprevir and ritonavir within rat liver tissue samples for PK studies.

Circulating heavy IgM in IgM nephropathy.

PubMed

Disciullo, S O; Abuelo, J G; Moalli, K; Pezzullo, J C

1988-09-01

IgM nephropathy (IgMN) causes nephrotic syndrome and is characterized by IgM mesangial deposits. It is speculated that these deposits are derived from circulating IgM aggregates or immune complexes, either of which would have a molecular weight heavier than that of normal IgM. To test this hypothesis the sera of 11 patients with IgMN, five patients with nephrotic syndrome of other etiologies, and 13 normal controls were analysed for such heavy IgM. The serum samples were passed over a Biogel A5M molecular sieve column and the fractions were tested for IgM concentration by enzyme linked immunosorbent assay (ELISA). The column effluent from the void volume to the IgM peak was divided into four equal regions, and the average IgM concentrations in each region were compared. The IgMN group had significantly higher IgM concentrations than normal controls in the heaviest region (0.81 +/- 0.84 vs. 0.32 +/- 0.17 micrograms/ml; P = 0.01) and in the lightest region (95.8 +/- 59.5 vs. 46.3 +/- 41.2 micrograms/ml; P = 0.02). Although the IgMN group appeared to have about double the IgM levels of the nephrotic control group in all four regions, this was only significant in the lightest (19S) region. In serum samples from two IgMN patient methods known to break antigen antibody bonds eliminated the heavy IgM; in one case we used gel filtration in potassium thiocyanate and in another ultracentrifugation at pH 2.8. In addition, the heavy IgM in this second patient exhibited complement fixation activity in a sandwich ELISA for IgM-C3 complexes. We conclude that IgMN patients have circulating heavy IgM, which by preliminary studies probably consists of complement fixing IgM immune complexes.

DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants.

PubMed

Gao, Yang; Widschwendter, Martin; Teschendorff, Andrew E

2018-05-04

Normal tissue at risk of neoplastic transformation is characterized by somatic mutations, copy-number variation and DNA methylation changes. It is unclear however, which type of alteration may be more informative of cancer risk. We analyzed genome-wide DNA methylation and copy-number calls from the same DNA assay in a cohort of healthy breast samples and age-matched normal samples collected adjacent to breast cancer. Using statistical methods to adjust for cell type heterogeneity, we show that DNA methylation changes can discriminate normal-adjacent from normal samples better than somatic copy-number variants. We validate this important finding in an independent dataset. These results suggest that DNA methylation alterations in the normal cell of origin may offer better cancer risk prediction and early detection markers than copy-number changes. Copyright © 2018. Published by Elsevier B.V.

The forensiX evidence collection tube and its impact on DNA preservation and recovery.

PubMed

Garvin, Alex M; Holzinger, Ralf; Berner, Florian; Krebs, Walter; Hostettler, Bernhard; Lardi, Elges; Hertli, Christian; Quartermaine, Roy; Stamm, Christoph

2013-01-01

Biological samples are vulnerable to degradation from the time they are collected until they are analysed at the laboratory. Biological contaminants, such as bacteria, fungi, and enzymes, as well as environmental factors, such as sunlight, heat, and humidity, can increase the rate of DNA degradation. Currently, DNA samples are normally dried or frozen to limit their degradation prior to their arrival at the laboratory. In this study, the effect of the sample drying rate on DNA preservation was investigated, as well as a comparison between drying and freezing methods. The drying performances of two commercially available DNA collection tools (swab and drying tube) with different drying rates were evaluated. The swabs were used to collect human saliva, placed into the drying tubes, and stored in a controlled environment at 25°C and 60% relative humidity, or frozen at -20°C, for 2 weeks. Swabs that were stored in fast sample drying tubes yielded 95% recoverable DNA, whereas swabs stored in tubes with slower sample drying rates yielded only 12% recoverable DNA; saliva stored in a microtube at -20°C was used as a control. Thus, DNA sampling tools that offer rapid drying can significantly improve the preservation of DNA collected on a swab, increasing the quantity of DNA available for subsequent analysis.

Job strain and male fertility.

PubMed

Hjollund, Niels Henrik I; Bonde, Jens Peter E; Henriksen, Tine Brink; Giwercman, Aleksander; Olsen, Jørn

2004-01-01

Job strain, defined as high job demands and low job control, has not previously been explored as a possible determinant of male fertility. We collected prospective data on job strain among men, and describe the associations with semen quality and probability of conceiving a clinical pregnancy during a menstrual cycle. Danish couples (N = 399) who were trying to become pregnant for the first time were followed for up to 6 menstrual periods. All men collected semen samples, and a blood sample was drawn from both partners. Job demand and job control were measured by a self-administered questionnaire at entry, and in each cycle the participants recorded changes in job control or job demand during the previous 30 days. In adjusted analyses, no associations were found between any semen characteristic or sexual hormones and any job strain variable. The odds for pregnancy were not associated with job strain. Psychologic job strain encountered in normal jobs in Denmark does not seem to affect male reproductive function.

Infrared trace element detection system

DOEpatents

Bien, F.; Bernstein, L.S.; Matthew, M.W.

1988-11-15

An infrared trace element detection system includes an optical cell into which the sample fluid to be examined is introduced and removed. Also introduced into the optical cell is a sample beam of infrared radiation in a first wavelength band which is significantly absorbed by the trace element and a second wavelength band which is not significantly absorbed by the trace element for passage through the optical cell through the sample fluid. The output intensities of the sample beam of radiation are selectively detected in the first and second wavelength bands. The intensities of a reference beam of the radiation are similarly detected in the first and second wavelength bands. The sensed output intensity of the sample beam in one of the first and second wavelength bands is normalized with respect to the other and similarly, the intensity of the reference beam of radiation in one of the first and second wavelength bands is normalized with respect to the other. The normalized sample beam intensity and normalized reference beam intensity are then compared to provide a signal from which the amount of trace element in the sample fluid can be determined. 11 figs.

Infrared trace element detection system

DOEpatents

Bien, Fritz; Bernstein, Lawrence S.; Matthew, Michael W.

1988-01-01

An infrared trace element detection system including an optical cell into which the sample fluid to be examined is introduced and removed. Also introduced into the optical cell is a sample beam of infrared radiation in a first wavelength band which is significantly absorbed by the trace element and a second wavelength band which is not significantly absorbed by the trace element for passage through the optical cell through the sample fluid. The output intensities of the sample beam of radiation are selectively detected in the first and second wavelength bands. The intensities of a reference beam of the radiation are similarly detected in the first and second wavelength bands. The sensed output intensity of the sample beam in one of the first and second wavelength bands is normalized with respect to the other and similarly, the intensity of the reference beam of radiation in one of the first and second wavelength bands is normalized with respect to the other. The normalized sample beam intensity and normalized reference beam intensity are then compared to provide a signal from which the amount of trace element in the sample fluid can be determined.

Chemosterilization of the sea lamprey (Petromyzon marinus)

USGS Publications Warehouse

Hanson, Lee H.; Manion, Patrick J.

1978-01-01

The chemical, P,P-bis(1-aziridinyl)-N-methylphosphinothioic amide (bisazir), was found in laboratory studies to be an effective sterilant for both sexes of adult sea lampreys (Petromyzon marinus) when given intraperitoneally at a dosage of 100 mg per kilogram of body weight. A total of 300 normal spawning-run sea lampreys and 300 injected with bisazir were released into the Big Garlic River, Marquette County, Michigan, (a small stream divided into five sections by natural barriers), to determine the effect of bisazir on the nesting and spawning behavior of the adults and on the production of larvae. The lampreys constructed and spawned in 95 nests. Sterile adults showed no abnormal nest building or spawning behavior. Sterile males competed effectively with normal males for females. Egg samples taken from nests indicated that eggs in nests where sterile males spawned with sterile or normal females did not hatch, although some embryonic development occurred. Extensive surveys with electric shockers produced no larvae in stream sections where sterile males spawned, but yielded numerous larvae in sections where normal males spawned with normal females. These findings suggest that the release of sterile males may be an effective tool in an integrated approach to control of sea lampreys in the Great Lakes.

Pilot Study: The Role of the Hemispheric Lateralization in Mental Disorders by Use of the Limb (Eye, Hand, Foot) Dominance.

PubMed

Goodarzi, Naser; Dabbaghi, Parviz; Valipour, Habib; Vafadari, Behnam

2015-04-01

Based on the previous studies, we know that the hemispheric lateralization defects, increase the probability of psychological disorders. We also know that dominant limb is controlled by dominant hemisphere and limb preference is used as an indicator for hemisphere dominance. In this study we attempted to explore the hemispheric dominance by the use of three limbs (hand, foot and eye). We performed this survey on two samples, psychiatric patients compared with normal population. For this purpose, knowing that the organ dominance is stabilized in adolescence, and age has no effect on the people above 15, we used 48 high school girls and 65 boys as the final samples of normal population. The patient group included 57 male and 26 female who were chronic psychiatric patients. The result shows that left-eye dominance is more in patients than the normal group (P=0.000) but the handedness and footedness differences are not significance. In psychotic, bipolar and depressive disorders, eye dominance had significant difference (P=0.018). But this is not true about hand and foot dominance. Our findings proved that generally in psychiatric patients, left-eye dominance is more common, left-eye dominance is also more in psychotic and depressive disorders. It is less common in bipolar disorders.

Analysis of polymorphisms in milk proteins from cloned and sexually reproduced goats.

PubMed

Xing, H; Shao, B; Gu, Y Y; Yuan, Y G; Zhang, T; Zang, J; Cheng, Y

2015-12-08

This study evaluates the relationship between the genotype and milk protein components in goats. Milk samples were collected from cloned goats and normal white goats during different postpartum (or abortion) phases. Two cloned goats, originated from the same somatic line of goat mammary gland epithelial cells, and three sexually reproduced normal white goats with no genetic relationships were used as the control. The goats were phylogenetically analyzed by polymerase chain reaction-restriction fragment length polymorphism. The milk protein components were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results indicated that despite the genetic fingerprints being identical, the milk protein composition differed between the two cloned goats. The casein content of cloned goat C-50 was significantly higher than that of cloned goat C-4. Conversely, although the genetic fingerprints of the normal white goats N-1, N-2, and N-3 were not identical, the milk protein profiles did not differ significantly in their milk samples (obtained on postpartum day 15, 20, 25, 30, and 150). These results indicated an association between milk protein phenotypes and genetic polymorphisms, epigenetic regulation, and/or non-chromosomal factors. This study extends the knowledge of goat milk protein polymorphisms, and provides new strategies for the breeding of high milk-yielding goats.

Towards hyperpolarized 13C-succinate imaging of brain cancer

PubMed Central

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2009-01-01

We describe a novel 13C enriched precursor molecule, sodium 1-13C acetylenedicarboxylate, which after hydrogenation by PASADE-NA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1-13C-glutamate, 5-13C-glutamate, 1-13C-glutamine and 5-13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood–brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images. PMID:17303454

Towards hyperpolarized 13C-succinate imaging of brain cancer

NASA Astrophysics Data System (ADS)

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2007-05-01

We describe a novel 13C enriched precursor molecule, sodium 1- 13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1- 13C-glutamate, 5- 13C-glutamate, 1- 13C-glutamine and 5- 13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.

Cognitive Vulnerability in Patients with Generalized Anxiety Disorder, Dysthymic Disorder and Normal Individuals.

PubMed

Al-Ghorabaie, Fateme Moin; Noferesti, Azam; Fadaee, Mahdi; Ganji, Nima

2016-08-01

The purpose of this study was to assess cognitive vulnerability and response style in clinical and normal individuals. A sample of 90 individuals was selected for each of the 3 groups of Generalized Anxiety disorder, Dysthymic disorder and normal individuals. They completed MCQ and RSQ. Results analyzed by MANOVA and post hoc showed significant differences among groups. Dysthymic group and GAD reported higher scores on cognitive confidence compared to the normal group. Individuals with GAD showed highly negative beliefs about need to control thought, compared to the other groups, but in cognitive self-consciousness they have no differences with the normal group. In regard to uncontrollability, danger and positive beliefs, GAD group had higher levels than the other groups. Although normal and GAD group didn't show any significant differences in response style, there was a significant difference between Dysthymic group and other groups in all response styles.  Beliefs and meta-cognitive strategies can be distinguished between clinical and non clinical individuals. Also, findings support the Self-Regulatory Executive Function model. ary committee was effective in recognizing, designing and implementing tailored interventions for reduction of medication errors. A systematic approach is urgently needed to decrease organizational susceptibility to errors, through providing required resources to monitor, analyze and implement effective interventions.

Novel strategies of Raman imaging for brain tumor research.

PubMed

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-10-17

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real-time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I 2930 /I 2845 at 2930 and 2845 cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number N I for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (N I =0) and oleic acid (N I =87). Most low grade tumors have N I similar to that of OA. The iodine number for arachidonic acid (AA) (N I =334) is much higher than those observed for all studied samples.

Novel strategies of Raman imaging for brain tumor research

PubMed Central

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-01-01

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real–time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm-1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number NI for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (NI=0) and oleic acid (NI=87). Most low grade tumors have NI similar to that of OA. The iodine number for arachidonic acid (AA) (NI=334) is much higher than those observed for all studied samples. PMID:29156720

Screening of pesticide residues in soil and water samples from agricultural settings

PubMed Central

Akogbéto, Martin C; Djouaka, Rousseau F; Kindé-Gazard, Dorothée A

2006-01-01

Background The role of agricultural practices in the selection of insecticide resistance in malaria vectors has so far been hypothesized without clear evidence. Many mosquito species, Anopheles gambiae in particular, lay their eggs in breeding sites located around agricultural settings. There is a probability that, as a result of farming activities, insecticide residues may be found in soil and water, where they exercise a selection pressure on the larval stage of various populations of mosquitoes. To confirm this hypothesis, a study was conducted in the Republic of Benin to assess the environmental hazards which can be generated from massive use of pesticides in agricultural settings. Methods Lacking an HPLC machine for direct quantification of insecticide residues in samples, this investigation was performed using indirect bioassays focussed on the study of factors inhibiting the normal growth of mosquito larvae in breeding sites. The speed of development was monitored as well as the yield of rearing An. gambiae larvae in breeding sites reconstituted with water and soil samples collected in agricultural areas known to be under pesticide pressure. Two strains of An. gambiae were used in this indirect bioassay: the pyrethroid-susceptible Kisumu strain and the resistant Ladji strain. The key approach in this methodology is based on comparison of the growth of larvae in test and in control breeding sites, the test samples having been collected from two vegetable farms. Results Results obtained clearly show the presence of inhibiting factors on test samples. A normal growth of larvae was observed in control samples. In breeding sites simulated by using a few grams of soil samples from the two vegetable farms under constant insecticide treatments (test samples), a poor hatching rate of Anopheles eggs coupled with a retarded growth of larvae and a low yield of adult mosquitoes from hatched eggs, was noticed. Conclusion Toxic factors inhibiting the hatching of anopheles eggs and the growth of larvae are probably pesticide residues from agricultural practices. Samples used during this indirect assay have been stored in the laboratory and will be analysed with HPLC techniques to confirm hypothesis of this study and to identify the various end products found in soil and water samples from agricultural settings under pesticide pressure. PMID:16563153

Typical aqueous rare earth element behavior in co-produced Brines, Wyoming

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

Nye, Charles; Quillinan, Scott; McLing, Travis

Normalization of Rare Earth Elements (REEs) is important to remove the distracting effects of the Oddo–Harkins rule and provide a meaningful baseline. Normalizations for rocks are well developed and include chondritic meteorites, UCC, PM, PAAS, and NASC. However normalizations for aqueous REEs are limited to oceanic regions such as the North Pacific Deep Water or North Atlantic Surface Water. This leaves water in contact with continental lithologies without a suitable normalization. We present a preliminary continental aqueous REE normalization derived from 38 deep basin hydrocarbon brines in Wyoming. The REEs in these waters are seven orders of magnitude more dilutemore » than NASC but with significant europium enrichment. Gromet 1984 reports NASC Eu/Eu* is 0.2179, whereas in the normalization offered here, Eu/Eu* is 3.868. These waters also are free from the distracting reduction-oxidation cerium behavior found in ocean normalizations. Because these samples exhibit both the uniform behavior of NASC and the absolute concentration of seawater, a normalization based upon them offers a unique combination of the advantages of both. We used single-peak gaussian analysis to quantify the mean values for each REE and estimate the distribution variability. Additional sample collection during the last year revealed that the Powder River Basin (PRB) is atypical relative to the other sampled basins of Wyoming. Those other basins are the Wind River Basin (WRB) Green River Basin (GRB) and Wamsutter Area (WA). A pre-normalization gadolinium anomaly (Gd/Gd*) of between 4 and 23 with a mean of 11.5, defines the PRB samples. Other basins in this study range from 1 to 7 with a mean of 2.8. Finally, we present a preliminary model for ligand-based behavior of REEs in these samples. This model identifies bicarbonate, bromide, and chloride as forming significant complexes with REEs contributing to REE solubility. The ligand model explains observed REEs in the sampled Cretaceous and Paleocene clastic reservoirs. However, the presence of more REEs than predicted in six samples suggests that there is an additional, unconsidered ligand contributing to REE dissolution. Further work will identify this ligand, which appears to be confined to calcium-cemented and dolostone systems.« less

Effects of Agitation and Storage Temperature on Measurements of Hydration Status.

PubMed

Adams, Heather M; Eberman, Lindsey E; Yeargin, Susan W; Niemann, Andrew J; Mata, Heather L; Dziedzicki, David J

2015-12-01

Hypohydration can have significant implications on normal physiological functions of the body. This study aimed to determine the impact of agitation, storage temperature, and storage time on urine osmolality compared to the criterion control. We used a descriptive diagnostic validity test design. To investigate agitation, we recruited 75 healthy individuals (males = 41, females = 34; mean age = 22 ± 5 years; mean self-reported height = 172 ± 23 cm and mass = 77 ± 17 kg) who provided one or more samples (total = 81). The independent variables were agitation (vortex, hand shaken, no agitation) and temperature (room temperature, freezer, and refrigerator) type. Participants completed informed consent, a health questionnaire and were asked to provide a urine sample, which was split and labeled according to agitation type or storage temperature. Urine osmolality was used to determine hydration status at two time points (within 2 hours [control], 48 hours). We used t-tests to determine the difference between each condition and the control and calculated percent error for each condition. No significant differences for no agitation (t79 = -0.079, P = 0.937), hand shaken (t79 = 1.395, P = 0.167) or vortex mixed (t79 = -0.753, P = 0.453) were identified when compared to the criterion control. No significant differences for room temperature (t82 = -0.720, P = 0.474), refrigerator (t82 = -2.697, P = 0.008) or freezer (t82 = 2.576, P = 0.012) were identified when compared to the criterion control. Our findings suggest agitation of urine specimen is not necessary and samples do not require refrigeration or freezing if assessed within 48 hours. Analysis within two hours of collection is not necessary and samples can be stored for up to 48 hours without impacting the hydration status of the sample.

The Influence of trisomy 21 on facial form and variability.

PubMed

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

2017-11-01

Triplication of chromosome 21 (trisomy 21) results in Down syndrome (DS), the most common live-born human aneuploidy. Individuals with DS have a unique facial appearance that can include form changes and altered variability. Using 3D photogrammatic images, 3D coordinate locations of 20 anatomical landmarks, and Euclidean Distance Matrix Analysis methods, we quantitatively test the hypothesis that children with DS (n = 55) exhibit facial form and variance differences relative to two different age-matched (4-12 years) control samples of euploid individuals: biological siblings of individuals with DS (n = 55) and euploid individuals without a sibling with DS (n = 55). Approximately 36% of measurements differ significantly between DS and DS-sibling samples, whereas 46% differ significantly between DS and unrelated control samples. Nearly 14% of measurements differ significantly in variance between DS and DS sibling samples, while 18% of measurements differ significantly in variance between DS and unrelated euploid control samples. Of those measures that showed a significant difference in variance, all were relatively increased in the sample of DS individuals. These results indicate that faces of children with DS are quantitatively more similar to their siblings than to unrelated euploid individuals and exhibit consistent, but slightly increased variation with most individuals falling within the range of normal variation established by euploid samples. These observations provide indirect evidence of the strength of the genetic underpinnings of the resemblance between relatives and the resistance of craniofacial development to genetic perturbations caused by trisomy 21, while underscoring the complexity of the genotype-phenotype map. © 2017 Wiley Periodicals, Inc.

[Partial pressure of CO2 and CO2 degassing fluxes of Huayuankou and Xiaolangdi Station affected by Xiaolangdi Reservoir].

PubMed

Zhang, Yong-ling; Yang, Xiao-lin; Zhang, Dong

2015-01-01

According to periodic sampling analysis per month in Xiaolangdi station and Huayuankou station from November 2011 to October 2012, combined with continuous sampling analysis of Xiaolangdi Reservoir during runoff and sediment control period in 2012, partial pressure of CO2 (pCO2) in surface water were calculated based on Henry's Law, pCO2 features and air-water CO2 degassing fluxes of Huayuankou station and Xiaolangdi station affected by Xiaolangdi Reservoir were studied. The results were listed as follows, when Xiaolangdi Reservoir operated normally, pCO2 in surface water of Xiaolangdi station and Huayuankou station varied from 82 to 195 Pa and from 99 to 228 Pa, moreover, pCO2 in surface water from July to September were distinctly higher than those in other months; meanwhile, pCO, in surface water from Huayuankou station were higher than that from Xiaolangdi station. During runoff and sediment control period of Xiaolangdi Reservoir, two hydrological stations commonly indicated that pCO2 in surface water during water draining were obviously lower than those during sediment releasing. Whether in the period of normal operation or runoff and sediment control, pCO2 in surface water had positive relations to DIC content in two hydrological stations. Since the EpCO,/AOU value was higher than the theoretical value of 0. 62, the biological aerobic respiration effect had distinct contribution to pCO2. Throughout the whole year, air-water CO2 degassing fluxes from Xiaolangdi station and Huayuankou station were 0.486 p.mol (m2 s) -l and 0.588 pmol (m2 x s)(-1) respectively; When Xiaolangdi Reservoir operated normally, air-water CO, degassing fluxes in Huayuankou station were higher than that in Xiaolangdi station; during runoff and sediment control from Xiaolangdi Reservoir, two hydrological stations had one observation result in common, namely, air-water CO2 degassing fluxes in the period of water draining were obviously lower than that in the period of sediment releasing.

Sampled-Data Techniques Applied to a Digital Controller for an Altitude Autopilot

NASA Technical Reports Server (NTRS)

Schmidt, Stanley F.; Harper, Eleanor V.

1959-01-01

Sampled-data theory, using the Z transformation, is applied to the design of a digital controller for an aircraft-altitude autopilot. Particular attention is focused on the sensitivity of the design to parameter variations and the abruptness of the response, that is, the normal acceleration required to carry out a transient maneuver. Consideration of these two characteristics of the system has shown that the finite settling time design method produces an unacceptable system, primarily because of the high sensitivity of the response to parameter variations, although abruptness can be controlled by increasing the sampling period. Also demonstrated is the importance of having well-damped poles or zeros if cancellation is attempted in the design methods. A different method of smoothing the response and obtaining a design which is not excessively sensitive is proposed, and examples are carried through to demonstrate the validity of the procedure. This method is based on design concepts of continuous systems, and it is shown that if no pole-zero cancellations are allowed in the design, one can obtain a response which is not too abrupt, is relatively insensitive to parameter variations, and is not sensitive to practical limits on control-surface rate. This particular design also has the simplest possible pulse transfer function for the digital controller. Simulation techniques and root loci are used for the verification of the design philosophy.

Investigation of the effect of hydration on dermal collagen in ex vivo human skin tissue using second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Samatham, Ravikant; Wang, Nicholas K.; Jacques, Steven L.

2016-02-01

Effect of hydration on the dermal collagen structure in human skin was investigated using second harmonic generation microscopy. Dog ears from the Mohs micrographic surgery department were procured for the study. Skin samples with subject aged between 58-90 years old were used in the study. Three dimensional Multiphoton (Two-photon and backward SHG) control data was acquired from the skin samples. After the control measurement, the skin tissue was either soaked in deionized water for 2 hours (Hydration) or kept at room temperature for 2 hours (Desiccation), and SHG data was acquired. The data was normalized for changes in laser power and detector gain. The collagen signal per unit volume from the dermis was calculated. The desiccated skin tissue gave higher backward SHG compared to respective control tissue, while hydration sample gave a lower backward SHG. The collagen signal decreased with increase in hydration of the dermal collagen. Hydration affected the packing of the collagen fibrils causing a change in the backward SHG signal. In this study, the use of multiphoton microscopy to study the effect of hydration on dermal structure was demonstrated in ex vivo tissue.

The validation of the Z-Scan technique for the determination of plasma glucose

NASA Astrophysics Data System (ADS)

Alves, Sarah I.; Silva, Elaine A. O.; Costa, Simone S.; Sonego, Denise R. N.; Hallack, Maira L.; Coppini, Ornela L.; Rowies, Fernanda; Azzalis, Ligia A.; Junqueira, Virginia B. C.; Pereira, Edimar C.; Rocha, Katya C.; Fonseca, Fernando L. A.

2013-11-01

Glucose is the main energy source for the human body. The concentration of blood glucose is regulated by several hormones including both antagonists: insulin and glucagon. The quantification of glucose in the blood is used for diagnosing metabolic disorders of carbohydrates, such as diabetes, idiopathic hypoglycemia and pancreatic diseases. Currently, the methodology used for this determination is the enzymatic colorimetric with spectrophotometric. This study aimed to validate the use of measurements of nonlinear optical properties of plasma glucose via the Z-Scan technique. For this we used samples of calibrator patterns that simulate commercial samples of patients (ELITech ©). Besides calibrators, serum glucose levels within acceptable reference values (normal control serum - Brazilian Society of Clinical Pathology and Laboratory Medicine) and also overestimated (pathological control serum - Brazilian Society of Clinical Pathology and Laboratory Medicine) were used in the methodology proposal. Calibrator dilutions were performed and determined by the Z-Scan technique for the preparation of calibration curve. In conclusion, Z-Scan method can be used to determinate glucose levels in biological samples with enzymatic colorimetric reaction and also to apply the same quality control parameters used in biochemistry clinical.

Quantitative Profiling of Colorectal Cancer-Associated Bacteria Reveals Associations between Fusobacterium spp., Enterotoxigenic Bacteroides fragilis (ETBF) and Clinicopathological Features of Colorectal Cancer

PubMed Central

Viljoen, Katie S.; Dakshinamurthy, Amirtha; Goldberg, Paul; Blackburn, Jonathan M.

2015-01-01

Various studies have presented clinical or in vitro evidence linking bacteria to colorectal cancer, but these bacteria have not previously been concurrently quantified by qPCR in a single cohort. We quantify these bacteria (Fusobacterium spp., Streptococcus gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Enteropathogenic Escherichia coli (EPEC), and afaC- or pks-positive E. coli) in paired tumour and normal tissue samples from 55 colorectal cancer patients. We further investigate the relationship between a) the presence and b) the level of colonisation of each bacterial species with site and stage of disease, age, gender, ethnicity and MSI-status. With the exception of S. gallolyticus, we detected all bacteria profiled here in both tumour and normal samples at varying frequencies. ETBF (FDR = 0.001 and 0.002 for normal and tumour samples) and afaC-positive E. coli (FDR = 0.03, normal samples) were significantly enriched in the colon compared to the rectum. ETBF (FDR = 0.04 and 0.002 for normal and tumour samples, respectively) and Fusobacterium spp. (FDR = 0.03 tumour samples) levels were significantly higher in late stage (III/IV) colorectal cancers. Fusobacterium was by far the most common bacteria detected, occurring in 82% and 81% of paired tumour and normal samples. Fusobacterium was also the only bacterium that was significantly higher in tumour compared to normal samples (p = 6e-5). We also identified significant associations between high-level colonisation by Fusobacterium and MSI-H (FDR = 0.05), age (FDR = 0.03) or pks-positive E. coli (FDR = 0.01). Furthermore, we exclusively identified atypical EPEC in our cohort, which has not been previously reported in association with colorectal cancer. By quantifying colorectal cancer-associated bacteria across a single cohort, we uncovered inter- and intra-individual patterns of colonization not previously recognized, as well as important associations with clinicopathological features, especially in the case of Fusobacterium and ETBF. PMID:25751261

Methylation, expression, and mutation analysis of the cell cycle control genes in human brain tumors.

PubMed

Yin, Dong; Xie, Dong; Hofmann, Wolf-Karsten; Miller, Carl W; Black, Keith L; Koeffler, H Phillip

2002-11-28

Methylation status of the p15(INK4B), p16(INK4A), p14(ARF) and retinoblastoma (RB) genes was studied using methylation specific polymerase chain reaction (MSP) in 85 human brain tumors of various subtypes and four normal brain samples. These genes play an important role in the control of the cell cycle. Twenty-four out of 85 cases (28%) had at least one of these genes methylated. The frequency of p14(ARF) methylation was 15 out of 85 (18%) cases, and the expression of p14(ARF) in methylated gliomas was significantly lower than in unmethylated gliomas. The incidence of methylation of p15(INK4B), p16(INK4A) and RB gene was 4%, 7%, and 4%, respectively. Samples with p14(ARF) methylation did not have p16(INK4A) methylation even though both genes physically overlap. None of the target genes was methylated in the normal brain samples. In addition, the p53 gene was mutated in 19 out of 85 (22%) samples as determined by single strand conformation polymorphism (SSCP) analysis and DNA sequencing. Thirty out of 85 (35%) brain tumors had either a p53 mutation or methylation of p14(ARF). Also, the p14(ARF) expression in p53 wild-type gliomas was lower than levels in p53 mutated gliomas. This finding is consistent with wild-type p53 being able to autoregulate its levels by down-regulating expression of p14(ARF). In summary, inactivation of the apoptosis pathway that included the p14(ARF) and p53 genes by hypermethylation and mutation, respectively, occurred frequently in human brain tumors. Down-regulation of p14(ARF) in gliomas was associated with hypermethylation of its promoter and the presence of a wild-type p53 in these samples.

Aging and memory: corrections for age, sex and education for three widely used memory tests.

PubMed

Zappalà, G; Measso, G; Cavarzeran, F; Grigoletto, F; Lebowitz, B; Pirozzolo, F; Amaducci, L; Massari, D; Crook, T

1995-04-01

The associate learning subtest from the Wechsler Memory Scale; Benton's Visual Retention test and a Controlled Word Association Task (FAS) were administered to a random sample of normal, healthy individuals whose age ranged from 20 to 79 years, recruited within the Italian peninsula. The neuropsychological examination took place on a mobile unit and the tests were given by the same team of neuropsychologists to reduce variability among examiners. The Research Project was known as Progetto Memoria. Corrections to the scores of these tests were calculated for age, sex, and education. These corrected values will allow clinicians to screen for memory impairment with greater precision among normally aging individuals, thus improving differential diagnosis between physiologic and pathologic deterioration of cognitive functions.

The Effect on Non-Normal Distributions on the Integrated Moving Average Model of Time-Series Analysis.

ERIC Educational Resources Information Center

Doerann-George, Judith

The Integrated Moving Average (IMA) model of time series, and the analysis of intervention effects based on it, assume random shocks which are normally distributed. To determine the robustness of the analysis to violations of this assumption, empirical sampling methods were employed. Samples were generated from three populations; normal,…

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

PubMed Central

Glenn, Wendy K.; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J.; Lawson, James S.

2012-01-01

Background The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. Materials and Methods All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). Results EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk – EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. Conclusions We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer. PMID:23183846

Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

PubMed

Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

2012-01-01

The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

Impact of Middle Eastern dust storms on indoor and outdoor composition of bioaerosol

NASA Astrophysics Data System (ADS)

Goudarzi, Gholamreza; Soleimani, Zahra; Sorooshian, Armin; Marzouni, Mohammad Bagherian; Maleki, Heidar

2016-08-01

The presence of microbes in airborne aerosol particles, especially dust, is a major public health concern in desert regions. This study is the first of its kind to examine the effect of dust storms on indoor and outdoor microbial air quality at a hospital on the western side of Iran (city of Ahvaz), which is notorious for being highly vulnerable to dust emissions. Air samples were collected inside and outside of the hospital environment for six months, with the unique advantage of this study being that the region and duration of measurements allow for a clear comparison between dusty and normal days. On normal days, the average concentrations (outdoor/indoor) of bacteria and fungi were 423/329 cfu m-3 and 596/386 cfu m-3, respectively, which increased to 1257/406 cfu m-3 and 1116/550 cfu m-3 on dust event days. Indoor/Outdoor ratios for bacteria and fungi are lower on dust event days (0.26-0.60) versus normal days (0.44-0.95). Bacillus spp., Micrococcus spp., Streptomyces spp., and Staphylococcus spp. were the dominant bacteria both indoors and outdoors on normal and dust event days. Gram positive bacteria exhibited higher concentrations than Gram negative bacteria in both outdoor and indoor air samples as well as during both normal and dust event days. The data suggest that Gram positive bacteria are more resistant to undesirable outdoor conditions (e.g., high incident solar radiation) as compared to Gram negative ones. These results have implications for other populated arid regions where more stringent control of indoor air quality can greatly benefit public health.

Serum TIMP1 and TIMP2 concentration in patients with different grades of meningioma.

PubMed

Mashayekhi, Farhad; Saberi, Alia; Mashayekhi, Sohail

2018-07-01

Meningiomas are common primary brain tumors that constitute about 13% of all intracranial tumors. Matrix metalloproteinase-9 (MMP-9) is able to degrade the extracellular matrix and basement membrane leading to cancer cell invasion and metastasis. MMPs are specifically inhibited by a family of small extracellular proteins known as the tissue inhibitors of metalloproteinases (TIMPs). The objective of this project was to evaluate serum concentration of TIMP-1 and TIMP-2 in patients with different grades of meningioma. Ninety samples from different stages of patients with meningitis (42 cases of grade I, 28 grade II, 20 grade III) and 51 samples from normal healthy were included in this study. Total protein concentration (TPC) and the level TIMP-1 and TIMP-2 serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay (ELISA), respectively. No significant change in the TPC was seen in the serum of patients with meningioma when compared with normal controls. Results obtained demonstrated that all serum samples presented TIMP-1 and TIMP-2 expression, whereas, starting from grade I to III meningiomas, a significant decrease of TIMP-1 and TIMP-2 expression was observed as compared to controls. The results of this study show that a low expression of TIMP1 and TIMP2 is correlated with advanced stages of meningioma. It is also concluded that the detection of serum TIMP1 and TIMP2 may be useful in classifying different grades of meningioma. Copyright © 2018 Elsevier B.V. All rights reserved.

Inductive reasoning and the understanding of intention in schizophrenia.

PubMed

Corcoran, Rhiannon

2003-08-01

The study explored the relationship between the understanding of intention in veiled speech acts and the ability to reason inductively. A total of 39 people with DSM-IV-defined schizophrenia with no behavioural signs and 44 healthy participants performed the Hinting Task, a measure of pragmatic language in which the speaker's intention must be inferred, and a measure of inductive reasoning (Aha! Sentences) in which the meaning of ambiguous nonsocial sentences had to be inferred. The participants also completed measures of general intellectual ability, immediate memory for narrative and social problem-solving ability. A substantial correlation was found between performance on the inductive reasoning task and the Hinting Task in the sample of people with schizophrenia. The same relationship was not seen in the normal control sample. The robust relationship between these two measures in this sample survived when the roles of immediate memory for narrative and intellectual ability were controlled for. Furthermore, the relationship was distinctly more compelling for the patients who were currently ill compared to those in remission. These data suggest that people with schizophrenia use a different strategy to infer the meaning behind pragmatic language than that used by normally functioning adults. It is suggested that a reliance on different, possibly less specialised, skills in this group to perform this simple social inference task underlies their deficient performance on this and other measures of social inference. The fact that the relationship between the tasks in patients in remission is not as robust implies that the use of specialised skills to perform social inference tasks may be compromised most significantly during acute phases.