An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes.

PubMed

Grinstein, Lev; Endter, Kristin; Hedrich, Christian M; Reinke, Sören; Luksch, Hella; Schulze, Felix; Robertson, Avril A B; Cooper, Matthew A; Rösen-Wolff, Angela; Winkler, Stefan

2018-06-01

The proinflammatory protease caspase-1 plays pivotal roles in central pathways of innate immunity, thereby contributing to pathogen clearance. Beside its physiological role, dysregulated activity of caspase-1 is known to contribute to an increasing number of diseases. In this study, we optimized and validated a low-volume human whole blood assay facilitating the measurement of caspase-1 activation and inflammasome-related gene expression upon stimulation of the NLRP3, NLRC4 or AIM2 inflammasome. Using the NLRP3 inflammasome specific inhibitor MCC950, we were able to measure the activity of canonical or alternative NLRP3 pathways, AIM2 and NLRC4 inflammasomes in whole blood. Based on our data we assume a superposition of NLRP3 and NLRC4 inflammasome activities in human whole blood following stimulation with S. typhimurium. The optimized whole blood assay may be suitable for diagnostic and research purposes for pediatric patients who can only donate small amounts of blood. Copyright © 2017 Elsevier Inc. All rights reserved.

In Vivo 18 FDG/18 Choline Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging

DTIC Science & Technology

2016-10-01

human prostate cancer xenografts. We have selected peptides from bacteriophage display libraries that target TF and ErbB2/ErbB3. The peptides have been...facilitate biomarker-specific diagnosis. The specific aims of the proposal are to: 1) select peptides that target the ErbB2/3 heterodimer using novel...parallel in vitro/in vivo phage display techniques; 2) generate NIR-QDs decorated with TF- and ErbB2/3-avid peptides for in vivo molecular

North Carolina Summer Undergraduate Prostate Cancer Research Program

DTIC Science & Technology

2017-08-01

Achieved: Mentees attend all activities and prepare a poster /abstract for presentation. Specific Aim 3: To track and guide trainees on their progress...a mini-symposium where students presented their results. Friday, July 22, 2016 11:00 – 11:15 am Arrive at the Cancer Center with posters ...2:50 – 3:20 pm Poster Sessions Location: 10th Floor, Comprehensive Cancer Center Conference Rm, 10B 3:25 – 3:55 pm Dr

Bowel Ultrasonography in the Management of Crohn's Disease. A Review with Recommendations of an International Panel of Experts.

PubMed

Calabrese, Emma; Maaser, Christian; Zorzi, Francesca; Kannengiesser, Klaus; Hanauer, Stephen B; Bruining, David H; Iacucci, Marietta; Maconi, Giovanni; Novak, Kerri L; Panaccione, Remo; Strobel, Deike; Wilson, Stephanie R; Watanabe, Mamoru; Pallone, Francesco; Ghosh, Subrata

2016-05-01

Bowel ultrasonography (US) is considered a useful technique for assessing mural inflammation and complications in Crohn's disease (CD). The aim of this review is to appraise the evidence on the accuracy of bowel US for CD. In addition, we aim to provide recommendations for its optimal use. Publications were identified by literature search from 1992 to 2014 and selected based on predefined criteria: 15 or more patients; bowel US for diagnosing CD, complications, postoperative recurrence, activity; adequate reference standards; prospective study design; data reported to allow calculation of sensitivity, specificity, agreement, or correlation values; articles published in English. The search yielded 655 articles, of which 63 were found to be eligible and retrieved as full-text articles for analysis. Bowel US showed 79.7% sensitivity and 96.7% specificity for the diagnosis of suspected CD, and 89% sensitivity and 94.3% specificity for initial assessment in established patients with CD. Bowel US identified ileal CD with 92.7% sensitivity, 88.2% specificity, and colon CD with 81.8% sensitivity, 95.3% specificity, with lower accuracy for detecting proximal lesions. The oral contrast agent improves the sensitivity and specificity in determining CD lesions and in assessing sites and extent. Bowel US is a tool for evaluation of CD lesions in terms of complications, postoperative recurrence, and monitoring response to medical therapy; it reliably detects postoperative recurrence and complications, as well as offers the possibility of monitoring disease progression.

Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity

PubMed Central

Chew, Benjamin; Ryu, Jae Ryun; Ng, Teclise; Ma, Dongliang; Dasgupta, Ananya; Neo, Sin Hui; Zhao, Jing; Zhong, Zhong; Bichler, Zoë; Sajikumar, Sreedharan; Goh, Eyleen L. K.

2015-01-01

Attempts have been made to use glycogen synthase kinase-3 beta (GSK3β) inhibitors for prophylactic treatment of neurocognitive conditions. However the use of lithium, a non-specific inhibitor of GSK3β results in mild cognitive impairment in humans. The effects of global GSK3β inhibition or knockout on learning and memory in healthy adult mice are also inconclusive. Our study aims to better understand the role of GSK3β in learning and memory through a more regionally, targeted approach, specifically performing lentiviral-mediated knockdown of GSK3β within the dentate gyrus (DG). DG-GSK3β-silenced mice showed impaired contextual fear memory retrieval. However, cue fear memory, spatial memory, locomotor activity and anxiety levels were similar to control. These GSK3β-silenced mice also showed increased induction and maintenance of DG long-term potentiation (DG-LTP) compared to control animals. Thus, this region-specific, targeted knockdown of GSK3β in the DG provides better understanding on the role of GSK3β in learning and memory. PMID:26157370

Ana o 3-specific IgE is a good predictor for clinically relevant cashew allergy in children.

PubMed

Lange, L; Lasota, L; Finger, A; Vlajnic, D; Büsing, S; Meister, J; Broekaert, I; Pfannenstiel, C; Friedrichs, F; Price, M; Trendelenburg, V; Niggemann, B; Beyer, K

2017-04-01

Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the ImmunoCAP-FEIA and a standardized diagnostic procedure including oral challenges where indicated. A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An integrative approach to energy, carbon, and redox metabolism in the cyanobacterium Synechocystis sp. PCC 6803

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

Overbeek, Ross; Fonstein, Veronika; Osterman, Andrei

2005-02-15

The team of the Fellowship for Interpretation of Genomes (FIG) under the leadership of Ross Overbeek, began working on this Project in November 2003. During the previous year, the Project was performed at Integrated Genomics Inc. A transition from the industrial environment to the public domain prompted us to adjust some aspects of the Project. Notwithstanding the challenges, we believe that these adjustments had a strong positive impact on our deliverables. Most importantly, the work of the research team led by R. Overbeek resulted in the deployment of a new open source genomic platform, the SEED (Specific Aim 1). Thismore » platform provided a foundation for the development of CyanoSEED a specialized portal to comparative analysis and metabolic reconstruction of all available cyanobacterial genomes (Specific Aim 3). The SEED represents a new generation of software for genome analysis. Briefly, it is a portable and extendable system, containing one of the largest and permanently growing collections of complete and partial genomes. The complete system with annotations and tools is freely available via browsing or via installation on a user's Mac or Linux computer. One of the important unique features of the SEED is the support of metabolic reconstruction and comparative genome analysis via encoding and projection of functional subsystems. During the project period, the FIG research team has validated the new software by developing a significant number of core subsystems, covering many aspects of central metabolism (Specific Aim 2), as well as metabolic areas specific for cyanobacteria and other photoautotrophic organisms (Specific Aim 3). In addition to providing a proof of technology and a starting point for further community-based efforts, these subsystems represent a valuable asset. An extensive coverage of central metabolism provides the bulk of information required for metabolic modeling in Synechocystis sp.PCC 6803. Detailed analysis of several subsystems covering energy, carbon, and redox metabolism in the Synechocystis sp. PCC 6803 and other cyanobacteria has been performed (Specific Aim 4). The main objectives for this year (adjusted to reflect a new, public domain, setting of the Project research team) were: Aim 1. To develop, test, and deploy a new open source system, the SEED, for integrating community-based annotation, and comparative analysis of all publicly available microbial genomes. Develop a comprehensive genomic database by integrating within SEED all publicly available complete and nearly complete genome sequences with special emphasis on genomes of cyanobacteria, phototrophic eukaryotes, and anoxygenic phototrophic bacteria--invaluable for comparative genomic studies of energy and carbon metabolism in Synechocystis sp. PCC 6803. Aim 2. To develop the SEED's biological content in the form of a collection of encoded Subsystems largely covering the conserved cellular machinery in prokaryotes (and central metabolic machinery in eukaryotes). Aim 3. To develop, utilizing core SEED technology, the CyanoSEED--a specialized WEB portal for community-based annotation, and comparative analysis of all publicly available cyanobacterial genomes. Encode the set of additional subsystems representing key metabolic transformations in cyanobacteria and other photoautotrophs. We envisioned this resource as complementary to other public access databases for comparative genomic analysis currently available to the cyanobacterial research community. Aim 4. Perform in-depth analysis of several subsystems covering energy, carbon, and redox metabolism in the Synechocystis sp. PCC 6803 and all other cyanobacteria with available genome sequences. Reveal inconsistencies and gaps in the current knowledge of these subsystems. Use functional and genome context analysis tools in CyanoSEED to predict, whenever possible, candidate genes for inferred functional roles. To disseminate freely these conjectures and predictions by publishing them on CyanoSEED (http://cyanoseed.thefig.info/) and the Subsystems Forum (http://brucella.uchicago.edu/SubsystemForum/) in order to facilitate experimental analysis by our collaborator on this Project and by other experimentalists working in various field of cyanobacterial physiology and biotechnology.« less

Body sway, aim point fluctuation and performance in rifle shooters: inter- and intra-individual analysis.

PubMed

Ball, Kevin A; Best, Russell J; Wrigley, Tim V

2003-07-01

In this study, we examined the relationships between body sway, aim point fluctuation and performance in rifle shooting on an inter- and intra-individual basis. Six elite shooters performed 20 shots under competition conditions. For each shot, body sway parameters and four aim point fluctuation parameters were quantified for the time periods 5 s to shot, 3 s to shot and 1 s to shot. Three parameters were used to indicate performance. An AMTI LG6-4 force plate was used to measure body sway parameters, while a SCATT shooting analysis system was used to measure aim point fluctuation and shooting performance. Multiple regression analysis indicated that body sway was related to performance for four shooters. Also, body sway was related to aim point fluctuation for all shooters. These relationships were specific to the individual, with the strength of association, parameters of importance and time period of importance different for different shooters. Correlation analysis of significant regressions indicated that, as body sway increased, performance decreased and aim point fluctuation increased for most relationships. We conclude that body sway and aim point fluctuation are important in elite rifle shooting and performance errors are highly individual-specific at this standard. Individual analysis should be a priority when examining elite sports performance.

Polyphenols and Prostate Cancer Chemoprevention

DTIC Science & Technology

2004-03-01

The polyphenols, catechin, (-)- epigallocatechin -3- gallate ( EGCG ), genistein and resveratrol, are associated with reduced incidences of prostate and...protective effect without adverse effects with possible elevated exposure. The specific aims are 1) to investigate the potential of genistein, EGCG and...genistein, EGCG and resveratrol to regulate sex steroid- and specific growth factor-receptor and ligand expression as mechanism of prostate cancer

The BESCT Lung Cancer Program (Biology, Education, Screening, Chemoprevention, and Treatment)

DTIC Science & Technology

2009-03-01

array CGH experiments to determine if other genomic changes have occurred. Specific Aim 3.8 To perform LOH studies at specific loci (if warranted from...strategies for lung cancer • To implement experimental molecular therapeutic approaches for lung cancer treatment Difficulties resulting from the...cancer has had an uncertain course ; however, inhibition of IGFR by either a monoclonal antibody or tyrosine kinase inhibitors (TKIs) is undergoing

Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

DTIC Science & Technology

2016-10-01

prostate cancer through sequencing xenografts and tissue samples. Qualify novel drivers of AR- prostate cancer through in vitro models. Develop novel...ability of RNASEH2A to modulate radio-sensitivity in prostate cancer cell lines and xenograft models. 3: Investigate RNASEH2A as a marker of radio...lung cancer clinical management. List of the Specific Aims: Aim 1: To establish patient-derived xenografts (PDX) models of pre-neoplastic lesions

The Face Perception System becomes Species-Specific at 3 Months: An Eye-Tracking Study

ERIC Educational Resources Information Center

Di Giorgio, Elisa; Meary, David; Pascalis, Olivier; Simion, Francesca

2013-01-01

The current study aimed at investigating own- vs. other-species preferences in 3-month-old infants. The infants' eye movements were recorded during a visual preference paradigm to assess whether they show a preference for own-species faces when contrasted with other-species faces. Human and monkey faces, equated for all low-level perceptual…

Liquid lipases for enzymatic concentration of n-3 polyunsaturated fatty acids in monoacylglycerols via ethanolysis: Catalytic specificity and parameterization.

PubMed

He, Yongjin; Li, Jingbo; Kodali, Sitharam; Balle, Thomas; Chen, Bilian; Guo, Zheng

2017-01-01

This work examined catalytic specificity and fatty acid selectivity of five liquid lipases C. antarctica lipase A and B (CAL-A/B), and lipase TL (T. lanuginosus), Eversa Transfrom and NS in ethanolysis of fish oil with the aim to concentrate n-3 PUFAs into monoacylglycerols (MAGs) products. Lipase TL, Eversa Transform & NS entail a much faster reaction and produce higher MAGs yield (>30%); whereas CAL-A obtains the highest concentration of n-3 PUFAs/DHA/EPA into MAGs products (88.30%); followed by lipase NS (81.02%). 13 C NMR analysis indicates that CAL-B and lipase TL are sn-1,3 specific; but CAL-A and lipase Eversa Transform are non-regiospecific or weak sn-2 specific; which plausibly explains high enrichment effect of the latter two lipases. All liquid lipases are observed reusable for a certain times (lipase Eversa Transform up to 12 times), demonstrating their competitive advantage over immobilized form for industrial application because of their higher activity and cheaper operation cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue-Specific and Cation/Anion-Specific DNA Methylation Variations Occurred in C. virgata in Response to Salinity Stress

PubMed Central

Gao, Xiang; Cao, Donghui; Liu, Jie; Wang, Xiaoping; Geng, Shujuan; Liu, Bao; Shi, Decheng

2013-01-01

Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na2SO4, NaHCO3, Na2CO3) and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na2CO3> NaHCO3> Na2SO4> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations. PMID:24223802

Tissue-specific and cation/anion-specific DNA methylation variations occurred in C. virgata in response to salinity stress.

PubMed

Gao, Xiang; Cao, Donghui; Liu, Jie; Wang, Xiaoping; Geng, Shujuan; Liu, Bao; Shi, Decheng

2013-01-01

Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na2SO4, NaHCO3, Na2CO3) and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na2CO3> NaHCO3> Na2SO4> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations.

In extremely preterm infants, do the Movement Assessment of Infants and the Alberta Infant Motor Scale predict 18-month outcomes using the Bayley-III?

PubMed

Lefebvre, Francine; Gagnon, Marie-Michèle; Luu, Thuy Mai; Lupien, Geneviève; Dorval, Véronique

2016-03-01

Extremely preterm infants are at high-risk for neurodevelopmental disabilities. The Movement Assessment of Infants (MAI) and the Alberta Infant Motor Scale (AIMS) have been designed to predict outcome with modest accuracy with the Bayley-I or Bayley-II. To examine and compare the predictive validity of the MAI and AIMS in determining neurodevelopmental outcome with the Bayley-III. Retrospective cohort study of 160 infants born at ≤ 28 weeks gestation. At their corrected age, infants underwent the MAI at 4 months, the AIMS at 4 and 10-12 months, and the Bayley-III and neurological examination at 18 months. Sensitivity and specificity were calculated. Infants had a mean gestation of 26.3 ± 1.4 weeks and birth weight of 906 ± 207 g. A high-risk score (≥ 14) for adverse outcome was obtained by 57% of infants on the MAI. On the AIMS, a high-risk score (<5th percentile) was obtained by 56% at 4 months and 30% at 10-12 months. At 18 months, infants with low-risk scores on either the MAI or AIMS had higher cognitive, language, and motor Bayley-III scores than those with high-risk scores. They were less likely to have severe neurodevelopmental impairment. To predict Bayley-III scores <70, sensitivity and specificity were 91% and 49%, respectively, for the MAI and 78% and 48%, respectively, for the AIMS. Extremely preterm infants with low-risk MAI at 4 months or AIMS scores at 4 or 10-12 months had better outcomes than those with high-risk scores. However, both tests lack specificity to predict individual neurodevelopmental status at 18 months. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Selective delivery of laser energy to ester bonds of triacylglycerol in lipid droplets of adipocyte using a quantum cascade laser

PubMed Central

Masaki, Noritaka; Okazaki, Shigetoshi

2018-01-01

The recent development of quantum cascade lasers (QCLs) has facilitated the irradiation of a mid-infrared laser beam that is specifically absorbed by a target molecular bond. Aiming for a selective delivery of laser energy to a specific absorption at 1,738 cm−1 by the ester bonds of triacylglycerol (TAG), a QCL beam with a wavenumber of 1,710 cm−1 was irradiated to 3T3–L1 adipocytes and preadipocytes. Neutral red staining, and FITC-labeled annexin V and ethidium homodimer-III assays revealed the occurrence of adipocyte-specific cell death 24 h after QCL irradiation. The selective delivery of laser energy to endogenous molecules can affect biological processes in a living organism. PMID:29760972

Selective delivery of laser energy to ester bonds of triacylglycerol in lipid droplets of adipocyte using a quantum cascade laser.

PubMed

Masaki, Noritaka; Okazaki, Shigetoshi

2018-05-01

The recent development of quantum cascade lasers (QCLs) has facilitated the irradiation of a mid-infrared laser beam that is specifically absorbed by a target molecular bond. Aiming for a selective delivery of laser energy to a specific absorption at 1,738 cm -1 by the ester bonds of triacylglycerol (TAG), a QCL beam with a wavenumber of 1,710 cm -1 was irradiated to 3T3-L1 adipocytes and preadipocytes. Neutral red staining, and FITC-labeled annexin V and ethidium homodimer-III assays revealed the occurrence of adipocyte-specific cell death 24 h after QCL irradiation. The selective delivery of laser energy to endogenous molecules can affect biological processes in a living organism.

Combining two serological assays optimises sensitivity and specificity for the identification of Streptococcus equi subsp. equi exposure.

PubMed

Robinson, Carl; Steward, Karen F; Potts, Nicola; Barker, Colin; Hammond, Toni-ann; Pierce, Karen; Gunnarsson, Eggert; Svansson, Vilhjálmur; Slater, Josh; Newton, J Richard; Waller, Andrew S

2013-08-01

The detection of anti-Streptococcus equi antibodies in the blood serum of horses can assist with the identification of apparently healthy persistently infected carriers and the prevention of strangles outbreaks. The aim of the current study was to use genome sequencing data to develop an indirect enzyme linked immunosorbent assay (iELISA) that targets two S. equi-specific protein fragments. The sensitivity and specificity of the antigen A and antigen C iELISAs were compared to an SeM-based iELISA marketed by IDvet - diagnostic Vétérinaire (IDvet). Individually, each assay compromised specificity in order to achieve sufficient sensitivity (SeM iELISA had a sensitivity of 89.9%, but a specificity of only 77.0%) or sensitivity to achieve high specificity. However, combining the results of the antigen A and antigen C iELISAs permitted optimisation of both sensitivity (93.3%) and specificity (99.3%), providing a robust assay for the identification of horses exposed to S. equi. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bone Marrow Failure Secondary to Cytokinesis Failure

DTIC Science & Technology

2015-12-01

SUPPLEMENTARY NOTES 14. ABSTRACT Fanconi anemia (FA) is a human genetic disease characterized by a progressive bone marrow failure and heightened...Fanconi anemia (FA) is the most commonly inherited bone marrow failure syndrome. FA patients develop bone marrow failure during the first decade of...experiments proposed in specific aims 1- 3 (Tasks 1-3). Task 1: To determine whether HSCs from Fanconi anemia mouse models have increased cytokinesis

Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials

DTIC Science & Technology

2004-09-01

Epstein - Barr virus infection by adoptive transfer of gene-modified virus -specific T lymphocytes. Nat Med 2:551. 52. Mailliard, R. B., S. Egawa, Q. Cai, A...3 DAMID17-01-1-0318 INTRODUCTION This project is focused on the development of novel tumor vaccines directed at MUC1, a transmembrane mucin that is...immunization strategies can be developed to overcome tolerance. Our specific aims are: 1) to assess the effectiveness of vaccine formulations against

Reliability and Factorial Validity of Non-Specific and Tennis-Specific Pre-Planned Agility Tests; Preliminary Analysis

PubMed Central

Sekulic, Damir; Uljevic, Ognjen; Peric, Mia; Spasic, Miodrag; Kondric, Miran

2017-01-01

Abstract Agility is an important quality in tennis, yet there is an evident lack of studies focussing on the applicability of tennis-specific agility performances and comparing them to equivalent non-specific agility performances. The aim of this study was to evaluate the reliability and factorial validity of three tests of pre-planned agility, performed in specific (with a tennis racquet) and non-specific (without a tennis racquet) conditions. The sample consisted of 33 tennis players (13 males and 20 females; age: 18.3 ± 1.1 years and 18.6 ± 1.3 years; body height: 185.4 ± 51 cm and 169.3 ± 4.2 cm, 74.0 ± 4.4 kg and 61.2 ± 3.1 kg, respectively). The variables comprised three agility tests: a 20-yard test, a T-test and the Illinois test, all performed in both specific and non-specific conditions. Between-subject and within-subject reliability were found to be high (Cronbach Alpha: 0.93 to 0.98; Coefficient of Variation: 3 to 8%), with better within-subject reliability and stability of the measurement for specific tests. Pearson’s product moment correlations between the non-specific and specific agility performances were high (r ≥0.84), while factor analysis extracted only one significant latent dimension on the basis of the Guttman-Kaiser criterion. The results of the 20-yard test were better when the test was conducted in the specific conditions (t-test = 2.66; p < 0.05). For the Illinois test, superior results were recorded in the non-specific conditions (t-test = 2.96; p < 0.05), which can be explained by the test duration (about 20 s) and non-specific locomotion forms such as rotational movements. Considering the findings of the present study, when testing tennis-specific pre-planned agility, we suggest using tests of short duration (less than 10 s) and sport-specific types of locomotion. PMID:28210343

The Climate Change Consortium of Wales (C3W)

NASA Astrophysics Data System (ADS)

Hendry, K. R.; Reis, J.; Hall, I. R.

2011-12-01

In response to the complexity and multidisciplinary nature of climate change research, the Climate Change Consortium of Wales (C3W) was formed in 2009 by the Welsh universities of Aberystwyth, Bangor, Cardiff and Swansea. Initially funded by Welsh Government, through the Higher Education Funding Council for Wales, the Countryside Council for Wales and the universities, C3W aims to bring together climate change researchers from a wide range of disciplines to explore scientific and sociological drivers, impacts and implications at local, national and international scale. The specific aims are to i) improve our fundamental understanding of the causes, nature, timing and consequences of climate change on Planet Earth's environment and on humanity, and ii) to reconfigure climate research in Wales as a recognisable centre of excellence on the world stage. In addition to improving the infrastructure for climate change research, we aim to improve communication, networking, collaborative research, and multidisciplinary data assimilation within and between the Welsh universities, and other UK and international institutions. Furthermore, C3W aims to apply its research by actively contributing towards national policy development, business development and formal and informal education activities within and beyond Wales.

Image Databases.

ERIC Educational Resources Information Center

Pettersson, Rune

Different kinds of pictorial databases are described with respect to aims, user groups, search possibilities, storage, and distribution. Some specific examples are given for databases used for the following purposes: (1) labor markets for artists; (2) document management; (3) telling a story; (4) preservation (archives and museums); (5) research;…

Physics and Analysis at a Hadron Collider - Making Measurements (3/3)

ScienceCinema

Glenzinski, Douglas

2018-02-26

This is the third lecture of three which together discuss the physics of hadron colliders with an emphasis on experimental techniques used for data analysis. This third lecture discusses techniques important for analyses making a measurement (e.g. determining a cross section or a particle property such as its mass or lifetime) using some CDF top-quark analyses as specific examples. The lectures are aimed at graduate students.

3D Modelling and Printing Technology to Produce Patient-Specific 3D Models.

PubMed

Birbara, Nicolette S; Otton, James M; Pather, Nalini

2017-11-10

A comprehensive knowledge of mitral valve (MV) anatomy is crucial in the assessment of MV disease. While the use of three-dimensional (3D) modelling and printing in MV assessment has undergone early clinical evaluation, the precision and usefulness of this technology requires further investigation. This study aimed to assess and validate 3D modelling and printing technology to produce patient-specific 3D MV models. A prototype method for MV 3D modelling and printing was developed from computed tomography (CT) scans of a plastinated human heart. Mitral valve models were printed using four 3D printing methods and validated to assess precision. Cardiac CT and 3D echocardiography imaging data of four MV disease patients was used to produce patient-specific 3D printed models, and 40 cardiac health professionals (CHPs) were surveyed on the perceived value and potential uses of 3D models in a clinical setting. The prototype method demonstrated submillimetre precision for all four 3D printing methods used, and statistical analysis showed a significant difference (p<0.05) in precision between these methods. Patient-specific 3D printed models, particularly using multiple print materials, were considered useful by CHPs for preoperative planning, as well as other applications such as teaching and training. This study suggests that, with further advances in 3D modelling and printing technology, patient-specific 3D MV models could serve as a useful clinical tool. The findings also highlight the potential of this technology to be applied in a variety of medical areas within both clinical and educational settings. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Development of Laser-Polarized Noble Gas Magnetic Resonance Imaging (MRI) Technology

NASA Technical Reports Server (NTRS)

Walsworth, Ronald L.

2004-01-01

We are developing technology for laser-polarized noble gas nuclear magnetic resonance (NMR), with the aim of enabling it as a novel biomedical imaging tool for ground-based and eventually space-based application. This emerging multidisciplinary technology enables high-resolution gas-space magnetic resonance imaging (MRI)-e.g., of lung ventilation, perfusion, and gas-exchange. In addition, laser-polarized noble gases (3He and 1BXe) do not require a large magnetic field for sensitive NMR detection, opening the door to practical MRI with novel, open-access magnet designs at very low magnetic fields (and hence in confined spaces). We are pursuing two specific aims in this technology development program. The first aim is to develop an open-access, low-field (less than 0.01 T) instrument for MRI studies of human gas inhalation as a function of subject orientation, and the second aim is to develop functional imaging of the lung using laser-polarized He-3 and Xe-129.

Online Stereo 3D Simulation in Studying the Spherical Pendulum in Conservative Force Field

ERIC Educational Resources Information Center

Zabunov, Svetoslav S.

2013-01-01

The current paper aims at presenting a modern e-learning method and tool that is utilized in teaching physics in the universities. An online stereo 3D simulation is used for e-learning mechanics and specifically the teaching of spherical pendulum as part of the General Physics course for students in the universities. This approach was realized on…

Pupils' Understanding of Air Pollution

ERIC Educational Resources Information Center

Dimitriou, Anastasia; Christidou, Vasilia

2007-01-01

This paper reports on a study of pupils' knowledge and understanding of atmospheric pollution. Specifically, the study is aimed at identifying: 1) the extent to which pupils conceptualise the term "air pollution" in a scientifically appropriate way; 2) pupils' knowledge of air pollution sources and air pollutants; and 3) pupils'…

Monte Carlo characterization of materials for prosthetic implants and dosimetric validation of Pinnacle 3 TPS

NASA Astrophysics Data System (ADS)

Palleri, Francesca; Baruffaldi, Fabio; Angelini, Anna Lisa; Ferri, Andrea; Spezi, Emiliano

2008-12-01

In external beam radiotherapy the calculation of dose distribution for patients with hip prostheses is critical. Metallic implants not only degrade the image quality but also perturb the dose distribution. Conventional treatment planning systems do not accurately account for high-Z prosthetic implants heterogeneities, especially at interfaces. The materials studied in this work have been chosen on the basis of a statistical investigation on the hip prostheses implanted in 70 medical centres. The first aim of this study is a systematic characterization of materials used for hip prostheses, and it has been provided by BEAMnrc Monte Carlo code. The second aim is to evaluate the capabilities of a specific treatment planning system, Pinnacle 3, when dealing with dose calculations in presence of metals, also close to the regions of high-Z gradients. In both cases it has been carried out an accurate comparison versus experimental measurements for two clinical photon beam energies (6 MV and 18 MV) and for two experimental sets-up: metallic cylinders inserted in a water phantom and in a specifically built PMMA slab. Our results show an agreement within 2% between experiments and MC simulations. TPS calculations agree with experiments within 3%.

Development of Specific Inhibitors for Breast Cancer-Associated Variants of ErbB2

DTIC Science & Technology

2015-10-01

activity measurements (Months 9-15) Specific Aim 3: Identifying inhibitors of ErbB2 mutants.* Major Task 5: Produce ErbB2 structures for drug -lead...identified the activated cancer- associated ErbB2 mutants that will be used for drug screening, and we have established enzyme assays that will be suitable...during protein expression and purification. We measured enzyme activity using two assays: (1) a continuous spectrophotometric assay. In this assay

Improving Care for Veterans with PTSD: Comparing Risks and Benefits of Antipsychotics Versus Other Medications to Augment First-Line Pharmacologic Therapy

DTIC Science & Technology

2017-10-01

for all project Aims. Timeline- months 3-6. Status: completed. Task 6: Complete primary analyses and hypothesis testing for Aim 2, including...glucose. For each of these lab tests , each VA site can name them something different and can change names over times. Labs should be linked to Logical...Observation Identifiers Names (LOINC) codes, an international standard system that assigns a numeric code to specific lab tests . However, VA data

Chromoendoscopy of gastric adenoma using an acetic acid indigocarmine mixture

PubMed Central

Kono, Yoshiyasu; Takenaka, Ryuta; Kawahara, Yoshiro; Okada, Hiroyuki; Hori, Keisuke; Kawano, Seiji; Yamasaki, Yasushi; Takemoto, Koji; Miyake, Takayoshi; Fujiki, Shigeatsu; Yamamoto, Kazuhide

2014-01-01

AIM: To investigate the usefulness of chromoendoscopy, using an acetic acid indigocarmine mixture (AIM), for gastric adenoma diagnosed by forceps biopsy. METHODS: A total of 54 lesions in 45 patients diagnosed as gastric adenoma by forceps biopsy were prospectively enrolled in this study and treated by endoscopic submucosal dissection (ESD) between January 2011 and January 2012. AIM-chromoendoscopy (AIM-CE) was performed followed by ESD. AIM solution was sprinkled and images were recorded every 30 s for 3 min. Clinical characteristics such as tumor size (< 2 cm, ≥ 2 cm), surface color in white light endoscopy (WLE) (whitish, normochromic or reddish), macroscopic appearance (flat or elevated, depressed), and reddish change in AIM-CE were selected as valuables. RESULTS: En bloc resection was achieved in all 54 cases, with curative resection of fifty two lesions (96.3%). Twenty three lesions (42.6%) were diagnosed as well-differentiated adenocarcinoma and the remaining 31 lesions (57.4%) were gastric adenoma. All adenocarcinoma lesions were well-differentiated tubular adenocarcinomas and were restricted within the mucosal layer. The sensitivity of reddish color change in AIM-CE is significantly higher than that in WLE (vs tumor size ≥ 2 cm, P = 0.016, vs normochromic or reddish surface color, P = 0.046, vs depressed macroscopic type, P = 0.0030). On the other hand, no significant differences were found in the specificity and accuracy. In univariate analysis, normochromic or reddish surface color in WLE (OR = 3.7, 95%CI: 1.2-12, P = 0.022) and reddish change in AIM-CE (OR = 14, 95%CI: 3.8-70, P < 0.001) were significantly related to diagnosis of early gastric cancer (EGC). In multivariate analysis, only reddish change in AIM-CE (OR = 11, 95%CI: 2.3-66, P = 0.0022) was a significant factor associated with diagnosis of EGC. CONCLUSION: AIM-CE may have potential for screening EGC in patients initially diagnosed as gastric adenoma by forceps biopsy. PMID:24803824

Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

DTIC Science & Technology

1984-10-01

lung tumor system the specific aims are: 1. To conduct studies of the effect of 3-methylchlanthrene (MCA) on DNA synthesis and cell proliferation in...alkylation of nucleic acids of the rat by N-methyl-N- nitrosourea , dimethylnitrosamine, dimethylsulfate, and methylmethanesulfonate. Biochem. J. 110:39-47

JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma

PubMed Central

Peterle, Gabriela Tonini; dos Santos, Marcelo; Trivilin, Leonardo Oliveira; Mendes, Suzanny Oliveira; de Oliveira, Mayara Mota; dos Santos, Joaquim Gasparini; Stur, Elaine; Agostini, Lidiane Pignaton; Couto, Cinthia Vidal Monteiro da Silva; Dalbó, Juliana; de Assis, Aricia Leone Evangelista Monteiro; Archanjo, Anderson Barros; Mercante, Ana Maria Da Cunha; Lopez, Rossana Veronica Mendoza; Nunes, Fábio Daumas; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Álvares-da-Silva, Adriana Madeira

2018-01-01

Aims Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. Methods and results We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. Conclusion JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets. PMID:29590186

Polyphenols and Prostate Cancer Chemoprevention

DTIC Science & Technology

2005-03-01

ABSTRACT (Maximum 200 Words) The goal of this research is to Investigate the potential of (-)- epigallocatechin -3- gallate ( EGCG ), genistein and resveratrol...prostate chemoprevention are the soy isoflavone, genistein, and the tea catechin, (-)- epigallocatechin -3- gallate ( EGCG ). Another polyphenol that has...adenocarcinoma (TRAMP)). The specific aims are 1) to investigate the potential of genistein, EGCG and resveratrol, alone and in combination, to

[New methods of patient selection for improved anticholinergic therapy].

PubMed

Neuhaus, J; Schwalenberg, T; Schlichting, N; Schulze, M; Horn, L-C; Stolzenburg, J-U

2007-09-01

M3-specific inhibitors are currently preferred for anticholinergic therapy of OAB. However, not all of the patients profit from this regimen. This might reflect a heterogeneity of the patient group. The aim of this work is to define subgroups of patients with specific alterations of receptor expression and to profile the receptor expression individually. These receptor profiles might be used for the development of evidence-based "tailored" therapies. Detrusor probes from bladder carcinoma patients (BCa, n=9 F, n=7 male) and interstitial cystitis patients (IC, n=9 female) were examined using confocal immunofluorescence and PCR. M2, M3, P2X1-3, and H1-3 mRNAs were demonstrated in detrusor tissue. As revealed by immunofluorescence, the M2 receptor expression was significantly higher in female compared to male BCa tissues. In addition, the M2 receptor was further upregulated in IC vs BCa in female detrusor. IC patients showed specific alterations of their receptor profile. Individual receptor profiles might be used to optimize medicinal therapies.

Cellular Mechanisms of Transcranial Direct Current Stimulation

DTIC Science & Technology

2016-07-14

32 Section 3 Electrical stimulation accelerates and boosts the capacity for synaptic learning ...................... 50 Section 4...Section 3: tDCS is thought to boost the learning of tasks or therapy applied at the same time. We provide a cellular mechanism for this. Moreover, we...show that thus “boosting” is specific to the trained task. [Aim 2] Section 4: tDCS is though to boost learning by promoting synaptic plasticity. We

Exploring the Hypersensitivity of PTEN Deleted Prostate Cancer Stem Cells to WEE1 Tyrosine Kinase Inhibitors

DTIC Science & Technology

2015-12-01

xenograft tumors. The results from these studies will reveal whether targeting PTEN-deficient human tumors with WEE1 inhibitors can induce specific... xenograft tumors formed by PTEN- PSAlo PCSCs in castrated male immunocompromised mice. What was accomplished under these goals? Aim 1. Examine...prostate cancer stem cells. Aim 3. Investigate the cytotoxicity of WEE1 inhibitors against recalcitrant xenograft tumors formed by PTEN- CSCs in

Diagnosis of Autism Spectrum Disorders in 2-Year-Olds: A Study of Community Practice

ERIC Educational Resources Information Center

Corsello, Christina M.; Akshoomoff, Natacha; Stahmer, Aubyn C.

2013-01-01

Background: Longitudinal research studies have demonstrated that experienced clinicians using standardized assessment measures can make a reliable diagnosis of autism spectrum disorders (ASDs) in children under age 3. Limited data are available regarding the sensitivity and specificity of these measures in community settings. The aims of this…

Personal Well-Being in Urban China

ERIC Educational Resources Information Center

Smyth, Russell; Nielsen, Ingrid; Zhai, Qingguo

2010-01-01

This article reports the findings of a survey administering the personal well-being index (PWI) in six Chinese cities (N = 3,390) to ascertain the personal well-being of China's urban population. The specific aims of the study were: (a) ascertain whether Chinese urban residents are satisfied with their lives; (b) validate the PWI using an urban…

Molecular differentiation of Russian wild ginseng using mitochondrial nad7 intron 3 region.

PubMed

Li, Guisheng; Cui, Yan; Wang, Hongtao; Kwon, Woo-Saeng; Yang, Deok-Chun

2017-07-01

Cultivated ginseng is often introduced as a substitute and adulterant of Russian wild ginseng due to its lower cost or misidentification caused by similarity in appearance with wild ginseng. The aim of this study is to develop a simple and reliable method to differentiate Russian wild ginseng from cultivated ginseng. The mitochondrial NADH dehydrogenase subunit 7 ( nad 7) intron 3 regions of Russian wild ginseng and Chinese cultivated ginseng were analyzed. Based on the multiple sequence alignment result, a specific primer for Russian wild ginseng was designed by introducing additional mismatch and allele-specific polymerase chain reaction (PCR) was performed for identification of wild ginseng. Real-time allele-specific PCR with endpoint analysis was used for validation of the developed Russian wild ginseng single nucleotide polymorphism (SNP) marker. An SNP site specific to Russian wild ginseng was exploited by multiple alignments of mitochondrial nad 7 intron 3 regions of different ginseng samples. With the SNP-based specific primer, Russian wild ginseng was successfully discriminated from Chinese and Korean cultivated ginseng samples by allele-specific PCR. The reliability and specificity of the SNP marker was validated by checking 20 individuals of Russian wild ginseng samples with real-time allele-specific PCR assay. An effective DNA method for molecular discrimination of Russian wild ginseng from Chinese and Korean cultivated ginseng was developed. The established real-time allele-specific PCR was simple and reliable, and the present method should be a crucial complement of chemical analysis for authentication of Russian wild ginseng.

The Literature Review of Analytical Support to Defence Transformation: Lessons Learned from Turkish Air Force Transformation Activities

DTIC Science & Technology

2010-04-01

available [11]. Additionally, Table-3 is a guide for DMAIC methodology including 29 different methods [12]. RTO-MP-SAS-081 6 - 4 NATO UNCLASSIFIED NATO...Table 3: DMAIC Methodology (5-Phase Methodology). Define Measure Analyze Improve Control Project Charter Prioritization Matrix 5 Whys Analysis...Methodology Scope [13] DMAIC PDCA Develop performance priorities This is a preliminary stage that precedes specific improvement projects, and the aim

Expressive timing in infant-directed singing between 3 and 6 months.

PubMed

Delavenne, Anne; Gratier, Maya; Devouche, Emmanuel

2013-02-01

This longitudinal study compared the temporal characteristics of maternal singing at 3 and then at 6 months. Infant-directed (ID) singing is claimed to have different functions in preverbal communication. However few studies have focused on the specific characteristics of ID singing that change across the first months of life. We aimed to explore these changes between 3 and 6 months because musical routines become prominent in the repertoire of games parents and infants spontaneously play during a period referred to as 'the period of games'. We focused specifically on expressive timing because it reflects how mothers dynamically adapt their singing to their infant's states of attention and involvement. We aimed to determine whether the expressive timing cues of maternal singing would be different at 3 and then at 6 months. To this end, the interactions of 18 mother-infant dyads were recorded while mothers were singing a popular French playsong for their infant at 3 and then at 6 months. Acoustic analyses revealed that mothers showed final-lengthening and tempo slowing for both age groups, but marked the ends of the hierarchical structural units of the song more saliently with their 6-month-olds. Unexpectedly, infant sex was also found to affect maternal singing: more exaggerated phrase-lengthening patterns were observed in singing to girls. Copyright © 2012 Elsevier Inc. All rights reserved.

Summary of Research Adaptions of Visceral and Cerebral Resistance Arteries to Simulated Microgravity

NASA Technical Reports Server (NTRS)

Delp, Michael

2003-01-01

The proposed studies were designed address the effects of simulated microgravity on vascular smooth muscle and endothelial cell function in resistance arteries isolated from visceral tissues (spleen, mesentery and kidneys) and cerebrum. Alterations in vascular function induced by microgravity are particularly relevant to the problems of orthostatic intolerance and reduced exercise capacity experienced by astronauts upon re-entry into the earth's gravitational field. Decrements in contractile function or enhanced vasodilatory responsiveness of peripheral resistance arteries could lead to decreased peripheral resistance and orthostatic hypotension. Alternatively, augmentation of contractile function in cerebral resistance arteries could lead to increased cerebral vascular resistance and diminished perfusion of the brain. The Specific Aims and hypotheses were proposed in this grant. Following each of the Specific Aims, progress toward addressing that specific aim is presented. With the exception of Specific Aim VI (see aim for details), all aims have been experimentally addressed as proposed. The final six months of the granting period will be used for manuscript preparation; manuscripts in preparation will contain results from Specific Aims I-IV. Results from Specific Aims V and VI have been published.

Best candidates for cognitive treatment of illness perceptions in chronic low back pain: results of a theory-driven predictor study.

PubMed

Siemonsma, Petra C; Stuvie, Ilse; Roorda, Leo D; Vollebregt, Joke A; Lankhorst, Gustaaf J; Lettinga, Ant T

2011-04-01

The aim of this study was to identify treatment-specific predictors of the effectiveness of a method of evidence-based treatment: cognitive treatment of illness perceptions. This study focuses on what treatment works for whom, whereas most prognostic studies focusing on chronic non-specific low back pain rehabilitation aim to reduce the heterogeneity of the population of patients who are suitable for rehabilitation treatment in general. Three treatment-specific predictors were studied in patients with chronic non-specific low back pain receiving cognitive treatment of illness perceptions: a rational approach to problem-solving, discussion skills and verbal skills. Hierarchical linear regression analysis was used to assess their predictive value. Short-term changes in physical activity, measured with the Patient-Specific Functioning List, were the outcome measure for cognitive treatment of illness perceptions effect. A total of 156 patients with chronic non-specific low back pain participated in the study. Rational problem-solving was found to be a significant predictor for the change in physical activity. Discussion skills and verbal skills were non-significant. Rational problem-solving explained 3.9% of the total variance. The rational problem-solving scale results are encouraging, because chronic non-specific low back pain problems are complex by nature and can be influenced by a variety of factors. A minimum score of 44 points on the rational problem-solving scale may assist clinicians in selecting the most appropriate candidates for cognitive treatment of illness perceptions.

A cluster randomized controlled platform trial comparing group MEmory specificity training (MEST) to group psychoeducation and supportive counselling (PSC) in the treatment of recurrent depression.

PubMed

Werner-Seidler, Aliza; Hitchcock, Caitlin; Bevan, Anna; McKinnon, Anna; Gillard, Julia; Dahm, Theresa; Chadwick, Isobel; Panesar, Inderpal; Breakwell, Lauren; Mueller, Viola; Rodrigues, Evangeline; Rees, Catrin; Gormley, Siobhan; Schweizer, Susanne; Watson, Peter; Raes, Filip; Jobson, Laura; Dalgleish, Tim

2018-06-01

Impaired ability to recall specific autobiographical memories is characteristic of depression, which when reversed, may have therapeutic benefits. This cluster-randomized controlled pilot trial investigated efficacy and aspects of acceptability, and feasibility of MEmory Specificity Training (MEST) relative to Psychoeducation and Supportive Counselling (PSC) for Major Depressive Disorder (N = 62). A key aim of this study was to determine a range of effect size estimates to inform a later phase trial. Assessments were completed at baseline, post-treatment and 3-month follow-up. The cognitive process outcome was memory specificity. The primary clinical outcome was symptoms on the Beck Depression Inventory-II at 3-month follow-up. The MEST group demonstrated greater improvement in memory specificity relative to PSC at post-intervention (d = 0.88) and follow-up (d = 0.74), relative to PSC. Both groups experienced a reduction in depressive symptoms at 3-month follow-up (d = 0.67). However, there was no support for a greater improvement in depressive symptoms at 3 months following MEST relative to PSC (d = -0.04). Although MEST generated changes on memory specificity and improved depressive symptoms, results provide no indication that MEST is superior to PSC in the resolution of self-reported depressive symptoms. Implications for later-phase definitive trials of MEST are discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Developing Novel Conjugate HIV-1 Subunit Therapeutic Vaccines.

DTIC Science & Technology

1996-06-01

significant CD4-binding was observed for gpl20-KLH conjugates prepared using 1 -ethyl- 3 -( 3 - dimethylaminopropyl )carbodiimide hydrochloride (EDC). EDC...Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503. 1 . AGENCY USE ONLY (Leave blank) 2. REPORT DATE 3 . REPORT TYPE AND...FOREWORD 3 TABLE OF CONTENTS 4 INTRODUCTION 5 RESULTS 6 Specific Aim # 1 : Production and characterization of HIV-JlV and HIV-1jR_ gp120 6 Development and

10 CFR 602.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... project. Research means basic and applied research and that part of development not related to the development of specific systems or products. The primary aim of research is scientific study and... Studies means research pertaining to potential health effects resulting from DOE or predecessor agency...

Diagnosis of Late-Stage, Early-Onset, Small-Fiber Polyneuropathy

DTIC Science & Technology

2016-10-01

develop biotechnology tools for simple diagnosis (sweat testing and pupilometry), 3) identify gene polymorphisms to detect risk for SFPN. None...Goal 4) Specific Aim 2: To develop and evaluate simple biotechnology devices for diagnosing and monitoring longstanding eoSFPN based on

Controlled ecological evaluation of an implemented exercise training programme to prevent lower limb injuries in sport: differences in implementation activity.

PubMed

Donaldson, Alex; Gabbe, Belinda J; Lloyd, David G; Cook, Jill; Finch, Caroline F

2018-04-24

The public health benefits of injury prevention programmes are maximised when programmes are widely adopted and adhered to. Therefore, these programmes require appropriate implementation support. This study evaluated implementation activity outcomes associated with the implementation of FootyFirst, an exercise training injury prevention programme for community Australian football, both with (FootyFirst+S) and without (FootyFirst+NS) implementation support. An evaluation plan based on the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) Sports Setting Matrix was applied in a controlled ecological evaluation of the implementation of FootyFirst. RE-AIM dimension-specific (range: 0-2) and total RE-AIM scores (range: 0-10) were derived by triangulating data from a number of sources (including surveys, interviews, direct observations and notes) describing FootyFirst implementation activities. The mean dimension-specific and total scores were compared for clubs in regions receiving FootyFirst+S and FootyFirst+NS, through analysis of variance. The mean total RE-AIM score forclubs in the FootyFirst+S regions was 2.4 times higher than for clubs in the FootyFirst+NS region (4.73 vs 1.94; 95% CI for the difference: 1.64 to 3.74). Similarly, all dimension-specific scores were significantly higher for clubs in the FootyFirst+S regions compared with clubs in the FootyFirst+NS region. In all regions, the dimension-specific scores were highest for reach and adoption, and lowest for implementation. Implementing exercise training injury prevention programmes in community sport is challenging. Delivering programme content supported by a context-specific and evidence-informed implementation plan leads to greater implementation activity, which is an important precursor to injury reductions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Combination of STOP-Bang Score with Mallampati Score fails to improve specificity in the prediction of sleep-disordered breathing.

PubMed

Dette, Frank G; Graf, Juergen; Cassel, Werner; Lloyd-Jones, Carla; Boehm, Stefan; Zoremba, Martin; Schramm, Patrick; Pestel, Gunther; Thal, Serge C

2016-06-01

Sleep-disordered breathing (SDB) is closely associated with perioperative complications. STOP-Bang score was validated for preoperative screening of SDB. However, STOP-Bang Score lacks adequately high specificity. We aimed to improve it by combining it with the Mallampati Score. The study included 347 patients, in which we assessed both STOP-Bang and Mallampati scores. Overnight oxygen saturation was measured to calculate ODI4%. We calculated the sensitivity and specificity for AHI and ODI4% of both scores separately and in combination. We found that STOP-Bang Score ≥3 was present in 71%, ODI≥5/h (AHI ≥5/h) in 42.6% (39.3%) and ODI≥15/h (AHI ≥15/h) in 13.5% (17.8%). For ODI4%≥5/h (AHI ≥5/h) we observed in men a response rate for sensitivity and specificity of STOP-Bang of 94.5% and 17.1% (90.9% and 12.5%) and in women 66% and 51% (57.8% and 46.9%). For ODI4%≥15/h (AHI≥15/h) it was 92% and 12% (84.6% and 10.3%) and 93% and 49% (75% and 49.2%). For ODI4%≥5 (AHI≥5) sensitivity and specificity of Mallampati score were in men 38.4% and 78.6% (27.3% and 68.2%) and in women 25% and 82.7% (21.9% and 81.3%), for ODI≥15 (AHI ≥15/h) 38.5% and 71.8% (26.9% and 69.2%) and 33.3% and 81.4% (17.9% and 79.6%). In combination, for ODI4%≥15/h, we found sensitivity in men to be 92.3% and in women 93.3%, specificity 10.3% and 41.4%. STOP-Bang Score combined with Mallampati Score fails to increase specificity. Low specificity should be considered when using both scores for preoperative screening of SDB.

3D Image Display Courses for Information Media Students.

PubMed

Yanaka, Kazuhisa; Yamanouchi, Toshiaki

2016-01-01

Three-dimensional displays are used extensively in movies and games. These displays are also essential in mixed reality, where virtual and real spaces overlap. Therefore, engineers and creators should be trained to master 3D display technologies. For this reason, the Department of Information Media at the Kanagawa Institute of Technology has launched two 3D image display courses specifically designed for students who aim to become information media engineers and creators.

The Sensory Nature of Episodic Memory: Sensory Priming Effects Due to Memory Trace Activation

ERIC Educational Resources Information Center

Brunel, Lionel; Labeye, Elodie; Lesourd, Mathieu; Versace, Remy

2009-01-01

The aim of this study was to provide evidence that memory and perceptual processing are underpinned by the same mechanisms. Specifically, the authors conducted 3 experiments that emphasized the sensory aspect of memory traces. They examined their predictions with a short-term priming paradigm based on 2 distinct phases: a learning phase consisting…

North Frisian: The North Frisian Language in Education in Germany, 3rd Edition. Regional Dossiers Series

ERIC Educational Resources Information Center

Walker, Alastair G. H., Comp.

2015-01-01

This regional dossier aims to provide a concise, description and basic statistics about minority language education in a specific region of Europe. Aspects that are addressed include features of the education system, recent educational policies, main actors, legal arrangements, and support structures, as well as quantitative aspects, such as the…

Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

PubMed

Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

2018-01-01

Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P < 0.05). Genes co-expressed with ANGPTL3 and CFHR5 were significantly enriched in metabolism pathways characterizing liver tissues, including "starch and sucrose metabolism" and "drug metabolism-cytochrome P450". Conclusions: For primary CRC with liver metastasis, both the liver metastases and corresponding primary colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

Use of the FLUKA Monte Carlo code for 3D patient-specific dosimetry on PET-CT and SPECT-CT images*

PubMed Central

Botta, F; Mairani, A; Hobbs, R F; Vergara Gil, A; Pacilio, M; Parodi, K; Cremonesi, M; Coca Pérez, M A; Di Dia, A; Ferrari, M; Guerriero, F; Battistoni, G; Pedroli, G; Paganelli, G; Torres Aroche, L A; Sgouros, G

2014-01-01

Patient-specific absorbed dose calculation for nuclear medicine therapy is a topic of increasing interest. 3D dosimetry at the voxel level is one of the major improvements for the development of more accurate calculation techniques, as compared to the standard dosimetry at the organ level. This study aims to use the FLUKA Monte Carlo code to perform patient-specific 3D dosimetry through direct Monte Carlo simulation on PET-CT and SPECT-CT images. To this aim, dedicated routines were developed in the FLUKA environment. Two sets of simulations were performed on model and phantom images. Firstly, the correct handling of PET and SPECT images was tested under the assumption of homogeneous water medium by comparing FLUKA results with those obtained with the voxel kernel convolution method and with other Monte Carlo-based tools developed to the same purpose (the EGS-based 3D-RD software and the MCNP5-based MCID). Afterwards, the correct integration of the PET/SPECT and CT information was tested, performing direct simulations on PET/CT images for both homogeneous (water) and non-homogeneous (water with air, lung and bone inserts) phantoms. Comparison was performed with the other Monte Carlo tools performing direct simulation as well. The absorbed dose maps were compared at the voxel level. In the case of homogeneous water, by simulating 108 primary particles a 2% average difference with respect to the kernel convolution method was achieved; such difference was lower than the statistical uncertainty affecting the FLUKA results. The agreement with the other tools was within 3–4%, partially ascribable to the differences among the simulation algorithms. Including the CT-based density map, the average difference was always within 4% irrespective of the medium (water, air, bone), except for a maximum 6% value when comparing FLUKA and 3D-RD in air. The results confirmed that the routines were properly developed, opening the way for the use of FLUKA for patient-specific, image-based dosimetry in nuclear medicine. PMID:24200697

WHO/INRUD patient care and facility-specific drug use indicators at primary health care centres in Eastern province, Saudi Arabia.

PubMed

El Mahalli, A A; Akl, O A M; Al-Dawood, S F; Al-Nehab, A A; Al-Kubaish, H A; Al-Saeed, S; Elkahky, A A A; Salem, A M A A

2012-11-01

This study aimed to measure the performance of primary health care centres in Eastern province, Saudi Arabia, using the WHO/International Network of Rational Use of Drugs patient care and facility-specific drug use indicators. In a cross-sectional study, 10 health centres were selected using systematic random sampling. A total of 300 patients were interviewed while visiting the centre from January to March 2011 and 10 pharmacists from the same centres were interviewed. Average consultation time was 7.3 min (optimal > or = 30 min), percentage of drugs adequately labelled was 10% (optimal 100%) and patient's knowledge of correct dosage was 79.3% (optimal 100%). The percentage of key drugs in stock was only 59.2% (optimal 100%). An overall index of rational facility-specific drug use was calculated and applied to rank the health centres for benchmarking.

Investigating Variation, Teacher's Edition. Probing the Natural World/3.

ERIC Educational Resources Information Center

Florida State Univ., Tallahassee. Dept. of Science Education.

The teacher's edition for the unit entitled "Investigating Variation" in Intermediate Science Curriculum Study Level III, provides numerous suggestions for teaching specific activities included in the unit. The unit is aimed at selected aspects of measurement and analysis. The chapters included are "The Road…

IDO and galectin-3 hamper the ex vivo generation of clinical grade tumor-specific T cells for adoptive cell therapy in metastatic melanoma.

PubMed

Melief, Sara M; Visser, Marten; van der Burg, Sjoerd H; Verdegaal, Els M E

2017-07-01

Adoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells proved to be successful for the treatment of metastatic melanoma patients. Mixed lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is far from optimal. We hypothesized that this is due to tumor intrinsic and extrinsic factors and aimed to identify and manipulate these factors so to optimize our clinical, GMP-compliant MLTC protocol. We found that the tumor cell produced IDO and/or galectin-3, and the accumulation of CD4 + CD25 hi FoxP3 + T cells suppressed the expansion of tumor-specific T cells in the MLTC. Strategies to eliminate CD4 + CD25 hi FoxP3 + T cells during culture required the depletion of the whole CD4 + T cell population and were found to be undesirable. Blocking of IDO and galectin-3 was feasible and resulted in improved efficiency of the MLTC. Implementation of these findings in clinical protocols for ex vivo expansion of tumor-reactive T cells holds promise for an increased therapeutic potential of adoptive cell transfer treatments with tumor-specific T cells.

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

PubMed Central

Wu, Xiaoyu; Cakmak, Sinan; Wortmann, Markus; Hakimi, Maani; Zhang, Jian; Böckler, Dittmar; Dihlmann, Susanne

2016-01-01

Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients. PMID:27474483

Preparation and fabrication of a full-scale, sagittal-sliced, 3D-printed, patient-specific radiotherapy phantom.

PubMed

Craft, Daniel F; Howell, Rebecca M

2017-09-01

Patient-specific 3D-printed phantoms have many potential applications, both research and clinical. However, they have been limited in size and complexity because of the small size of most commercially available 3D printers as well as material warping concerns. We aimed to overcome these limitations by developing and testing an effective 3D printing workflow to fabricate a large patient-specific radiotherapy phantom with minimal warping errors. In doing so, we produced a full-scale phantom of a real postmastectomy patient. We converted a patient's clinical CT DICOM data into a 3D model and then sliced the model into eleven 2.5-cm-thick sagittal slices. The slices were printed with a readily available thermoplastic material representing all body tissues at 100% infill, but with air cavities left open. Each slice was printed on an inexpensive and commercially available 3D printer. Once the printing was completed, the slices were placed together for imaging and verification. The original patient CT scan and the assembled phantom CT scan were registered together to assess overall accuracy. The materials for the completed phantom cost $524. The printed phantom agreed well with both its design and the actual patient. Individual slices differed from their designs by approximately 2%. Registered CT images of the assembled phantom and original patient showed excellent agreement. Three-dimensional printing the patient-specific phantom in sagittal slices allowed a large phantom to be fabricated with high accuracy. Our results demonstrate that our 3D printing workflow can be used to make large, accurate, patient-specific phantoms at 100% infill with minimal material warping error. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

3D virtual character reconstruction from projections: a NURBS-based approach

NASA Astrophysics Data System (ADS)

Triki, Olfa; Zaharia, Titus B.; Preteux, Francoise J.

2004-05-01

This work has been carried out within the framework of the industrial project, so-called TOON, supported by the French government. TOON aims at developing tools for automating the traditional 2D cartoon content production. This paper presents preliminary results of the TOON platform. The proposed methodology concerns the issues of 2D/3D reconstruction from a limited number of drawn projections, and 2D/3D manipulation/deformation/refinement of virtual characters. Specifically, we show that the NURBS-based modeling approach developed here offers a well-suited framework for generating deformable 3D virtual characters from incomplete 2D information. Furthermore, crucial functionalities such as animation and non-rigid deformation can be also efficiently handled and solved. Note that user interaction is enabled exclusively in 2D by achieving a multiview constraint specification method. This is fully consistent and compliant with the cartoon creator traditional practice and makes it possible to avoid the use of 3D modeling software packages which are generally complex to manipulate.

Numerical Capacities as Domain-Specific Predictors beyond Early Mathematics Learning: A Longitudinal Study

PubMed Central

Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

2013-01-01

The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3rd and 4th grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively “start-up” tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school. PMID:24255710

Numerical capacities as domain-specific predictors beyond early mathematics learning: a longitudinal study.

PubMed

Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

2013-01-01

The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3(rd) and 4(th) grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively "start-up" tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school.

FOXP3 Expression in GARP-Transduced Helper T Cells Is Not Associated with FOXP3 TSDR Demethylation

PubMed Central

Kehrmann, Jan; Zeschnigk, Michael; Buer, Jan; Probst-Kepper, Michael

2011-01-01

Aim: Glycoprotein A repetitions predominant (GARP or LRRC32) represents a human regulatory CD4+ CD25hi FOXP3+ T (Treg) cell-specific receptor that controls FOXP3. Ectopic expression of GARP in helper T (Th) cells has been shown to be sufficient for the induction of FOXP3 and generation of a stable regulatory phenotype. Since expression of FOXP3 in Treg cells is epigenetically controlled by a conserved motif, the so-called Treg-specific demethylated region (TSDR), we asked whether GARP-mediated upregulation of FOXP3 in Th cells is similarly accompanied by demethylation of the TSDR. Methods: DNA methylation of the FOXP3 TSDR was analyzed by direct sequencing of polymerase chain reaction (PCR) products from bisulfite-treated genomic DNA. Results: Although GARP-transduced Th cells exhibit constitutive FOXP3 expression and a regulatory phenotype, the FOXP3 TSDR is completely methylated as in naive Th cells. GARP-mediated FOXP3 upregulation in Th cells is not associated with Treg-specific demethylation of the FOXP3 TSDR. Conclusion: Although GARP-engineered Th cells exhibit stable FOXP3 expression and a phenotypic reprogramming towards Treg cells in vitro, these cells do not completely mimic the epigenotype of natural Treg cells. Thus, concepts based on the genetic modification of Th cells as cellular therapies to treat autoimmune diseases or to control transplantation tolerance should be critically tested before any clinical application. PMID:22670117

FOXP3 Expression in GARP-Transduced Helper T Cells Is Not Associated with FOXP3 TSDR Demethylation.

PubMed

Kehrmann, Jan; Zeschnigk, Michael; Buer, Jan; Probst-Kepper, Michael

2011-10-01

AIM: Glycoprotein A repetitions predominant (GARP or LRRC32) represents a human regulatory CD4+ CD25(hi) FOXP3+ T (T(reg)) cell-specific receptor that controls FOXP3. Ectopic expression of GARP in helper T (T(h)) cells has been shown to be sufficient for the induction of FOXP3 and generation of a stable regulatory phenotype. Since expression of FOXP3 in Treg cells is epigenetically controlled by a conserved motif, the so-called T(reg)-specific demethylated region (TSDR), we asked whether GARP-mediated upregulation of FOXP3 in Th cells is similarly accompanied by demethylation of the TSDR. METHODS: DNA methylation of the FOXP3 TSDR was analyzed by direct sequencing of polymerase chain reaction (PCR) products from bisulfite-treated genomic DNA. RESULTS: Although GARP-transduced T(h) cells exhibit constitutive FOXP3 expression and a regulatory phenotype, the FOXP3 TSDR is completely methylated as in naive T(h) cells. GARP-mediated FOXP3 upregulation in T(h) cells is not associated with T(reg)-specific demethylation of the FOXP3 TSDR. CONCLUSION: Although GARP-engineered T(h) cells exhibit stable FOXP3 expression and a phenotypic reprogramming towards T(reg) cells in vitro, these cells do not completely mimic the epigenotype of natural T(reg) cells. Thus, concepts based on the genetic modification of T(h) cells as cellular therapies to treat autoimmune diseases or to control transplantation tolerance should be critically tested before any clinical application.

Neural Correlates of Expert Behavior During a Domain-Specific Attentional Cueing Task in Badminton Players.

PubMed

Wang, Chun-Hao; Tu, Kuo-Cheng

2017-06-01

The present study aimed to investigate the neural correlates associated with sports expertise during a domain-specific task in badminton players. We compared event-related potentials activity from collegiate male badminton players and a set of matched athletic controls when they performed a badminton-specific attentional cueing task in which the uncertainty and validity were manipulated. The data showed that, regardless of cue type, the badminton players had faster responses along with greater P3 amplitudes than the athletic controls on the task. Specifically, the contingent negative variation amplitude was smaller for the players than for the controls in the condition involving higher uncertainty. Such an effect, however, was absent in the condition with lower uncertainty. We conclude that expertise in sports is associated with proficient modulation of brain activity during cognitive and motor preparation, as well as response execution, when performing a task related to an individual's specific sport domain.

Focal calcium monitoring with targeted nanosensors at the cytosolic side of endoplasmic reticulum

NASA Astrophysics Data System (ADS)

Hou, Yanyan; Arai, Satoshi; Takei, Yoshiaki; Murata, Atsushi; Takeoka, Shinji; Suzuki, Madoka

2016-01-01

Ca2+ distribution is spatially and temporally non-uniform inside cells due to cellular compartmentalization. However, Ca2+ sensing with small organic dyes, such as fura-2 and fluo-4, has been practically applied at a single cell level where the averaged signal from freely diffusing dye molecules is acquired. In this study, we aimed to target azide-functionalized fura-2 (N3-fura-2) to a specific site of subcellular compartments to realize focal Ca2+ sensing. Using scAVD (single-chain avidin)-biotin interaction and a copper-free click reaction system, we linked N3-fura-2 to specifically-targeted scAVD protein fused with a red fluorescent protein mCherry, so that Ca2+ sensors conjugated with four N3-fura-2 dyes with dibenzocyclooctyne (DBCO)-PEG4-biotin as a linker were generated at subcellular compartments in living cells. In cytoplasm, N3-fura-2 showed a prolonged retention period after binding to scAVD. Furthermore, the reacted N3-fura-2 was retained inside cells even after free dyes were washed out by methanol fixation. When scAVD was overexpressed on endoplasmic reticulum (ER) membranes, N3-fura-2 was accumulated on ER membranes. Upon histamine stimulation, which increases cytosolic Ca2+ concentration, ER-localized N3-fura-2 successfully sensed the Ca2+ level changes at the cytosolic side of ER membrane. Our study demonstrated specific targeting of N3-fura-2 to subcellular compartments and the ability of sensing focal Ca2+ level changes with the specifically targeted Ca2+ sensors.

Turbine Internal and Film Cooling Modeling For 3D Navier-Stokes Codes

NASA Technical Reports Server (NTRS)

DeWitt, Kenneth; Garg Vijay; Ameri, Ali

2005-01-01

The aim of this research project is to make use of NASA Glenn on-site computational facilities in order to develop, validate and apply aerodynamic, heat transfer, and turbine cooling models for use in advanced 3D Navier-Stokes Computational Fluid Dynamics (CFD) codes such as the Glenn-" code. Specific areas of effort include: Application of the Glenn-HT code to specific configurations made available under Turbine Based Combined Cycle (TBCC), and Ultra Efficient Engine Technology (UEET) projects. Validating the use of a multi-block code for the time accurate computation of the detailed flow and heat transfer of cooled turbine airfoils. The goal of the current research is to improve the predictive ability of the Glenn-HT code. This will enable one to design more efficient turbine components for both aviation and power generation. The models will be tested against specific configurations provided by NASA Glenn.

Isolation and characterization of an RNA aptamer for the HPV-16 E7 oncoprotein.

PubMed

Toscano-Garibay, Julia D; Benítez-Hess, María L; Alvarez-Salas, Luis M

2011-02-01

Cervical cancer is a common neoplastic disease affecting women worldwide. Expression of human papillomavirus type 16 (HPV-16) E6/E7 genes is frequently associated with cervical cancer, representing ideal targets for diagnostic and therapeutic strategies. Aptamers are oligonucleotide ligands capable of binding with high affinity and specificity to relevant markers in therapeutics and disease detection. The aim of the study was to isolate an RNA aptamer specific for the HPV-16 E7 protein. Aptamers were selected from a randomized oligonucleotide library using a modified SELEX method and recombinant HPV-16 E7 protein. Isolated aptamers were cloned and sequenced for in silico analysis. Interaction and electromobility shift assays (EMSA) were performed to establish aptamer specificity and affinity for E7. RNase footprinting and serial deletions of the aptamer and the E7 protein were made to characterize the aptamer-protein complex. Sandwich slot-blot assays were used for K(D) determination. After several rounds of SELEX, an aptamer (G5α3N.4) exhibited specificity for E7 using cell-free and protein extracts. G5α3N.4 binding yielded a K(D) comparable to aptamers directed to other small targets. Enzymatic and genetic analysis of G5α3N.4 binding showed a secondary structure with two stem-loop domains joined by single-stranded region contacting E7 in a clamp-like manner. The G5α3N.4 aptamer also produced specific complexes in HPV-positive cervical carcinoma cells. The affinity and specificity of G5α3N.4 binding domains for the HPV-16 E7 protein may be used for the detection of papillomavirus infection and cervical cancer. Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.

Digital PET compliance to EARL accreditation specifications.

PubMed

Koopman, Daniëlle; Groot Koerkamp, Maureen; Jager, Pieter L; Arkies, Hester; Knollema, Siert; Slump, Cornelis H; Sanches, Pedro G; van Dalen, Jorn A

2017-12-01

Our aim was to evaluate if a recently introduced TOF PET system with digital photon counting technology (Philips Healthcare), potentially providing an improved image quality over analogue systems, can fulfil EANM research Ltd (EARL) accreditation specifications for tumour imaging with FDG-PET/CT. We have performed a phantom study on a digital TOF PET system using a NEMA NU2-2001 image quality phantom with six fillable spheres. Phantom preparation and PET/CT acquisition were performed according to the European Association of Nuclear Medicine (EANM) guidelines. We made list-mode ordered-subsets expectation maximization (OSEM) TOF PET reconstructions, with default settings, three voxel sizes (4 × 4 × 4 mm 3 , 2 × 2 × 2 mm 3 and 1 × 1 × 1 mm 3 ) and with/without point spread function (PSF) modelling. On each PET dataset, mean and maximum activity concentration recovery coefficients (RC mean and RC max ) were calculated for all phantom spheres and compared to EARL accreditation specifications. The RCs of the 4 × 4 × 4 mm 3 voxel dataset without PSF modelling proved closest to EARL specifications. Next, we added a Gaussian post-smoothing filter with varying kernel widths of 1-7 mm. EARL specifications were fulfilled when using kernel widths of 2 to 4 mm. TOF PET using digital photon counting technology fulfils EARL accreditation specifications for FDG-PET/CT tumour imaging when using an OSEM reconstruction with 4 × 4 × 4 mm 3 voxels, no PSF modelling and including a Gaussian post-smoothing filter of 2 to 4 mm.

A lentiviral vector with a short troponin-I promoter for tracking cardiomyocyte differentiation of human embryonic stem cells.

PubMed

Gallo, P; Grimaldi, S; Latronico, M V G; Bonci, D; Pagliuca, A; Gallo, P; Ausoni, S; Peschle, C; Condorelli, G

2008-02-01

Human embryonic stem cells (hESCs) may become important for cardiac repair due to their potentially unlimited ability to generate cardiomyocytes (CMCs). Moreover, genetic manipulation of hESC-derived CMCs would be a very promising technique for curing myocardial disorders. At the present time, however, inducing the differentiation of hESCs into CMCs is extremely difficult and, therefore, an easy and standardizable technique is needed to evaluate differentiation strategies. Vectors driving cardiac-specific expression may represent an important tool not only for monitoring new cardiac-differentiation strategies, but also for the manipulation of cardiac differentiation of ESCs. To this aim, we generated cardiac-specific lentiviral vectors (LVVs) in which expression is driven by a short fragment of the cardiac troponin-I proximal promoter (TNNI3) with a human cardiac alpha-actin enhancer, and tested its suitability in inducing tissue-specific gene expression and ability to track the CMC lineage during differentiation of ESCs. We determined that (1) TNNI3-LVVs efficiently drive cardiac-specific gene expression and mark the cardiomyogenic lineage in human and mouse ESC differentiation systems (2) the cardiac alpha-actin enhancer confers a further increase in gene-expression specificity of TNNI3-LVVs in hESCs. Although this technique may not be useful in tracking small numbers of cells, data suggested that TNNI3-based LVVs are a powerful tool for manipulating human ESCs and modifying hESC-derived CMCs.

The effect of St John’s wort extracts on CYP3A: a systematic review of prospective clinical trials

PubMed Central

Whitten, D L; Myers, S P; Hawrelak, J A; Wohlmuth, H

2006-01-01

Aim The aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John’s wort extracts on the metabolism of drugs by CYP3A. Methods Prospective clinical trials assessing the effect of St John’s wort (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. Results Thirty-one studies met the eligibility criteria. More than two-thirds of the studies employed a before-and-after design, less than one-third of the studies used a crossover design, and only three studies were double-blind and placebo controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated the specific SJW extract used. Results from 26 studies, including all of the 19 studies that used high-dose hyperforin extracts (>10 mg day−1), had outcomes consistent with CYP3A induction. The three studies using low-dose hyperforin extracts (<4 mg day−1) demonstrated no significant effect on CYP3A. Conclusion There is reasonable evidence to suggest that high-dose hyperforin SJW extracts induce CYP3A. More studies are required to determine whether decreased CYP3A induction occurs after low-dose hyperforin extracts. Future studies should adopt study designs with a control phase or control group, identify the specific SJW extract employed and provide quantitative analyses of key constituents. PMID:17010103

Transport of steroid 3-sulfates and steroid 17-sulfates by the sodium-dependent organic anion transporter SOAT (SLC10A6).

PubMed

Grosser, Gary; Bennien, Josefine; Sánchez-Guijo, Alberto; Bakhaus, Katharina; Döring, Barbara; Hartmann, Michaela; Wudy, Stefan A; Geyer, Joachim

2018-05-01

The sodium-dependent organic anion transporter SOAT/Soat shows highly specific transport activity for sulfated steroids. SOAT substrates identified so far include dehydroepiandrosterone sulfate, 16α-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17β-estradiol-3-sulfate, and androstenediol sulfate. Apart from these compounds, many other sulfated steroids occur in mammals. Therefore, we aimed to expand the substrate spectrum of SOAT and analyzed the SOAT-mediated transport of eight different sulfated steroids by combining in vitro transport experiments in SOAT-transfected HEK293 cells with LC-MS/MS analytics of cell lysates. In addition, we aimed to better understand the structural requirements for SOAT substrates and so selected structural pairs varying only at specific positions: 3α/3β-sulfate, 17α/17β-sulfate, mono-sulfate/di-sulfate, and 17α-hydroxylation. We found significant and sodium-dependent SOAT-mediated transport of 17α-hydroxypregnenolone sulfate, 17β-estradiol-17-sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and 5α-dihydrotestosterone sulfate. However, 17β-estradiol-3,17-disulfate was not transported by SOAT. SOAT substrates from the group of sulfated steroids are characterized by a planar and lipophilic steroid backbone in trans-trans-trans conformation of the rings and a negatively charged mono-sulfate group at positions 3' or 17' with flexibility for α- or β- orientation. Furthermore, 5α-reduction, 16α-hydroxylation, and 17α-hydroxylation are acceptable for SOAT substrate recognition, whereas addition of a second negatively charged sulfate group seems to abolish substrate binding to SOAT, and so 17β-estradiol-3,17-disulfate is not transported by SOAT. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Validity of a standard questionnaire to assess physical activity for specific medical checkups and health guidance].

PubMed

Kawakami, Ryoko; Miyachi, Motohiko

2010-10-01

This study aimed to determine the validity of a standard questionnaire to assess amount of physical activity (PA) and cardiorespiratory fitness (VO2peak). A total of 483 men and women, aged 20 to 69 years, participated. The standard questionnaire included 3 items about exercise, PA, and walking speed. All questions were designed to require an answer of Yes or No. Subjects were classified into one of four groups regarding the number of Yes answers to the three questions, giving activity levels of 0 to 3. The amount of PA was measured objectively with a tn-axial accelerometer which could also calculate daily step counts, and the amounts of PA under 3 metabolic equivalents (METs) and at 3 METs or more. VO2peak. was measured by incremental cycle exercise tests with indirect calorimetry. The daily step counts, the amount of PA at 3 METs or more, and the VO2peak. were significantly higher in subjects who answered Yes to each question than in those who answered No. Sensitivity and specificity of each question were 62-73% and 45-71% for the amount of PA established with the "Exercise and Physical Activity Reference for Health Promotion 2006 (EPAR2006)". The sum of sensitivity and specificity was the highest when the cutoff value was activity level 2 (sensitivity 73%, specificity 68%). Sensitivity and specificity for VO2max established by EPAR2006 were lower than those for the amount of PA. These results suggest that only answering simple questions with a standard questionnaire is sufficient for estimation of PA levels for specific medical checkups and health guidance, even though the accuracy is somewhat limited.

The Role of Telomeric Repeat Binding Factor 1 (TRF1) in Telomere Maintenance and as a Potential Prognostic Indicator in Human Breast Cancer

DTIC Science & Technology

2006-04-01

for Specific Aim #3 have yet been initiated, and are proceeding on schedule. The PhD candidate has completed her educational goals. 13 Appendix A ... LEVELS OF TELOMERE PROTEIN MRNAS ARE PREDICTIVE OF TELOMERE CONTENT IN HUMAN BREAST TUMORS Kimberly S. Butler, William C. Hines, Diana Roberts

Trek2a regulates gnrh3 expression under control of melatonin receptor Mt1 and α2-adrenoceptor.

PubMed

Loganathan, Kavinash; Moriya, Shogo; Parhar, Ishwar S

2018-02-12

Gonadotrophin-releasing hormone (GnRH) expression is associated with the two-pore domain potassium ion (K + ) channel-related K + (TREK) channel trek2a expression and melatonin levels. We aimed to investigate correlation of trek2a expression with gnrh3 expression, and regulatory mechanisms of trek2a expression by the melatonin receptor Mt1 and α 2 -adrenoceptor which are regulated by melatonin. trek2a specific siRNA, Mt1 antagonist luzindole and α 2 -adrenoceptor antagonist prazosin were administered into the adult zebrafish brain and gene expressions were examined by real-time PCR. trek2a specific siRNA administration significantly reduced expression levels of trek2a, gnrh3 and mt1. Luzindole administration suppressed trek2a and gnrh3 expressions. Prazosin administration reduced trek2a and gnrh3 expressions. It is suggested that Trek2a regulates gnrh3 expression under the control of Mt1 and α 2 -adrenoceptor. Copyright © 2018 Elsevier Inc. All rights reserved.

Sensitivity and Specificity of Fenyö-Lindberg and Teicher Scores in the Diagnosis of Acute Appendicitis in Women

PubMed

Madžar, Zrinko; Kopljar, Mario; Madžar, Tomislav; Mesić, Marko; Mužina Mišić, Dubravka; Čiček, Slaven; Zovak, Mario

2016-12-01

The aim of the study was to assess diagnostic accuracy (sensitivity and specificity) of Fenyö-Lindberg and Teicher scores for distinguishing patients that need immediate surgical treatment from the others, in a female population from an urban setting. The study prospectively included 130 female patients admitted to the emergency department with abdominal pain indicating acute appendicitis. The scores and parameters of validity were calculated and compared to definitive diagnosis. For Fenyö-Lindberg score of -17 or less, 84.5% sensitivity, 55.6% specificity, 87.9% positive predictive value (PPV) and 48.4% negative predictive value (NPV) were recorded. For cut-off value greater or equal to -2, there was 59.2% sensitivity, 77.8% specificity, 91% PPV and 33.3% NPV. The Receiver Operating Characteristic (ROC) curve analysis of Fenyö-Lindberg score showed that the best single cut-off value for discriminating acute appendicitis in the study population was -15. For Teicher score, values greater than -3 yielded 89.3% sensitivity and 22.2% specificity, 81.4% PPV and 35.3% NPV. In conclusion, Fenyö-Lindberg score could be used as an additional tool to exclude appendicitis and avoid unnecessary appendectomies. Teicher score may help in recognizing patients with appendicitis. None of the two scores can indicate or decline appendectomy in all cases. Scoring systems may be useful for pointing to important clinical signs and symptoms in specific subpopulations.

The Art of Science Writing.

ERIC Educational Resources Information Center

Worsley, Dale; Mayer, Bernadette

Aimed at secondary school science and English teachers, this book presents practical advice for developing good student writing in science and mathematics. Five main sections cover: (1) an essay development workshop; (2) 47 specific writing assignments; (3) over 30 questions teachers ask about science writing, and the answers; (4) an anthology of…

Intuitive presentation of clinical forensic data using anonymous and person-specific 3D reference manikins.

PubMed

Urschler, Martin; Höller, Johannes; Bornik, Alexander; Paul, Tobias; Giretzlehner, Michael; Bischof, Horst; Yen, Kathrin; Scheurer, Eva

2014-08-01

The increasing use of CT/MR devices in forensic analysis motivates the need to present forensic findings from different sources in an intuitive reference visualization, with the aim of combining 3D volumetric images along with digital photographs of external findings into a 3D computer graphics model. This model allows a comprehensive presentation of forensic findings in court and enables comparative evaluation studies correlating data sources. The goal of this work was to investigate different methods to generate anonymous and patient-specific 3D models which may be used as reference visualizations. The issue of registering 3D volumetric as well as 2D photographic data to such 3D models is addressed to provide an intuitive context for injury documentation from arbitrary modalities. We present an image processing and visualization work-flow, discuss the major parts of this work-flow, compare the different investigated reference models, and show a number of cases studies that underline the suitability of the proposed work-flow for presenting forensically relevant information in 3D visualizations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Urinary neutrophil gelatinase-associated lipocalin for diagnosis and estimating activity in lupus nephritis: a meta-analysis.

PubMed

Fang, Y G; Chen, N N; Cheng, Y B; Sun, S J; Li, H X; Sun, F; Xiang, Y

2015-12-01

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is relatively specific in lupus nephritis (LN) patients. However, its diagnostic value has not been evaluated. The aim of this review was to determine the value of uNGAL for diagnosis and estimating activity in LN. A comprehensive search was performed on PubMed, EMBASE, Web of Knowledge, Cochrane electronic databases through December 2014. Meta-analysis of sensitivity and specificity was performed with a random-effects model. Additionally, summary receiver operating characteristic (SROC) curves and area under the curve (AUC) values were calculated. Fourteen studies were selected for this review. With respect to diagnosing LN, the pooled sensitivity and specificity were 73.6% (95% confidence interval (CI), 61.9-83.3) and 78.1% (95% CI, 69.0-85.6), respectively. The SROC-AUC value was 0.8632. Regarding estimating LN activity, the pooled sensitivity and specificity were 66.2% (95% CI, 60.4-71.7) and 62.1% (95% CI, 57.9-66.3), respectively. The SROC-AUC value was 0.7583. In predicting renal flares, the pooled sensitivity and specificity were 77.5% (95% CI, 68.1-85.1) and 65.3% (95% CI, 60.0-70.3), respectively. The SROC-AUC value was 0.7756. In conclusion, this meta-analysis indicates that uNGAL has relatively fair sensitivity and specificity in diagnosing LN, estimating LN activity and predicting renal flares, suggesting that uNGAL is a potential biomarker in diagnosing LN and monitoring LN activity. © The Author(s) 2015.

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

PubMed

Pavlov, K A; Shkoporov, A N; Khokhlova, E V; Korchagina, A A; Sidorenkov, A V; Grigor'ev, M É; Pushkar', D Iu; Chekhonin, V P

2013-01-01

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

Integrating Occupational Therapy Specific Assessments in Practice: Exploring Practitioner Experiences

PubMed Central

Nakamura, Mio; Asaba, Akie; Kottorp, Anders

2017-01-01

Background Occupational therapists sometimes find it challenging to integrate client-centered and occupational therapy specific assessments in practice. The aim of this study was to explore the use of occupational therapy specific assessments such as the Assessment of Motor and Process Skills (AMPS) among occupational therapists in Sweden and Japan. Methods Interviews and qualitative thematic analyses were utilized. Findings Four themes are reported: (1) use it or lose it, (2) simply no space until after hours, (3) biggest barriers can be colleagues, and (4) being more specific: communication. Conclusion In keeping with previous studies, occupational therapists often find it challenging to implement client-centered and occupation-based assessment tools into practice. However, more work is needed to understand how best practices can be incorporated into a changing occupational therapy daily practice. PMID:29333112

Alk2/ACVR1 and Alk3/BMPR1A Provide Essential Function for Bone Morphogenetic Protein-Induced Retinal Angiogenesis.

PubMed

Lee, Heon-Woo; Chong, Diana C; Ola, Roxana; Dunworth, William P; Meadows, Stryder; Ka, Jun; Kaartinen, Vesa M; Qyang, Yibing; Cleaver, Ondine; Bautch, Victoria L; Eichmann, Anne; Jin, Suk-Won

2017-04-01

Increasing evidence suggests that bone morphogenetic protein (BMP) signaling regulates angiogenesis. Here, we aimed to define the function of BMP receptors in regulating early postnatal angiogenesis by analysis of inducible, endothelial-specific deletion of the BMP receptor components Bmpr2 (BMP type 2 receptor), Alk1 (activin receptor-like kinase 1), Alk2 , and Alk3 in mouse retinal vessels. Expression analysis of several BMP ligands showed that proangiogenic BMP ligands are highly expressed in postnatal retinas. Consistently, BMP receptors are also strongly expressed in retina with a distinct pattern. To assess the function of BMP signaling in retinal angiogenesis, we first generated mice carrying an endothelial-specific inducible deletion of Bmpr2 . Postnatal deletion of Bmpr2 in endothelial cells substantially decreased the number of angiogenic sprouts at the vascular front and branch points behind the front, leading to attenuated radial expansion. To identify critical BMPR1s (BMP type 1 receptors) associated with BMPR2 in retinal angiogenesis, we generated endothelial-specific inducible deletion of 3 BMPR1s abundantly expressed in endothelial cells and analyzed the respective phenotypes. Among these, endothelial-specific deletion of either Alk2 / acvr1 or Alk3 / Bmpr1a caused a delay in radial expansion, reminiscent of vascular defects associated with postnatal endothelial-specific deletion of BMPR2, suggesting that ALK2/ACVR1 and ALK3/BMPR1A are likely to be the critical BMPR1s necessary for proangiogenic BMP signaling in retinal vessels. Our data identify BMP signaling mediated by coordination of ALK2/ACVR1, ALK3/BMPR1A, and BMPR2 as an essential proangiogenic cue for retinal vessels. © 2017 The Authors.

Development of a Recombinant Protein-Based Enzyme-Linked Immunosorbent Assay for Diagnosis of Mycoplasma bovis Infection in Cattle

PubMed Central

Wawegama, Nadeeka K.; Kanci, Anna; Marenda, Marc S.; Markham, Philip F.

2014-01-01

Mycoplasma bovis causes a range of diseases in cattle, including mastitis, arthritis, and pneumonia. However, accurate serological diagnosis of infection remains problematic. The studies described here aimed to identify an antigen that might be used to develop a more specific and sensitive diagnostic assay. A 226-kDa immunogenic protein was consistently detected in Western blots by antibodies in sera from calves experimentally infected with M. bovis. This protein was shown to be a membrane protein with lipase activity and was named mycoplasma immunogenic lipase A (MilA). Different regions of MilA were expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins and recombinant products from the amino-terminal end shown to have strong immunoreactivity with M. bovis-specific bovine sera. The most immunoreactive fusion protein, GST-MilA-ab, was used to develop indirect IgM and IgG enzyme-linked immunosorbent assays (ELISAs). The IgM ELISA detected M. bovis-specific IgM antibody 2 weeks after infection with 97.1% sensitivity and had a specificity of 63.3%, while the IgG ELISA detected M. bovis-specific IgG 3 weeks after infection with 92.86% sensitivity and had a specificity of 98.7%, demonstrating that the IgG ELISA has potential for use as a sensitive and specific assay for detecting infection in cattle. PMID:24334686

Microtensile bond strength of silorane-based composite specific adhesive system using different bonding strategies.

PubMed

Bastos, Laura Alves; Sousa, Ana Beatriz Silva; Drubi-Filho, Brahim; Panzeri Pires-de-Souza, Fernanda de Carvalho; Garcia, Lucas da Fonseca Roberti

2015-02-01

The aim of this study was to evaluate the effect of pre-etching on the bond strength of silorane-based composite specific adhesive system to dentin. Thirty human molars were randomly divided into 5 groups according to the different bonding strategies. For teeth restored with silorane-based composite (Filtek Silorane, 3M ESPE), the specific self-etching adhesive system (Adhesive System P90, 3M ESPE) was used with and without pre-etching (Pre-etching/Silorane and Silorane groups). Teeth restored with methacrylate based-composite (Filtek Z250, 3M ESPE) were hybridized with the two-step self-etching system (Clearfil SE Bond, Kuraray), with and without pre-etching (Pre-etching/Methacrylate and Methacrylate groups), or three-step adhesive system (Adper Scotchbond Multi-Purpose, 3M ESPE) (Three-step/Methacrylate group) (n = 6). The restored teeth were sectioned into stick-shaped test specimens (1.0 × 1.0 mm), and coupled to a universal test machine (0.5 mm/min) to perform microtensile testing. Pre-etching/Methacrylate group presented the highest bond strength values, with significant difference from Silorane and Three-step/Methacrylate groups (p < 0.05). However, it was not significantly different from Preetching/Silorane and Methacrylate groups. Pre-etching increased bond strength of silorane-based composite specific adhesive system to dentin.

Small-sided games for young athletes: is game specificity influential?

PubMed

Harrison, Craig B; Kilding, Andrew E; Gill, Nicholas D; Kinugasa, Taisuke

2014-01-01

This study aimed to quantify and compare the physiological, physical and technical demands of a sport-specific and non-sport-specific small-sided game (SSG) in young athletes. Ten male soccer players (mean ± SD: age, 13.0 ± 0.3 years, [Formula: see text]O2peak, 54.4 ± 4.9 ml · kg(-1) · min(-1)) completed 3 vs. 3 and 6 vs. 6 soccer and "bucketball" SSGs twice. Games lasted for 16 min and were performed in a randomised order, at least 48 h apart. Movement patterns and heart rate were measured using 4 Hz global positioning systems. Technical skill executions were assessed by video analysis and ratings of perceived exertion (RPE) using the Borg scale (RPEs, 6-20). Total distance (4.9 ± 4.1% and 8.3 ± 6.6%), distance at 7-12.9 km · h(-1) (14.5 ± 12.5% and 14.9 ± 16.1%), total possessions (14.7 ± 18.0% and 12.9 ± 18.9%) and percentage of successful passes (24.1 ± 11.7% and 30.1 ± 17.6%) were higher for bucketball compared to soccer (3 vs. 3 and 6 vs. 6, respectively). Total distance at 13-17.9 km · h(-1) was higher for 6 vs. 6 than 3 vs. 3 bucketball (32.3 ± 21.2%). There was likely substantial difference for %HRpeak (89.5 ± 3.1 vs. 87.4 ± 2.8 b · min(-1)) and time above 90% HRpeak (570 ± 288 s vs. 361 ± 288 s) between bucketball and soccer (3 vs. 3 and 6 vs. 6, respectively). Young players travelled further at higher overall speeds, experienced higher physiological workloads and performed more successful technical executions during the non-sport-specific SSG.

Development and evaluation of a truncated recombinant NS3 antigen-based indirect ELISA for detection of pestivirus antibodies in sheep and goats.

PubMed

Kalaiyarasu, Semmannan; Mishra, Niranjan; Rajukumar, Katherukamem; Nema, Ram Kumar; Behera, Sthita Pragnya

2015-01-01

The aim of this study was to develop an indirect ELISA using the helicase domain of bovine viral diarrhoea virus (BVDV) NS3 protein instead of full-length NS3 protein for detection of BVDV and BDV antibodies in sheep and goats and its validation by comparing its sensitivity and specificity with virus neutralization test (VNT) as the reference test. The purified 50 kDa recombinant NS3 protein was used as the coating antigen in the ELISA. The optimal concentration of antigen was 320 ng/well at a serum dilution of 1:20 and the optimal positive cut-off optical density value was 0.40 based on test results of 418 VNT negative sheep and goat sera samples. When 569 serum samples from sheep (463) and goats (106) were tested, the ELISA showed a sensitivity of 91.71% and specificity of 94.59% with BVDV VNT. A good correlation (93.67%) was observed between the two tests. It showed a sensitivity of 85% and specificity of 86.6% with VNT in detecting BDV antibody positive or negative samples. This study demonstrates the efficacy of truncated recombinant NS3 antigen based ELISA for seroepidemiological study of pestivirus infection in sheep and goats.

Exuberant and inhibited children: Person-centered profiles and links to social adjustment.

PubMed

Dollar, Jessica M; Stifter, Cynthia A; Buss, Kristin A

2017-07-01

The current study aimed to substantiate and extend our understanding regarding the existence and developmental pathways of 3 distinct temperament profiles-exuberant, inhibited, and average approach-in a sample of 3.5-year-old children (n = 121). The interactions between temperamental styles and specific types of effortful control, inhibitory control and attentional control, were also examined in predicting kindergarten peer acceptance. Latent profile analysis identified 3 temperamental styles: exuberant, inhibited, and average approach. Support was found for the adaptive role of inhibitory control for exuberant children and attentional control for inhibited children in promoting peer acceptance in kindergarten. These findings add to our current understanding of temperamental profiles by using sophisticated methodology in a slightly older, community sample, as well as the importance of examining specific types of self-regulation to identify which skills lower risk for children of different temperamental styles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Meat-based functional foods for dietary equilibrium omega-6/omega-3.

PubMed

Reglero, Guillermo; Frial, Paloma; Cifuentes, Alejandro; García-Risco, Mónica R; Jaime, Laura; Marin, Francisco R; Palanca, Vicente; Ruiz-Rodríguez, Alejandro; Santoyo, Susana; Señoráns, Francisco J; Soler-Rivas, Cristina; Torres, Carlos; Ibañez, Elena

2008-10-01

Nutritionists encourage improving the diet by combining meat products with fish or other sea-related foods, in order to equilibrate the omega-6/omega-3 ratio. Strong scientific evidence supports the beneficial health effects of a balanced omega-6/omega-3 PUFA (poly unsaturated fatty acids) diets. In the present work, the scientific bases of new functional meat products with both a balanced omega-6/omega-3 ratio and a synergic combination of antioxidants are discussed. The aim is to contribute to the dietary equilibrium omega-6/omega-3 and to increase the antioxidant intake. Conventional meat products supplemented with a specific fatty acids and antioxidants combination led to functional foods with healthier nutritional parameters.

The Relationship between Listening Strategies Used by Egyptian EFL College Sophomores and Their Listening Comprehension and Self-Efficacy

ERIC Educational Resources Information Center

Kassem, Hassan M.

2015-01-01

The present study explored listening strategy use among a group of Egyptian EFL college sophomores (N = 84). More specifically, it aimed to identify 1) the strategies used more often by participants, 2) the relationship between listening strategy use, and listening comprehension and self-efficacy, and 3) differences in listening comprehension and…

Referential Communication Abilities and Theory of Mind Development in Preschool Children

ERIC Educational Resources Information Center

Resches, Mariela; Pereira, Miguel Perez

2007-01-01

This work aims to analyse the specific contribution of social abilities (here considered as the capacity for attributing knowledge to others) in a particular communicative context. 74 normally developing children (aged 3;4 to 5;9, M=4.6) were given two Theory of Mind (ToM) tasks, which are considered to assess increasing complexity levels of…

Industrial Development of a 3D-Printed Nutraceutical Delivery Platform in the Form of a Multicompartment HPC Capsule.

PubMed

Melocchi, Alice; Parietti, Federico; Maccagnan, Simone; Ortenzi, Marco Aldo; Antenucci, Stefano; Briatico-Vangosa, Francesco; Maroni, Alessandra; Gazzaniga, Andrea; Zema, Lucia

2018-06-05

Following recent advances in nutrigenomics and nutrigenetics, as well as in view of the increasing use of nutraceuticals in combination with drug treatments, considerable attention is being directed to the composition, bioefficacy, and release performance of dietary supplements. Moreover, the interest in the possibility of having such products tailored to meet specific needs is fast growing among costumers. To fulfill these emerging market trends, 3D-printed capsular devices originally intended for conveyance and administration of drugs were proposed for delivery of dietary supplements. Being composed of separate inner compartments, such a device could yield customized combinations of substances, relevant doses, and release kinetics. In particular, the aim of this work was to face early-stage industrial development of the processes involved in fabrication of nutraceutical capsules for oral pulsatile delivery. A pilot plant for extrusion of filaments based on pharmaceutical-grade polymers and intended for 3D printing was set up, and studies aimed at demonstrating feasibility of fused deposition modeling in 3D printing of capsule shells according to Current Good Manufacturing Practices for dietary supplements were undertaken. In this respect, the stability of the starting material after hot processing and of the resulting items was investigated, and compliance of elemental and microbiological contaminants, as well as of by-products, with internal specifications was assessed. Finally, operating charts highlighting critical process variables and parameters that would serve as indices of both intermediate and final product quality were developed.

Acute Total and Chronic Partial Sleep Deprivation: Effects on Neurobehavioral Functions, Waking EEG and Renin-Angiotensin System

NASA Technical Reports Server (NTRS)

Dijk, Derk-Jan

1999-01-01

Total sleep deprivation leads to decrements in neurobehavioral performance and changes in electroencephalographic (EEG) oscillations as well as the incidence of slow eye movements ad detected in the electro-oculogram (EOG) during wakefulness. Although total sleep deprivation is a powerful tool to investigate the association of EEG/EOG and neurobehavioral decrements, sleep loss during space flight is usual only partial. Furthermore exposure to the microgravity environment leads to changes in sodium and volume homeostasis and associated renal and cardio-endocrine responses. Some of these changes can be induced in head down tilt bedrest studies. We integrate research tools and research projects to enhance the fidelity of the simulated conditions of space flight which are characterized by complexity and mutual interactions. The effectiveness of countermeasures and physiologic mechanisms underlying neurobehavioral changes and renal-cardio endocrine changes are investigated in Project 3 of the Human Performance Team and Project 3 of the Cardiovascular Alterations Team respectively. Although the. specific aims of these two projects are very different, they employ very similar research protocols. Thus, both projects investigate the effects of posture/bedrest and sleep deprivation (total or partial) on outcome measures relevant to their specific aims. The main aim of this enhancement grant is to exploit the similarities in research protocols by including the assessment of outcome variables relevant to the Renal-Cardio project in the research protocol of Project 3 of the Human Performance Team and by including the assessment of outcome variables relevant to the Quantitative EEG and Sleep Deprivation Project in the research protocols of Project 3 of the Cardiovascular Alterations team. In particular we will assess Neurobehavioral Function and Waking EEG in the research protocols of the renal-cardio endocrine project and renin-angiotensin and cardiac function in the research protocol of the Quantitative EEG and Waking Neurobehavioral Function project. This will allow us to investigate two additional specific aims: 1) Test the hypothesis that chronic partial sleep deprivation during a 17 day bed rest experiment results in deterioration of neurobehavioral function during waking and increases in EEG power density in the theta frequencies, especially in frontal areas of the brain, as well as the nonREM- REM cycle dependent modulation of heart-rate variability. 2) Test the hypothesis that acute total sleep deprivation modifies the circadian rhythm of the renin-angiotensin system, changes the acute responsiveness of this system to posture beyond what a microgravity environment alone does and affects the nonREM-REM cycle dependent modulation of heart-rate variability.

Cell Kinetic and Histomorphometric Analysis of Microgravitational Osteopenia: PARE.03B

NASA Technical Reports Server (NTRS)

Roberts, W. Eugene; Garetto, Lawrence P.

1997-01-01

The final report includes the hypotheses and specific aims of the project as well as summaries of the experimental findings. Descriptions of several figures that are not included in the report are also presented. A list of publications that resulted from the research is also given. The three experimental summaries are entitled: (1) Pre-flight Experiment to compare 5-Bromo-2'Deoxyuridine (BrdU) Immunohistochemistry and 3H-Thymidine (3HT) Autoradiography; (2) Recovery of Osteoblast Histogenesis in Rat Periodontal Ligament following a 9-day Spaceflight (PARE.03); and (3) Analysis of Mandibular Condyles from PARE.03 Flight Experiment.

Coregulation of srGAP1 by Wnt and Androgen Receptor Signaling: A New Target for Treatment of CRPC

DTIC Science & Technology

2015-10-01

Specific Aim 1: Test the... Specific Aim2: Test the hypothesis that down regulating srGAP1 in CRPC cells change phenotypic...direct interaction between AR and β-catenin seemed to elicit a specific expression of a set of target genes in low androgen conditions in CRPC.

Calorie Restriction in Overweight SeniorS: Response of Older Adults to a Dieting Study: The CROSSROADS Randomized Controlled Clinical Trial

PubMed Central

Haas, Marilyn C.; Bodner, Eric V.; Brown, Cynthia J.; Bryan, David; Buys, David R.; Keita, Akilah Dulin; Flagg, Lee Anne; Goss, Amy; Gower, Barbara; Hovater, Martha; Hunter, Gary; Ritchie, Christine S.; Roth, David L.; Wingo, Brooks C.; Ard, Jamy; Locher, Julie L.

2014-01-01

We conducted a study designed to evaluate whether the benefits of intentional weight loss exceed the potential risks in a group of community-dwelling, obese, older adults who were at increased risk for cardiometabolic disease. The CROSSROADS trial used a prospective randomized controlled design to compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition and adipose tissue deposition (Specific Aim #1: To compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition, namely visceral adipose tissue (VAT)), cardiometabolic disease risk (Specific Aim #2: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on cardiometabolic disease risk), functional status and quality of life (Specific Aim #3: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on functional status and quality of life). Participants were randomly assigned to one of three groups: Exercise Only (Control) Intervention, Exercise + Diet Quality + Weight Maintenance Intervention, or Exercise + Diet Quality + Weight Loss Intervention. CROSSROADS utilized a lifestyle intervention approach consisting of exercise, dietary, and behavioral components. The development and implementation of the CROSSROADS protocol, including a description of the methodology, detailing specific elements of the lifestyle intervention, assurances of treatment fidelity, and participant retention; outcome measures and adverse event monitoring; as well as unique data management features of the trial results, are presented in this article. PMID:25424512

Calorie restriction in overweight seniors: response of older adults to a dieting study: the CROSSROADS randomized controlled clinical trial.

PubMed

Haas, Marilyn C; Bodner, Eric V; Brown, Cynthia J; Bryan, David; Buys, David R; Keita, Akilah Dulin; Flagg, Lee Anne; Goss, Amy; Gower, Barbara; Hovater, Martha; Hunter, Gary; Ritchie, Christine S; Roth, David L; Wingo, Brooks C; Ard, Jamy; Locher, Julie L

2014-01-01

We conducted a study designed to evaluate whether the benefits of intentional weight loss exceed the potential risks in a group of community-dwelling obese older adults who were at increased risk for cardiometabolic disease. The CROSSROADS trial used a prospective randomized controlled design to compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition and adipose tissue deposition (Specific Aim #1: To compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition, namely visceral adipose tissue), cardiometabolic disease risk (Specific Aim #2: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on cardiometabolic disease risk), and functional status and quality of life (Specific Aim #3: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on functional status and quality of life). Participants were randomly assigned to one of three groups: Exercise Only (Control) Intervention, Exercise + Diet Quality + Weight Maintenance Intervention, or Exercise + Diet Quality + Weight Loss Intervention. CROSSROADS utilized a lifestyle intervention approach consisting of exercise, dietary, and behavioral components. The development and implementation of the CROSSROADS protocol, including a description of the methodology, detailing specific elements of the lifestyle intervention, assurances of treatment fidelity, and participant retention; outcome measures and adverse event monitoring; as well as unique data management features of the trial results, are presented in this article.

An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane 3β, 17β diol

PubMed Central

Handa, Robert J.; Pak, Toni R.; Kudwa, Andrea E.; Lund, Trent D.; Hinds, Laura

2008-01-01

The complexity of gonadal steroid hormone actions is reflected in their broad and diverse effects on a host of integrated systems including reproductive physiology, sexual behavior, stress responses, immune function, cognition, and neural protection. Understanding the specific contributions of androgens and estrogens in neurons that mediate these important biological processes is central to the study of neuroendocrinology. Of particular interest in recent years has been the biological role of androgen metabolites. The goal of this review is to highlight recent data delineating the specific brain targets for the dihydrotestosterone metabolite, 5α-androstane, 3β, 17β-diol (3β-Diol). Studies using both in vitro and in vivo approaches provide compelling evidence that 3β-Diol is an important modulator of the stress response mediated by the hypothalmo-pituitary-adrenal axis. Further, the actions of 3β-Diol are mediated by estrogen receptors, and not androgen receptors, often through a canonical estrogen response element in the promoter of a given target gene. These novel findings compel us to re-evaluate the interpretation of past studies and the design of future experiments aimed at elucidating the specific effects of androgen receptor signaling pathways. PMID:18067894

Food-related advertising on preschool television: building brand recognition in young viewers.

PubMed

Connor, Susan M

2006-10-01

This study used content analysis to explore how much and what type of advertising is present in television programming aimed at toddlers and preschool-aged children and what methods of persuasion are being used to sell products and to promote brands to the youngest viewers. Four randomly selected, 4-hour blocks (9 am to 1 pm) were recorded in spring 2005 from each of 3 stations airing programming aimed specifically at toddlers and preschool-aged children (Public Broadcasting Service, Disney, and Nickelodeon). All content that aired in the spaces between programs was examined. Data recorded for food-related advertisements included the primary appeals used to promote products or brands, whether advertisements were aimed at children or adults, whether advertisements used primarily animation or live action, whether advertisements showed food, and whether licensed characters were used. In 96 half-hour blocks of preschool programming, the 3 stations had a total of 130 food-related advertisements (1.354 food advertisements per half-hour). More than one half of all food advertisements (76 of 130 advertisements) were aimed specifically at children, and the majority of those were for fast food chains (50 advertisements) or sweetened cereals (18 advertisements). The primary advertising appeals used associated products with fun and happiness and/or with excitement and energy. Fast food advertisements in particular seemed to focus on building brand recognition and positive associations, through the use of licensed characters, logos, and slogans. The majority of child-oriented food advertisements viewed seemed to take a branding approach, focusing on creating lifelong customers rather than generating immediate sales. Promotional spots on advertisement-supported (Nickelodeon) and sponsor-supported (Public Broadcasting Service and Disney) networks took similar approaches and used similar appeals, seeming to promote the equation that food equals fun and happiness.

Maternal HIV-1 envelope–specific antibody responses and reduced risk of perinatal transmission

PubMed Central

Permar, Sallie R.; Fong, Youyi; Vandergrift, Nathan; Fouda, Genevieve G.; Gilbert, Peter; Parks, Robert; Jaeger, Frederick H.; Pollara, Justin; Martelli, Amanda; Liebl, Brooke E.; Lloyd, Krissey; Yates, Nicole L.; Overman, R. Glenn; Shen, Xiaoying; Whitaker, Kaylan; Chen, Haiyan; Pritchett, Jamie; Solomon, Erika; Friberg, Emma; Marshall, Dawn J.; Whitesides, John F.; Gurley, Thaddeus C.; Von Holle, Tarra; Martinez, David R.; Cai, Fangping; Kumar, Amit; Xia, Shi-Mao; Lu, Xiaozhi; Louzao, Raul; Wilkes, Samantha; Datta, Saheli; Sarzotti-Kelsoe, Marcella; Liao, Hua-Xin; Ferrari, Guido; Alam, S. Munir; Montefiori, David C.; Denny, Thomas N.; Moody, M. Anthony; Tomaras, Georgia D.; Gao, Feng; Haynes, Barton F.

2015-01-01

Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1–transmitting mothers and 165 propensity score–matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1–infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3–specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT. PMID:26053661

Comparison of DWI and PET/CT in evaluation of lymph node metastasis in uterine cancer

PubMed Central

Kitajima, Kazuhiro; Yamasaki, Erena; Kaji, Yasushi; Murakami, Koji; Sugimura, Kazuro

2012-01-01

AIM: To investigate diffusion-weighted imaging (DWI) and positron emission tomography and computed tomography (PET/CT) with IV contrast for the preoperative evaluation of pelvic lymph node (LN) metastasis in uterine cancer. METHODS: Twenty-five patients with endometrial or cervical cancer who underwent both DWI and PET/CT before pelvic lymphadenectomy were included in this study. For area specific analysis, LNs were divided into eight regions: both common iliac, external iliac, internal iliac areas, and obturator areas. The classification for malignancy on DWI was a focally abnormal signal intensity in a location that corresponded to the LN chains on the T1WI and T2WI. The criterion for malignancy on PET/CT images was increased tracer uptake by the LN. RESULTS: A total of 36 pathologically positive LN areas were found in 9 patients. With DWI, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detecting metastatic LNs on an LN area-by-area analysis were 83.3%, 51.2%, 27.3%, 93.3% and 57.0%, respectively, while the corresponding values for PET/CT were 38.9%, 96.3%, 70.0%, 87.8% and 86.0%. Differences in sensitivity, specificity and accuracy were significant (P < 0.0005). CONCLUSION: DWI showed higher sensitivity and lower specificity than PET/CT. Neither DWI nor PET/CT were sufficiently accurate to replace lymphadenectomy. PMID:22761980

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

PubMed

Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors provide novel scaffolds that enable exploiting the prime side of the protease active site, with the aim of achieving better specificity and lower hydrophilicity than those of current scaffolds in the design of antiflaviviral inhibitors. Copyright © 2017 American Society for Microbiology.

A comparison between intrastomal 3D ultrasonography, CT scanning and findings at surgery in patients with stomal complaints.

PubMed

Näsvall, P; Wikner, F; Gunnarsson, U; Rutegård, J; Strigård, K

2014-10-01

Since there are no reliable investigative tools for imaging parastomal hernia, new techniques are needed. The aim of this study was to assess the validity of intrastomal three-dimensional ultrasonography (3D) as an alternative to CT scanning for the assessment of stomal complaints. Twenty patients with stomal complaints, indicating surgery, were examined preoperatively with a CT scan in the supine position and 3D intrastomal ultrasonography in the supine and erect positions. Comparison with findings at surgery, considered to be the true state, was made. Both imaging methods, 3D ultrasonography and CT scanning, showed high sensitivity (ultrasound 15/18, CT scan 15/18) and specificity (ultrasound 2/2, CT scan 1/2) when judged by a dedicated radiologist. Corresponding values for interpretation of CT scans in routine clinical practice was for sensitivity 17/18 and for specificity 1/2. 3D ultrasonography has a high validity and is a promising alternative to CT scanning in the supine position to distinguish a bulge from a parastomal hernia.

Development and Validation of Search Filters to Identify Articles on Family Medicine in Online Medical Databases

PubMed Central

Pols, David H.J.; Bramer, Wichor M.; Bindels, Patrick J.E.; van de Laar, Floris A.; Bohnen, Arthur M.

2015-01-01

Physicians and researchers in the field of family medicine often need to find relevant articles in online medical databases for a variety of reasons. Because a search filter may help improve the efficiency and quality of such searches, we aimed to develop and validate search filters to identify research studies of relevance to family medicine. Using a new and objective method for search filter development, we developed and validated 2 search filters for family medicine. The sensitive filter had a sensitivity of 96.8% and a specificity of 74.9%. The specific filter had a specificity of 97.4% and a sensitivity of 90.3%. Our new filters should aid literature searches in the family medicine field. The sensitive filter may help researchers conducting systematic reviews, whereas the specific filter may help family physicians find answers to clinical questions at the point of care when time is limited. PMID:26195683

Cell-SELEX-Based Identification of a Human and Mouse Cross-Reactive Endothelial Cell-Internalizing Aptamer.

PubMed

Dua, Pooja; Kang, Sinae; Shin, Hye-Soo; Kim, Soyoun; Lee, Dong-Ki

2018-04-02

Increased interest and insights gained by researchers on the roles of endothelial cells in the pathophysiology of cancer, inflammatory, and cardiovascular diseases have led to the design of pharmacological interventions aimed at the endothelium lining in the diseased sites. Toward this end, we used established brain microvascular endothelial cell lines mouse (bEND3), human (hCMEC/D3), and Toggle Cell-SELEX to identify a species cross-reactive, endothelial cell-internalizing aptamer R11-3. This 2'F-modified RNA aptamer is specific for endothelial cells as no internalization was seen with cells of nonendothelial origin. R11-3 was truncated in size, and its potential in endothelial targeted therapeutics was established using VEGFR2 targeting long interfering RNA (liRNA) aptamer chimera. Due to its specificity for both mouse and human endothelial cells, we believe that this aptamer not only fits for development of endothelial targeted drug development for human diseases but is also suitable for preclinical evaluation in mice.

Clinical Validity of hearScreen™ Smartphone Hearing Screening for School Children.

PubMed

Mahomed-Asmail, Faheema; Swanepoel, De Wet; Eikelboom, Robert H; Myburgh, Hermanus C; Hall, James

2016-01-01

The study aimed to determine the validity of a smartphone hearing screening technology (hearScreen™) compared with conventional screening audiometry in terms of (1) sensitivity and specificity, (2) referral rate, and (3) test time. One thousand and seventy school-age children in grades 1 to 3 (8 ± 1.1 average years) were recruited from five public schools. Children were screened twice, once using conventional audiometry and once with the smartphone hearing screening. Screening was conducted in a counterbalanced sequence, alternating initial screen between conventional or smartphone hearing screening. No statistically significant difference in performance between techniques was noted, with smartphone screening demonstrating equivalent sensitivity (75.0%) and specificity (98.5%) to conventional screening audiometry. While referral rates were lower with the smartphone screening (3.2 vs. 4.6%), it was not significantly different (p > 0.05). Smartphone screening (hearScreen™) was 12.3% faster than conventional screening. Smartphone hearing screening using the hearScreen™ application is accurate and time efficient.

Influence and adjustment goals: sources of cultural differences in ideal affect.

PubMed

Tsai, Jeanne L; Miao, Felicity F; Seppala, Emma; Fung, Helene H; Yeung, Dannii Y

2007-06-01

Previous studies have found that in American culture high-arousal positive states (HAP) such as excitement are valued more and low-arousal positive states (LAP) such as calm are valued less than they are in Chinese culture. What specific factors account for these differences? The authors predicted that when people and cultures aimed to influence others (i.e., assert personal needs and change others' behaviors to meet those needs), they would value HAP more and LAP less than when they aimed to adjust to others (i.e., suppress personal needs and change their own behaviors to meet others' needs). They test these predictions in 1 survey and 3 experimental studies. The findings suggest that within and across American and Chinese contexts, differences in ideal affect are due to specific interpersonal goals. (c) 2007 APA, all rights reserved.

Three-Dimensional Printing: Custom-Made Implants for Craniomaxillofacial Reconstructive Surgery

PubMed Central

Matias, Mariana; Zenha, Horácio; Costa, Horácio

2017-01-01

Craniomaxillofacial reconstructive surgery is a challenging field. First it aims to restore primary functions and second to preserve craniofacial anatomical features like symmetry and harmony. Three-dimensional (3D) printed biomodels have been widely adopted in medical fields by providing tactile feedback and a superior appreciation of visuospatial relationship between anatomical structures. Craniomaxillofacial reconstructive surgery was one of the first areas to implement 3D printing technology in their practice. Biomodeling has been used in craniofacial reconstruction of traumatic injuries, congenital disorders, tumor removal, iatrogenic injuries (e.g., decompressive craniectomies), orthognathic surgery, and implantology. 3D printing has proven to improve and enable an optimization of preoperative planning, develop intraoperative guidance tools, reduce operative time, and significantly improve the biofunctional and the aesthetic outcome. This technology has also shown great potential in enriching the teaching of medical students and surgical residents. The aim of this review is to present the current status of 3D printing technology and its practical and innovative applications, specifically in craniomaxillofacial reconstructive surgery, illustrated with two clinical cases where the 3D printing technology was successfully used. PMID:28523082

Electronic data collection for the analysis of surgical maneuvers on patients submitted to rhinoplasty

PubMed Central

Berger, Cezar; Freitas, Renato; Malafaia, Osvaldo; Pinto, José Simão de Paula; Mocellin, Marcos; Macedo, Evaldo; Fagundes, Marina Serrato Coelho

2012-01-01

Summary Introduction: In the health field, computerization has become increasingly necessary in professional practice, since it facilitates data recovery and assists in the development of research with greater scientific rigor. Objective: the present work aimed to develop, apply, and validate specific electronic protocols for patients referred for rhinoplasty. Methods: The prospective research had 3 stages: (1) preparation of theoretical data bases; (2) creation of a master protocol using Integrated System of Electronic Protocol (SINPE©); and (3) elaboration, application, and validation of a specific protocol for the nose and sinuses regarding rhinoplasty. Results: After the preparation of the master protocol, which dealt with the entire field of otorhinolaryngology, we idealized a specific protocol containing all matters related to the patient. In particular, the aesthetic and functional nasal complaints referred for surgical treatment (i.e., rhinoplasty) were organized into 6 main hierarchical categories: anamnesis, physical examination, complementary exams, diagnosis, treatment, and outcome. This protocol utilized these categories and their sub-items: finality; access; surgical maneuvers on the nasal dorsum, tip, and base; clinical evolution after 3, 6, and 12 months; revisional surgery; and quantitative and qualitative evaluations. Conclusion: The developed electronic-specific protocol is feasible and important for information registration from patients referred to rhinoplasty. PMID:25991979

Mexican-American Mental Health Issues: Present Realities and Future Strategies.

ERIC Educational Resources Information Center

Boucher, Stanley W., Ed.; And Others

In June 1970, the Western Interstate Commission on Higher Education Conference on Mexican American Mental Health Issues was held at Goleta, California Primary goal of the conference was to promote learning, not specific action, program funding, or legislation. Planned by Chicanos, the 3-day conference was aimed at bringing together Chicanos from…

Interactive Learning to Stimulate the Brain's Visual Center and to Enhance Memory Retention

ERIC Educational Resources Information Center

Yun, Yang H.; Allen, Philip A.; Chaumpanich, Kritsakorn; Xiao, Yingcai

2014-01-01

This short paper describes an ongoing NSF-funded project on enhancing science and engineering education using the latest technology. More specifically, the project aims at developing an interactive learning system with Microsoft Kinect™ and Unity3D game engine. This system promotes active, rather than passive, learning by employing embodied…

Developing of Indicators of an E-Learning Benchmarking Model for Higher Education Institutions

ERIC Educational Resources Information Center

Sae-Khow, Jirasak

2014-01-01

This study was the development of e-learning indicators used as an e-learning benchmarking model for higher education institutes. Specifically, it aimed to: 1) synthesize the e-learning indicators; 2) examine content validity by specialists; and 3) explore appropriateness of the e-learning indicators. Review of related literature included…

Incremental Learning With Selective Memory (ILSM): Towards Fast Prostate Localization for Image Guided Radiotherapy

PubMed Central

Gao, Yaozong; Zhan, Yiqiang

2015-01-01

Image-guided radiotherapy (IGRT) requires fast and accurate localization of the prostate in 3-D treatment-guided radiotherapy, which is challenging due to low tissue contrast and large anatomical variation across patients. On the other hand, the IGRT workflow involves collecting a series of computed tomography (CT) images from the same patient under treatment. These images contain valuable patient-specific information yet are often neglected by previous works. In this paper, we propose a novel learning framework, namely incremental learning with selective memory (ILSM), to effectively learn the patient-specific appearance characteristics from these patient-specific images. Specifically, starting with a population-based discriminative appearance model, ILSM aims to “personalize” the model to fit patient-specific appearance characteristics. The model is personalized with two steps: backward pruning that discards obsolete population-based knowledge and forward learning that incorporates patient-specific characteristics. By effectively combining the patient-specific characteristics with the general population statistics, the incrementally learned appearance model can localize the prostate of a specific patient much more accurately. This work has three contributions: 1) the proposed incremental learning framework can capture patient-specific characteristics more effectively, compared to traditional learning schemes, such as pure patient-specific learning, population-based learning, and mixture learning with patient-specific and population data; 2) this learning framework does not have any parametric model assumption, hence, allowing the adoption of any discriminative classifier; and 3) using ILSM, we can localize the prostate in treatment CTs accurately (DSC ∼0.89) and fast (∼4 s), which satisfies the real-world clinical requirements of IGRT. PMID:24495983

Prevalence and characteristics of antidepressant drug prescriptions in older Italian patients.

PubMed

Marengoni, A; Bianchi, G; Nobili, A; Tettamanti, M; Pasina, L; Corrao, S; Salerno, F; Iorio, A; Marcucci, M; Mannucci, P M

2012-04-01

During last few decades, the proportion of elderly persons prescribed with antidepressants for the treatment of depression and anxiety has increased. The aim of this study was to evaluate prevalence of antidepressant prescription and related factors in elderly in-patients, as well as the consistency between prescription of antidepressants and specific diagnoses requiring these medications. Thirty-four internal medicine and four geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI study during 2008. In all, 1,155 in-patients, 65 years or older, were enrolled. Prevalence of the use of antidepressants was calculated at both admission and discharge. Logistic regression was used to evaluate the association between patients' characteristics (age, gender, Charlson Index, number of drugs, specific diseases, other psychotropic medications) and the prescription of antidepressants. The number of patients treated with antidepressant medication at hospital admission was 115 (9.9%) and at discharge 119 (10.3%). In a multivariate analysis, a higher number of drugs (OR = 1.2; 95% CI = 1.1-1.3), use of anxiolytic drugs (OR = 2.1; 95% CI = 1.2-3.6 and OR = 3.8; 95% CI = 2.1-6.8), and a diagnosis of dementia (OR = 6.1; 95% CI = 3.1-11.8 and OR = 5.8; 95% CI = 3.3-10.3, respectively, at admission and discharge) were independently associated with antidepressant prescription. A specific diagnosis requiring the use of antidepressants was present only in 66 (57.4%) patients at admission and 76 (66.1%) at discharge. Antidepressants are commonly prescribed in geriatric patients, especially in those receiving multiple drugs, other psychotropic drugs, and those affected by dementia. There is an inconsistency between the prescription of antidepressants and a specific diagnosis that the hospitalization only slightly improves.

Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

NASA Astrophysics Data System (ADS)

McCall, Keisha C.

Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

Integrative View of α2,3-Sialyltransferases (ST3Gal) Molecular and Functional Evolution in Deuterostomes: Significance of Lineage-Specific Losses

PubMed Central

Petit, Daniel; Teppa, Elin; Mir, Anne-Marie; Vicogne, Dorothée; Thisse, Christine; Thisse, Bernard; Filloux, Cyril; Harduin-Lepers, Anne

2015-01-01

Sialyltransferases are responsible for the synthesis of a diverse range of sialoglycoconjugates predicted to be pivotal to deuterostomes’ evolution. In this work, we reconstructed the evolutionary history of the metazoan α2,3-sialyltransferases family (ST3Gal), a subset of sialyltransferases encompassing six subfamilies (ST3Gal I–ST3Gal VI) functionally characterized in mammals. Exploration of genomic and expressed sequence tag databases and search of conserved sialylmotifs led to the identification of a large data set of st3gal-related gene sequences. Molecular phylogeny and large scale sequence similarity network analysis identified four new vertebrate subfamilies called ST3Gal III-r, ST3Gal VII, ST3Gal VIII, and ST3Gal IX. To address the issue of the origin and evolutionary relationships of the st3gal-related genes, we performed comparative syntenic mapping of st3gal gene loci combined to ancestral genome reconstruction. The ten vertebrate ST3Gal subfamilies originated from genome duplication events at the base of vertebrates and are organized in three distinct and ancient groups of genes predating the early deuterostomes. Inferring st3gal gene family history identified also several lineage-specific gene losses, the significance of which was explored in a functional context. Toward this aim, spatiotemporal distribution of st3gal genes was analyzed in zebrafish and bovine tissues. In addition, molecular evolutionary analyses using specificity determining position and coevolved amino acid predictions led to the identification of amino acid residues with potential implication in functional divergence of vertebrate ST3Gal. We propose a detailed scenario of the evolutionary relationships of st3gal genes coupled to a conceptual framework of the evolution of ST3Gal functions. PMID:25534026

Visual versus semi-quantitative analysis of 18F-FDG-PET in amnestic MCI: an European Alzheimer's Disease Consortium (EADC) project.

PubMed

Morbelli, Silvia; Brugnolo, Andrea; Bossert, Irene; Buschiazzo, Ambra; Frisoni, Giovanni B; Galluzzi, Samantha; van Berckel, Bart N M; Ossenkoppele, Rik; Perneczky, Robert; Drzezga, Alexander; Didic, Mira; Guedj, Eric; Sambuceti, Gianmario; Bottoni, Gianluca; Arnaldi, Dario; Picco, Agnese; De Carli, Fabrizio; Pagani, Marco; Nobili, Flavio

2015-01-01

We aimed to investigate the accuracy of FDG-PET to detect the Alzheimer's disease (AD) brain glucose hypometabolic pattern in 142 patients with amnestic mild cognitive impairment (aMCI) and 109 healthy controls. aMCI patients were followed for at least two years or until conversion to dementia. Images were evaluated by means of visual read by either moderately-skilled or expert readers, and by means of a summary metric of AD-like hypometabolism (PALZ score). Seventy-seven patients converted to AD-dementia after 28.6 ± 19.3 months of follow-up. Expert reading was the most accurate tool to detect these MCI converters from healthy controls (sensitivity 89.6%, specificity 89.0%, accuracy 89.2%) while two moderately-skilled readers were less (p < 0.05) specific (sensitivity 85.7%, specificity 79.8%, accuracy 82.3%) and PALZ score was less (p < 0.001) sensitive (sensitivity 62.3%, specificity 91.7%, accuracy 79.6%). Among the remaining 67 aMCI patients, 50 were confirmed as aMCI after an average of 42.3 months, 12 developed other dementia, and 3 reverted to normalcy. In 30/50 persistent MCI patients, the expert recognized the AD hypometabolic pattern. In 13/50 aMCI, both the expert and PALZ score were negative while in 7/50, only the PALZ score was positive due to sparse hypometabolic clusters mainly in frontal lobes. Visual FDG-PET reads by an expert is the most accurate method but an automated, validated system may be particularly helpful to moderately-skilled readers because of high specificity, and should be mandatory when even a moderately-skilled reader is unavailable.

Spatial distribution of the messenger ribonucleic acid and protein of the nuclear receptor coactivator, amplified in breast cancer-3, in mice.

PubMed

Zhang, Hao; Liao, Lan; Kuang, Shao-Qing; Xu, Jianming

2003-04-01

Transcriptional activities of nuclear receptors are modulated by coactivators and corepressors. The amplified in breast cancer-3 protein (AIB3, also known as ASC-2, RAP250, PRIP, TRBP, and NCR) is a newly identified nuclear receptor coactivator that is amplified and overexpressed in breast cancers. This study aims to investigate the spatial expression of AIB3 mRNA and protein in various murine tissues. Quantitative measurements revealed that the concentrations of AIB3 mRNA differ substantially in different tissues in a descending order from the following: testis, brain, thymus, white fat, pituitary, ovary, adrenal gland, lung, uterus, kidney, heart, skeletal muscle, liver, and virgin mammary gland. The AIB3 mRNA level in the testis is 165-fold higher than that in the virgin mammary gland. Specific antiserum was generated and used to map the distribution of AIB3 protein by immunohistochemistry. Although AIB3 protein was detected in many tissues, the AIB3 immunoreactivities varied significantly from cell type to cell type. High levels of AIB3 immunoreactivity were observed in hormone target cells including the testicular Sertoli cells, follicular granulosa cells, and epithelial cells of the prostate, uterus, mammary gland, and kidney tubules. Medium and low levels of AIB3 immunoreactivities were also detected in a variety of other cell types. These results demonstrate that AIB3 mRNA and protein are preferentially expressed in specific cell types, suggesting that AIB3 may support the function of nuclear receptors in a cell type-specific manner.

Brain metabolic pattern analysis using a magnetic resonance spectra classification software in experimental stroke.

PubMed

Jiménez-Xarrié, Elena; Davila, Myriam; Candiota, Ana Paula; Delgado-Mederos, Raquel; Ortega-Martorell, Sandra; Julià-Sapé, Margarida; Arús, Carles; Martí-Fàbregas, Joan

2017-01-13

Magnetic resonance spectroscopy (MRS) provides non-invasive information about the metabolic pattern of the brain parenchyma in vivo. The SpectraClassifier software performs MRS pattern-recognition by determining the spectral features (metabolites) which can be used objectively to classify spectra. Our aim was to develop an Infarct Evolution Classifier and a Brain Regions Classifier in a rat model of focal ischemic stroke using SpectraClassifier. A total of 164 single-voxel proton spectra obtained with a 7 Tesla magnet at an echo time of 12 ms from non-infarcted parenchyma, subventricular zones and infarcted parenchyma were analyzed with SpectraClassifier ( http://gabrmn.uab.es/?q=sc ). The spectra corresponded to Sprague-Dawley rats (healthy rats, n = 7) and stroke rats at day 1 post-stroke (acute phase, n = 6 rats) and at days 7 ± 1 post-stroke (subacute phase, n = 14). In the Infarct Evolution Classifier, spectral features contributed by lactate + mobile lipids (1.33 ppm), total creatine (3.05 ppm) and mobile lipids (0.85 ppm) distinguished among non-infarcted parenchyma (100% sensitivity and 100% specificity), acute phase of infarct (100% sensitivity and 95% specificity) and subacute phase of infarct (78% sensitivity and 100% specificity). In the Brain Regions Classifier, spectral features contributed by myoinositol (3.62 ppm) and total creatine (3.04/3.05 ppm) distinguished among infarcted parenchyma (100% sensitivity and 98% specificity), non-infarcted parenchyma (84% sensitivity and 84% specificity) and subventricular zones (76% sensitivity and 93% specificity). SpectraClassifier identified candidate biomarkers for infarct evolution (mobile lipids accumulation) and different brain regions (myoinositol content).

Overview of the INEX 2008 Book Track

NASA Astrophysics Data System (ADS)

Kazai, Gabriella; Doucet, Antoine; Landoni, Monica

This paper provides an overview of the INEX 2008 Book Track. Now in its second year, the track aimed at broadening its scope by investigating topics of interest in the fields of information retrieval, human computer interaction, digital libraries, and eBooks. The main topics of investigation were defined around challenges for supporting users in reading, searching, and navigating the full texts of digitized books. Based on these themes, four tasks were defined: 1) The Book Retrieval task aimed at comparing traditional and book-specific retrieval approaches, 2) the Page in Context task aimed at evaluating the value of focused retrieval approaches for searching books, 3) the Structure Extraction task aimed to test automatic techniques for deriving structure from OCR and layout information, and 4) the Active Reading task aimed to explore suitable user interfaces for eBooks enabling reading, annotation, review, and summary across multiple books. We report on the setup and results of each of these tasks.

Alk2/ACVR1 and Alk3/BMPR1A Provide Essential Function for Bone Morphogenetic Protein Induced Retinal Angiogenesis

PubMed Central

Lee, Heon-Woo; Chong, Diana C.; Ola, Roxana; Dunworth, William P.; Meadows, Stryder; Ka, Jun; Kaartinen, Vesa M.; Qyang, Yibing; Cleaver, Ondine; Bautch, Victoria L.; Eichmann, Anne; Jin, Suk-Won

2017-01-01

Objective Increasing evidence suggests that Bone Morphogenetic Protein (BMP) signaling regulates angiogenesis. Here, we aimed to define the function of BMP receptors in regulating early post-natal angiogenesis by analysis of inducible, endothelial specific deletion of the BMP receptor components Bmpr2, Alk1, Alk2 and Alk3 in mouse retinal vessels. Approach and Results Expression analysis of several BMP ligands showed that pro-angiogenic BMP ligands are highly expressed in postnatal retinas. Consistently, BMP receptors are also strongly expressed in retina with a distinct pattern. To assess the function of BMP signaling in retinal angiogenesis, we first generated mice carrying an endothelial-specific inducible deletion of BMP Type 2 receptor (Bmpr2). Postnatal deletion of Bmpr2 in endothelial cells substantially decreased the number of angiogenic sprouts at the vascular front and branchpoints behind the front, leading to attenuated radial expansion. To identify critical BMPR1s associated with BMPR2 in retinal angiogenesis, we generated endothelial-specific inducible deletion of three BMPR1s abundantly expressed in endothelial cells and analyzed the respective phenotypes. Among these, endothelial specific deletion of either Alk2/acvr1 or Alk3/Bmpr1a caused a delay in radial expansion, reminiscent of vascular defects associated with postnatal endothelial specific deletion of BMPR2, suggesting that ALK2/ACVR1 and ALK3/BMPR1A are likely to be the critical BMPR1s necessary for pro-angiogenic BMP signaling in retinal vessels. Conclusions Our data identify BMP signaling mediated by coordination of ALK2/ACVR1, ALK3/BMPR1A, and BMPR2 as an essential pro-angiogenic cue for retinal vessels. PMID:28232325

Diagnostic criteria for hepatocellular carcinoma ⩽3 cm with hepatocyte-specific contrast-enhanced magnetic resonance imaging.

PubMed

Choi, Sang Hyun; Byun, Jae Ho; Lim, Young-Suk; Yu, Eunsil; Lee, So Jung; Kim, So Yeon; Won, Hyung Jin; Shin, Yong Moon; Kim, Pyo Nyun

2016-05-01

Current diagnostic imaging criteria for hepatocellular carcinoma (HCC) are dedicated to imaging with nonspecific extracellular contrast agents. This study aimed to evaluate diagnostic criteria for HCC ⩽3 cm on magnetic resonance imaging (MRI) with a hepatocyte-specific contrast agent through an inception cohort study. Of 291 patients with chronic liver disease and new nodules of 1-3 cm in diameter at surveillance ultrasonography, 295 solid nodules (194 HCCs, 98 benign nodules, and three other malignancies) in 198 patients with a confirmed final diagnosis or ⩾24 months follow-up were evaluated on gadoxetic acid-enhanced MRI. Through univariate and multivariate logistic regression analyses, various diagnostic criteria were developed by combining significant MRI findings for diagnosing HCC. The diagnostic performance of each criterion was compared with that of the European Association for the Study of the Liver (EASL) criteria. Four MRI findings (arterial-phase hyperintensity, transitional-phase hypointensity, hepatobiliary-phase hypointensity, and rim enhancement) were independently significant for diagnosis of HCC ⩽3 cm. For whole nodules, EASL criteria showed the best performance for diagnosing HCC (sensitivity, 83.5%; specificity, 81.2%). For nodules ⩽2 cm in diameter, a new criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) showed a significantly higher sensitivity than that of the EASL criteria (83.0% vs. 74.5%, p=0.008), without a significantly different specificity (76.7% vs. 81.1%, p=0.125). EASL criteria exhibit the best diagnostic performance for HCC ⩽3 cm on hepatocyte-specific contrast-enhanced MRI. A newly identified criterion (arterial-phase hyperintensity and hepatobiliary-phase hypointensity) may increase the diagnostic sensitivity of small (⩽2 cm) HCC. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Genotyping of coeliac-specific human leucocyte antigen in children with type 1 diabetes: does this screening method make sense?

PubMed

Binder, Elisabeth; Loinger, Martina; Mühlbacher, Annelies; Edlinger, Michael; Steichen, Elisabeth; Meraner, Dagmar; Loacker, Lorin; Weigel, Guenter; Müller, Thomas; Fröhlich-Reiterer, Elke; Hofer, Sabine E

2017-07-01

Due to a high linkage disequilibrium of diabetes and coeliac-specific human leucocyte antigen (HLA) genotypes, the prevalence of coeliac disease (CD) in children and adolescents with diabetes mellitus type 1 (T1D) is much higher than in the general population. Recently, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) revised new screening guidelines in which genotyping for coeliac-specific HLA alleles is recommended for high-risk patients as patients with T1D. The aim of our study was to investigate the frequency and distribution of coeliac-specific HLA genotypes in paediatric patients with T1D. HLA genotyping was performed on paediatric patients with T1D, recruited at the Medical University Hospital of Innsbruck and Graz. The test was done by PCR. Statistical analysis was performed with IBM-SPSS V.20. In 121 paediatric patients with T1D (52% male), mean age 13.3 (SD 3.9) years, mean age at diabetes diagnosis 7.4 (SD 3.8) and mean diabetes duration of 5.9 (SD 3.3) years, HLA genotyping was conducted. Ninety-two per cent showed positive HLA DQ2 and/or HLA DQ8 genotypes. Thirty-four per cent carried HLA DQ2, 33% were HLA DQ2+DQ8 positive and 25% of the patients showed positive results for HLA DQ8 alone. Only 8% had no coeliac-specific HLA markers. Four (3%) patients were diagnosed with CD. The majority of paediatric patients with T1D has positive coeliac-specific HLA genotypes DQ2 and/or DQ8. Therefore, genotyping for coeliac-specific HLA alleles as a first-line test in patients with T1D as recommended in the ESPGHAN guidelines does not seem reasonable. Screening for coeliac-specific antibodies needs to be performed on a regular basis for patients with T1D. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Designing Polyamide Inhibitors of TWIST 1 for Prosenescence Therapy

DTIC Science & Technology

2014-09-01

Pyrrole -Imidazole Polyamides; TWIST1; KRAS; non-small cell lung cancer (NSCLC); senescence 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF... Pyrrole -Imidazole Polyamides (PIP) are a class of cell permeable programmable small-molecule heterocyclic amino acid oligomers that can be designed...The original specific aims are below: Specific Aim#1. Design and synthesize a TWIST1-inhibitory specific Pyrrole -Imidazole Polyamides (PIP

GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development.

PubMed

Brichard, Vincent G; Lejeune, Diane

2007-09-27

From the first evidence that the immune system could recognize tumors, different types of tumor antigens have been identified and deeply characterized. Several different approaches aimed at targeting these antigens have already been the subject of clinical studies. In this field, the GSK Biologicals' approach relying on recombinant proteins combined with an immunological Adjuvant System in a specific clinical setting, has entertained hopes of developing a new class of well tolerated anti-cancer therapy. This methodology led to promising advances with MAGE-A3 immunotherapy in NSCLC and has the potential to be applied to all tumor types.

Prediction of vesicoureteral reflux after a first febrile urinary tract infection in children: validation of a clinical decision rule

PubMed Central

Leroy, S; Marc, E; Adamsbaum, C; Gendrel, D; Bréart, G; Chalumeau, M

2006-01-01

Aims To test the reproducibility of a highly sensitive clinical decision rule proposed to predict vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children. This rule combines clinical (family history of uropathology, male gender, young age), biological (raised C reactive protein), and radiological (urinary tract dilation on renal ultrasound) predictors in a score, and provides 100% sensitivity. Methods A retrospective hospital based cohort study included all children, 1 month to 4 years old, with a first febrile urinary tract infection. The sensitivities and specificities of the rule at the two previously proposed score thresholds (⩽0 and ⩽5) to predict respectively, all‐grade or grade ⩾3 VUR, were calculated. Results A total of 149 children were included. VUR prevalence was 25%. The rule yielded 100% sensitivity and 3% specificity for all‐grade VUR, and 93% sensitivity and 13% specificity for grade ⩾3 VUR. Some methodological weaknesses explain this lack of reproducibility. Conclusions The reproducibility of the previously proposed decision rule was poor and its potential contribution to clinical management of children with febrile urinary tract infection seems to be modest. PMID:15890693

3D-printed upper limb prostheses: a review.

PubMed

Ten Kate, Jelle; Smit, Gerwin; Breedveld, Paul

2017-04-01

This paper aims to provide an overview with quantitative information of existing 3D-printed upper limb prostheses. We will identify the benefits and drawbacks of 3D-printed devices to enable improvement of current devices based on the demands of prostheses users. A review was performed using Scopus, Web of Science and websites related to 3D-printing. Quantitative information on the mechanical and kinematic specifications and 3D-printing technology used was extracted from the papers and websites. The overview (58 devices) provides the general specifications, the mechanical and kinematic specifications of the devices and information regarding the 3D-printing technology used for hands. The overview shows prostheses for all different upper limb amputation levels with different types of control and a maximum material cost of $500. A large range of various prostheses have been 3D-printed, of which the majority are used by children. Evidence with respect to the user acceptance, functionality and durability of the 3D-printed hands is lacking. Contrary to what is often claimed, 3D-printing is not necessarily cheap, e.g., injection moulding can be cheaper. Conversely, 3D-printing provides a promising possibility for individualization, e.g., personalized socket, colour, shape and size, without the need for adjusting the production machine. Implications for rehabilitation Upper limb deficiency is a condition in which a part of the upper limb is missing as a result of a congenital limb deficiency of as a result of an amputation. A prosthetic hand can restore some of the functions of a missing limb and help the user in performing activities of daily living. Using 3D-printing technology is one of the solutions to manufacture hand prostheses. This overview provides information about the general, mechanical and kinematic specifications of all the devices and it provides the information about the 3D-printing technology used to print the hands.

Facile construction of 3D graphene/MoS2 composites as advanced electrode materials for supercapacitors

NASA Astrophysics Data System (ADS)

Sun, Tianhua; Li, Zhangpeng; Liu, Xiaohong; Ma, Limin; Wang, Jinqing; Yang, Shengrong

2016-11-01

Flower-like molybdenum disulfide (MoS2) microstructures are synthesized based on three-dimensional graphene (3DG) skeleton via a simple and facile one-step hydrothermal method, aiming at constructing series of novel composite electrode materials of 3DG/MoS2 with high electrochemical performances for supercapacitors. The electrochemical properties of the samples are evaluated by cyclic voltammetry and galvanostatic charge/discharge tests. Specifically, the optimal 3DG/MoS2 composite exhibits remarkable performances with a high specific capacitance of 410 F g-1 at a current density of 1 A g-1 and an excellent cycling stability with ca. 80.3% capacitance retention after 10,000 continuous charge-discharge cycles at a high current density of 2 A g-1, making it adaptive for high-performance supercapacitors. The enhanced electrochemical performances can be ascribed to the combination of 3DG and flower-like MoS2, which provides excellent charge transfer network and electrolyte diffusion channels while effectively prevents the collapse, aggregation and morphology change of active materials during charge-discharge process. The results demonstrate that 3DG/MoS2 composite is one of the attractive electrode materials for supercapacitors.

MIDAS questionnaire modification for a new MIDAS junior questionnaire: a clinical experience at the Neurological Institute "C. Besta".

PubMed

Grazzi, L

2004-10-01

During the last decade researchers have begun to employ standardised methodologies to investigate the global impact of primary headaches. Disease-specific instruments have been developed to measure headache-related disability. The MIDAS questionnaire, which is the most extensively studied of these instruments, was designed to assess the overall impact of headaches over the 3 months before compilation. The MIDAS questionnaire is an optimal tool to assess headache-related disability in adults in relation to patients' daily activities. Primary headaches are a recurrent problem for children and adolescents. Forty percent of children have experienced headaches by the age of 7 years increasing to 75% by the age of 15. In a recent report we determined the suitability of the MIDAS questionnaire in its original form for assessing disability in children and adolescents suffering from different kinds of headache. This was the first step of a line of research aimed to develop a new MIDAS questionnaire adapted for young patients. In this second study the aims were: (1) to produce a new version of the MIDAS questionnaire specific for young patients suffering from different forms of headache; (2) to assess the reliability of this new instrument; (3) to assess its sensitivity to treatment intervention.

Polyphenois and Prostate Cancer Chemoprevention

DTIC Science & Technology

2006-03-01

The goal of this research is to investigate the potential of resveratrol genistein and (-) epigallocatechin -3- gallate ( EGCG ), alone in combination...to protect against prostate cancer in a transgenic rat model (TRAMP). The specific aims are 1) to investigate the potential of genistein, EGCG and...we have demonstrated that pure resveratrol in the diet, but not EGCG in the water, suppressed spontaneously developing prostate tumors in TRAMPs

Low performance on mathematical tasks in preschoolers: the importance of domain-general and domain-specific abilities.

PubMed

Costa, H M; Nicholson, B; Donlan, C; Van Herwegen, J

2018-04-01

Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether this also holds for preschool low achievers (LAs) and how domain-specific and domain-general abilities contribute to mathematical difficulties at a young age. The aim of this study was to explore the cognitive characteristics of a sample of preschool LAs and identify sub-types of LAs. 81 children were identified as LAs from 283 preschoolers aged 3 to 5 years old and were assessed on a number of domain-general and domain-specific tasks. Cluster analysis revealed four subgroups of LAs in mathematics: (1) a weak processing sub-type; (2) a general mathematical LAs sub-type; (3) a mixed abilities sub-type; and (4) a visuo-spatial deficit sub-type. Whilst two of the groups showed specific domain-general difficulties, none showed only domain-specific difficulties. Current findings suggest that preschool LAs constitute a heterogeneous group and stress the importance of domain-general factors for the development of mathematical abilities during the preschool years. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Science Library of Test Items. Volume Eight. Mastery Testing Program. Series 3 & 4 Supplements to Introduction and Manual.

ERIC Educational Resources Information Center

New South Wales Dept. of Education, Sydney (Australia).

Continuing a series of short tests aimed at measuring student mastery of specific skills in the natural sciences, this supplementary volume includes teachers' notes, a users' guide and inspection copies of test items 27 to 50. Answer keys and test scoring statistics are provided. The items are designed for grades 7 through 10, and a list of the…

Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial Joints

DTIC Science & Technology

2016-10-01

test whether the pathological accumulation of a specific substance found in joint fluid following an injury mediated altered synovial fluid...joint injury contributes to the development of post-traumatic OA and is due, in part, to the pathological accumulation of a...studies, SF samples will be analyzed for the suspected pathological substance as well as lubrication function. 3.b.ii. Aim 2b

Biomedical Investigations with Laser-Polarized Noble Gas Magnetic Resonance

NASA Technical Reports Server (NTRS)

Walsworth, Ronald L.

2001-01-01

We are developing laser-polarized noble gas nuclear magnetic resonance (NMR) as a novel biomedical imaging tool for ground-based and eventually space-based application. This emerging multidisciplinary technology enables high-resolution gas-space magnetic resonance imaging (MRI) (e.g., of lung ventilation) as well as studies of tissue perfusion. In addition, laser-polarized noble gases (He-3 and Xe-129) do not require a large magnetic field for sensitive detection, opening the door to practical MRI at very low magnetic fields with an open, lightweight, and low-power device. We are pursuing two specific aims in this research. The first aim is to develop a low-field (< 0.01 T) instrument for noble gas MRI of humans, and the second aim is to develop functional MRI of the lung using laser-polarized Xe-129 and related techniques.

Genetics of solvent-producing clostridia. Final technical report

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

NONE

Specific Aims 1 and 2 of the original project proposal were specifically addressed during this project period. This involved the development of the pCAK1 phagemid delivery vector, refinement of the C. acetobutylicum electroporation protocol, selection and characterization of the engB cellulase gene from C. cellulovorans and the introduction and successful expression of this heterologous engB gene from C. cellulovorans in C. acetobutylicum. The successful expression of a heterologous engB gene from C. cellulovorans in C. acetobutylicum ATCC 824 has important industrial significance for the utilization of cellulose by this ABE fermentation microorganism. Conversion efficiency testing of the developed recombinant strainsmore » in batch and continuous culture (Specific Aim 3) will be carried out once suitable strains have been developed which can utilize cellulose as sole carbon source. The functionality of pCAK1 in the E. coli host system, especially in generating ssDNA, in the absence of impairing E. coli cell viability, together with successful introduction of pCAK1 into C. acetobutylicum and C. perfringens is the basis for the construction of a M13-like genetic system for the genus Clostridium and is expected to allow for more sophisticated molecular genetic analysis of this genus.« less

The Memory Alteration Test Discriminates between Cognitively Healthy Status, Mild Cognitive Impairment and Alzheimer's Disease

PubMed Central

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Nuñez del Prado, Liza; Parodi, José; Guevara-Silva, Erik; Castro-Suarez, Sheila; Montesinos, Rosa; Cortijo, Patricia

2014-01-01

Background/Aims Dementia is a worldwide public health problem and there are several diagnostic tools for its assessment. The aim of this study was to evaluate the performance of the Memory Alteration Test (M@T) to discriminate between patients with early Alzheimer's disease (AD), patients with amnestic mild cognitive impairment (a-MCI), and subjects with a cognitively healthy status (CHS). Methods The discriminative validity was assessed in a sample of 90 patients with AD, 45 patients with a-MCI, and 180 subjects with CHS. Clinical, functional, and cognitive studies were independently performed in a blinded fashion and the gold standard diagnosis was established by consensus on the basis of these results. The test performance was assessed by means of a receiver operating characteristic curve analysis as area under the curve (AUC). Results M@T mean scores were 17.7 (SD = 5.7) in AD, 30.8 (SD = 2.3) in a-MCI, and 44.5 (SD = 3.1) in CHS. A cutoff score of 37 points had a sensitivity of 98.3% and a specificity of 97.8% to differentiate a-MCI from CHS (AUC = 0.999). A cutoff score of 27 points had a sensitivity of 100% and a specificity of 98.9% to differentiate mild AD from a-MCI and from CHS (AUC = 1.000). Conclusions The M@T had a high performance in the discrimination between early AD, a-MCI and CHS. PMID:25298775

The Impact of Mechanical and Restricted Kinematic Alignment on Knee Anatomy in Total Knee Arthroplasty.

PubMed

Almaawi, Abdulaziz M; Hutt, Jonathan R B; Masse, Vincent; Lavigne, Martin; Vendittoli, Pascal-Andre

2017-07-01

Total knee arthroplasty (TKA), aiming at neutral mechanical alignment (MA), inevitably modifies the patient's native knee anatomy. Another option is kinematic alignment (KA), which aims to restore the original anatomy of the knee. The aim of this study was to evaluate the variations in lower limb anatomy of a patient population scheduled for TKA, and to assess the use of a restricted KA TKA protocol and compare the resulting anatomic modifications with the standard MA technique. A total of 4884 knee computed tomography scans were analyzed from a database of patients undergoing TKA with patient-specific instrumentation. The lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and hip-knee-ankle angle (HKA) were measured. Bone resections were compared using a standard MA and a restricted KA aiming for independent tibial and femoral cuts of maximum ±5° deviation from the coronal mechanical axis and a resulting overall coronal HKA within ±3° of neutral. The mean preoperative MPTA was 2.9° varus, LDFA was 2.7° valgus, and overall HKA was 0.1° varus. Using our protocol, 2475 knees (51%) could have undergone KA without adjustment. To include 4062 cases (83%), mean corrections of 0.5° for MPTA and 0.3° for LDFA were needed, significantly less than with MA (3.3° for MPTA and 3.2° for LDFA; P < .001). The range of knee anatomy in patients scheduled for TKA is wide. MA leads to greater modifications of knee joint anatomy. To avoid reproducing extreme anatomy, the proposed restricted KA protocol provides an interesting hybrid option between MA and true KA. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome.

PubMed

Kumbak, Banu; Oral, Engin; Karlikaya, Guvenc; Lacin, Selman; Kahraman, Semra

2006-10-01

The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and beta-human chorionic gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG-beta) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP (P

Cartilage Dysfunction in ALS Patients as Side Effect of Motion Loss: 3D Mechano-Electrochemical Computational Model

PubMed Central

Gaffney, Eamonn A.; Doblaré, Manuel

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease characterized by progressive weakness, muscle atrophy, and fasciculation. This fact results in a continuous degeneration and dysfunction of articular soft tissues. Specifically, cartilage is an avascular and nonneural connective tissue that allows smooth motion in diarthrodial joints. Due to the avascular nature of cartilage tissue, cells nutrition and by-product exchange are intermittently occurring during joint motions. Reduced mobility results in a change of proteoglycan density, osmotic pressure, and permeability of the tissue. This work aims to demonstrate the abnormal cartilage deformation in progressive immobilized articular cartilage for ALS patients. For this aim a novel 3D mechano-electrochemical model based on the triphasic theory for charged hydrated soft tissues is developed. ALS patient parameters such as tissue porosity, osmotic coefficient, and fixed anions were incorporated. Considering different mobility reduction of each phase of the disease, results predicted the degree of tissue degeneration and the reduction of its capacity for deformation. The present model can be a useful tool to predict the evolution of joints in ALS patients and the necessity of including specific cartilage protectors, drugs, or maintenance physical activities as part of the symptomatic treatment in amyotrophic lateral sclerosis. PMID:24991537

Center for Innovative Minimally Invasive Therapy

DTIC Science & Technology

1999-11-01

discrete layers within the image. In vivo OCT image of a stent deployed in a swine coronary artery. Shadowing of the metallic stent is seen as areas of...Task 3: Vascular Stent -Grafts Specific Aim 1: Develop novel procedures for the treatment of aneurysms and vascular trauma using percutaneous...applied to coronary anastomoses in chronic studies. One particularly interesting application may be as an external stent to maintain or increase the

The Link between Preschoolers' Executive Function and Theory of Mind and the Role of Epistemic States

ERIC Educational Resources Information Center

Henning, Anne; Spinath, Frank M.; Aschersleben, Gisa

2011-01-01

The aim of this study was to assess the specific relation between 3- to 6-year-olds' performance on a task measuring executive function (EF), the Dimensional Change Card Sort task (DCCS), and different developmental attainments in their theory of mind (ToM) by employing a battery of scaled ToM tasks that were comparable in task format and task…

Novel insights on nutrient management of sarcopenia in elderly.

PubMed

Rondanelli, Mariangela; Faliva, Milena; Monteferrario, Francesca; Peroni, Gabriella; Repaci, Erica; Allieri, Francesca; Perna, Simone

2015-01-01

Sarcopenia is defined as a syndrome characterized by progressive and generalized loss of muscle mass and strength. The more rationale approach to delay the progression of sarcopenia is based on the combination of proper nutrition, possibly associated with the use of dietary supplements and a regular exercise program. We performed a narrative literature review to evaluate the till-now evidence regarding (1) the metabolic and nutritional correlates of sarcopenia; (2) the optimum diet therapy for the treatment of these abnormalities. This review included 67 eligible studies. In addition to the well recognized link between adequate intake of proteins/amino acids and sarcopenia, the recent literature underlines that in sarcopenic elderly subjects there is an unbalance in vitamin D synthesis and in omega-6/omega-3 PUFA ratio. Given the detrimental effect of these metabolic abnormalities, a change in the lifestyle must be the cornerstone in the treatment of sarcopenia. The optimum diet therapy for the sarcopenia treatment must aim at achieving specific metabolic goals, which must be reached through accession of the elderly to specific personalized dietary program aimed at achieving and/or maintaining muscle mass; increasing their intake of fish (4 times/week) or taking omega-3 PUFA supplements; taking vitamin D supplementation, if there are low serum levels.

Novel Insights on Nutrient Management of Sarcopenia in Elderly

PubMed Central

Rondanelli, Mariangela; Faliva, Milena; Monteferrario, Francesca; Peroni, Gabriella; Repaci, Erica

2015-01-01

Sarcopenia is defined as a syndrome characterized by progressive and generalized loss of muscle mass and strength. The more rationale approach to delay the progression of sarcopenia is based on the combination of proper nutrition, possibly associated with the use of dietary supplements and a regular exercise program. We performed a narrative literature review to evaluate the till-now evidence regarding (1) the metabolic and nutritional correlates of sarcopenia; (2) the optimum diet therapy for the treatment of these abnormalities. This review included 67 eligible studies. In addition to the well recognized link between adequate intake of proteins/amino acids and sarcopenia, the recent literature underlines that in sarcopenic elderly subjects there is an unbalance in vitamin D synthesis and in omega-6/omega-3 PUFA ratio. Given the detrimental effect of these metabolic abnormalities, a change in the lifestyle must be the cornerstone in the treatment of sarcopenia. The optimum diet therapy for the sarcopenia treatment must aim at achieving specific metabolic goals, which must be reached through accession of the elderly to specific personalized dietary program aimed at achieving and/or maintaining muscle mass; increasing their intake of fish (4 times/week) or taking omega-3 PUFA supplements; taking vitamin D supplementation, if there are low serum levels. PMID:25705670

Can hip abduction and external rotation discriminate sacroiliac joint pain?

PubMed

Adhia, Divya Bharatkumar; Tumilty, Steve; Mani, Ramakrishnan; Milosavljevic, Stephan; Bussey, Melanie D

2016-02-01

The primary aim of the study is to determine if Hip Abduction and External Rotation (HABER) test is capable of reproducing familiar pain in individuals with low back pain (LBP) of sacroiliac joint (SIJ) origin (SIJ-positive) when compared with LBP of Non-SIJ origin (SIJ-negative). If so, the secondary aim is to determine the diagnostic accuracy of HABER test against the reference standard of pain provocation tests, and to determine which increments of the HABER test has highest sensitivity and specificity for identifying SIJ-positive individuals. Single-blinded diagnostic accuracy study. Participants [n(122)] between ages of 18-50 y, suffering from chronic non-specific LBP (≥3 months) volunteered in the study. An experienced musculoskeletal physiotherapist evaluated and classified participants into either SIJ-positive [n(45)] or SIJ-negative [n(77)], based on reference standard of pain provocation tests [≥3 positive tests = SIJ-positive]. Another musculoskeletal physiotherapist, blinded to clinical groups, evaluated participants for reproduction of familiar pain during each increment (10°, 20°, 30°, 40°, and 50°) of HABER test. The HABER test reproduced familiar pain in SIJ-positive individuals when compared with SIJ-negative individuals [p (0.001), R(2) (0.38), Exp(β) (5.95-10.32)], and demonstrated moderate level of sensitivity (67%-78%) and specificity (71%-72%) for identifying SIJ-positive individuals. Receiver operator curve analysis demonstrated that the HABER increments of ≥30° have the highest sensitivity (83%-100%) and specificity (52%-64%). The HABER test is capable of reproducing familiar pain in SIJ-positive LBP individuals and has moderate levels of sensitivity and specificity for identifying SIJ-positive LBP individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comparison of 3-T magnetic resonance imaging and computed tomography arthrography to identify structural cartilage defects of the fetlock joint in the horse.

PubMed

Hontoir, Fanny; Nisolle, Jean-François; Meurisse, Hubert; Simon, Vincent; Tallier, Max; Vanderstricht, Renaud; Antoine, Nadine; Piret, Joëlle; Clegg, Peter; Vandeweerd, Jean-Michel

2014-01-01

Articular cartilage defects are prevalent in metacarpo/metatarsophalangeal (MCP/MTP) joints of horses. The aim of this study was to determine and compare the sensitivity and specificity of 3-Tesla magnetic resonance imaging (3-T MRI) and computed tomography arthrography (CTA) to identify structural cartilage defects in the equine MCP/MTP joint. Forty distal cadaver limbs were imaged by CTA (after injection of contrast medium) and by 3-T MRI using specific sequences, namely, dual-echo in the steady-state (DESS), and sampling perfection with application-optimised contrast using different flip-angle evolutions (SPACE). Gross anatomy was used as the gold standard to evaluate sensitivity and specificity of both imaging techniques. CTA sensitivity and specificity were 0.82 and 0.96, respectively, and were significantly higher than those of MRI (0.41 and 0.93, respectively) in detecting overall cartilage defects (no defect vs. defect). The intra and inter-rater agreements were 0.96 and 0.92, respectively, and 0.82 and 0.88, respectively, for CT and MRI. The positive predictive value for MRI was low (0.57). CTA was considered a valuable tool for assessing cartilage defects in the MCP/MTP joint due to its short acquisition time, its specificity and sensitivity, and it was also more accurate than MRI. However, MRI permits assessment of soft tissues and subchondral bone and is a useful technique for joint evaluation, although clinicians should be aware of the limitations of this diagnostic technique, including reduced accuracy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessment of five different guideline indication criteria for spirometry, including modified GOLD criteria, in order to detect COPD: data from 5,315 subjects in the PLATINO study

PubMed Central

Luize, Ana P; Menezes, Ana Maria B; Perez-Padilla, Rogelio; Muiño, Adriana; López, Maria Victorina; Valdivia, Gonzalo; Lisboa, Carmem; Montes de Oca, Maria; Tálamo, Carlos; Celli, Bartolomé; Nascimento, Oliver A; Gazzotti, Mariana R; Jardim, José R

2014-01-01

Background: Spirometry is the gold standard for diagnosing chronic obstructive pulmonary disease (COPD). Although there are a number of different guideline criteria for deciding who should be selected for spirometric screening, to date it is not known which criteria are the best based on sensitivity and specificity. Aims: Firstly, to evaluate the proportion of subjects in the PLATINO Study that would be recommended for spirometry testing according to Global initiative for Obstructive Lung Disease (GOLD)-modified, American College of Chest Physicians (ACCP), National Lung Health Education Program (NLHEP), GOLD and American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. Secondly, we aimed to compare the sensitivity, specificity, and positive predictive and negative predictive values, of these five different criteria. Methods: Data from the PLATINO study included information on respiratory symptoms, smoking and previous spirometry testing. The GOLD-modified spirometry indication criteria are based on three positive answers out of five questions: the presence of cough, phlegm in the morning, dyspnoea, age over 40 years and smoking status. Results: Data from 5,315 subjects were reviewed. Fewer people had an indication for spirometry (41.3%) according to the GOLD-modified criteria, and more people had an indication for spirometry (80.4%) by the GOLD and ATS/ERS criteria. A low percentage had previously had spirometry performed: GOLD-modified (14.5%); ACCP (13.2%); NLHEP (12.6%); and GOLD and ATS/ERS (12.3%). The GOLD-modified criteria showed the least sensitivity (54.9) and the highest specificity (61.0) for detecting COPD, whereas GOLD and ATS/ERS criteria showed the highest sensitivity (87.9) and the least specificity (20.8). Conclusion: There is a considerable difference in the indication for spirometry according to the five different guideline criteria. The GOLD-modified criteria recruit less people with the greatest sum of sensitivity and specificity. PMID:25358021

3D reconstruction from non-uniform point clouds via local hierarchical clustering

NASA Astrophysics Data System (ADS)

Yang, Jiaqi; Li, Ruibo; Xiao, Yang; Cao, Zhiguo

2017-07-01

Raw scanned 3D point clouds are usually irregularly distributed due to the essential shortcomings of laser sensors, which therefore poses a great challenge for high-quality 3D surface reconstruction. This paper tackles this problem by proposing a local hierarchical clustering (LHC) method to improve the consistency of point distribution. Specifically, LHC consists of two steps: 1) adaptive octree-based decomposition of 3D space, and 2) hierarchical clustering. The former aims at reducing the computational complexity and the latter transforms the non-uniform point set into uniform one. Experimental results on real-world scanned point clouds validate the effectiveness of our method from both qualitative and quantitative aspects.

The Impact of Childhood Abuse on Inpatient Substance Users: Specific Links with Risky Sex, Aggression, and Emotion Dysregulation

PubMed Central

Banducci, Anne N.; Hoffman, Elana M.; Lejuez, C.W.; Koenen, Karestan

2014-01-01

Adults with substance use disorders (SUDs) report a high prevalence of childhood abuse. Research in the general population suggests specific types of abuse lead to particular negative outcomes; it is not known whether this pattern holds for adults with SUDs. We hypothesized that specific types of abuse would be associated with particular behavioral and emotional outcomes among substance users. That is, childhood sexual abuse would be associated with risky sex behaviors, childhood physical abuse with aggression, and childhood emotional abuse with emotion dysregulation. 280 inpatients (M age = 43.3; 69.7% male; 88.4% African American) in substance use treatment completed the Childhood Trauma Questionnaire (CTQ), HIV Risk-Taking Behavior Scale, Addiction Severity Index, Difficulties with Emotion Regulation Scale (DERS), Distress Tolerance Scale (DTS), and Affect Intensity and Dimensions of Affiliation Motivation (AIM). Consistent with our hypotheses, the CTQ Sexual Abuse subscale uniquely predicted exchanging sex for cocaine and heroin, number of arrests for prostitution, engaging in unprotected sex with a casual partner during the prior year, and experiencing low sexual arousal when sober. The Physical Abuse subscale uniquely predicted number of arrests for assault and weapons offenses. The Emotional Abuse subscale uniquely predicted the DERS total score, AIM score, and DTS score. Among substance users, different types of abuse are uniquely associated with specific negative effects. Assessment of specific abuse types among substances users may be informative in treatment planning and relapse prevention. PMID:24521524

The impact of childhood abuse on inpatient substance users: specific links with risky sex, aggression, and emotion dysregulation.

PubMed

Banducci, Anne N; Hoffman, Elana M; Lejuez, C W; Koenen, Karestan C

2014-05-01

Adults with substance use disorders (SUDs) report a high prevalence of childhood abuse. Research in the general population suggests specific types of abuse lead to particular negative outcomes; it is not known whether this pattern holds for adults with SUDs. We hypothesized that specific types of abuse would be associated with particular behavioral and emotional outcomes among substance users. That is, childhood sexual abuse would be associated with risky sex behaviors, childhood physical abuse with aggression, and childhood emotional abuse with emotion dysregulation. 280 inpatients (M age=43.3; 69.7% male; 88.4% African American) in substance use treatment completed the Childhood Trauma Questionnaire (CTQ), HIV Risk-Taking Behavior Scale, Addiction Severity Index, Difficulties with Emotion Regulation Scale (DERS), Distress Tolerance Scale (DTS), and Affect Intensity and Dimensions of Affiliation Motivation (AIM). Consistent with our hypotheses, the CTQ sexual abuse subscale uniquely predicted exchanging sex for cocaine and heroin, number of arrests for prostitution, engaging in unprotected sex with a casual partner during the prior year, and experiencing low sexual arousal when sober. The physical abuse subscale uniquely predicted number of arrests for assault and weapons offenses. The emotional abuse subscale uniquely predicted the DERS total score, AIM score, and DTS score. Among substance users, different types of abuse are uniquely associated with specific negative effects. Assessment of specific abuse types among substance users may be informative in treatment planning and relapse prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

What does it mean to "employ" the RE-AIM model?

PubMed

Kessler, Rodger S; Purcell, E Peyton; Glasgow, Russell E; Klesges, Lisa M; Benkeser, Rachel M; Peek, C J

2013-03-01

Many grant proposals identify the use of a given evaluation model or framework but offer little about how such models are implemented. The authors discuss what it means to employ a specific model, RE-AIM, and key dimensions from this model for program planning, implementation, evaluation, and reporting. The authors report both conceptual and content specifications for the use of the RE-AIM model and a content review of 42 recent dissemination and implementation grant applications to National Institutes of Health that proposed the use of this model. Outcomes include the extent to which proposals addressed the overall RE-AIM model and specific items within the five dimensions in their methods or evaluation plans. The majority of grants used only some elements of the model (less than 10% contained thorough measures across all RE-AIM dimensions). Few met criteria for "fully developed use" of RE-AIM and the percentage of key issues addressed varied from, on average, 45% to 78% across the RE-AIM dimensions. The results and discussion of key criteria should help investigators in their use of RE-AIM and illuminate the broader issue of comprehensive use of evaluation models.

Microtensile bond strength of silorane-based composite specific adhesive system using different bonding strategies

PubMed Central

Bastos, Laura Alves; Sousa, Ana Beatriz Silva; Drubi-Filho, Brahim; Panzeri Pires-de-Souza, Fernanda de Carvalho

2015-01-01

Objectives The aim of this study was to evaluate the effect of pre-etching on the bond strength of silorane-based composite specific adhesive system to dentin. Materials and Methods Thirty human molars were randomly divided into 5 groups according to the different bonding strategies. For teeth restored with silorane-based composite (Filtek Silorane, 3M ESPE), the specific self-etching adhesive system (Adhesive System P90, 3M ESPE) was used with and without pre-etching (Pre-etching/Silorane and Silorane groups). Teeth restored with methacrylate based-composite (Filtek Z250, 3M ESPE) were hybridized with the two-step self-etching system (Clearfil SE Bond, Kuraray), with and without pre-etching (Pre-etching/Methacrylate and Methacrylate groups), or three-step adhesive system (Adper Scotchbond Multi-Purpose, 3M ESPE) (Three-step/Methacrylate group) (n = 6). The restored teeth were sectioned into stick-shaped test specimens (1.0 × 1.0 mm), and coupled to a universal test machine (0.5 mm/min) to perform microtensile testing. Results Pre-etching/Methacrylate group presented the highest bond strength values, with significant difference from Silorane and Three-step/Methacrylate groups (p < 0.05). However, it was not significantly different from Preetching/Silorane and Methacrylate groups. Conclusions Pre-etching increased bond strength of silorane-based composite specific adhesive system to dentin. PMID:25671209

Domain-specific cognitive impairment in patients with COPD and control subjects

PubMed Central

Cleutjens, Fiona AHM; Franssen, Frits ME; Spruit, Martijn A; Vanfleteren, Lowie EGW; Gijsen, Candy; Dijkstra, Jeanette B; Ponds, Rudolf WHM; Wouters, Emiel FM; Janssen, Daisy JA

2017-01-01

Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls. PMID:28031706

Implementing a Systematic Process for Consistent Nursing Care in a NICU: A Quality Improvement Project.

PubMed

McCarley, Renay Marie; Dowling, Donna A; Dolansky, Mary A; Bieda, Amy

2018-03-01

The global aim of this quality improvement project was to develop and implement a systematic process to assign and maintain consistent bedside nurses for infants and families. A systematic process based on a primary care nursing model was implemented to assign consistent care for a 48-bed, single-family room NICU. Four PDSA cycles were necessary to obtain agreement from the nursing staff as to the best process for assigning primary nurses. Post-intervention data revealed a 9.5 percent decrease of consistent caregivers for infants in the NICU ≤ 28 days and a 2.3 percent increase of consistent caregivers for infants in the NICU ≥ 29 days. Although these findings did not meet the goal of the specific aim, a systematic process was created to assign bedside nurses to infants. Further PDSAs will be needed to refine the process to reach the aim.

The effect of neck-specific exercise with, or without a behavioral approach, on pain, disability, and self-efficacy in chronic whiplash-associated disorders: a randomized clinical trial.

PubMed

Ludvigsson, Maria L; Peterson, Gunnel; O'Leary, Shaun; Dedering, Åsa; Peolsson, Anneli

2015-04-01

The aim of this study was to compare the effect on self-rated pain, disability, and self-efficacy of 3 interventions for the management of chronic whiplash-associated disorders: physiotherapist-led neck-specific exercise (NSE), physiotherapist-led NSE with the addition of a behavioral approach, or Prescription of Physical Activity (PPA). A total of 216 volunteers with chronic whiplash-associated disorders participated in this randomized, assessor blinded, clinical trial of 3 exercise interventions. Self-rated pain/pain bothersomeness (Visual Analogue Scale), disability (Neck Disability Index), and self-efficacy (Self-Efficacy Scale) were evaluated at baseline and at 3 and 6 months. The proportion of patients reaching substantial reduction in pain bothersomness (at least 50% reduction) was more evident (P<0.01) in the 2 NSE groups (29% to 48%) compared with the PPA group (5%) at 3 months. At 6 months 39% to 44% of the patients in the 2 neck-specific groups and 28% in the PPA group reported substantial pain reduction. Reduction of disability was also larger in the 2 neck-specific exercise groups at both 3 and 6 months (P<0.02). Self-efficacy was only improved in the NSE group without a behavioral approach (P=0.02). However, there were no significant differences in any outcomes between the 2 physiotherapist-led NSE groups. NSE resulted in superior outcomes compared with PPA in this study, but the observed benefits of adding a behavioral approach to the implementation of exercise in this study were inconclusive.

Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

PubMed

Erfani, Mostafa; Shafiei, Mohammad; Mazidi, Mohammad; Goudarzi, Mostafa

2013-04-01

Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), β-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

Effects of a Carbohydrate-Electrolyte Drink on Specific Soccer Tests and Performance

PubMed Central

Ostojic, Sergej M.; Mazic, Sanja

2002-01-01

The aim of this study was to examine the effects of a carbohydrate-electrolyte drink on specific soccer tests and performance. Twenty-two professional male soccer players volunteered to participate in the study. The players were allocated to two assigned trials ingesting carbohydrate-electrolyte drink (7% carbohydrates, sodium 24 mmol.l-1, chloride 12 mmol.l-1, potassium 3 mmol.l-1) or placebo during a 90 min on-field soccer match. The trials were matched for subjects’ age, weight, height and maximal oxygen uptake. Immediately after the match, players completed four soccer-specific skill tests. Blood glucose concentration [mean (SD)] was higher at the end of the match-play in the carbohydrate-electrolyte trial than in the placebo trial (4.4 (0.3) vs. 4.0 (0.3) mmol.l-1, P < 0.05). Subjects in the carbohydrate-electrolyte trial finished the specific dribble test faster in comparison with subjects in the placebo trial (12.9 (0.4) vs. 13.6 (0.5) s, P < 0.05). Ratings of the precision test were higher in the carbohydrate-electrolyte trial as compared to the placebo trial (17.2 (4.8) vs. 15.1 (5.2), P < 0.05) but there were no differences in coordination test and power test results between trials. The main finding of the present study indicates that supplementation with carbohydrate-electrolyte solution improved soccer-specific skill performance and recovery after an on-field soccer match compared with ingestion of placebo. This suggests that soccer players should consume carbohydrate-electrolyte fluid throughout a game to help prevent deterioration in specific skill performance. PMID:24688270

[Mental health in adolescents in Germany: A comparison with regard to migration background and country of origin].

PubMed

Brettschneider, Anna-Kristin; Hölling, H; Schlack, R; Ellert, U

2015-04-01

Many children and adolescents in Germany grow up in families with a migration background. Different cultural, religious, and linguistic backgrounds have an influence on their behavior in various ways. Health status can be affected both negatively and positively by a migration background. The aim of this study was to analyze associations between migration background and self-reported psychological problems. In addition, it was tested whether country of origin had a differential effect on the associations found. Because of its migration-specific approach, the baseline survey (2003-2006) of the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS) offers a solid basis for migrant-specific analyses. Self-reported mental health problems were assessed using the Strengths and Difficulties Questionnaire (SDQ), which was completed by 6,719 adolescents aged 11-17 years. Adolescents with a two-sided migration background (i.e., both parents) reported higher SDQ total difficulties scores compared with adolescents without a migration background (16.9 vs 11.5%) or those with a one-sided migration background (16.9 vs 11.3%). Adolescents with a Turkish background had higher odds (boys: OR 2.0; 95%CI 1.3-3.2; girls: OR 2.0; 95%CI 1.2-3.4) of reporting mental health problems than adolescents without a migration background. Also, girls with a migration background from Western Europe, the USA or Canada had higher odds (OR 2.2; 95%CI 1.3-3.6). In some cases, adjusting for socioeconomic status led to insignificant associations with regard to the country of origin. The findings underline the importance of migrant-specific and culture-sensitive prevention, which also takes the environment and culture-specific characteristics into account.

Age and Gender Effects on Coping in Children and Adolescents.

ERIC Educational Resources Information Center

Hampel, Petra; Petermann, Franz

2005-01-01

The aim of this study was to investigate age and gender effects of children's and adolescents' coping with common stressors in 3 age groups (late childhood, early, and middle adolescence). Furthermore, age and developmental differences in situation-specific coping with 2 stress domains were examined. N = 1,123 participants (ages 8 to 13 years)…

Relationships between Structural and Acoustic Properties of Maternal Talk and Children's Early Word Recognition

ERIC Educational Resources Information Center

Suttora, Chiara; Salerni, Nicoletta; Zanchi, Paola; Zampini, Laura; Spinelli, Maria; Fasolo, Mirco

2017-01-01

This study aimed to investigate specific associations between structural and acoustic characteristics of infant-directed (ID) speech and word recognition. Thirty Italian-acquiring children and their mothers were tested when the children were 1;3. Children's word recognition was measured with the looking-while-listening task. Maternal ID speech was…

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population

PubMed Central

Gimenez, Lucas G.; Momany, Allison M.; Poletta, Fernando A.; Krupitzki, Hugo B.; Gili, Juan A.; Busch, Tamara D.; Saleme, Cesar; Cosentino, Viviana R.; Pawluk, Mariela S.; Campaña, Hebe; Gadow, Enrique C.; Murray, Jeffrey C.; Lopez-Camelo, Jorge S.

2017-01-01

Background Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation: Idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB. Methods 24 SNPs were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 PTB-PPROM, and 210 PTB-M. These data were analyzed with a Family-Based Association. Results PTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, 3 SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M. Conclusions Our study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes. PMID:28426651

The influence of surface integrin binding patterns on specific biomaterial-cell interactions

NASA Astrophysics Data System (ADS)

Beranek, Maggi Marie

As the future of biomaterials progresses toward bioactivity, the biomaterial surface must control non-specific protein adsorption and encourage selective protein and cell adsorption. Integrins alphavbeta3, alpha 1beta1, alpha5beta1 and alpha Mbeta2 are expressed on cells involved in endothelialization, inflammation, and intimal hyperplasia. These cellular events play a vital role in biomaterial biocompatibility, especially in the vascular environment. The overall hypothesis of these studies is that biomaterial surfaces exhibit selective integrin binding, which then specifies differential cell binding. To test this hypothesis, four specific aims were developed. The first aim was designed to determine whether metal and polymeric biomaterials exhibit selective integrin binding. The tested materials included 316L stainless steel, nitinol, gold, Elgiloy RTM, poly(D, L-lactide-co-glycolide), polycarbonate urethane and expanded polytetrafluoroethylene. Discrete integrin binding patterns were detected microscopically using integrin specific fluorescent antibodies. Stainless steel exhibited high level integrin alpha1beta 1 and low level integrin alphaMbeta2 binding pattern. This suggests that this metal surface should selectively encourage endothelial cell to inflammatory cell binding. In contrast, gold bound ten times the amount of integrin alphaMbeta2 compared to integrin alpha1beta1, which should encourage inflammatory cell adhesion. The 65/35 poly(D, L-lactide-co-glycolide) was the only polymeric biomaterial tested that had integrin binding levels comparable to metal biomaterials. Based on these observations, a combinational biomaterial with a surface pattern of 65/35 poly(D, L-lactide-co-glycolide) dots on a 316L stainless steel background was created. A pattern of high level integrin alpha1beta1 binding and low level integrin alpha Mbeta2 binding on this combinational surface indicates that this surface should selectively favor endothelial cell binding. In the second aim, the response of surface-bound integrins to flow-related shear stress was examined. Based on fluorescent analysis, total alphavbeta 3, alpha1beta1, and alpha5beta 1 appeared to increase on stainless steel after 90-minute low shear stress exposure, whereas only alpha5beta1 appeared to increase when exposed to high shear. 65/35 poly(D, L-lactide-co-glycolide) exhibited increased total binding of alpha5beta1 and alphaMbeta2, when exposed to either shear stress level. Exposure to either shear stress regimen appeared to increase binding of all integrins on the combinational surface. These responses to shear stress suggest differential integrin binding affinity compared to stainless steel. Using antibodies specific to the integrin subunits, the apparent increase in surface-bound integrins was found to be related to a surface disassociation of alpha and beta subunits. The third aim evaluated human aortic endothelial cells and acute monocytic leukemia cells (THP-1) cell binding to the tested biomaterial surfaces under both static and flow conditions. Both stainless steel and the combinational surface had increased endothelial cell binding compared to monocyte attachment. Pre-incubation of the surface with the specific integrins significantly inhibited human aortic endothelial cell binding. Aim four was designed to investigate the influence of surface bound integrins on human aortic endothelial cell migration under shear stress. If biomaterial surface integrin binding patterns are specific, then pre-bound surface integrins should competitively inhibit binding of cellular integrins to the surface. Cell migration distance on to alphavbeta3, alpha 1beta1, and alpha5beta1 pre-incubated stainless steel was decreased ten-fold, and decreased by three-fold on both 65/35 poly(D, L-lactide-coglycolide) and combinational surfaces compared to the respective bare surfaces. In contrast, migration distance on to alphaMbeta2 pre-coated stainless steel and combinational surface was decreased by only sixty percent and only fifty percent on alphaMbeta2 precoated 65/35 poly(D, L -lactide-co-glycolide). These results suggested that surface binding sites are selective and critical in governing endothelial cell migration. In conclusion, these results support the hypothesis that a surface that encourages specific integrin binding would promote differential cell binding. The novel integrin binding model used in this investigation may be a methodology that can be employed to evaluate potential vascular biomaterials.

The Effect of Neck-specific Exercise With, or Without a Behavioral Approach, on Pain, Disability, and Self-Efficacy in Chronic Whiplash-associated Disorders

PubMed Central

Peterson, Gunnel; O’Leary, Shaun; Dedering, Åsa; Peolsson, Anneli

2015-01-01

Objectives: The aim of this study was to compare the effect on self-rated pain, disability, and self-efficacy of 3 interventions for the management of chronic whiplash-associated disorders: physiotherapist-led neck-specific exercise (NSE), physiotherapist-led NSE with the addition of a behavioral approach, or Prescription of Physical Activity (PPA). Materials and Methods: A total of 216 volunteers with chronic whiplash-associated disorders participated in this randomized, assessor blinded, clinical trial of 3 exercise interventions. Self-rated pain/pain bothersomeness (Visual Analogue Scale), disability (Neck Disability Index), and self-efficacy (Self-Efficacy Scale) were evaluated at baseline and at 3 and 6 months. Results: The proportion of patients reaching substantial reduction in pain bothersomness (at least 50% reduction) was more evident (P<0.01) in the 2 NSE groups (29% to 48%) compared with the PPA group (5%) at 3 months. At 6 months 39% to 44% of the patients in the 2 neck-specific groups and 28% in the PPA group reported substantial pain reduction. Reduction of disability was also larger in the 2 neck-specific exercise groups at both 3 and 6 months (P<0.02). Self-efficacy was only improved in the NSE group without a behavioral approach (P=0.02). However, there were no significant differences in any outcomes between the 2 physiotherapist-led NSE groups. Discussion: NSE resulted in superior outcomes compared with PPA in this study, but the observed benefits of adding a behavioral approach to the implementation of exercise in this study were inconclusive. PMID:24918474

Can magnetic resonance imaging at 3.0-Tesla reliably detect patients with endometriosis? Initial results.

PubMed

Thomeer, Maarten G; Steensma, Anneke B; van Santbrink, Evert J; Willemssen, Francois E; Wielopolski, Piotr A; Hunink, Myriam G; Spronk, Sandra; Laven, Joop S; Krestin, Gabriel P

2014-04-01

The aim of this study was to determine whether an optimized 3.0-Tesla magnetic resonance imaging (MRI) protocol is sensitive and specific enough to detect patients with endometriosis. This was a prospective cohort study with consecutive patients. Forty consecutive patients with clinical suspicion of endometriosis underwent 3.0-Tesla MRI, including a T2-weighted high-resolution fast spin echo sequence (spatial resolution=0.75 ×1.2 ×1.5 mm³) and a 3D T1-weighted high-resolution gradient echo sequence (spatial resolution=0.75 ×1.2 × 2.0 mm³). Two radiologists reviewed the dataset with consensus reading. During laparoscopy, which was used as reference standard, all lesions were characterized according to the revised criteria of the American Fertility Society. Patient-level and region-level sensitivities and specificities and lesion-level sensitivities were calculated. Patient-level sensitivity was 42% for stage I (5/12) and 100% for stages II, III and IV (25/25). Patient-level specificity for all stages was 100% (3/3). The region-level sensitivity and specificity was 63% and 97%, respectively. The sensitivity per lesion was 61% (90% for deep lesions, 48% for superficial lesions and 100% for endometriomata). The detection rate of obliteration of the cul-the-sac was 100% (10/10) with no false positive findings. The interreader agreement was substantial to perfect (kappa=1 per patient, 0.65 per lesion and 0.71 for obliteration of the cul-the-sac). An optimized 3.0-Tesla MRI protocol is accurate in detecting stage II to stage IV endometriosis. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells.

PubMed

Zhao, Ming-Tao; Shao, Ning-Yi; Hu, Shijun; Ma, Ning; Srinivasan, Rajini; Jahanbani, Fereshteh; Lee, Jaecheol; Zhang, Sophia L; Snyder, Michael P; Wu, Joseph C

2017-11-10

Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression. We profiled genome-wide transcriptional activity and a variety of epigenetic marks in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in human endothelial cells (CD31 + CD144 + ), cardiac progenitor cells (Sca-1 + ), fibroblasts (DDR2 + ), and their respective induced pluripotent stem cells. We uncovered 2 classes of regulatory DNA elements: class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. Both class I and class II regulatory elements exhibited stimulatory roles in nearby gene expression in a given cell type. However, class I promoters displayed more dominant regulatory effects on transcriptional abundance regardless of distal enhancers. Transcription factor network analysis indicated that human induced pluripotent stem cells and somatic cells from the heart selected their preferential regulatory elements to maintain cell type-specific gene expression. In addition, we validated the function of these enhancer elements in transgenic mouse embryos and human cells and identified a few enhancers that could possibly regulate the cardiac-specific gene expression. Given that a large number of genetic variants associated with human diseases are located in regulatory DNA elements, our study provides valuable resources for deciphering the epigenetic modulation of regulatory DNA elements that fine-tune spatiotemporal gene expression in human cardiac development and diseases. © 2017 American Heart Association, Inc.

Identification of a gag-encoded cytotoxic T-lymphocyte epitope from FBL-3 leukemia shared by Friend, Moloney, and Rauscher murine leukemia virus-induced tumors.

PubMed Central

Chen, W; Qin, H; Chesebro, B; Cheever, M A

1996-01-01

FBL-3 is a highly immunogenic murine leukemia of C57BL/6 origin induced by Friend murine leukemia virus (MuLV). Immunization of C57BL/6 mice with FBL-3 readily elicits CD8+ cytotoxic T lymphocytes (CTL) capable of lysing FBL-3 as well as syngeneic leukemias induced by Moloney and Rauscher MuLV. The aim of this current study was to identify the immunogenic epitope(s) recognized by the FBL-3-specific CD8+ CTL. A series of FBL-3-specific CD8+ CTL clones were generated from C57BL/6 mice immunized to FBL-3. The majority of CTL clones (32 of 38) were specific for F-MuLV gag-encoded antigen. By using a series of recombinant vaccinia viruses expressing full-length and truncated F-MuLV gag genes, the antigenic epitope recognized by the FBL-3 gag-specific CTL clones, as well as by bulk-cultured CTL from spleens of mice immune to FBL-3, was localized to the leader sequence of gPr80gag protein. The precise amino acid sequence of the CTL epitope in the leader sequence was identified as CCLCLTVFL (positions 85-93) by examining lysis of targets incubated with a series of synthetic leader sequence peptides. No evidence of other CTL epitopes in the gPr80gag or Pr65gag core virion structural polyproteins was found. The identity of CCLCLTVFL as the target peptide was validated by showing that immunization with the peptide elicited CTL that lysed FBL-3. The CTL elicited by the Gag peptide also specifically lysed syngeneic leukemia cells induced by Moloney and Rauscher MuLV (MBL-2 and RBL-5). The transmembrane peptide was shown to be the major gag-encoded antigenic epitope recognized by bulk-cultured CTL derived from C57BL/6 mice immunized to MBL-2 or RBL-5. Thus, the CTL epitope of FBL-3 is localized to the transmembrane anchor domain of the nonstructural Gag polyprotein and is shared by leukemia/lymphoma cell lines induced by Friend, Moloney, and Rauscher MuLV. PMID:8892898

Prognostic significance of DSG3 in rectal adenocarcinoma treated with preoperative chemoradiotherapy.

PubMed

Chao, Tung-Bo; Li, Chien-Feng; Lin, Ching-Yih; Tian, Yu-Feng; Chang, I-Wei; Sheu, Ming-Jen; Lee, Ying-En; Chan, Ti-Chun; He, Hong-Lin

2016-06-01

This study aimed to investigate the prognostic significance of DSG3 and its association with response to neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer. Data mining of a publicly available dataset was performed to find genes associated with CCRT response. Immunohistochemistry was applied to evaluate DSG3 expression. The relationships between DSG3 expression and various clinicopathological parameters and survival were analyzed. The DSG3 gene was significantly associated with CCRT response. The expression of DSG3 negatively correlated with poorer tumor regression (p < 0.001) and had an independent negative impact on disease-specific survival (p = 0.011), local recurrence-free survival (p = 0.031) and metastasis-free survival (p = 0.029). DSG3 was a key prognostic factor and predictor for CCRT response in rectal cancer patients.

Effect of Core Training on Male Handball Players’ Throwing Velocity

PubMed Central

García-Ruiz, José; Cortell-Tormo, Juan Manuel; Tortosa-Martínez, Juan

2017-01-01

Abstract In handball, throwing velocity is considered to be one of the essential factors in achieving the ultimate aim of scoring a goal. The objective of the present study was to analyze the effect of a core training program on throwing velocity in 30 handball players (age 18.7 ± 3.4 years, body height 179.3 ± 7.0 cm, body mass 78.9 ± 7.7 kg), 16 of whom were in the junior category and 14 of whom were in the senior category. The 30 players were randomly divided into two groups, the control group (n = 15) and the experimental group (n = 15). For a period of ten weeks, both groups attended their regular handball training sessions (four per week), but in addition, the experimental group participated in a program specifically aimed at progressively strengthening the lumbo-pelvic region and consisting of seven exercises performed after the general warm-up in each regular session. Pre- and post-tests were carried out to analyze each player’s throwing velocity from different throwing positions and thus assess the effects of this specific training program. Statistically significant differences (p ≤ 0.05) in throwing velocity were observed between the experimental group, which presented a percentage improvement of 4.5%, and the control group, which did not show any improvement. The results seem to indicate that an increase in the strength and stability of the lumbo-pelvic region can contribute to an improvement in the kinetic chain of the specific movement of throwing in handball, thus, increasing throwing velocity. PMID:28469756

Effect of Core Training on Male Handball Players' Throwing Velocity.

PubMed

Manchado, Carmen; García-Ruiz, José; Cortell-Tormo, Juan Manuel; Tortosa-Martínez, Juan

2017-02-01

In handball, throwing velocity is considered to be one of the essential factors in achieving the ultimate aim of scoring a goal. The objective of the present study was to analyze the effect of a core training program on throwing velocity in 30 handball players (age 18.7 ± 3.4 years, body height 179.3 ± 7.0 cm, body mass 78.9 ± 7.7 kg), 16 of whom were in the junior category and 14 of whom were in the senior category. The 30 players were randomly divided into two groups, the control group (n = 15) and the experimental group (n = 15). For a period of ten weeks, both groups attended their regular handball training sessions (four per week), but in addition, the experimental group participated in a program specifically aimed at progressively strengthening the lumbo-pelvic region and consisting of seven exercises performed after the general warm-up in each regular session. Pre- and post-tests were carried out to analyze each player's throwing velocity from different throwing positions and thus assess the effects of this specific training program. Statistically significant differences (p ≤ 0.05) in throwing velocity were observed between the experimental group, which presented a percentage improvement of 4.5%, and the control group, which did not show any improvement. The results seem to indicate that an increase in the strength and stability of the lumbo-pelvic region can contribute to an improvement in the kinetic chain of the specific movement of throwing in handball, thus, increasing throwing velocity.

Restoring Proprioception via a Cortical Prosthesis: A Novel Learning Based Approach

DTIC Science & Technology

2016-10-01

microstimulation from the neural recordings used for BMI control. This allows us to move to a much more efficient paradigm with continuous brain “ read out” for...microstimulation; movement control 3. ACCOMPLISHMENTS: What were the major goals of the project? Specific Aim 1: Determine whether animals ... animals . However, that signal will correlate on a millisecond timescale with visual feedback of the virtual limb. Based on the previous work (Dadarlat

DSM-5 cannabis use disorder, substance use and DSM-5 specific substance-use disorders: Evaluating comorbidity in a population-based sample.

PubMed

Hayley, Amie C; Stough, Con; Downey, Luke A

2017-08-01

Cannabis use disorder (CUD) is frequently associated with concurrent substance use and/or comorbid substance use disorders (SUDs); however there is little specificity with regard to commonly abused individual drug types/classes. This study therefore aimed to provide insight into the degree of these co-occurring relationships across several specific newer and older generation illicit and prescription drugs. 36,309 adults aged 18+ from wave 3 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) were assessed. Weighted cross-tabulations and multivariable logistic regression analyses were used to evaluate comorbidity between current DSM-5 CUD, substance use and DSM-5 SUD. Current DSM-5 CUD is associated with greater lifetime use of all examined drug classes, and previous 12-month use of several newer-class illicit and prescription stimulant-based substances (all p< 0.05). Current DSM-5 CUD was similarly associated with increased incidence of a range of DSM-5 SUDs and was independently associated with concurrently reporting current DSM-5; sedative (Adjusted OR= 5.1, 95%CI 2.9-9.0), cocaine (AOR= 9.3, 95%CI 5.6-15.5), stimulant (AOR= 4.3, 95%CI 2.3-7.9), club drug (AOR= 16.1, 95%CI 6.3-40.8), opioid (AOR= 4.6, 95%CI 3.0-6.8) and alcohol-use disorder (AOR= 3.0, 95%CI 2.5-3.7); but not heroin or 'other' drug use disorder (both p>0.05). High comorbidity exists between DSM-5 CUD and many specific DSM-5 SUDs. Newer-class illicit and prescription stimulant-based drug use disorders are overrepresented among those with DSM-5 CUD. These findings underscore the need for tailored treatment programs for those presenting with DSM-5 CUD, and for greater treatment specification where poly-drug use is evident. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients

PubMed Central

Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

2014-01-01

Objectives To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. Methods A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. Results There were 47 181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Discussion Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. Conclusions The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. PMID:24496386

Comparative Evaluation of Four Phenotypic Tests for Detection of Carbapenemase-Producing Gram-Negative Bacteria

PubMed Central

Noël, Audrey; Berhin, Catherine; Hoebeke, Martin; Bouchahrouf, Warda; Yunus, Sami; Bogaerts, Pierre; Glupczynski, Youri

2016-01-01

ABSTRACT Four screening assays aimed for rapid detection of carbapenemase production from Gram-negative bacterial isolates, i.e., the Neo-Rapid Carb kit (Rosco Diagnostica A/S), the Rapidec Carba NP test (bioMérieux SA), the β Carba test (Bio-Rad Laboratories N.V.), and a homemade electrochemical assay (BYG Carba test) were evaluated against a panel comprising 328 clinical isolates (Enterobacteriaceae [n = 198] and nonfermentative Gram-negative bacilli [n = 130]) with previously characterized resistance mechanisms to carbapenems. Among Enterobacteriaceae isolates, the BYG Carba test and the β Carba test showed excellent sensitivities (respectively, 100% and 97.3%) and specificities (respectively, 98.9% and 97.7%). The two other assays yielded poorer performances with sensitivity and specificity of 91.9% and 83.9% for the Rapidec Carba NP test and of 89.2% and 89.7% for the Neo-Rapid Carb kit, respectively. Among Pseudomonas spp., sensitivities and specificities ranged, respectively, from 87.3% to 92.7% and from 88.2% to 94.1%. Finally, all tests performed poorly against Acinetobacter spp., with sensitivities and specificities, respectively, ranging from 27.3% to 75.8% and from 75 to 100%. Among commercially available assays, the β Carba test appeared to be the most convenient for routine use and showed the best overall performances, especially against OXA-48-like producers. The excellent performance of the BYG Carba test against Enterobacteriaceae was confirmed (100% sensitivity and 98.9% specificity). PMID:27927915

Comprehensive preclinical evaluation of a multi-physics model of liver tumor radiofrequency ablation.

PubMed

Audigier, Chloé; Mansi, Tommaso; Delingette, Hervé; Rapaka, Saikiran; Passerini, Tiziano; Mihalef, Viorel; Jolly, Marie-Pierre; Pop, Raoul; Diana, Michele; Soler, Luc; Kamen, Ali; Comaniciu, Dorin; Ayache, Nicholas

2017-09-01

We aim at developing a framework for the validation of a subject-specific multi-physics model of liver tumor radiofrequency ablation (RFA). The RFA computation becomes subject specific after several levels of personalization: geometrical and biophysical (hemodynamics, heat transfer and an extended cellular necrosis model). We present a comprehensive experimental setup combining multimodal, pre- and postoperative anatomical and functional images, as well as the interventional monitoring of intra-operative signals: the temperature and delivered power. To exploit this dataset, an efficient processing pipeline is introduced, which copes with image noise, variable resolution and anisotropy. The validation study includes twelve ablations from five healthy pig livers: a mean point-to-mesh error between predicted and actual ablation extent of 5.3 ± 3.6 mm is achieved. This enables an end-to-end preclinical validation framework that considers the available dataset.

'Drinking with respect': Drinking constructions of men who live in a Cape Winelands farm community in South Africa.

PubMed

Lesch, Elmien; Casper, Rozanne

2017-03-01

This article aims to provide a community-specific understanding of a subgroup of South African men who exhibit particularly high rates of hazardous alcohol consumption. Adopting a social constructionist framework, we interviewed 13 Cape Winelands men who lived on farms to explore their drinking constructions. We present three themes that shed light on problematic drinking in this group: (1) the notion of weekend binge-drinking as 'respectable' drinking, (2) drinking as shared activity that fulfils various psycho-social needs and (3) a sense of powerlessness to affect their own or their children's alcohol consumption. These findings are viewed against a specific socio-historical backdrop.

Casualty Evacuation Delay and Outcomes

DTIC Science & Technology

2003-01-01

consequences of delay in therapy on wounded individuals. The contractor was charged with studying the effect of delay on evacuation on outcome of...process. 3 There are a remarkably small proportion of patient diagnoses and states in which time has an effect on outcome . This is because the vast...emphasis on estimating the effect of delayed evacuation on injury outcome and means to mitigating such effects . Since some of the Specific Aims were

High IL-10 production by aged AIDS patients is related to high frequency of Tr-1 phenotype and low in vitro viral replication.

PubMed

Andrade, Regis M; Hygino, Joana; Kasahara, Taissa M; Vieira, Morgana M; Xavier, Luciana F; Blanco, Bernardo; Damasco, Paulo V; Silva, Rodrigo M; Lima, Dirce B; Oliveira, Ariane L; Lemos, Alberto S; Andrade, Arnaldo F B; Bento, Cleonice A M

2012-10-01

This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4(+)FoxP3(+)CD25(+)Treg cells in this patient group, high frequencies of IL-10-producing CD4(+)FoxP3(-) T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4(+)FoxP3(-)CD152(+) T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1β by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals. Copyright © 2012 Elsevier Inc. All rights reserved.

Age and Gender-Specific Reference Intervals for ProGRP in Healthy Chinese Han Ethnic Adults using the Roche Cobas Immunoassay.

PubMed

Zhu, Yanhui; Yuan, Yulin; Yang, Xiafang; Lu, Qiuwei; Lu, Xiaoxu; Huang, Huayi

2018-06-01

Pro-gastrin-releasing peptide (ProGRP) is a kind of tumor marker applied more and more commonly in recent years. This study was aimed at determining the age and gender-specific reference intervals (RIs) for ProGRP in healthy Han ethnic adults from Guangxi, China. A total of 2,045 apparently healthy males and 1,740 apparently healthy females aged from 21 to 90 years were included in this study. The serum ProGRP values were determined by electrochemiluminescence immunoassay (ECLIA). The one-sided upper 95th percentile of ProGRP concentrations were used to define the RIs. The reference limits in different age groups (21 - 40, 41 - 50, 51 - 60, 61 - 70, and > 70 years) were 37.3, 39.7, 45.7, 47.3, and 61.3 pg/mL for males, and 36.3, 38.1, 42.7, 53.5, and 60.1 pg/mL for females, respectively. There was no significant difference in the levels of ProGRP between males and females. The serum ProGRP levels were positively correlated with age. We established the age and gender-specific RIs for ProGRP in the adults from Guangxi, China. It will be valuable for future clinical and laboratory studies.

Vibratory Stimuli: A Novel Rehabilitation Method for Preventing Post-Traumatic Knee Osteoarthritis

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-15-1-0287 TITLE: Vibratory Stimuli, A Novel Rehabilitation Method for Preventing Post – Traumatic Knee Osteoarthritis ...August 2015 – 31 July 2016 4. TITLE AND SUBTITLE Vibratory Stimuli, A Novel Rehabilitation Method for Preventing Post – Traumatic Knee Osteoarthritis ... osteoarthritis . While the specific aims will not be realized and cannot be analyzed until the study’s completion in Year 3 due to the single-blind

Validation of an enzyme-linked immunosorbent assay for the quantification of citrullinated histone H3 as a marker for neutrophil extracellular traps in human plasma.

PubMed

Thålin, Charlotte; Daleskog, Maud; Göransson, Sophie Paues; Schatzberg, Daphne; Lasselin, Julie; Laska, Ann-Charlotte; Kallner, Anders; Helleday, Thomas; Wallén, Håkan; Demers, Mélanie

2017-06-01

There is an emerging interest in the diverse functions of neutrophil extracellular traps (NETs) in a variety of disease settings. However, data on circulating NETs rely largely upon surrogate NET markers such as cell-free DNA, nucleosomes, and NET-associated enzymes. Citrullination of histone H3 by peptidyl arginine deiminase 4 (PAD4) is central for NET formation, and citrullinated histone H3 (H3Cit) is considered a NET-specific biomarker. We therefore aimed to optimize and validate a new enzyme-linked immunosorbent assay (ELISA) to quantify the levels of H3Cit in human plasma. A standard curve made of in vitro PAD4-citrullinated histones H3 allows for the quantification of H3Cit in plasma using an anti-histone antibody as capture antibody and an anti-histone H3 citrulline antibody for detection. The assay was evaluated for linearity, stability, specificity, and precision on plasma samples obtained from a human model of inflammation before and after lipopolysaccharide injection. The results revealed linearity and high specificity demonstrated by the inability of detecting non-citrullinated histone H3. Coefficients of variation for intra- and inter-assay variability ranged from 2.1 to 5.1% and from 5.8 to 13.5%, respectively, allowing for a high precision. Furthermore, our results support an inflammatory induction of a systemic NET burden by showing, for the first time, clear intra-individual elevations of plasma H3Cit in a human model of lipopolysaccharide-induced inflammation. Taken together, our work demonstrates the development of a new method for the quantification of H3Cit by ELISA that can reliably be used for the detection of NETs in human plasma.

Biceps-Related Physical Findings Are Useful to Prevent Misdiagnosis of Cervical Spondylotic Amyotrophy as a Rotator Cuff Tear.

PubMed

Iwata, Eiichiro; Shigematsu, Hideki; Inoue, Kazuya; Egawa, Takuya; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Yamamoto, Yusuke; Sakamoto, Yoshihiro; Koizumi, Munehisa; Tanaka, Yasuhito

2018-02-01

Case-control study. The aim of the present study was to identify physical findings useful for differentiating between cervical spondylotic amyotrophy (CSA) and rotator cuff tears to prevent the misdiagnosis of CSA as a rotator cuff tear. CSA and rotator cuff tears are often confused among patients presenting with difficulty in shoulder elevation. Twenty-five patients with CSA and 27 with rotator cuff tears were enrolled. We included five physical findings specific to CSA that were observed in both CSA and rotator cuff tear patients. The findings were as follows: (1) weakness of the deltoid muscle, (2) weakness of the biceps muscle, (3) atrophy of the deltoid muscle, (4) atrophy of the biceps muscle, and (5) swallow-tail sign (assessment of the posterior fibers of the deltoid). Among 25 CSA patients, 10 (40.0%) were misdiagnosed with a rotator cuff tear on initial diagnosis. The sensitivity and specificity of each physical finding were as follows: (1) deltoid weakness (sensitivity, 92.0%; specificity, 55.6%), (2) biceps weakness (sensitivity, 80.0%; specificity, 100%), (3) deltoid atrophy (sensitivity, 96.0%; specificity, 77.8%), (4) biceps atrophy (sensitivity, 88.8%; specificity, 92.6%), and (5) swallow-tail sign (sensitivity, 56.0%; specificity, 74.1%). There were statistically significant differences in each physical finding. CSA is likely to be misdiagnosed as a rotator cuff tear; however, weakness and atrophy of the biceps are useful findings for differentiating between CSA and rotator cuff tears to prevent misdiagnosis.

Early Detection of NSCLC Using Stromal Markers in Peripheral Blood

DTIC Science & Technology

2017-11-01

transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating myeloid cells may provide us unique...signature, which may be useful for early lung cancer diagnosis. The specific aims are: Aim 1. To identify a NSCLC- dependent transcriptomic signature in...circulating myeloid cells are transcriptionally altered and the alteration is tumor dependent . The specific transcriptomic signature of circulating

Submovement control processes in discrete aiming as a function of space-time constraints.

PubMed

Hsieh, Tsung-Yu; Liu, Yeou-Teh; Newell, Karl M

2017-01-01

There is preliminary evidence that there are several types of submovements in movement aiming that reflect different processes of control and can result from particular task constraints. The purpose of the study was to investigate the effect of movement space and time task criteria on the prevalence of different submovement control characteristics in discrete aiming. Twelve participants completed 3 distance x 5 time conditions each with 100 trials in a target-aiming movement task. The kinematic structure of the trajectory determined the prevalence of 5 submovement types (none; pre-peak, post-peak movement velocity; undershoot, overshoot). The findings showed that the overall number of submovements increased in the slower space-time conditions and was predominantly characterized by post-peak trajectory submovements rather than discrete overshoot submovements. Overshoot submovements were more frequent in the high average movement velocity and short time duration conditions. We concluded that there are qualitatively different distributional patterns of submovement types in discrete aiming tasks that are organized by the quantitative scaling of the average movement velocity arising from multiple control processes to meet the specific space-time task constraints.

In vitro antigen-specific induction of IL-22 in human subjects that resolved HCV infection

PubMed Central

Cusick, Matthew F; Libbey, Jane E; Fujinami, Robert S; Eckels, David D

2012-01-01

Aims To determine if in vitro production of IL-22 and IL-17 correlated with resolution of HCV infection. Materials & methods Human peripheral blood cells isolated from a well-defined cohort of resolved and chronic HCV-infected subjects were used to measure HCV-, influenza- and mitogen-activated T-cell proliferation. In addition, IL-22 and IL-17 production was measured via ELISAs and flow cytometry. Results Resolved HCV subjects had a significantly higher T-cell proliferative response to recombinant NS3 protein compared with chronic HCV subjects. Resolved subjects had a dose-dependent IL-22 response to recombinant NS3 compared with chronic HCV subjects. Conclusion IL-22 production is associated with antigen-specific induction of CD4 + T cells in individuals that resolved HCV infection, suggesting a potential role for IL-22 in HCV clearance. PMID:23185211

Bio-AIMS Collection of Chemoinformatics Web Tools based on Molecular Graph Information and Artificial Intelligence Models.

PubMed

Munteanu, Cristian R; Gonzalez-Diaz, Humberto; Garcia, Rafael; Loza, Mabel; Pazos, Alejandro

2015-01-01

The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.

Latex immunotherapy: evidence of effectiveness

PubMed Central

Nucera, Eleonora; Mezzacappa, Simona; Buonomo, Alessandro; Centrone, Michele; Rizzi, Angela; Manicone, Paolo Francesco; Patriarca, Giampiero; Schiavino, Domenico

2018-01-01

Introduction The only etiological and decisive therapy, able to influence the natural history of latex allergy is the specific desensitization. Aim To verify the clinical efficacy and immunological changes determined by latex sublingual immunotherapy in allergic patients who underwent this treatment for at least 3 years. Material and methods We enrolled 76 patients (16 males and 60 females, mean age 34 years old) with evidence of a natural rubber latex allergy. To assess the effectiveness of the immunotherapy we performed a latex skin prick test, specific IgE and IgG4 and challenge tests before and after at least 3 years of desensitization. Results We observed a reduction in the mean diameter of the wheal area at the skin prick test and a decrease in latex specific IgE while no significant changes of latex IgG4 values were found. Moreover a reduction of symptoms and scores at the provocation tests were remarked. Conclusions Although the primary prevention (which still remains the gold standard treatment for patients suffering from the latex allergy) sublingual immunotherapy can be offered with efficacy in addition to symptomatic treatment to selected patients. PMID:29760613

Optimization of ultrasound-assisted extraction of pectinase enzyme from guava (Psidium guajava) peel: Enzyme recovery, specific activity, temperature, and storage stability.

PubMed

Amid, Mehrnoush; Murshid, Fara Syazana; Manap, Mohd Yazid; Islam Sarker, Zaidul

2016-01-01

This study aimed to investigate the effects of the ultrasound-assisted extraction conditions on the yield, specific activity, temperature, and storage stability of the pectinase enzyme from guava peel. The ultrasound variables studied were sonication time (10-30 min), ultrasound temperature (30-50 °C), pH (2.0-8.0), and solvent-to-sample ratio (2:1 mL/g to 6:1 mL/g). The main goal was to optimize the ultrasound-assisted extraction conditions to maximize the recovery of pectinase from guava peel with the most desirable enzyme-specific activity and stability. Under the optimum conditions, a high yield (96.2%), good specific activity (18.2 U/mg), temperature stability (88.3%), and storage stability (90.3%) of the extracted enzyme were achieved. The optimal conditions were 20 min sonication time, 40 °C temperature, at pH 5.0, using a 4:1 mL/g solvent-to-sample ratio. The study demonstrated that optimization of ultrasound-assisted process conditions for the enzyme extraction could improve the enzymatic characteristics and yield of the enzyme.

Susceptibility of Hep3B cells in different phases of cell cycle to tBid.

PubMed

Ma, Shi-Hong; Chen, George G; Ye, Caiguo; Leung, Billy C S; Ho, Rocky L K; Lai, Paul B S

2011-01-01

tBid is a pro-apoptotic molecule. Apoptosis inducers usually act in a cell cycle-specific fashion. The aim of this study was to elucidate whether effect of tBid on hepatocellular carcinoma (HCC) Hep3B cells was cell cycle phase specific. We synchronized Hep3B cells at G0/G1, S or G2/M phases by chemicals or flow sorting and tested the susceptibility of the cells to recombinant tBid. Cell viability was measured by MTT assay and apoptosis by TUNEL. The results revealed that tBid primarily targeted the cells at G0/G1 phase of cell cycle, and it also increased the cells at the G2/M phase. 5-Fluorouracil (5-FU), on the other hand, arrested Hep3B cells at the G0/G1 phase, but significantly reduced cells at G2/M phase. The levels of cell cycle-related proteins and caspases were altered in line with the change in the cell cycle. The combination of tBid with 5-FU caused more cells to be apoptotic than either agent alone. Therefore, the complementary effect of tBid and 5-FU on different phases of the cell cycle may explain their synergistric effect on Hep3B cells. The elucidation of the phase-specific effect of tBid points to a possible therapeutic option that combines different phase specific agents to overcome resistance of HCC. Copyright © 2010 Elsevier B.V. All rights reserved.

Does Lesion Size Affect the Value of Shear Wave Elastography for Differentiating Between Benign and Malignant Thyroid Nodules?

PubMed

Wang, Fen; Chang, Cai; Chen, Min; Gao, Yi; Chen, Ya-Ling; Zhou, Shi-Chong; Li, Jia-Wei; Zhi, Wen-Xiang

2018-03-01

We aimed to investigate the diagnostic performance of shear wave elastography (SWE) combined with conventional ultrasonography (US) for differentiating between benign and malignant thyroid nodules of different sizes. A total of 445 thyroid nodules from 445 patients were divided into 3 groups based on diameter (group 1, ≤ 10 mm; group 2, 10-20 mm; and group 3, > 20 mm). The mean elasticity index of the whole lesion was automatically calculated, and the threshold for differentiation between benign and malignant nodules was constructed by a receiver operating characteristic curve analysis. Diagnostic performances of conventional US and SWE were compared by using pathologic results as reference standards. The mean elasticity was significantly higher in malignant versus benign nodules for all size groups. The differences in mean elasticity in the size groups were not statistically significant for malignant or benign nodules. The specificity of US combined with SWE for group 1 was significantly higher than that for groups 2 and 3 (77.8% versus 62.9% and 53.3%; P < .05), and compared with group 1, the sensitivity was significantly higher for groups 2 and 3 (92.4% and 94.3% versus 80.7%; P < .05). When SWE was added, the specificity increased and the sensitivity and diagnostic accuracy decreased for group 1, and the sensitivity increased and the specificity decreased for groups 2 and 3; however, the differences were not significant. Combined with SWE, US yielded higher specificity for nodules of 10 mm and smaller and higher sensitivity for nodules larger than 10 mm. © 2017 by the American Institute of Ultrasound in Medicine.

[Correlation between positive skin tests to molds, total IgE, and specific IgE using ELISA and mold cultures from the environment of the pediatric allergy patient].

PubMed

García Caballero, R; Nader, O; Morfin Maciel, B

2001-01-01

The aim of this study was to made a correlation between allergic symptoms, positive skin prick test to fungi, total and specific IgE and mold culture in the patient's environmental. There were included 35 children (3-16 years), with skin prick test positive to fungi. The most frequent were: Rhizopus, Aspergillus, Cladosporium and Candida. Total and specific IgE were measured with ELISA, with titers high in 77.2% and 31.4% respectively. Fungal cultures were collected from dwellings and schools. The most frequently isolated mold genera were Cladosporium, Alternaria and Penicillium in the same proportion in both places: dwellings and schools. We concluded fungi are commonly found in children's environment.

Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG bands in patients with clinically isolated and Guillain-Barré syndrome.

PubMed

Ferraro, Diana; Galli, Veronica; Simone, Anna Maria; Bedin, Roberta; Vitetta, Francesca; Merelli, Elisa; Nichelli, Paolo Frigio; Sola, Patrizia

2017-04-01

Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS) pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barré syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB and CIS patients' CSF, MRI, and clinical variables. There was no difference in the proportion of CIS and GB patients with positivity for anti-EBV-specific IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor were they predictive of a higher disability at 3 years.

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

2016-05-01

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

CAPER 3.0: A Scalable Cloud-Based System for Data-Intensive Analysis of Chromosome-Centric Human Proteome Project Data Sets.

PubMed

Yang, Shuai; Zhang, Xinlei; Diao, Lihong; Guo, Feifei; Wang, Dan; Liu, Zhongyang; Li, Honglei; Zheng, Junjie; Pan, Jingshan; Nice, Edouard C; Li, Dong; He, Fuchu

2015-09-04

The Chromosome-centric Human Proteome Project (C-HPP) aims to catalog genome-encoded proteins using a chromosome-by-chromosome strategy. As the C-HPP proceeds, the increasing requirement for data-intensive analysis of the MS/MS data poses a challenge to the proteomic community, especially small laboratories lacking computational infrastructure. To address this challenge, we have updated the previous CAPER browser into a higher version, CAPER 3.0, which is a scalable cloud-based system for data-intensive analysis of C-HPP data sets. CAPER 3.0 uses cloud computing technology to facilitate MS/MS-based peptide identification. In particular, it can use both public and private cloud, facilitating the analysis of C-HPP data sets. CAPER 3.0 provides a graphical user interface (GUI) to help users transfer data, configure jobs, track progress, and visualize the results comprehensively. These features enable users without programming expertise to easily conduct data-intensive analysis using CAPER 3.0. Here, we illustrate the usage of CAPER 3.0 with four specific mass spectral data-intensive problems: detecting novel peptides, identifying single amino acid variants (SAVs) derived from known missense mutations, identifying sample-specific SAVs, and identifying exon-skipping events. CAPER 3.0 is available at http://prodigy.bprc.ac.cn/caper3.

Virtual Reality Simulation of the Effects of Microgravity in Gastrointestinal Physiology

NASA Technical Reports Server (NTRS)

Compadre, Cesar M.

1998-01-01

The ultimate goal of this research is to create an anatomically accurate three-dimensional (3D) simulation model of the effects of microgravity in gastrointestinal physiology and to explore the role that such changes may have in the pharmacokinetics of drugs given to the space crews for prevention or therapy. To accomplish this goal the specific aims of this research are: 1) To generate a complete 3-D reconstructions of the human GastroIntestinal (GI) tract of the male and female Visible Humans. 2) To develop and implement time-dependent computer algorithms to simulate the GI motility using the above 3-D reconstruction.

Novel Therapeutic Targets to Treat Social Behavior Deficits in Autism and Related Disorders

DTIC Science & Technology

2013-10-01

effects of D- 22 on serotonin uptake in vitro and in vivo: To measure the ability of D- 22 to block [3H] 5- HT ...blocked by D- 22 and corticosterone in those preparations. Specific Aim 3, effects of D- 22 on murine social behavior: Two tests have been used to...levels of 5- HT available. Studies are now underway 6 to assess the effects of D- 22 administration on social behavior in C57BL/6, DBA1 and

Determination of 1,2/1,3-diglycerides in Sicilian extra-virgin olive oils by 1H-NMR over a one-year storage period.

PubMed

Salvo, Andrea; Rotondo, Archimede; La Torre, Giovanna Loredana; Cicero, Nicola; Dugo, Giacomo

2017-04-01

This study is aimed to monitor by 1 H NMR spectroscopy the effect of a 12-month storage period on the 1,2-diglycerides over 1,3-diglycerides ratio for five mono-cultivar 'extra virgin olive oils' (EVOO) (Arbequina, Arbosana, Cerasuola, Nocellara and FS17) and one blend of two different cultivars (Nocellara + Biancolilla) preserved in the dark and at room temperature. These quantifications, at 500 MHz, are readily extracted through a specific and original integration difference method. Albeit it was known that the isomerisation rate is affected by the free acidity, we here demonstrate that it also depends on the presence of specific macromolecules (lipases), indeed, different EVOO cultivars with similar free acidity, show different isomerisation rate. Our results are consistent with similar diglyceride monitoring performed on Greek and Spanish EVOOs by 31 P NMR.

Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma

PubMed Central

Gawrych, Katarzyna; Casjens, Swaantje; Brik, Alexander; Lehnert, Martin; Taeger, Dirk; Pesch, Beate; Kollmeier, Jens; Bauer, Torsten T.; Johnen, Georg; Brüning, Thomas

2017-01-01

The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance. PMID:28321148

Assessment of multifunctional activity of bioactive peptides derived from fermented milk by specific Lactobacillus plantarum strains.

PubMed

Aguilar-Toalá, J E; Santiago-López, L; Peres, C M; Peres, C; Garcia, H S; Vallejo-Cordoba, B; González-Córdova, A F; Hernández-Mendoza, A

2017-01-01

Milk-derived bioactive peptides with a single activity (e.g., antioxidant, immunomodulatory, or antimicrobial) have been previously well documented; however, few studies describe multifunctional bioactive peptides, which may be preferred over single-activity peptides, as they can simultaneously trigger, modulate, or inhibit multiple physiological pathways. Hence, the aim of this study was to assess the anti-inflammatory, antihemolytic, antioxidant, antimutagenic, and antimicrobial activities of crude extracts (CE) and peptide fractions (<3 and 3-10 kDa) obtained from fermented milks with specific Lactobacillus plantarum strains. Overall, CE showed higher activity than both peptide fractions (<3 and 3-10 kDa) in most of the activities assessed. Furthermore, activity of <3 kDa was generally higher, or at least equal, to the 3 to 10 kDa peptide fractions. In particular, L. plantarum 55 crude extract or their fractions showed the higher anti-inflammatory (723.68-1,759.43μg/mL of diclofenac sodium equivalents), antihemolytic (36.65-74.45% of inhibition), and antioxidant activity [282.8-362.3µmol of Trolox (Sigma-Aldrich, St. Louis, MO) equivalents]. These results provide valuable evidence of multifunctional role of peptides derived of fermented milk by the action of specific L. plantarum strains. Thus, they may be considered for the development of biotechnological products to be used to reduce the risk of disease or to enhance a certain physiological function. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of a monoclonal antibody against the CD3ε of olive flounder (Paralichthys olivaceus) and its application in evaluating immune response related to CD3ε.

PubMed

Jung, Jae Wook; Lee, Jung Seok; Kim, Young Rim; Im, Se Pyeong; Kim, Si Won; Lazarte, Jassy Mary S; Kim, Jaesung; Thompson, Kim D; Suh, Jong Pyo; Jung, Tae Sung

2017-06-01

The T cell receptor (TCR) is the binding site of antigen and is responsible for specifically activating the adaptive immune response. CD3, an essential component of the CD3-TCR complex, is known to be composed of γδ and ε chains in teleost. However, there are few monoclonal antibodies (mAb) available to identify these molecules on T cells, so we aimed to produce a mAb against CD3ε to improve our understanding of T cell immune response in olive flounder (Paralichthys olivaceus). CD3ε recombinant protein was expressed in yeast, the expression of which was confirmed by SDS-PAGE, MALDI-TOF/TOF MS and Western blot analysis. A CD3ε-specific mAb 4B2 was selected, the specificity of which was examined by confocal microscopy, flow cytometry and RT-PCR, and the mAb was subsequently used to examine the CD3ε lymphocyte population in several different immune organs, with relatively high percentages of these cells seen in trunk-kidney and spleen, while lower percentages were seen in the liver and peripheral blood of olive flounder. During a viral hemorrhagic septicemia virus (VHSV) infection in olive flounder, the number of CD3ε lymphocytes was seen to gradually increase in the liver, spleen and trunk-kidney of infected fish until 7 days post infection (dpi). In peripheral blood, on the other hand, the increase in CD3ε lymphocyte numbers peaked by 3 dpi. These results suggest that CD3ε lymphocytes might be involved in the immune response against VHSV. Copyright © 2017 Elsevier Ltd. All rights reserved.

An evidence-based environmental perspective of manufactured silver nanoparticle in syntheses and applications: a systematic review and critical appraisal of peer-reviewed scientific papers.

PubMed

Tolaymat, Thabet M; El Badawy, Amro M; Genaidy, Ash; Scheckel, Kirk G; Luxton, Todd P; Suidan, Makram

2010-02-01

Most recently, renewed interest has arisen in manufactured silver nanomaterials because of their unusually enhanced physicochemical properties and biological activities compared to the bulk parent materials. A wide range of applications has emerged in consumer products ranging from disinfecting medical devices and home appliances to water treatment. Because the hypothesized mechanisms that govern the fate and transport of bulk materials may not directly apply to materials at the nanoscale, there are great concerns in the regulatory and research communities about potential environmental impacts associated with the use of silver nanoparticles. In particular, the unlimited combinations of properties emerging from the syntheses and applications of silver nanoparticles are presenting an urgent need to document the predominant salt precursors, reducing agents and stabilizing agents utilized in the synthesis processes of silver nanoparticles to guide the massive efforts required for environmental risk assessment and management. The primary objective of this study is to present an evidence-based environmental perspective of silver nanoparticle properties in syntheses and applications. The following specific aims are designed to achieve the study objective: Aim 1--to document the salt precursors and agents utilized in synthesizing silver nanoparticles; Aim 2--to determine the characteristics of silver nanoparticles currently in use in the scientific literature when integrated in polymer matrices to form nanocomposites and combined with other metal nanoparticles to form bimetallic nanoparticles; Aim 3--to provide a summary of the morphology of silver nanoparticles; and (4) Aim 4--to provide an environmental perspective of the evidence presented in Aims 1 to 3. A comprehensive electronic search of scientific databases was conducted in support of the study objectives. Specific inclusion criteria were applied to gather the most pertinent research articles. Data and information extraction relied on the type of synthesis methods, that is, synthesized silver nanoparticles in general and specific applications, nanocomposites, and bimetallic techniques. The following items were gathered for: type of silver salt, solvent, reducing agent, stabilizing agent, size, and type of application/nanocomposite/bimetallic, and template (for nanocomposites). The description of evidence was presented in tabular format. The critical appraisal was analyzed in graphical format and discussed. An analysis of the scientific literature suggests that most synthesis processes produce spherical silver nanoparticles with less than 20nm diameter. Silver nanoparticles are often synthesized via reduction of AgNO(3), dissolution in water, and utilization of reductants also acting as capping or stabilizing agents for the control of particle size to ensure a relatively stable suspension. Two of the most commonly used reductants and stabilizing agents are NaBH(4) and citrate which yield particles with a negative surface charge over the environmental pH range (3-10). The environmental perspectives of these parameters are discussed. It is expected that the antibacterial property of bulk silver is carried over and perhaps enhanced, to silver nanoparticles. Therefore, when one examines the environmental issues associated with the manufacture and use of silver nanoparticle-based products, the antibacterial effects should always be taken into account particularly at the different stages of the product lifecycle. Currently, there are two arguments in the scientific literature about the mechanisms of antimicrobial properties of silver nanoparticles as they relate to colloidal silver particles and inonic silver. Methodologies of risk assessment and control have to account for both arguments. Published by Elsevier B.V.

The effect of mixed dopants on the stability of Fricke gel dosimeters

NASA Astrophysics Data System (ADS)

Penev, K.; Mequanint, K.

2013-06-01

Auto-oxidation and fast diffusion in Fricke gels are major drawbacks to wide-spread application of these gels in 3D dosimetry. Aiming to limit both processes, we used mixed dopants: the ferric-specific ligand xylenol orange with a ferrous-specific ligand (1,10-phenanthroline) and/or a bi-functional cross-linking agent (glyoxal). Markedly improved auto-oxidation stability was observed in the xylenol orange and phenanthroline doped gel at the expense of increased background absorbance and faster diffusion. Addition of glyoxal limited the diffusion rate and led to a partial bleaching of the gel. It is conceivable that these two new compositions may find useful practical application.

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population.

PubMed

Gimenez, Lucas G; Momany, Allison M; Poletta, Fernando A; Krupitzki, Hugo B; Gili, Juan A; Busch, Tamara D; Saleme, Cesar; Cosentino, Viviana R; Pawluk, Mariela S; Campaña, Hebe; Gadow, Enrique C; Murray, Jeffrey C; Lopez-Camelo, Jorge S

2017-09-01

BackgroundPreterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation as follows: idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB.MethodsTwenty-four single-nucleotide polymorphisms (SNPs) were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 were PTB-PPROM, and 210 were PTB-M. These data were analyzed with a Family-Based Association.ResultsPTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, three SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M.ConclusionOur study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes.

Feasibility and Effectiveness of Memory Specificity Training in Depressed Outpatients: A Pilot Study.

PubMed

Eigenhuis, Eline; Seldenrijk, Adrie; van Schaik, Anneke; Raes, Filip; van Oppen, Patricia

2017-01-01

Research has shown that depressed patients suffer from reduced autobiographical memory specificity (rAMS). This cognitive phenomenon is associated with the maintenance and recurrence of depressive symptoms. This pilot study aims to investigate the feasibility and effectiveness of a relatively new group-based intervention (Memory Specificity Training; MeST) that aims to reduce rAMS in an outpatient setting. Twenty-six depressed outpatients received MeST during the waiting period prior to psychotherapy. The Client Satisfaction Questionnaire (CSQ-8) was used to measure client satisfaction after the training. The Autobiographical Memory Test (AMT) was used to measure memory specificity before and after the training. Depressive symptoms were measured using the Beck Depression Inventory (BDI-II) and the Montgomery Asberg Depression Rating Scale (MADRS), before and after the training, and at a 3-month follow-up. Participants as well as trainers were positive about the use of MeST. Participants also showed an increase in memory specificity and a decrease in depressive symptoms. This study suggests that MeST is feasible in an outpatient setting, that it increases autobiographical memory specificity and that it may decrease depressive symptoms. A randomized controlled trial is recommended to examine MeST and its effects on autobiographical memory specificity, depressive symptoms and depressive relapse more extensively. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message: Research suggests that modification of rAMS can advance recovery and reduce the chance of developing a depression relapse. However, most existing psychotherapies for depression do not include these specific interventions. This is the first study to show that MeST in an outpatient setting is feasible and can lead to an increase in autobiographical memory specificity and that it may decrease depressive symptoms. A larger scale randomized controlled trial is required to examine whether the addition of MeST to care as usual decreases depressive symptoms more effectively than care as usual without MeST, and to examine whether subgroups of patients benefit specifically from this intervention (e.g. patients with more severely decreased memory specificity). Copyright © 2015 John Wiley & Sons, Ltd.

Development of Cooperative Communication Techniques for a Network of Small Satellites and Cubesats in Deep Space

NASA Technical Reports Server (NTRS)

Babuscia, Alessandra; Cheung, Kar-Ming; Divsalar, Dariush; Lee, Charles

2014-01-01

This paper aims to address this problem by proposing cooperative communication approaches in which multiple CubeSats communicate cooperatively together to improve the link performance with respect to the case of a single satellite transmitting. Three approaches are proposed: a beam-forming approach, a coding approach, and a network approach. The approaches are applied to the specific case of a proposed constellation of CubeSats at the Lunar Lagrangian point L1 which aims to perform radio astronomy at very low frequencies (30 KHz -3 MHz). The paper describes the development of the approaches, the simulation and a graphical user interface developed in Matlab which allows to perform trade-offs across multiple constellation's configurations.

Variable Food-Specific IgG Antibody Levels in Healthy and Symptomatic Chinese Adults

PubMed Central

Wu, Liu-Xin; Li, Hong; Sun, Zhi-Jian; Li, Jing-Bo; Jiang, Hong-Xia; Chen, Zhi-Heng; Wang, Qi-Bin; Chen, Wei-Wei

2013-01-01

Background The presence of food-specific IgG antibodies in human serum may be useful for diagnosis of adverse food reactions. However, the clinical utility of tesing for such antibodies remains very controversial. The aim of this study was to evaluate the serum levels and population distribution of food-specific IgGs and their association with chronic symptoms in a large-scale Chinese population. Methodology/Principal Findings A total of 21305 adult participants from different regions of China had 14 type of food-specific serum IgG antibodies that were measured by enzyme-linked immunosorbent assay. Amongthese, 5,394 participants were randomly chosen to complete follow-up questionnaire surveys on their dietary characteristics and chronic symptoms. The concentrations of food-specific IgGs against 14 foods ranged from a median (interquartile range) of 7.3 (3.8, 12.6) U/mL of pork-specfic IgG to 42.3 (28.8, 60.2) U/mL of crab-specific IgG. The concentration of food-specific IgGs was closely related to gender; after adjustment for region and age, women had higher concentrations of food-specific IgGs against all of the 14 foods except chicken (regression coefficient (95% CI): 0.01 (−0.003, 0.023); P = 0.129) and corn (0.002 (−0.013, 0.016); P = 0.825). Similar results were also found in the relationship of geographic region to the food-specific IgG concentrations for the 14 foods. Chronic symptoms were negatively associated with the concentrations of a few food-specific IgGs, and were positively associated with the concentrations of other food-specific IgGs. Conclusions The levels of food-specific IgGs were variable both in healthy and in symptomatic Chinese adults. These findings raise awareness that demographic factors, the type of food and specific chronic symptoms should be considered before food elimination treatment based on IgG testing in patients with chronic symptoms is used in clinical practice. PMID:23301096

Cyclosporine a inhibits apoptosis of rat gingival epithelium.

PubMed

Ma, Su; Liu, Peihong; Li, Yanwu; Hou, Lin; Chen, Li; Qin, Chunlin

2014-08-01

The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia. Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats. CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

Kinetics of Epstein-Barr virus load and virus-specific CD8+ T cells in acute infectious mononucleosis.

PubMed

Hoshino, Yo; Nishikawa, Kazuo; Ito, Yoshinori; Kuzushima, Kiyotaka; Kimura, Hiroshi

2011-03-01

During the convalescent phase of acute infectious mononucleosis (AIM), Epstein-Barr virus (EBV) load shrinks rapidly in association with a rapid decline in the number of EBV-specific CD8(+) T cells. The actual contribution of EBV-specific CD8(+) T cells in reducing EBV load, however, is not known. To clarify the impact of EBV-specific CD8(+) T cells on the contraction of EBV load in AIM, we estimated half-lives of both EBV load and EBV-specific CD8(+) T cells. Blood was serially taken from five pediatric patients with AIM during the convalescent period, including the very early phase, and both EBV load and EBV-specific CD8(+) T cell numbers were assayed. EBV load declined rapidly (half-life 1.5 d) during the first 2 weeks after onset of symptoms. This half-life was seven-fold shorter than that reported for CD27(+) memory B cells. Subsequently, the EBV load declined much more slowly, with a half-life of 38.7 d. EBV-specific CD8(+) T cell numbers also declined concomitantly with the decrease in EBV load. The half-life of EBV-specific CD8(+) T cells during first 2 weeks was 2.9 d. The number of EBV-specific CD8(+) T cells and the rate of change of viral load correlated significantly (R(2) ≥ 0.8; p ≤ 0.02). The short half-life of EBV load, together with the strong correlation between the number of EBV-specific CD8(+) T cells and the rate of change of viral load indicates an active role for EBV-specific CD8(+) T cells in elimination of EBV in AIM. Copyright © 2010 Elsevier B.V. All rights reserved.

Microstructural evolution of neutron irradiated 3C-SiC

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

Sprouster, David J.; Koyanagi, Takaaki; Dooryhee, Eric

The microstructural response of neutron irradiated 3C-SiC have been investigated over a wide irradiation temperature and fluence range via qualitative and quantitative synchrotron-based X-ray diffraction characterization. Here, we identify several neutron fluence- and irradiation temperature-dependent changes in the microstructure, and directly highlight the specific defects introduced through the course of irradiation. By quantifying the microstructure, we aim to develop a more detailed understanding of the radiation response of SiC. Such studies are important to build mechanistic models of material performance and to understand the susceptibility of various microstructures to radiation damage for advanced energy applications.

Microstructural evolution of neutron irradiated 3C-SiC

DOE PAGES

Sprouster, David J.; Koyanagi, Takaaki; Dooryhee, Eric; ...

2017-03-18

The microstructural response of neutron irradiated 3C-SiC have been investigated over a wide irradiation temperature and fluence range via qualitative and quantitative synchrotron-based X-ray diffraction characterization. Here, we identify several neutron fluence- and irradiation temperature-dependent changes in the microstructure, and directly highlight the specific defects introduced through the course of irradiation. By quantifying the microstructure, we aim to develop a more detailed understanding of the radiation response of SiC. Such studies are important to build mechanistic models of material performance and to understand the susceptibility of various microstructures to radiation damage for advanced energy applications.

Altering the Composition of Caseicins A and B as a Means of Determining the Contribution of Specific Residues to Antimicrobial Activity ▿

PubMed Central

Norberg, Sarah; O'Connor, Paula M.; Stanton, Catherine; Ross, R. Paul; Hill, Colin; Fitzgerald, Gerald F.; Cotter, Paul D.

2011-01-01

Caseicin A (IKHQGLPQE) and caseicin B (VLNENLLR) are antimicrobial peptides generated through the bacterial fermentation of sodium caseinate, and on the basis of this and previous studies, they are active against many Gram-negative pathogens (Cronobacter sakazakii, Cronobacter muytjensii, Salmonella enterica serovar Typhimurium, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas fluorescens) as well as the Gram-positive organism Staphylococcus aureus. Here we describe further studies with the aim of establishing the importance of specific (charged and nonpolar aliphatic) residues within the caseicin peptides and the effects that they have on the bacteria listed above. In order to achieve our objective, we created four derivatives of each caseicin (A1 to A4 and B1 to B4) in which specific residues were altered, and results obtained with these derivatives were compared to wild-type caseicin activity. Although conversion of cationic residues to alanine in caseicins B1 (R8A change), A1 (K2A), A2 (H3A), and A3 (K2A-H3A) generally resulted in their activity against microbial targets being reduced or unaltered, C. sakazakii DPC6440 was unusual in that it displayed enhanced sensitivity to three peptides (caseicins A1, A3, and B2) in which positively charged residues had been eliminated. While the replacement of leucine with alanine in selected variants (B3 and B4) resulted in reduced activity against a number of strains of Cronobacter and, in some cases, S. Typhimurium, these changes enhanced the activities of these peptides against DPC6440 and a number of S. aureus strains. It is thus apparent that the importance of specific residues within the caseicin peptides is dependent on the strain being targeted. PMID:21296933

Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes.

PubMed

Parray, Hilal Ahmad; Lone, Jameel; Park, Jong Pil; Choi, Jang Won; Yun, Jong Won

2018-06-01

The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively. Induction of thermogenesis and suppression of oxidative stress in 3T3-L1 adipocytes were further validated by immunofluorescence. Magnolol significantly enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cd137, Prdm16, Cidea, and Tbx1) and proteins (UCP1, PRDM16, and PGC-1α). Increased expression of UCP1 and other brown fat-specific markers contributed to the browning of 3T3-L1 adipocytes possibly via activation of the AMPK, PPARγ, and protein kinase A (PKA) pathways. In addition, magnolol up-regulated key fatty acid oxidation and lipolytic markers (CPT1, ACSL1, SIRT1, and PLIN) and down-regulated lipogenic markers (FAS and SREBP1). Magnolol also reduced the production and release of reactive oxygen species. The current data suggest possible roles for magnolol in browning of white adipocytes, augmentation of lipolysis, and thermogenesis, as well as repression of oxidative stress and lipogenesis. Thus, magnolol may be explored as a potentially promising therapeutic agent for the prevention of obesity and other metabolic disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of 1.5- and 3-T MR imaging for evaluating the articular cartilage of the knee.

PubMed

Van Dyck, Pieter; Kenis, Christoph; Vanhoenacker, Filip M; Lambrecht, Valérie; Wouters, Kristien; Gielen, Jan L; Dossche, Lieven; Parizel, Paul M

2014-06-01

The aim of this prospective study was to compare routine MRI scans of the knee at 1.5 and 3 T obtained in the same individuals in terms of their performance in the diagnosis of cartilage lesions. One hundred patients underwent MRI of the knee at 1.5 and 3 T and subsequent knee arthroscopy. All MR examinations consisted of multiplanar 2D turbo spin-echo sequences. Three radiologists independently graded all articular surfaces of the knee joint seen at MRI. With arthroscopy as the reference standard, the sensitivity, specificity, and accuracy of 1.5- and 3-T MRI for detecting cartilage lesions and the proportion of correctly graded cartilage lesions within the knee joint were determined and compared using resampling statistics. For all readers and surfaces combined, the respective sensitivity, specificity, and accuracy for detecting all grades of cartilage lesions in the knee joint using MRI were 60, 96, and 87% at 1.5 T and 69, 96, and 90% at 3 T. There was a statistically significant improvement in sensitivity (p < 0.05), but not specificity or accuracy (n.s.) for the detection of cartilage lesions at 3 T. There was also a statistically significant (p < 0.05) improvement in the proportion of correctly graded cartilage lesions at 3 T as compared to 1.5 T. A 3-T MR protocol significantly improves diagnostic performance for the purpose of detecting cartilage lesions within the knee joint, when compared with a similar protocol performed at 1.5 T. III.

Asthma cases in childhood attributed to atopy in tropical area in Brazil.

PubMed

Souza da Cunha, Sergio; Barreto, Mauricio Lima; Fiaccone, Rosemeire Leovigildo; Cooper, Philip J; Alcantara-Neves, Neuza Maria; Simões, Silvia de Magalhães; Cruz, Alvaro Augusto; Rodrigues, Laura Cunha

2010-12-01

This study aimed to explore the association between asthma and atopy in a cohort of children living in a large urban center in Brazil. Atopy was defined by the presence of allergen-specific IgE in serum or by a positive skin prick test. In a sample of 1 445 Brazilian children, the association between the prevalence of asthma, skin prick test positivity, and allergen-specific IgE in serum was investigated. The prevalence of asthma was 22.6%. The presence of serum allergen-specific IgE was frequent in asthmatics and nonasthmatics, and the prevalence of asthma increased only with levels of allergen-specific IgE > 3.5 kilounits/L. The proportion of asthma attributable to atopy was estimated to be 24.5% when atopy was defined by the presence of allergen-specific IgE. With a given level of specific IgE, no association between skin test reactivity and asthma was observed. Skin prick tests were less sensitive than specific IgE for detection of atopy. Most asthma cases in an urban underprivileged setting in Brazil were not attributable to atopy. This observation has important implications for understanding the risk factors for the asthma epidemic in Latin America.

Inducible Transgenic Models of BRCA1 Function

DTIC Science & Technology

1998-10-01

development, and for signs of hyperplasia, dysplasia and neoplasia. Specific Aim 3. Inducibly abolish Brcal expression in the mammary epithelium of...abnormalities in mammary epithelial proliferation, differentiation and development, and for signs of hyperplasia, dysplasia and neoplasia. 6...Lyu MS, Kozak CA and Leder P. Expression of Brcal is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice

Role of Dendritic Cells in Immune Dysfunction

NASA Technical Reports Server (NTRS)

Savary, Cherylyn A.

1997-01-01

Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

Development and Validation of Search Filters to Identify Articles on Family Medicine in Online Medical Databases.

PubMed

Pols, David H J; Bramer, Wichor M; Bindels, Patrick J E; van de Laar, Floris A; Bohnen, Arthur M

2015-01-01

Physicians and researchers in the field of family medicine often need to find relevant articles in online medical databases for a variety of reasons. Because a search filter may help improve the efficiency and quality of such searches, we aimed to develop and validate search filters to identify research studies of relevance to family medicine. Using a new and objective method for search filter development, we developed and validated 2 search filters for family medicine. The sensitive filter had a sensitivity of 96.8% and a specificity of 74.9%. The specific filter had a specificity of 97.4% and a sensitivity of 90.3%. Our new filters should aid literature searches in the family medicine field. The sensitive filter may help researchers conducting systematic reviews, whereas the specific filter may help family physicians find answers to clinical questions at the point of care when time is limited. © 2015 Annals of Family Medicine, Inc.

Effect of Heart rate on Basketball Three-Point Shot Accuracy

PubMed Central

Ardigò, Luca P.; Kuvacic, Goran; Iacono, Antonio D.; Dascanio, Giacomo; Padulo, Johnny

2018-01-01

The three-point shot (3S) is a fundamental basketball skill used frequently during a game, and is often a main determinant of the final result. The aim of the study was to investigate the effect of different metabolic conditions, in terms of heart rates, on 3S accuracy (3S%) in 24 male (Under 17) basketball players (age 16.3 ± 0.6 yrs). 3S performance was specifically investigated at different heart rates. All sessions consisted of 10 consecutive 3Ss from five different significant field spots just beyond the FIBA three-point line, i.e., about 7 m from the basket (two counter-clockwise “laps”) at different heart rates: rest (0HR), after warm-up (50%HRMAX [50HR]), and heart rate corresponding to 80% of its maximum value (80%HRMAX [80HR]). We found that 50HR does not significantly decrease 3S% (−15%, P = 0.255), while 80HR significantly does when compared to 0HR (−28%, P = 0.007). Given that 50HR does not decrease 3S% compared to 0HR, we believe that no preliminary warm-up is needed before entering a game in order to specifically achieve a high 3S%. Furthermore, 3S training should be performed in conditions of moderate-to-high fatigued state so that a high 3S% can be maintained during game-play. PMID:29467676

Arteriolar and Venular Remodeling Are Differentially Regulated by Bone Marrow-Derived Cell-Specific CX3CR1 and CCR2 Expression

PubMed Central

Meisner, Joshua K.; Song, Ji; Price, Richard J.

2012-01-01

The chemokine receptors CCR2 and CX3CR1 are critical for the recruitment of “inflammatory” and “resident” monocytes, respectively, subpopulations that differentially affect vascular remodeling in atherosclerosis. Here, we tested the hypothesis that bone marrow-derived cell (BMC)-specific CCR2 and CX3CR1 differentially control venular and arteriolar remodeling. Venular and arteriolar lumenal remodeling were observed by intravital microscopy in mice with either CCR2 or CX3CR1 deficient BMCs after implantation of a dorsal skinfold window chamber, a model in which arterioles and venules lumenally enlarge in wild-type (WT) mice. Arteriolar remodeling was abolished in mice with either CCR2 or CX3CR1-deficient BMCs. In contrast, the loss of CX3CR1 from BMCs, but not CCR2, significantly reduced small venule remodeling compared to WT controls. We conclude that microvascular remodeling is differentially regulated by BMC-expressed chemokine receptors. Both CCR2 and CX3CR1 regulate arteriole growth; however, only BMC-expressed CX3CR1 impacts small venule growth. These findings may provide a basis for additional investigations aimed at determining how patterns of monocyte subpopulation recruitment spatially influence microvascular remodeling. PMID:23029475

Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population.

PubMed

Tsamandouras, Nikolaos; Guo, Yingying; Wendling, Thierry; Hall, Stephen; Galetin, Aleksandra; Aarons, Leon

2017-01-01

Ethnicity plays a modulating role in atorvastatin pharmacokinetics (PK), with Asian patients reported to have higher exposure compared with Caucasians. Therefore, it is difficult to safely extrapolate atorvastatin PK data and models across ethnic groups. This work aims to develop a population PK model for atorvastatin and its pharmacologically active metabolites specifically for the Japanese population. Subsequently, it aimed to identify genetic polymorphisms affecting atorvastatin PK in this population. Atorvastatin acid (ATA) and ortho-hydroxy-atorvastatin acid (o-OH-ATA) plasma concentrations, clinical/demographic characteristics and genotypes for 18 (3, 3, 1, 1, 7, 2 and 1 in the ABCB1, ABCG2, CYP3A4, CYP3A5, SLCO1B1, SLCO2B1 and PPARA genes, respectively) genetic polymorphisms were collected from 27 Japanese individuals (taking 10 mg atorvastatin once daily) and analysed using a population PK modelling approach. The population PK model developed (one-compartment for ATA linked through metabolite formation to an additional compartment describing the disposition of o-OH-ATA) accurately described the observed data and the associated population variability. Our analysis suggested that patients carrying one variant allele for the rs2622604 polymorphism (ABCG2) show a 55% (95% confidence interval: 16-131%) increase in atorvastatin oral bioavailability relative to the value in individuals without the variant allele. The current work reports the identification in the Japanese population of a BCRP polymorphism, not previously associated with the PK of any statin, that markedly increases ATA and o-OH-ATA exposure. The model developed may be of clinical importance to guide dosing recommendations tailored specifically for the Japanese.

Enhancing Propriospinal Relays to Improve Functional Recovery After SCI

DTIC Science & Technology

2017-10-01

injury to the spinal cord. We have completed experiments for subtask 1 – 4 of specific aim 1 and subtasks 1 for specific aim 2. This Aim 2 of the...previously observed PAP2 to induce robust regeneration in a dorsal hemisection model and thought it might enhance regeneration and sprouting after the more...spontaneous recovery is often observed after incomplete injuries, leading to partial recovery over time. Spontaneous recovery is thought to be

Evaluation of two real time PCR assays for the detection of bacterial DNA in amniotic fluid.

PubMed

Girón de Velasco-Sada, Patricia; Falces-Romero, Iker; Quiles-Melero, Inmaculada; García-Perea, Adela; Mingorance, Jesús

2018-01-01

The aim of this study was to evaluate two non-commercial Real-Time PCR assays for the detection of microorganisms in amniotic fluid followed by identification by pyrosequencing. We collected 126 amniotic fluids from 2010 to 2015 for the evaluation of two Real-Time PCR assays for detection of bacterial DNA in amniotic fluid (16S Universal PCR and Ureaplasma spp. specific PCR). The method was developed in the Department of Microbiology of the University Hospital La Paz. Thirty-seven samples (29.3%) were positive by PCR/pyrosequencing and/or culture, 4 of them were mixed cultures with Ureaplasma urealyticum. The Universal 16S Real-Time PCR was compared with the standard culture (81.8% sensitivity, 97.4% specificity, 75% positive predictive value, 98% negative predictive value). The Ureaplasma spp. specific Real-Time PCR was compared with the Ureaplasma/Mycoplasma specific culture (92.3% sensitivity, 89.4% specificity, 50% positive predictive value, 99% negative predictive value) with statistically significant difference (p=0.005). Ureaplasma spp. PCR shows a rapid response time (5h from DNA extraction until pyrosequencing) when comparing with culture (48h). So, the response time of bacteriological diagnosis in suspected chorioamnionitis is reduced. Copyright © 2017 Elsevier B.V. All rights reserved.

Pure animal phobia is more specific than other specific phobias: epidemiological evidence from the Zurich Study, the ZInEP and the PsyCoLaus.

PubMed

Ajdacic-Gross, Vladeta; Rodgers, Stephanie; Müller, Mario; Hengartner, Michael P; Aleksandrowicz, Aleksandra; Kawohl, Wolfram; Heekeren, Karsten; Rössler, Wulf; Angst, Jules; Castelao, Enrique; Vandeleur, Caroline; Preisig, Martin

2016-09-01

Interest in subtypes of mental disorders is growing in parallel with continuing research progress in psychiatry. The aim of this study was to examine pure animal phobia in contrast to other specific phobias and a mixed subtype. Data from three representative Swiss community samples were analysed: PsyCoLaus (n = 3720), the ZInEP Epidemiology Survey (n = 1500) and the Zurich Study (n = 591). Pure animal phobia and mixed animal/other specific phobias consistently displayed a low age at onset of first symptoms (8-12 years) and clear preponderance of females (OR > 3). Meanwhile, other specific phobias started up to 10 years later and displayed almost a balanced sex ratio. Pure animal phobia showed no associations with any included risk factors and comorbid disorders, in contrast to numerous associations found in the mixed subtype and in other specific phobias. Across the whole range of epidemiological parameters examined in three different samples, pure animal phobia seems to represent a different entity compared to other specific phobias. The etiopathogenetic mechanisms and risk factors associated with pure animal phobias appear less clear than ever.

Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors ▿ †

PubMed Central

Bonsignori, Mattia; Hwang, Kwan-Ki; Chen, Xi; Tsao, Chun-Yen; Morris, Lynn; Gray, Elin; Marshall, Dawn J.; Crump, John A.; Kapiga, Saidi H.; Sam, Noel E.; Sinangil, Faruk; Pancera, Marie; Yongping, Yang; Zhang, Baoshan; Zhu, Jiang; Kwong, Peter D.; O'Dell, Sijy; Mascola, John R.; Wu, Lan; Nabel, Gary J.; Phogat, Sanjay; Seaman, Michael S.; Whitesides, John F.; Moody, M. Anthony; Kelsoe, Garnett; Yang, Xinzhen; Sodroski, Joseph; Shaw, George M.; Montefiori, David C.; Kepler, Thomas B.; Tomaras, Georgia D.; Alam, S. Munir; Liao, Hua-Xin; Haynes, Barton F.

2011-01-01

V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B.9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies. PMID:21795340

A soil-specific agro-ecological strategy for sustainable production in Argentina farm fields

NASA Astrophysics Data System (ADS)

Zamora, Martin; Barbera, Agustin; Castro-Franco, Mauricio; Hansson, Alejandro; Domenech, Marisa

2017-04-01

The continuous increment of frequencies and doses of pesticides, glyphosate and fertilizers, the deterioration of the structure, biotic balance and fertility of soils and the ground water pollution are characteristics of the current Argentinian agricultural model. In this context, agro-ecological innovations are needed to develop a real sustainable agriculture, enhancing the food supply. Precision agriculture technologies can strengthen the expansion of agro-ecological farming in experimental farm fields. The aim of this study was to propose a soil-specific agro-ecological strategy for sustainable production at field scale focused on the use of soil sensors and digital soil mapping techniques. This strategy has been developed in 15 hectares transition agro-ecological farm field, located at Barrow Experimental Station (Lat:-38.322844, Lon:-60.25572) Argentina. The strategy included five steps: (i) to measure apparent electrical conductivity (ECa) and elevation within agro-ecological farm field; (ii) to apply a clustering method using MULTISPATI-PCA algorithm to delimitate three soil-specific zones (Z1, Z2 and Z3); (iii) to determine three soil sampling points by zone, using conditioned Latin hypercube method, in addition to elevation and ECa as auxiliary information; (iv) to collect soil samples at 2-10 cm depth in each point and to determine in laboratory: total organic carbon content (TOC), cation-exchange capacity (CEC), pH and phosphorus availability (P-Bray). In addition, soil bulk density (SBD) was measured at 0-20 cm depth. Finally, (v) according to each soil-specific zone, a management strategy was recommended. Important differences in soil properties among zones could suggest that the strategy developed was able to apply an agro ecological soil-specific practice management. pH and P-Bray were significantly (p<0.05) higher in Z1 than in Z2 and Z3. TOC did not show significant difference among zones, but it was higher in Z2. CEC was significantly (p<0.05) lower in Z3 than in the other ones. SBD did not show significant difference among zones; however it had a higher content in Z1. From these results, we propose an agro ecology strategy which involves a continuous nutrient cycling. During the first two years, P-Bray levels will be adjusted among zones, by using different external phosphorous sources. Only in Z3, this strategy will be achieved adding P fertilizer and also rotating plots with high stocking rate. The aim is to increase soil organic matter content and CEC. Furthermore, P content will be supplied through manure because the animal nutrition will include wheat husk, in order to achieve similar P levels among zones. The proposed strategy demonstrated that the agro-ecology soil-specific management allows a sustainable scheme in Argentinian agro-productive systems.

Clinical accuracy of a patient-specific femoral osteotomy guide in minimally-invasive posterior hip arthroplasty.

PubMed

Schneider, Adrian K; Pierrepont, Jim W; Hawdon, Gabrielle; McMahon, Stephen

2018-04-01

Patient specific guides can be a valuable tool in improving the precision of planned femoral neck osteotomies, especially in minimally invasive hip surgery, where bony landmarks are often inaccessible. The aim of our study was to validate the accuracy of a novel patient specific femoral osteotomy guide for THR through a minimally invasive posterior approach, the direct superior approach (DSA). As part of our routine preoperative planning 30 patients underwent low dose CT scans of their arthritic hip. 3D printed patient specific femoral neck osteotomy guides were then produced. Intraoperatively, having cleared all soft tissue from the postero-lateral neck of the enlocated hip, the guide was placed and pinned onto the posterolateral femoral neck. The osteotomy was performed using an oscillating saw and the uncemented hip components were implanted as per routine. Postoperatively, the achieved level of the osteotomy at the medial calcar was compared with the planned level of resection using a 3D/2D matching analysis (Mimics X-ray module, Materialise, Belgium). A total of 30 patients undergoing uncemented Trinity™ acetabular and TriFit TS™ femoral component arthroplasty (Corin, UK) were included in our analysis. All but one of our analysed osteotomies were found to be within 3 mm from the planned height of osteotomy. In one patient the level of osteotomy deviated 5 mm below the planned level of resection. Preoperative planning and the use of patient specific osteotomy guides provides an accurate method of performing femoral neck osteotomies in minimally invasive hip arthroplasty using the direct superior approach. IV (Case series).

The Development of a "Neighborhood in Solidarity" in Switzerland.

PubMed

Zwygart, Marion; Plattet, Alain; Ammor, Sarah

2017-01-01

This article presents a case study based on the "Neighborhood in Solidarity" (NS) methodology to illustrate its application in a locality of 8,000 inhabitants in Switzerland. This specific project is proposed to exemplify the global aim of the NS methodology. That aim is to increase the integration of elderly persons in societies in order to improve their quality of life. The case study demonstrates the enhancement of the capacity of the older people to remain actively engaged in their neighborhood. The article focuses on the creation of an autonomous community of empowered older people who can resolve their own problems after a 5-year project. The construction of the local community is presented throughout the six steps of the methodology: (1) preliminary analysis, (2) diagnostic, (3) construction, (4) project design, (5) project implementation, and (6) empowerment and with three degrees of involvement (community, participative, and integrative involvement). Performance and output indicators, quality indicators, and social determinants of health assess the development of the local project. The impacts of the projects which are illustrated in this specific example motivated this publication to inspire practitioners from other countries.

Pediatric trauma BIG score: Predicting mortality in polytraumatized pediatric patients.

PubMed

El-Gamasy, Mohamed Abd El-Aziz; Elezz, Ahmed Abd El Basset Abo; Basuni, Ahmed Sobhy Mohamed; Elrazek, Mohamed El Sayed Ali Abd

2016-11-01

Trauma is a worldwide health problem and the major cause of death and disability, particularly affecting the young population. It is important to remember that pediatric trauma care has made a significant improvement in the outcomes of these injured children. This study aimed at evaluation of pediatric trauma BIG score in comparison with New Injury Severity Score (NISS) and Pediatric Trauma Score (PTS) in Tanta University Emergency Hospital. The study was conducted in Tanta University Emergency Hospital to all multiple trauma pediatric patients attended to the Emergency Department for 1 year. Pediatric trauma BIG score, PTS, and NISS scores were calculated and results compared to each other and to observed mortality. BIG score ≥12.7 has sensitivity 86.7% and specificity 71.4%, whereas PTS at value ≤3.5 has sensitivity 63.3% and specificity 68.6% and NISS at value ≥39.5 has sensitivity 53.3% and specificity 54.3%. There was a significant positive correlation between BIG score value and mortality rate. The pediatric BIG score is a reliable mortality-prediction score for children with traumatic injuries; it uses international normalization ratio (INR), Base Excess (BE), and Glasgow Coma Scale (GCS) values that can be measured within a few minutes of sampling, so it can be readily applied in the Pediatric Emergency Department, but it cannot be applied on patients with chronic diseases that affect INR, BE, or GCS.

The natural history of Leydig cell testicular tumours: an analysis of the National Cancer Registry.

PubMed

Nason, G J; Redmond, E J; Considine, S W; Omer, S I; Power, D; Sweeney, P

2018-05-01

Leydig cell tumour (LCT) of the testis is a rare histological subtype of stromal tumours, accounting for 1 to 3% of testicular neoplasms. The natural history of LCT is poorly understood. The aim of this study was to assess the incidence and natural history of Leydig cell tumours (LCT) of the testes. A search of the National Cancer Registry of Ireland database was performed regarding Leydig cell testicular tumours. Recurrence free survival (RFS) and disease-specific survival (DSS) were analysed. Between 1994 and 2013, 2755 new cases of testicular cancer were diagnosed in Ireland. Of these, 22 (0.79%) were Leydig cell tumours. Nineteen were invasive (stage T1) and three were in situ (stage Tis). One patient developed a local recurrence following an organ preserving procedure and underwent a completion orchidectomy 107 days after initial diagnosis. No further treatment was required. There have been no disease-specific deaths. The 1-, 3- and 5-year overall survival (OS) rates were 95.5, 88.2 and 73.3%, respectively. The 5-year disease-specific survival (DSS) was 100% and the 5-year recurrence free survival (RFS) was 93.3%. From the National Cancer Registry, LCT has been shown to be a rare subtype of testicular tumour. Due to the relatively favourable natural history, it may be possible to tailor less aggressive surveillance regimens in these patients.

Monoterpene phenolic compound thymol promotes browning of 3T3-L1 adipocytes.

PubMed

Choi, Jae Heon; Kim, Sang Woo; Yu, Rina; Yun, Jong Won

2017-10-01

Appearance of brown-like adipocytes within white adipose tissue depots (browning) is associated with improved metabolic phenotypes, and thus a wide variety of dietary agents that contribute to browning of white adipocytes are being studied. The aim of this study was to assess the browning effect of thymol, a dietary monoterpene phenolic compound, in 3T3-L1 white adipocytes. Thymol-induced fat browning was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR and immunoblot analysis, respectively. Moreover, the molecular mechanism underlying the fat-browning effect of thymol was investigated by determining expression levels of key players responsible for browning in the presence of kinase inhibitors. Thymol promoted mitochondrial biogenesis and enhanced expression of a core set of brown fat-specific markers as well as increased protein levels of PPARγ, PPARδ, pAMPK, pACC, HSL, PLIN, CPT1, ACO, PGC-1α, and UCP1, suggesting its possible role in browning of white adipocytes, augmentation of lipolysis, fat oxidation, and thermogenesis, and reduction of lipogenesis. Increased expression of UCP1 and other brown fat-specific markers by thymol was tightly coordinated with activation of β3-AR as well as AMPK, PKA, and p38 MAPK. Our findings suggest that 3T3-L1 is a potential cell model for screening browning agents. Thymol plays multiple modulatory roles in the form of inducing the brown-like phenotype as well as enhancing lipid metabolism. Thus, thymol may be explored as a potentially promising food additive for prevention of obesity.

Home oximetry to screen for obstructive sleep apnoea in Down syndrome.

PubMed

Hill, Catherine M; Elphick, Heather E; Farquhar, Michael; Gringras, Paul; Pickering, Ruth M; Kingshott, Ruth N; Martin, Jane; Reynolds, Janine; Joyce, Anna; Gavlak, Johanna C; Evans, Hazel J

2018-05-14

Children with Down syndrome are at high risk of obstructive sleep apnoea (OSA) and screening is recommended. Diagnosis of OSA should be confirmed with multichannel sleep studies. We aimed to determine whether home pulse oximetry (HPO) discriminates children at high risk of OSA, who need further diagnostic multichannel sleep studies. Cross-sectional prospective study in a training sample recruited through three UK centres. Validation sample used single-centre retrospective analysis of clinical data. Children with Down syndrome aged 0.5-6 years. Diagnostic multichannel sleep study and HPO. Sensitivity and specificity of HPO to predict moderate-to-severe OSA. 161/202 children with Down syndrome met quality criteria for inclusion and 25 had OSA. In this training sample, the best HPO parameter predictors of OSA were the delta 12 s index >0.555 (sensitivity 92%, specificity 65%) and 3% oxyhaemoglobin (SpO 2 ) desaturation index (3% ODI)>6.15 dips/hour (sensitivity 92%, specificity 63%). Combining variables (delta 12 s index, 3% ODI, mean and minimum SpO 2 ) achieved sensitivity of 96% but reduced specificity to 52%. All predictors retained or improved sensitivity in a clinical validation sample of 50 children with variable loss of specificity, best overall was the delta 12 s index, a measure of baseline SpO 2 variability (sensitivity 92%; specificity 63%). HPO screening could halve the number of children with Down syndrome needing multichannel sleep studies and reduce the burden on children, families and health services alike. This approach offers a practical universal screening approach for OSA in Down syndrome that is accessible to the non-specialist paediatrician. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

SNCA 3'UTR genetic variants in patients with Parkinson's disease and REM sleep behavior disorder.

PubMed

Toffoli, M; Dreussi, E; Cecchin, E; Valente, M; Sanvilli, N; Montico, M; Gagno, S; Garziera, M; Polano, M; Savarese, M; Calandra-Buonaura, G; Placidi, F; Terzaghi, M; Toffoli, G; Gigli, G L

2017-07-01

REM sleep behavior disorder (RBD) is an early marker of Parkinson's disease (PD); however, it is still unclear which patients with RBD will eventually develop PD. Single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of alpha-synuclein (SNCA) have been associated with PD, but at present, no data is available about RBD. The 3'UTR hosts regulatory regions involved in gene expression control, such as microRNA binding sites. The aim of this study was to determine RBD specific genetic features associated to an increased risk of progression to PD, by sequencing of the SNCA-3'UTR in patients with "idiopathic" RBD (iRBD) and in patients with PD. We recruited 113 consecutive patients with a diagnosis of iRBD (56 patients) or PD (with or without RBD, 57 patients). Sequencing of SNCA-3'UTR was performed on genomic DNA extracted from peripheral blood samples. Bioinformatic analyses were carried out to predict the potential effect of the identified genetic variants on microRNA binding. We found three SNCA-3'UTR SNPs (rs356165, rs3857053, rs1045722) to be more frequent in PD patients than in iRBD patients (p = 0.014, 0.008, and 0.008, respectively). Four new or previously reported but not annotated specific genetic variants (KP876057, KP876056, NM_000345.3:c*860T>A, NM_000345.3:c*2320A>T) have been observed in the RBD population. The in silico approach highlighted that these variants could affect microRNA-mediated gene expression control. Our data show specific SNPs in the SNCA-3'UTR that may bear a risk for RBD to be associated with PD. Moreover, new genetic variants were identified in patients with iRBD.

TAM receptor knockout mice are susceptible to retinal autoimmune induction.

PubMed

Ye, Fei; Li, Qiutang; Ke, Yan; Lu, Qingjun; Han, Lixia; Kaplan, Henry J; Shao, Hui; Lu, Qingxian

2011-06-16

TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU). TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology. Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina. Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.

Timely Visualization of the Collaterals Formed during Acute Ischemic Stroke with Fe3 O4 Nanoparticle-based MR Imaging Probe.

PubMed

Wang, Ting; Hou, Yi; Bu, Bo; Wang, Wenxin; Ma, Tiancong; Liu, Chunyan; Lin, Lan; Ma, Lin; Lou, Xin; Gao, Mingyuan

2018-04-17

Ischemic stroke is one of the major leading causes for long-term disability and mortality. Collateral vessels provide an alternative pathway to protect the brain against ischemic injury after arterial occlusion. Aiming at visualizing the collaterals occurring during acute ischemic stroke, an integrin α v β 3 -specific Fe 3 O 4 -Arg-Gly-Asp (RGD) nanoprobe is prepared for magnetic resonance imaging (MRI) of the collaterals. Rat models are constructed by occluding the middle cerebral artery for imaging studies of cerebral ischemia and ischemia-reperfusion on 7.0 Tesla MRI using susceptibility-weighted imaging sequence. To show the binding specificity to the collaterals, the imaging results acquired with the Fe 3 O 4 -RGD nanoprobe and the Fe 3 O 4 mother nanoparticles, respectively, are carefully compared. In addition, an RGD blocking experiment is also carried out to support the excellent binding specificity of the Fe 3 O 4 -RGD nanoprobe. Following the above experiments, cerebral ischemia-reperfusion studies show the collateral dynamics upon reperfusion, which is very important for the prognosis of various revascularization therapies in the clinic. The current study has, for the first time, enabled the direct observation of collaterals in a quasi-real time fashion and further disclosed that the antegrade flow upon reperfusion dominates the blood supply of primary ischemic tissue during the early stage of infarction, which is significantly meaningful for clinical treatment of stroke. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Risk of thyroid cancer in first-degree relatives of patients with non-medullary thyroid cancer by histology type and age at diagnosis: a joint study from five Nordic countries.

PubMed

Fallah, Mahdi; Pukkala, Eero; Tryggvadottir, Laufey; Olsen, Jörgen H; Tretli, Steinar; Sundquist, Kristina; Hemminki, Kari

2013-06-01

We aimed to estimate lifetime cumulative risk of thyroid cancer (CRTC) in first-degree relatives of patients with non-medullary thyroid cancers (NMTC), including papillary (PTC)/follicular/oxyphilic/anaplastic thyroid carcinoma, by histology and age at diagnosis in patients and their relatives. A population-based cohort of 63 495 first-degree relatives of 11 206 NMTC patients diagnosed in 1955-2009 in Nordic countries was followed for cancer incidence. Standardised incidence ratios (SIRs) were calculated using histology-specific, age-specific, sex-specific, period-specific and country-specific incidence rates as reference. The 0-84-year CRTC in female relatives of a patient with PTC was 2%, representing a threefold increase over the general population risk (SIR=2.9, 95% CI 2.4 to 3.4; Men: CRTC=1%, SIR=2.5, 95% CI 1.9 to 3.3). When there were ≥2 PTC patients diagnosed at age <60 years in a family, CRTC for female relatives was 10% (male 24%). Twins had a 23-fold increased risk of concordant PTC. Family history of follicular/oxyphilic/anaplastic carcinoma increased CRTC in relatives to about 1-2%. Although no familial case of concordant oxyphilic/anaplastic carcinoma was found, familial risks of discordant histology types of NMTC were interchangeably high for most of the types, for example, higher risk of PTC when a first-degree relative had follicular (SIR=3.0, 95%CI 1.7 to 4.9) or anaplastic (SIR=3.6, 95% CI 1.2 to 8.4) carcinoma. The earlier a patient was diagnosed with PTC in a family, the higher was the SIR in his/her younger relatives. There was a tendency towards concordant age at diagnosis of thyroid cancer among relatives of PTC patients. This study provides clinically relevant risk estimates for family members of NMTC patients.

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells.

PubMed

Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

2016-11-22

One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.

An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells

PubMed Central

Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

2016-01-01

One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes. PMID:27765913

High-precision spectra for dynamical Dark Energy cosmologies from constant-w models

NASA Astrophysics Data System (ADS)

Casarini, Luciano

2010-08-01

Spanning the whole functional space of cosmologies with any admissible DE state equations w(a) seems a need, in view of forthcoming observations, namely those aiming to provide a tomography of cosmic shear. In this paper I show that this duty can be eased and that a suitable use of results for constant-w cosmologies can be sufficient. More in detail, I ``assign'' here six cosmologies, aiming to span the space of state equations w(a) = wo+wa(1-a), for wo and wa values consistent with WMAP5 and WMAP7 releases and run N-body simulations to work out their non-linear fluctuation spectra at various redshifts z. Such spectra are then compared with those of suitable auxiliary models, characterized by constant w. For each z a different auxiliary model is needed. Spectral discrepancies between the assigned and the auxiliary models, up to k simeq 2-3 h Mpc-1, are shown to keep within 1 %. Quite in general, discrepancies are smaller at greater z and exhibit a specific trend across the wo and wa plane. Besides of aiming at simplifying the evaluation of spectra for a wide range of models, this paper also outlines a specific danger for future studies of the DE state equation, as models fairly distant on the w0-wa plane can be easily confused.

Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less.

PubMed

Liu, Xin; Tang, Jie; Fei, Xiang; Li, Qiu-Yang

2015-11-01

We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings.

A Concise and Practical Framework for the Development and Usability Evaluation of Patient Information Websites.

PubMed

Peute, L W; Knijnenburg, S L; Kremer, L C; Jaspers, M W M

2015-01-01

The Website Developmental Model for the Healthcare Consumer (WDMHC) is an extensive and successfully evaluated framework that incorporates user-centered design principles. However, due to its extensiveness its application is limited. In the current study we apply a subset of the WDMHC framework in a case study concerning the development and evaluation of a website aimed at childhood cancer survivors (CCS). To assess whether the implementation of a limited subset of the WDMHC-framework is sufficient to deliver a high-quality website with few usability problems, aimed at a specific patient population. The website was developed using a six-step approach divided into three phases derived from the WDMHC: 1) information needs analysis, mock-up creation and focus group discussion; 2) website prototype development; and 3) heuristic evaluation (HE) and think aloud analysis (TA). The HE was performed by three double experts (knowledgeable both in usability engineering and childhood cancer survivorship), who assessed the site using the Nielsen heuristics. Eight end-users were invited to complete three scenarios covering all functionality of the website by TA. The HE and TA were performed concurrently on the website prototype. The HE resulted in 29 unique usability issues; the end-users performing the TA encountered eleven unique problems. Four issues specifically revealed by HE concerned cosmetic design flaws, whereas two problems revealed by TA were related to website content. Based on the subset of the WDMHC framework we were able to deliver a website that closely matched the expectancy of the end-users and resulted in relatively few usability problems during end-user testing. With the successful application of this subset of the WDMHC, we provide developers with a clear and easily applicable framework for the development of healthcare websites with high usability aimed at specific medical populations.

X-ray computed tomography uncovers root-root interactions: quantifying spatial relationships between interacting root systems in three dimensions.

PubMed

Paya, Alexander M; Silverberg, Jesse L; Padgett, Jennifer; Bauerle, Taryn L

2015-01-01

Research in the field of plant biology has recently demonstrated that inter- and intra-specific interactions belowground can dramatically alter root growth. Our aim was to answer questions related to the effect of inter- vs. intra-specific interactions on the growth and utilization of undisturbed space by fine roots within three dimensions (3D) using micro X-ray computed tomography. To achieve this, Populus tremuloides (quaking aspen) and Picea mariana (black spruce) seedlings were planted into containers as either solitary individuals, or inter-/intra-specific pairs, allowed to grow for 2 months, and 3D metrics developed in order to quantify their use of belowground space. In both aspen and spruce, inter-specific root interactions produced a shift in the vertical distribution of the root system volume, and deepened the average position of root tips when compared to intra-specifically growing seedlings. Inter-specific interactions also increased the minimum distance between root tips belonging to the same root system. There was no effect of belowground interactions on the radial distribution of roots, or the directionality of lateral root growth for either species. In conclusion, we found that significant differences were observed more often when comparing controls (solitary individuals) and paired seedlings (inter- or intra-specific), than when comparing inter- and intra-specifically growing seedlings. This would indicate that competition between neighboring seedlings was more responsible for shifting fine root growth in both species than was neighbor identity. However, significant inter- vs. intra-specific differences were observed, which further emphasizes the importance of biological interactions in competition studies.

Comparison of allele-specific PCR, created restriction-site PCR, and PCR with primer-introduced restriction analysis methods used for screening complex vertebral malformation carriers in Holstein cattle

PubMed Central

Altınel, Ahmet

2017-01-01

Complex vertebral malformation (CVM) is an inherited, autosomal recessive disorder of Holstein cattle. The aim of this study was to compare sensitivity, specificity, positive and negative predictive values, accuracy, and rapidity of allele-specific polymerase chain reaction (AS-PCR), created restriction-site PCR (CRS-PCR), and PCR with primer-introduced restriction analysis (PCR-PIRA), three methods used in identification of CVM carriers in a Holstein cattle population. In order to screen for the G>T mutation in the solute carrier family 35 member A3 (SLC35A3) gene, DNA sequencing as the gold standard method was used. The prevalence of carriers and the mutant allele frequency were 3.2% and 0.016, respectively, among Holstein cattle in the Thrace region of Turkey. Among the three methods, the fastest but least accurate was AS-PCR. Although the rapidity of CRS-PCR and PCR-PIRA were nearly equal, the accuracy of PCR-PIRA was higher than that of CRS-PCR. Therefore, among the three methods, PCR-PIRA appears to be the most efficacious for screening of mutant alleles when identifying CVM carriers in a Holstein cattle population. PMID:28927256

Medical students' clinical performance in general practice - Triangulating assessments from patients, teachers and students.

PubMed

Braend, Anja Maria; Gran, Sarah Frandsen; Frich, Jan C; Lindbaek, Morten

2010-01-01

Formative assessment of medical students' clinical performance during general practice clerkship is necessary to learn consultation skills. Our aim was to triangulate feedback using patient questionnaires, written self-assessment and teachers' observation-based assessment, and to describe the content of this feedback. We developed StudentPEP, a 15-item version of EUROPEP, a tool for measuring patients' evaluation of quality in general practice. The teacher and student forms consisted of five StudentPEP-items and open-ended questions asking for approval and improvement needed on four aspects. Quantitative scores were analyzed statistically. Free-text comments were analyzed and categorized into 'specific and concrete' versus 'general and unspecific'. One hundred seventy-three students returned data from 2643 consultations. Mean patients' scores for 15 items were 4.3-4.8 on a five-point Likert scale. Mean teacher scores were 4.4 on five items, while students' mean self-assessments were 3.6-3.8. In an analysis of 380 consultations, students were more specific and concrete in their self-evaluation compared with teachers (p < 0.01). Patients scored students' performance high compared with students' self-assessments. Teachers' scores were in accordance with patients' scores. Teachers' written evaluations of students were often general. There is a potential for improving teachers' feedback in terms of more specific and concrete comments.

A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer

DTIC Science & Technology

2007-06-01

to demonstrate that fusogenic oncolytic HSVs are a potent anti -tumor agent for advanced ovarian cancer; 2) to prove that fusogenic oncolytic HSVs...oncolytic herpes simplex virus (HSV) can significantly enhance the anti -tumor effect of the virus. Three specific aims have been proposed and they are: 1...have the same safety profile as their non-fusogenic counterparts; 3) to explore novel delivery strategies that can evade host’s anti -viral immunity

Preterm delivery at low gestational age: risk factors for short latency. A multivariated analysis

PubMed Central

Marzano, Sara; Padula, Francesco; Meloni, Paolo; Anceschi, Maurizio Marco

2008-01-01

Objective The aim of this study is to identify the risk factors for a short latency in preterm delivery at low gestational ages (GA). Study design A retrospective analysis involving, between January 2004 and May 2006, 204 singleton pregnancies with admission diagnosis of preterm labor and, in particular, 91 pregnant women admitted between 24+0 and 31+6 weeks’ gestation. Results In pregnant women with a diagnosis of preterm labor at 24-31+6 weeks’ gestation, at ROC curve, a value of considering WBC and cervical dilatation, combined in the following formula (75.237 - (2.290 * “WBC”) - (10.787 * “cervical dilatation”)) <=33.101 has a 74.2% Sensitivity and a 78.3% Specificity in predicting a latency =< 4 days (+LR 3.42 and -LR 0.33) and a 70% Sensitivity and a 84.3% Specificity in predicting GA at delivery at 24-31 weeks’ gestation (+LR 4.46 and -LR 0.36). Conclusion We suggest a more strictly monitoring and a more aggressive therapy in presence of prognostic parameters of shorter latency. PMID:22439021

Topology search of 3-DOF translational parallel manipulators with three identical limbs for leg mechanisms

NASA Astrophysics Data System (ADS)

Wang, Mingfeng; Ceccarelli, Marco

2015-07-01

Three-degree of freedom(3-DOF) translational parallel manipulators(TPMs) have been widely studied both in industry and academia in the past decades. However, most architectures of 3-DOF TPMs are created mainly on designers' intuition, empirical knowledge, or associative reasoning and the topology synthesis researches of 3-DOF TPMs are still limited. In order to find out the atlas of designs for 3-DOF TPMs, a topology search is presented for enumeration of 3-DOF TPMs whose limbs can be modeled as 5-DOF serial chains. The proposed topology search of 3-DOF TPMs is aimed to overcome the sensitivities of the design solution of a 3-DOF TPM for a LARM leg mechanism in a biped robot. The topology search, which is based on the concept of generation and specialization in graph theory, is reported as a step-by-step procedure with desired specifications, principle and rules of generalization, design requirements and constraints, and algorithm of number synthesis. In order to obtain new feasible designs for a chosen example and to limit the search domain under general considerations, one topological generalized kinematic chain is chosen to be specialized. An atlas of new feasible designs is obtained and analyzed for a specific solution as leg mechanisms. The proposed methodology provides a topology search for 3-DOF TPMs for leg mechanisms, but it can be also expanded for other applications and tasks.

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

PubMed Central

Dreussi, Eva; Cecchin, Erika; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Boso, Caterina; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Bergamo, Francesca; Gagno, Sara; De Mattia, Elena; Pucciarelli, Salvatore; De Paoli, Antonino; Toffoli, Giuseppe

2016-01-01

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. PMID:27608007

Ultrasonographic Fetal Weight Estimation: Should Macrosomia-Specific Formulas Be Utilized?

PubMed

Porter, Blake; Neely, Cherry; Szychowski, Jeff; Owen, John

2015-08-01

This study aims to derive an estimated fetal weight (EFW) formula in macrosomic fetuses, compare its accuracy to the 1986 Hadlock IV formula, and assess whether including maternal diabetes (MDM) improves estimation. Retrospective review of nonanomalous live-born singletons with birth weight (BWT) ≥ 4 kg and biometry within 14 days of birth. Formula accuracy included: (1) mean error (ME = EFW - BWT), (2) absolute mean error (AME = absolute value of [1]), and (3) mean percent error (MPE, [1]/BWT × 100%). Using loge BWT as the dependent variable, multivariable linear regression produced a macrosomic-specific formula in a "training" dataset which was verified by "validation" data. Formulas specific for MDM were also developed. Out of the 403 pregnancies, birth gestational age was 39.5 ± 1.4 weeks, and median BWT was 4,240 g. The macrosomic formula from the training data (n = 201) had associated ME = 54 ± 284 g, AME = 234 ± 167 g, and MPE = 1.6 ± 6.2%; evaluation in the validation dataset (n = 202) showed similar errors. The Hadlock formula had associated ME = -369 ± 422 g, AME = 451 ± 332 g, MPE = -8.3 ± 9.3% (all p < 0.0001). Diabetes-specific formula errors were similar to the macrosomic formula errors (all p = NS). With BWT ≥ 4 kg, the macrosomic formula was significantly more accurate than Hadlock IV, which systematically underestimates fetal/BWT. Diabetes-specific formulas did not improve accuracy. A specific formula should be considered when macrosomia is suspected. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Estrone specific molecularly imprinted polymeric nanospheres: synthesis, characterization and applications for electrochemical sensor development.

PubMed

Congur, Gulsah; Senay, Hilal; Turkcan, Ceren; Canavar, Ece; Erdem, Arzum; Akgol, Sinan

2013-06-28

The aim of this study is (i) to prepare estrone-imprinted nanospheres (nano-EST-MIPs) and (ii) to integrate them into the electrochemical sensor as a recognition layer. N-methacryloyl-(l)-phenylalanine (MAPA) was chosen as the complexing monomer. Firstly, estrone (EST) was complexed with MAPA and the EST-imprinted poly(2-hyroxyethylmethacrylate-co-N-methacryloyl-(l)-phenylalanine) [EST-imprinted poly(HEMA-MAPA)] nanospheres were synthesized by surfactant- free emulsion polymerization method. The specific surface area of the EST-imprinted poly(HEMA-MAPA) nanospheres was found to be 1275 m2/g with a size of 163.2 nm in diameter. According to the elemental analysis results, the nanospheres contained 95.3 mmole MAPA/g nanosphere. The application of EST specific MIP nanospheres for the development of an electrochemical biosensor was introduced for the first time in our study by using electrochemical impedance spectroscopy (EIS) technique. This nano-MIP based sensor presented a great specificity and selectivity for EST.

A Morphological Approach to the Modeling of the Cold Spray Process

NASA Astrophysics Data System (ADS)

Delloro, F.; Jeandin, M.; Jeulin, D.; Proudhon, H.; Faessel, M.; Bianchi, L.; Meillot, E.; Helfen, L.

2017-12-01

A coating buildup model was developed, the aim of which was simulating the microstructure of a tantalum coating cold sprayed onto a copper substrate. To do so, first was operated a fine characterization of the irregular tantalum powder in 3D, using x-ray microtomography and developing specific image analysis algorithms. Particles were grouped by shape in seven classes. Afterward, 3D finite element simulations of the impact of the previously observed particles were realized. To finish, a coating buildup model was developed, based on the results of finite element simulations of particle impact. In its first version, this model is limited to 2D.

Dissociated effects of distractors on saccades and manual aiming.

PubMed

McIntosh, Robert D; Buonocore, Antimo

2012-08-01

The remote distractor effect (RDE) is a robust phenomenon whereby target-directed saccades are delayed by the appearance of a distractor. This effect persists even when the target location is perfectly predictable. The RDE has been studied extensively in the oculomotor domain but it is unknown whether it generalises to other spatially oriented responses. In three experiments, we tested whether the RDE generalises to manual aiming. Experiment 1 required participants to move their hand or eyes to predictable targets presented alone or accompanied by a distractor in the opposite hemifield. The RDE was observed for the eyes but not for the hand. Experiment 2 replicated this dissociation in a more naturalistic task in which eye movements were not constrained during manual aiming. Experiment 3 confirmed the lack of manual RDE across a wider range of distractor delays (0, 50, 100, and 150 ms). Our data imply that the RDE is specific to the oculomotor system, at least for non-foveal distractors. We suggest that the oculomotor RDE reflects competitive interactions between target and distractor representations in the superior colliculus, which are not necessarily shared by manual aiming.

The manipulation of vision during the powerlift squat: exploring the boundaries of the specificity of learning hypothesis.

PubMed

Bennett, S; Davids, K

1995-09-01

The available information for controlling a multidegree-of-freedom sport action was manipulated in 2 experiments. In the first, 10 intermediate lifters were participants; for the second, 8 skilled and 8 less skilled lifters were observed. Three single repetitions of a powerlift squat were performed under 3 vision conditions (i.e., full, ambient, no vision). The less skilled and intermediate lifters' technical performance decreased significantly with the removal of visual information. There was no detrimental effect in the skilled group. Despite the differing information constraints, skilled lifters exhibited a high level of positioning accuracy and timing consistency across conditions. These data fail to support the theoretical predictions of the specificity of learning hypothesis. The differences between the task constraints in this study and those in manual aiming investigations may represent a boundary to the current propositions of the specificity of learning hypothesis.

Beyond valence in the perception of likelihood: the role of emotion specificity.

PubMed

DeSteno, D; Petty, R E; Wegener, D T; Rucker, D D

2000-03-01

Positive and negative moods have been shown to increase likelihood estimates of future events matching these states in valence (e.g., E. J. Johnson & A. Tversky, 1983). In the present article, 4 studies provide evidence that this congruency bias (a) is not limited to valence but functions in an emotion-specific manner, (b) derives from the informational value of emotions, and (c) is not the inevitable outcome of likelihood assessment under heightened emotion. Specifically, Study 1 demonstrates that sadness and anger, 2 distinct, negative emotions, differentially bias likelihood estimates of sad and angering events. Studies 2 and 3 replicate this finding in addition to supporting an emotion-as-information (cf. N. Schwarz & G. L. Clore, 1983), as opposed to a memory-based, mediating process for the bias. Finally, Study 4 shows that when the source of the emotion is salient, a reversal of the bias can occur given greater cognitive effort aimed at accuracy.

BIOLOGICAL NETWORK EXPLORATION WITH CYTOSCAPE 3

PubMed Central

Su, Gang; Morris, John H.; Demchak, Barry; Bader, Gary D.

2014-01-01

Cytoscape is one of the most popular open-source software tools for the visual exploration of biomedical networks composed of protein, gene and other types of interactions. It offers researchers a versatile and interactive visualization interface for exploring complex biological interconnections supported by diverse annotation and experimental data, thereby facilitating research tasks such as predicting gene function and pathway construction. Cytoscape provides core functionality to load, visualize, search, filter and save networks, and hundreds of Apps extend this functionality to address specific research needs. The latest generation of Cytoscape (version 3.0 and later) has substantial improvements in function, user interface and performance relative to previous versions. This protocol aims to jump-start new users with specific protocols for basic Cytoscape functions, such as installing Cytoscape and Cytoscape Apps, loading data, visualizing and navigating the network, visualizing network associated data (attributes) and identifying clusters. It also highlights new features that benefit experienced users. PMID:25199793

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

Maruyama, Yoko; Department of Pediatrics, School of Medicine, Keio University, Tokyo 160-8582; Sou, Yu-Shin

Highlights: • Knockdown of LC3 or GABARAP families did not affect the basal autophagy. • LC3B has a higher affinity for the autophagy-specific substrate, p62, than GABARAPs. • siRNA-mediated knockdown of LC3B, but not that of GABARAPs, resulted in significant accumulation of p62. - Abstract: Autophagy is a unique intracellular protein degradation system accompanied by autophagosome formation. Besides its important role through bulk degradation in supplying nutrients, this system has an ability to degrade certain proteins, organelles, and invading bacteria selectively to maintain cellular homeostasis. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based onmore » its membrane fusion property and interaction with autophagy adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. The aim of this study was to determine the separate roles of LC3 and GABARAP families in basal/constitutive and/or selective autophagy. While the combined knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs.« less

A Controlled Pharmacogenetic Trial of Sibutramine on Weight Loss and Body Composition in Obese or Overweight Adults

PubMed Central

Grudell, April B.M.; Sweetser, Seth; Camilleri, Michael; Eckert, Deborah J.; Vazquez-Roque, Maria I.; Carlson, Paula J.; Burton, Duane D.; Braddock, Autumn E.; Clark, Matthew M.; Graszer, Karen M.; Kalsy, Sarah A.; Zinsmeister, Alan R.

2008-01-01

Background/ Aim Weight loss in response to sibutramine is highly variable. We assessed the association of specific markers of polymorphisms of candidate a2A adrenoreceptor, 5-HT transporter and GNβ3 genes and weight loss with sibutramine. Methods We conducted a randomized, double-blind, pharmacogenetic study of behavioral therapy and sibutramine (10 or 15 mg daily) or placebo for 12 weeks in 181 overweight or obese participants. We measured body weight, BMI, body composition, gastric emptying and genetic variation (α2A C1291G, 5-HTTLPR, and GNβ3 C825T genotypes). ANCOVA was used to assess treatment effects on, and associations of the specific markers of candidate genes with weight loss and body composition. Results Sibutramine, 10 and 15 mg, caused significant weight loss (p = 0.009); there was a statistically significant gene by dose interaction for GNβ3 genotype. For each candidate gene, significant treatment effects at 12 weeks were observed (p<0.017) for all specific genotype variants (delta weight loss in the 2 sibutramine doses versus placebo): α2A CC genotype ( Δ ~5kg), GNβ3 TC/TT genotype (Δ ~6kg), and 5-HTTLPR LS/SS (Δ ~4.5kg). Gene pairs resulted in significantly greater sibutramine treatment effects on weight (both p<0.002): in participants with 5-HTTLPR LS/SS with GNβ3 TC/TT, Δ ~6kg and those with a2A CC with GNβ3 TC/TT, Δ ~8kg; however, effects were not synergistic. Treatment with sibutramine also resulted in significantly greater reduction of body fat for specific α2A CC and GNβ3 TC/TT genotype variants individually (both p<0.02). Conclusions Selection of patients with obesity based on candidate genes may enhance response to multidimensional sibutramine and behavioral therapy. PMID:18725220

Testing a Novel 3D Printed Radiographic Imaging Device for Use in Forensic Odontology.

PubMed

Newcomb, Tara L; Bruhn, Ann M; Giles, Bridget; Garcia, Hector M; Diawara, Norou

2017-01-01

There are specific challenges related to forensic dental radiology and difficulties in aligning X-ray equipment to teeth of interest. Researchers used 3D printing to create a new device, the combined holding and aiming device (CHAD), to address the positioning limitations of current dental X-ray devices. Participants (N = 24) used the CHAD, soft dental wax, and a modified external aiming device (MEAD) to determine device preference, radiographer's efficiency, and technique errors. Each participant exposed six X-rays per device for a total of 432 X-rays scored. A significant difference was found at the 0.05 level between the three devices (p = 0.0015), with the MEAD having the least amount of total errors and soft dental wax taking the least amount of time. Total errors were highest when participants used soft dental wax-both the MEAD and the CHAD performed best overall. Further research in forensic dental radiology and use of holding devices is needed. © 2016 American Academy of Forensic Sciences.

Prognostic value of biological markers in myocardial infarction patients.

PubMed

Berezin, Alexander E; Samura, Tatiana A

2013-04-01

The aim of this study was to compare the prognostic value of matrix metalloproteinase-3 and -9, and NT-pro-natriuretic peptide for fatal and nonfatal complications in Q-wave myocardial infarction patients in the acute and postinfarction periods. 85 men and women with documented Q-wave myocardial infarction were observed for 1 year after hospitalization. Clinical endpoints were identified through the hospital patient-tracking system, with a review of medical records for each recorded endpoint. Left ventricular ejection fraction and wall motion index were calculated. Measurements of matrix metalloproteinases and NT-pro-natriuretic peptide were performed by an enzyme-linked immunosorbent assay. A cutoff value of 9.7 ng·mL(-1) for matrix metalloproteinase-3 showed the best discriminatory power (sensitivity = 77.8%, specificity = 90.8%). The optimal cutoff value of matrix metalloproteinase-9 was 18.1 ng·mL(-1) (sensitivity, 70.5%; specificity, 75%), and the cutoff for NT-pro-natriuretic peptide was 885 pmol·L(-1) (sensitivity, 58%; specificity, 68.6%). Matrix metalloproteinase-3 and -9 were strongly related with a positive prognostic value of 70% (sensitivity and specificity, 84% and 82%, respectively). These data may be helpful for further stratification of patients into cardiovascular mortality risk groups.

Calibration procedure for a laser triangulation scanner with uncertainty evaluation

NASA Astrophysics Data System (ADS)

Genta, Gianfranco; Minetola, Paolo; Barbato, Giulio

2016-11-01

Most of low cost 3D scanning devices that are nowadays available on the market are sold without a user calibration procedure to correct measurement errors related to changes in environmental conditions. In addition, there is no specific international standard defining a procedure to check the performance of a 3D scanner along time. This paper aims at detailing a thorough methodology to calibrate a 3D scanner and assess its measurement uncertainty. The proposed procedure is based on the use of a reference ball plate and applied to a triangulation laser scanner. Experimental results show that the metrological performance of the instrument can be greatly improved by the application of the calibration procedure that corrects systematic errors and reduces the device's measurement uncertainty.

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

PubMed Central

Jayasooriya, Shamanthi; de Silva, Thushan I.; Njie-jobe, Jainaba; Sanyang, Chilel; Leese, Alison M.; Bell, Andrew I.; McAulay, Karen A.; Yanchun, Peng; Long, Heather M.; Dong, Tao; Whittle, Hilton C.; Rickinson, Alan B.; Rowland-Jones, Sarah L.; Hislop, Andrew D.; Flanagan, Katie L.

2015-01-01

Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14–18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms. PMID:25816224

Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.

PubMed

Nagata, Takanobu; Yasukawa, Hideo; Kyogoku, Sachiko; Oba, Toyoharu; Takahashi, Jinya; Nohara, Shoichiro; Minami, Tomoko; Mawatari, Kazutoshi; Sugi, Yusuke; Shimozono, Koutatsu; Pradervand, Sylvain; Hoshijima, Masahiko; Aoki, Hiroki; Fukumoto, Yoshihiro; Imaizumi, Tsutomu

2015-01-01

Myocardial ischemia reperfusion injury (IRI) adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT) 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS)-3, an intrinsic negative feedback regulator of the Janus kinase (JAK)-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT-activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO). The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI.

Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules

PubMed Central

Nagata, Takanobu; Yasukawa, Hideo; Kyogoku, Sachiko; Oba, Toyoharu; Takahashi, Jinya; Nohara, Shoichiro; Minami, Tomoko; Mawatari, Kazutoshi; Sugi, Yusuke; Shimozono, Koutatsu; Pradervand, Sylvain; Hoshijima, Masahiko; Aoki, Hiroki; Fukumoto, Yoshihiro; Imaizumi, Tsutomu

2015-01-01

Myocardial ischemia reperfusion injury (IRI) adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT) 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS)-3, an intrinsic negative feedback regulator of the Janus kinase (JAK)-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT–activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO). The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI. PMID:26010537

Narrative Exposure Therapy: A Proposed Model to Address Intimate Partner Violence-Related PTSD in Parenting and Pregnant Adolescents.

PubMed

Volpe, Ellen M; Quinn, Camille R; Resch, Kathryn; Sommers, Marilyn S; Wieling, Elizabeth; Cerulli, Catherine

Pregnant and parenting adolescents experience high rates of intimate partner violence (IPV) and its sequelae posttraumatic stress disorder (PTSD) and depression. Narrative exposure therapy (NET) is an innovative intervention that has demonstrated strong preliminary evidence in improving mental health. The specific aims of this article are 3-fold: (1) provide a brief background about IPV-related PTSD and depression among pregnant and parenting adolescents; (2) describe NET's theoretical principles, its therapeutic process, and provide a review of existing evidence; and (3) discuss NET as a potential treatment to address the mental health burden among adolescents experiencing IPV-related PTSD and depression.

Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060

PubMed Central

Krijthe, Bouwe P.; Kunst, Anton; Benjamin, Emelia J.; Lip, Gregory Y.H.; Franco, Oscar H.; Hofman, Albert; Witteman, Jacqueline C.M.; Stricker, Bruno H.; Heeringa, Jan

2013-01-01

Aims Since atrial fibrillation (AF) is associated with increased risks of cardiovascular and cerebrovascular complications, estimations on the number of individuals with AF are relevant to healthcare planning. We aimed to project the number of individuals with AF in the Netherlands and in the European Union from 2000 to 2060. Methods and results Age- and sex-specific AF prevalence estimates were obtained from the prospective community-based Rotterdam Study. Population projections for the Netherlands and the European Union were obtained from the European Union's statistics office. In the age stratum of 55–59 years, the prevalence of AF was 1.3% in men (95% CI: 0.4–3.6%) and 1.7% in women (95% CI: 0.7–4.0%). The prevalence of AF increased to 24.2% in men (95% CI: 18.5–30.7%), and 16.1% in women (95% CI: 13.1–19.4%), for those >85 years of age. This age- and sex-specific prevalence remained stable during the years of follow-up. Furthermore, we estimate that in the European Union, 8.8 million adults over 55 years had AF in 2010 (95% CI: 6.5–12.3 million). We project that this number will double by 2060 to 17.9 million (95% CI: 13.6–23.7 million) if the age- and sex-specific prevalence remains stable. Conclusion We estimate that from 2010 to 2060, the number of adults 55 years and over with AF in the European Union will more than double. As AF is associated with significant morbidities and mortality, this increasing number of individuals with AF may have major public health implications. PMID:23900699

Sensitivity and Specificity of Interictal EEG-fMRI for Detecting the Ictal Onset Zone at Different Statistical Thresholds

PubMed Central

Tousseyn, Simon; Dupont, Patrick; Goffin, Karolien; Sunaert, Stefan; Van Paesschen, Wim

2014-01-01

There is currently a lack of knowledge about electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) specificity. Our aim was to define sensitivity and specificity of blood oxygen level dependent (BOLD) responses to interictal epileptic spikes during EEG-fMRI for detecting the ictal onset zone (IOZ). We studied 21 refractory focal epilepsy patients who had a well-defined IOZ after a full presurgical evaluation and interictal spikes during EEG-fMRI. Areas of spike-related BOLD changes overlapping the IOZ in patients were considered as true positives; if no overlap was found, they were treated as false-negatives. Matched healthy case-controls had undergone similar EEG-fMRI in order to determine true-negative and false-positive fractions. The spike-related regressor of the patient was used in the design matrix of the healthy case-control. Suprathreshold BOLD changes in the brain of controls were considered as false positives, absence of these changes as true negatives. Sensitivity and specificity were calculated for different statistical thresholds at the voxel level combined with different cluster size thresholds and represented in receiver operating characteristic (ROC)-curves. Additionally, we calculated the ROC-curves based on the cluster containing the maximal significant activation. We achieved a combination of 100% specificity and 62% sensitivity, using a Z-threshold in the interval 3.4–3.5 and cluster size threshold of 350 voxels. We could obtain higher sensitivity at the expense of specificity. Similar performance was found when using the cluster containing the maximal significant activation. Our data provide a guideline for different EEG-fMRI settings with their respective sensitivity and specificity for detecting the IOZ. The unique cluster containing the maximal significant BOLD activation was a sensitive and specific marker of the IOZ. PMID:25101049

Direct comparison of two actigraphy devices with polysomnographically recorded naps in healthy young adults.

PubMed

Cellini, Nicola; Buman, Matthew P; McDevitt, Elizabeth A; Ricker, Ashley A; Mednick, Sara C

2013-06-01

The last 20 yrs have seen a marked increase in studies utilizing actigraphy in free-living environments. The aim of the present study is to directly compare two commercially available actigraph devices with concurrent polysomnography (PSG) during a daytime nap in healthy young adults. Thirty healthy young adults, ages 18-31 (mean 20.77 yrs, SD 3.14 yrs) simultaneously wore AW-64 and GT3X+ devices during a polysomnographically recorded nap. Mann-Whitney U (M-U) test, intraclass correlation coefficients, and Bland-Altman statistic were used to compare total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE) between the two actigraphs and PSG. Epoch-by-epoch (EBE) agreement was calculated to determine accuracy, sensitivity, specificity, predictive values for sleep (PVS) and wake (PVW), and kappa and prevalence- and bias-adjusted kappa (PABAK) coefficients. All frequency settings provided by the devices were examined. For both actigraphs, EBE analysis found accuracy, sensitivity, specificity, PVS, and PVW comparable to previous reports of other similar devices. Kappa and PABAK coefficients showed moderate to high agreement with PSG depending on device settings. The GT3X+ overestimated TST and SE, and underestimated SOL and WASO, whereas no significant difference was found between AW-64 and PSG. However, GT3X+ showed overall better EBE agreements to PSG than AW-64. We conclude that both actigraphs are valid and reliable devices for detecting sleep/wake diurnal patterns. The choice between devices should be based on several parameters as reliability, cost of the device, scoring algorithm, target population, experimental condition, and aims of the study (e.g., sleep and/or physical activity).

Analysis of the key enzymes of butyric and acetic acid fermentation in biogas reactors

PubMed Central

Gabris, Christina; Bengelsdorf, Frank R; Dürre, Peter

2015-01-01

This study aimed at the investigation of the mechanisms of acidogenesis, which is a key process during anaerobic digestion. To expose possible bottlenecks, specific activities of the key enzymes of acidification, such as acetate kinase (Ack, 0.23–0.99 U mg−1 protein), butyrate kinase (Buk, < 0.03 U mg−1 protein) and butyryl-CoA:acetate-CoA transferase (But, 3.24–7.64 U mg−1 protein), were determined in cell free extracts of biogas reactor content from three different biogas reactors. Furthermore, the detection of Ack was successful via Western blot analysis. Quantification of corresponding functional genes encoding Buk (buk) and But (but) was not feasible, although an amplification was possible. Thus, phylogenetic trees were constructed based on respective gene fragments. Four new clades of possible butyrate-producing bacteria were postulated, as well as bacteria of the genera Roseburia or Clostridium identified. The low Buk activity was in contrast to the high specific But activity in the analysed samples. Butyrate formation via Buk activity does barely occur in the investigated biogas reactor. Specific enzyme activities (Ack, Buk and But) in samples drawn from three different biogas reactors correlated with ammonia and ammonium concentrations (NH3 and NH4+-N), and a negative dependency can be postulated. Thus, high concentrations of NH3 and NH4+-N may lead to a bottleneck in acidogenesis due to decreased specific acidogenic enzyme activities. PMID:26086956

Skill-Specific Changes in Somatosensory Nogo Potentials in Baseball Players

PubMed Central

Yamashiro, Koya; Sato, Daisuke; Onishi, Hideaki; Sugawara, Kazuhiro; Nakazawa, Sho; Shimojo, Hirofumi; Akatsuka, Kosuke; Nakata, Hiroki; Maruyama, Atsuo

2015-01-01

Athletic training is known to induce neuroplastic alterations in specific somatosensory circuits, which are reflected by changes in somatosensory evoked potentials and event-related potentials. The aim of this study was to clarify whether specific athletic training also affects somatosensory Nogo potentials related to the inhibition of movements. The Nogo potentials were recorded at nine cortical electrode positions (Fz, Cz, Pz, F3, F4, C3, C4, P3 and P4) in 12 baseball players (baseball group) and in 12 athletes in sports, such as track and field events and swimming, that do not require response inhibition, such as batting for training or performance (sports group). The Nogo potentials and Go/Nogo reaction times (Go/Nogo RTs) were measured under a somatosensory Go/Nogo paradigm in which subjects were instructed to rapidly push a button in response to stimulus presentation. The Nogo potentials were obtained by subtracting the Go trial from the Nogo trial. The peak Nogo-N2 was significantly shorter in the baseball group than that in the sports group. In addition, the amplitude of Nogo-N2 in the frontal area was significantly larger in the baseball group than that in the sports group. There was a significant positive correlation between the latency of Nogo-N2 and Go/Nogo RT. Moreover, there were significant correlations between the Go/Nogo RT and both the amplitude of Nogo-N2 and Nogo-P3 (i.e., amplitude of the Nogo-potentials increases with shorter RT). Specific athletic training regimens may induce neuroplastic alterations in sensorimotor inhibitory processes. PMID:26600391

Skill-Specific Changes in Somatosensory Nogo Potentials in Baseball Players.

PubMed

Yamashiro, Koya; Sato, Daisuke; Onishi, Hideaki; Sugawara, Kazuhiro; Nakazawa, Sho; Shimojo, Hirofumi; Akatsuka, Kosuke; Nakata, Hiroki; Maruyama, Atsuo

2015-01-01

Athletic training is known to induce neuroplastic alterations in specific somatosensory circuits, which are reflected by changes in somatosensory evoked potentials and event-related potentials. The aim of this study was to clarify whether specific athletic training also affects somatosensory Nogo potentials related to the inhibition of movements. The Nogo potentials were recorded at nine cortical electrode positions (Fz, Cz, Pz, F3, F4, C3, C4, P3 and P4) in 12 baseball players (baseball group) and in 12 athletes in sports, such as track and field events and swimming, that do not require response inhibition, such as batting for training or performance (sports group). The Nogo potentials and Go/Nogo reaction times (Go/Nogo RTs) were measured under a somatosensory Go/Nogo paradigm in which subjects were instructed to rapidly push a button in response to stimulus presentation. The Nogo potentials were obtained by subtracting the Go trial from the Nogo trial. The peak Nogo-N2 was significantly shorter in the baseball group than that in the sports group. In addition, the amplitude of Nogo-N2 in the frontal area was significantly larger in the baseball group than that in the sports group. There was a significant positive correlation between the latency of Nogo-N2 and Go/Nogo RT. Moreover, there were significant correlations between the Go/Nogo RT and both the amplitude of Nogo-N2 and Nogo-P3 (i.e., amplitude of the Nogo-potentials increases with shorter RT). Specific athletic training regimens may induce neuroplastic alterations in sensorimotor inhibitory processes.

Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

PubMed

Chen, Chengshui; Shi, Lin; Li, Yuping; Wang, Xiangdong; Yang, Shuanying

2016-06-01

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics. Plasma was sampled from the healthy as controls or patients with SP infected with bacteria or infection-associated SP-ARDS on the day of admission, day 3, and day 7. About 15 or 52 cytokines showed significant difference between SP and SP-ARDS patients with controls or 13 between SP-ARDS with SP alone and controls, including bone morphogenetic protein-15 (BMP-15), chemokine (C-X-C motif) ligand 16 (CXCL16), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-6 (IL-6), protein NOV homolog (NOV/CCN3), glypican 3, insulin-like growth factor binding protein 4 (IGFBP-4), IL-5, IL-5 R alpha, IL-22 BP, leptin, MIP-1d, and orexin B with a significant correlation with Digital Evaluation Score System (DESS) scores. ARDS patients with overexpressed IL-6, CXCL16, or IGFBP-4 had significantly longer hospital stay and higher incidence of secondary infection. We also found higher levels of those mediators were associated with poor survival rates in patients with lung cancer and involved in the process of the epithelial mesenchymal transition of alveolar epithelial cells. Our preliminary study suggested that integration of proteomic profiles with clinical informatics as part of clinical bioinformatics is important to validate and optimize disease-specific and disease-staged biomarkers.

Validity of the Test of Infant Motor Performance for prediction of 6-, 9- and 12-month scores on the Alberta Infant Motor Scale.

PubMed

Campbell, Suzann K; Kolobe, Thubi H A; Wright, Benjamin D; Linacre, John Michael

2002-04-01

The Test of Infant Motor Performance (TIMP) is a test of functional movement in infants from 32 weeks' post-conceptional age to 4 months postterm. The purpose of this study was to assess in 96 infants (44 females, 52 males) with varying risk, the relation between measures on the TIMP at 7, 30, 60, and 90 days after term age and percentile ranks (PR) on the Alberta Infant Motor Scale (AIMS). Correlation between scores on the TIMP and the AIMS was highest for TIMP tests at 90 days and AIMS testing at 6 months (r=0.67, p=0.0001), but all comparisons were statistically significant except those between the TIMP at 7 days and AIMS PR at 9 months. In a multiple regression analysis combining a perinatal risk score and 7-day TIMP measures to predict 12-month AIMS PR, risk, but not TIMP, predicted outcome (21% of variance explained). At older ages TIMP measures made increasing contributions to prediction of 12-month AIMS PR (30% of variance explained by 90-day TIMP). The best TIMP score to maximize specificity and correctly identify 84% of the infants above versus below the 10th PR at 6 months was a cut-off point of 1 SD below the mean. The same cut-off point correctly identified 88% of the infants at 12 months. A cut-off of -0.5 SD, however, maximized sensitivity at 92%. A negative test result, i.e. score above -0.5 SD at 3 months, carried only a 2% probability of a poor 12-month outcome. We conclude that TIMP scores significantly predict AIMS PR 6 to 12 months later, but the TIMP at 3 months of age has the greatest degree of validity for predicting motor performance on the AIMS at 12 months and can be used clinically to identify infants likely to benefit from intervention.

[Knowledge retain of BLS and BLS-D theoretical contents in a long-term follow-up].

PubMed

Paolini, Enrico; Conti, Elettra; Guerra, Federico; Capucci, Alessandro

2018-03-01

Despite the many recent improvements in basic life support (BLS) and the widespread training to a great number of lay rescuers, out-of-hospital cardiac arrest (OHCA) is still a major cause of death. Nowadays, BLS teaching protocols ask for many concepts to be learned and specific algorithms to be applied, without any available data on how much all these inputs are retained by the students. The present survey aims to evaluate how BLS is really retained by those rescuers (laypersons and nurses) who do not often put it into practice. The first survey was targeted at laypersons who are responsible for security in their work environment. The second survey was targeted at nurses operating in low-intensity wards or out-of-hospital clinics. Both surveys were anonymous and asked specific questions aimed at evaluating how BLS/BLS-D (BLS and defibrillation) information was retained on an average of 3 years after training completion. Lay rescuers showed difficulties in recognizing specific signs of OHCA, were unsure on when to call the emergency medical service and retained few and sometime erroneous information on the correct BLS sequence to perform. The nurses operating in low-intensity settings performed better in terms of OHCA recognition and advanced medical assistance activation, while how to set and operate an automatic external defibrillation was seldom clear. BLS information is usually not retained after a 3-year follow-up by people who are not involved in OHCA management as part of their everyday job. It should be useful to lower the number of concepts taught in current BLS courses in order to focus on the most significant aspects of it, such as prompt emergency medical system activation and early defibrillation.

Defense AT and L. Volume 45, Number 3

DTIC Science & Technology

2016-06-01

CRM ). During the 1980s, the commercial airlines and military invested heavily in CRM training, aiming to increase crew coordination and improve...cockpit management. These CRM training programs focused on human factors train- ing—also called man-machine interfaces—with specific concentration on...leadership and decision making. CRM has evolved over the years with emphasis now placed on the acquisition of timely, appropriate infor- mation

Physical Fitness in Spanish Schoolchildren Aged 6-12 Years: Reference Values of the Battery EUROFIT and Associated Cardiovascular Risk

ERIC Educational Resources Information Center

Gulías-González, Roberto; Sánchez-López, Mairena; Olivas-Bravo, Ángel; Solera-Martínez, Montserrat; Martínez-Vizcaíno, Vicente

2014-01-01

Background: Physical fitness is considered an important indicator of health in children. The aims of this study were to (1) provide sex- and age-specific EUROFIT battery levels of fitness in Spanish children; (2) compare Spanish children's fitness levels with those of children from other countries; and (3) determine the percentage of Spanish…

Targeting Premalignant Lesions - Implications for Early Breast Cancer Detection and Intervention

DTIC Science & Technology

2017-04-01

lesions. Peptide conjugated AgNP were injected intravenously in mice and mammary glands were isolated and analyzed for nanoparticle accumulation by silver ...Furthermore, these probes will be used to develop targeted therapeutic nanoparticles for early intervention in breast cancer. 2. KEYWORDS...cancer (Months 18-24) (To be done) Specific Aim 3: Target premalignant lesions utilizing peptide-conjugated nanoparticles to prevent/delay

Evaluation of an automated breast 3D-ultrasound system by comparing it with hand-held ultrasound (HHUS) and mammography.

PubMed

Golatta, Michael; Baggs, Christina; Schweitzer-Martin, Mirjam; Domschke, Christoph; Schott, Sarah; Harcos, Aba; Scharf, Alexander; Junkermann, Hans; Rauch, Geraldine; Rom, Joachim; Sohn, Christof; Heil, Joerg

2015-04-01

Automated three-dimensional (3D) breast ultrasound (US) systems are meant to overcome the shortcomings of hand-held ultrasound (HHUS). The aim of this study is to analyze and compare clinical performance of an automated 3D-US system by comparing it with HHUS, mammography and the clinical gold standard (defined as the combination of HHUS, mammography and-if indicated-histology). Nine hundred and eighty three patients (=1,966 breasts) were enrolled in this monocentric, explorative and prospective cohort study. All examinations were analyzed blinded to the patients´ history and to the results of the routine imaging. The agreement of automated 3D-US with HHUS, mammography and the gold standard was assessed with kappa statistics. Sensitivity, specificity and positive and negative predictive value were calculated to assess the test performance. Blinded to the results of the gold standard the agreement between automated 3D-US and HHUS or mammography was fair, given by a Kappa coefficient of 0.31 (95% CI [0.26;0.36], p < 0.0001) and 0.25 (95% CI [0.2;0.3], p < 0.0001), respectively. Our results showed a high negative predictive value (NPV) of 98%, a high specificity of 85% and a sensitivity of 74% based on the cases with US-guided biopsy. Including the cases where the lesion was seen in a second-look automated 3D-US the sensitivity improved to 84% (NPV = 99%, specificity = 85%). The results of this study let us suggest, that automated 3D-US might be a helpful new tool in breast imaging, especially in screening.

Application of Faecalibacterium 16S rDNA genetic marker for accurate identification of duck faeces.

PubMed

Sun, Da; Duan, Chuanren; Shang, Yaning; Ma, Yunxia; Tan, Lili; Zhai, Jun; Gao, Xu; Guo, Jingsong; Wang, Guixue

2016-04-01

The aim of this study was to judge the legal duty of pollution liabilities by assessing a duck faeces-specific marker, which can exclude distractions of residual bacteria from earlier contamination accidents. With the gene sequencing technology and bioinformatics method, we completed the comparative analysis of Faecalibacterium sequences, which were associated with ducks and other animal species, and found the sequences unique to duck faeces. Polymerase chain reaction (PCR) and agarose gel electrophoresis techniques were used to verify the reliability of both human and duck faeces-specific primers. The duck faeces-specific primers generated an amplicon of 141 bp from 43.3 % of duck faecal samples, 0 % of control samples and 100 % of sewage wastewater samples that contained duck faeces. We present here the initial evidence of Faecalibacterium-based applicability as human faeces-specificity in China. Meanwhile, this study represents the initial report of a Faecalibacterium marker for duck faeces and suggests an independent or supplementary environmental biotechnology of microbial source tracking (MST).

Algorithm for early discharge after total thyroidectomy using PTH to predict hypocalcemia: prospective study.

PubMed

Schlottmann, F; Arbulú, A L Campos; Sadava, E E; Mendez, P; Pereyra, L; Fernández Vila, J M; Mezzadri, N A

2015-10-01

Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine whether postoperative parathyroid hormone (PTH) levels predict hypocalcemia in order to design an algorithm for early discharge. We present a prospective study including patients who underwent total thyroidectomy. Hypocalcemia was defined as serum ionized calcium < 1.09 mmol/L or clinical evidence of hypocalcemia. PTH measurement was performed preoperatively and at 1, 3, and 6 h postoperatively. The percent decline of preoperative values was calculated for each time point. One hundred and six patients were included. Thirty-six (33.9%) patients presented hypocalcemia. A 50% decline in PTH levels at 3 h postoperatively showed the highest sensitivity and specificity to predict hypocalcemia (91 and 73%, respectively). No patients with a decrease <35% developed hypocalcemia (100% sensitivity), and all patients with a decrease >80% had hypocalcemia (100% specificity). PTH determination at 3 h postoperatively is a reliable predictor of hypocalcemia. According to the proposed algorithm, patients with less than 80% drop in PTH levels can be safely discharged the day of the surgery.

Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells

PubMed Central

Cirelli, Kimberly M.; Dan, Jennifer M.; Morou, Antigoni; Daigneault, Audrey; Brassard, Nathalie; Silvestri, Guido; Routy, Jean-Pierre; Havenar-Daughton, Colin; Crotty, Shane

2017-01-01

The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM). Here, we compare two such assays based on concurrent expression of CD69 plus CD40L (CD154) or expression of OX40 plus CD25, and we develop additional AIM assays based on OX40 plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for detection of vaccine and natural infection-induced CD4 T cell responses and show that these assays identify distinct, but overlapping populations of antigen-specific CD4 T cells, a subpopulation of which can also be detected on the basis of cytokine synthesis. Bystander activation had minimal effect on AIM markers. However, some T regulatory cells upregulate CD25 upon antigen stimulation. We therefore validated AIM assays designed to exclude most T regulatory cells, for both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through head-to-head comparisons and methodological improvements, we show that AIM assays represent a sensitive and valuable method for the detection of antigen-specific CD4 T cells. PMID:29065175

A gene expression signature that correlates with CD8+T cell expansion in acute Epstein Barr virus infection1

PubMed Central

Greenough, Thomas C.; Straubhaar, Juerg R.; Kamga, Larisa; Weiss, Eric R.; Brody, Robin M.; McManus, Margaret M.; Lambrecht, Linda K.; Somasundaran, Mohan; Luzuriaga, Katherine F.

2015-01-01

Virus specific CD8+ T cells expand dramatically during acute Epstein Barr virus (EBV) infection, and their persistence is important for lifelong control of EBV-related disease. To better define the generation and maintenance of these effective CD8+ T cell responses, we used microarrays to characterize gene expression in total and EBV-specific CD8+ T cells isolated from the peripheral blood of ten individuals followed from acute infectious mononucleosis (AIM) into convalescence (CONV). In total CD8+ T cells, differential expression of genes in AIM and CONV was most pronounced among those encoding proteins important in T cell activation/differentiation, cell division/metabolism, chemokines/cytokines and receptors, signaling and transcription factors (TF), immune effector functions, and negative regulators. Within these categories, we identified 28 genes that correlated with CD8+ T cell expansion in response to an acute EBV infection. In EBV-specific CD8+ T cells, we identified 33 genes that were differentially expressed in AIM and CONV. Two important TF, T-bet and Eomesodermin (Eomes), were upregulated and maintained at similar levels in both AIM and CONV; by contrast, protein expression declined from AIM to CONV. Expression of these TF varied among cells with different epitope specificities. Altogether, gene and protein expression patterns suggest that a large proportion, if not a majority of CD8+ T cells in AIM are virus-specific, activated, dividing, and primed to exert effector activities. High expression of T-bet and Eomes may help to maintain effector mechanisms in activated cells, and to enable proliferation and transition to earlier differentiation states in CONV. PMID:26416268

Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells.

PubMed

Reiss, Samantha; Baxter, Amy E; Cirelli, Kimberly M; Dan, Jennifer M; Morou, Antigoni; Daigneault, Audrey; Brassard, Nathalie; Silvestri, Guido; Routy, Jean-Pierre; Havenar-Daughton, Colin; Crotty, Shane; Kaufmann, Daniel E

2017-01-01

The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM). Here, we compare two such assays based on concurrent expression of CD69 plus CD40L (CD154) or expression of OX40 plus CD25, and we develop additional AIM assays based on OX40 plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for detection of vaccine and natural infection-induced CD4 T cell responses and show that these assays identify distinct, but overlapping populations of antigen-specific CD4 T cells, a subpopulation of which can also be detected on the basis of cytokine synthesis. Bystander activation had minimal effect on AIM markers. However, some T regulatory cells upregulate CD25 upon antigen stimulation. We therefore validated AIM assays designed to exclude most T regulatory cells, for both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through head-to-head comparisons and methodological improvements, we show that AIM assays represent a sensitive and valuable method for the detection of antigen-specific CD4 T cells.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

PubMed

Chen, Mee-Yew; Kirkwood, Carl D; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

2017-05-04

Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.

GATA3 expression in primary vulvar Paget disease: a potential pitfall leading to misdiagnosis of pagetoid urothelial intraepithelial neoplasia.

PubMed

Morbeck, Diogo; Tregnago, Aline C; Baiocchi, Glauco; Sacomani, Carlos; Peresi, Patricia M; Osório, Cynthia T; Schutz, Luciana; Bezerra, Stephania M; de Brot, Louise; Cunha, Isabela W

2017-02-01

GATA3 has been reported as a specific urothelial marker among organs in the pelvic region, and has been classified as highly sensitive and specific for urothelial and breast carcinomas. Our aim was to verify GATA3 expression in extramammary Paget disease, and to determine whether it can be use to differentiate primary vulvar Paget disease from pagetoid urothelial intraepithelial neoplasia (PUIN). We also analysed HER2 protein expression and HER2 gene amplification and their roles as prognostic factors in extramammary Paget disease. We analysed GATA3 and HER2 expression in 11 primary vulvar Paget disease cases and two PUIN cases. All cases showed nuclear expression of GATA3. Of 13 cases, five were equivocal for HER2 expression (score 2+) and one was positive (3+). Fluorescence in-situ hybridization results showed amplification in two of these six cases. Both HER2-amplified cases were invasive. GATA3 was positive in all extramammary Paget disease cases tested (13 cases), and it has no value for differentiating between primary and secondary vulvar Paget disease from the urological tract. HER2 amplification might confer an aggressive and invasive pattern in primary vulvar Paget disease, as both amplified cases showed an invasive pattern. © 2016 John Wiley & Sons Ltd.

Sickness absence due to back pain or depressive episode and the risk of all-cause and diagnosis-specific disability pension: A Swedish cohort study of 4,823,069 individuals.

PubMed

Dorner, T E; Alexanderson, K; Svedberg, P; Ropponen, A; Stein, K V; Mittendorfer-Rutz, E

2015-10-01

The aim of this study was to investigate the associations between sickness absence due to back pain or depressive episode with future all-cause and diagnosis-specific disability pension, while adjusting for comorbidity and socio-demographics, for all and stratifying for sex. In total, 4,823,069 individuals aged 16-64 years, living in Sweden at the end of 2004, not on old-age or disability pension in 2005 and without ongoing sickness absence at the turn of 2004/2005 formed the study population. Crude and adjusted hazard ratios (HRs) for all-cause and diagnosis-specific disability pension (2006-2010) in relation to diagnosis-specific sickness absence with sickness benefits paid by the Social Insurance Agency were estimated using Cox regression. The HR for all-cause disability pension was 7.52 (7.25-7.52) in individuals with an incident sick-leave spell due to back pain, compared to individuals without sickness absence in 2005 in the fully adjusted (socio-demographics and comorbidity) model. The fully adjusted (multivariate) HRs for diagnosis-specific disability pension were musculoskeletal diagnoses 23.87 (22.75-25.04), mental 2.49 (2.27-2.73) or all other diagnoses, 3.44 (3.17-3.75). In individuals with an incident sick-leave spell due to a depressive episode in 2005, the multivariate adjusted HR for all-cause disability pension was 12.87 (12.42-13.35), while the multivariate HRs for disability pension due to musculoskeletal diagnoses were 4.39 (3.89-4.96), for mental diagnoses 25.32 (24.29-26.38) and for all other somatic diagnoses 3.44 (3.09-3.82). Men who were sickness absent due to a depressive episode had a higher HR for disability pension compared to women. Results indicate that sickness absence due to a depressive episode or back pain is a strong risk factor for a future disability pension due to mental, musculoskeletal or other somatic diagnoses. © 2015 European Pain Federation - EFIC®

Mimotopes for Api g 5, a Relevant Cross-reactive Allergen, in the Celery-Mugwort-Birch-Spice Syndrome.

PubMed

Lukschal, Anna; Wallmann, Julia; Bublin, Merima; Hofstetter, Gerlinde; Mothes-Luksch, Nadine; Breiteneder, Heimo; Pali-Schöll, Isabella; Jensen-Jarolim, Erika

2016-03-01

In the celery-mugwort-birch-spice syndrome, a significant proportion of IgE is directed against high molecular weight (HMW) glycoproteins, including the celery allergen Api g 5. BIP3, a monoclonal antibody originally raised against birch pollen, recognizes HMW allergens in birch and mugwort pollens, celery, and Apiaceae spices. Our aim was to generate mimotopes using BIP3 for immunization against the HMW allergens relevant in the celery-mugwort-birch-spice cross reactivity syndrome. Mimotopes were selected from a random-peptide display library by BIP3 and applied in IgE inhibition assays. The 3 phage clones with the highest inhibitory capacity were chosen for immunization of BALB/c mice. Mouse immune sera were tested for IgG binding to blotted birch pollen extract and used for inhibiting patients' IgE binding. Furthermore, sera were tested for binding to Api g 5, to horseradish peroxidase (HRP) as a second glycoprotein, or to non-glycosylated control allergen Phl p 5 in ELISA, and the specific Api g 5-specific IgG titers were determined. Three rounds of biopanning resulted in phage clones exhibiting 7 different sequences including 1 dominant, 1-6-cyclo-CHKLRCDKAIA. Three phage clones had the capacity to inhibit human IgE binding and induced IgG to the HMW antigen when used for immunizing BALB/c mice. The induced BIP3-mimotope IgG reached titers of 1:500 specifically to Api g 5, but hardly reacted to glycoprotein HRP, revealing a minor role of carbohydrates in their epitope. The mimotopes characterized in this study mimic the epitope of BIP3 relevant for Api g 5, one of the cross-reactive HMW allergens relevant in the celery-mugwort-birch-spice syndrome. BIP3 mimotopes may be used in the future for hyposensitization in this clinical syndrome by virtue of good and specific immunogenicity.

Preparation of poly-L-lysine functionalized magnetic nanoparticles and their influence on viability of cancer cells

NASA Astrophysics Data System (ADS)

Khmara, I.; Koneracka, M.; Kubovcikova, M.; Zavisova, V.; Antal, I.; Csach, K.; Kopcansky, P.; Vidlickova, I.; Csaderova, L.; Pastorekova, S.; Zatovicova, M.

2017-04-01

This study was aimed at development of biocompatible amino-functionalized magnetic nanoparticles as carriers of specific antibodies able to detect and/or target cancer cells. Poly-L-lysine (PLL)-modified magnetic nanoparticle samples with different PLL/Fe3O4 content were prepared and tested to define the optimal PLL/Fe3O4 weight ratio. The samples were characterized for particle size and morphology (SEM, TEM and DLS), and surface properties (zeta potential measurements). The optimal PLL/Fe3O4 weight ratio of 1.0 based on both zeta potential and DLS measurements was in agreement with the UV/VIS measurements. Magnetic nanoparticles with the optimal PLL content were conjugated with antibody specific for the cancer biomarker carbonic anhydrase IX (CA IX), which is induced by hypoxia, a physiologic stress present in solid tumors and linked with aggressive tumor behavior. CA IX is localized on the cell surface with the antibody-binding epitope facing the extracellular space and is therefore suitable for antibody-based targeting of tumor cells. Here we showed that PLL/Fe3O4 magnetic nanoparticles exhibit cytotoxic activities in a cell type-dependent manner and bind to cells expressing CA IX when conjugated with the CA IX-specific antibody. These data support further investigations of the CA IX antibody-conjugated, magnetic field-guided/activated nanoparticles as tools in anticancer strategies.

Deciphering the Sensitivity and Specificity of the Implantable Doppler in Free Flap Monitoring.

PubMed

Chang, Edward I; Ibrahim, Amir; Zhang, Hong; Liu, Jun; Nguyen, Alexander T; Reece, Gregory P; Yu, Peirong

2015-11-19

The efficacy of implantable Dopplers (iD) remains an area of considerable debate. Our study aims to decipher the sensitivity and specificity of the iD for free flap monitoring. A retrospective review of all free flaps with an iD was performed between 2000-2012. A Cook-Swartz iD was used in 439 patients (head and neck: n=364, breast: n=53, and extremity: n=22), and demonstrated equivalent sensitivity and specificity between flap types. The overall sensitivity and specificity was 77.8% and 88.4% respectively. The iD was placed on the artery in 267 patients, the vein in 101 patients, and 71 patients had a Doppler placed on both the artery and vein with significantly greater specificity for monitoring the artery than the vein (94.2% vs. 74.0%, p<0.001), but no difference between monitoring both the artery and the vein. Venous monitoring was significantly associated with a takeback (OR: 3.17, CI: 1.70-5.91; p=0.0003). There were 284 flaps that also had a monitoring segment in addition to the iD which significantly increased specificity for microvascular complications (OR: 17.71, CI: 3.39-92.23; p=0.0006). The specificity (90.5% vs. 84.8%) and sensitivity (80.0% vs. 66.7%) were significantly higher for clinically monitored flaps. The takeback rate was 13.0%, with positive findings in 59.6%, and 5.2% total flap loss. The use of implantable Dopplers has high sensitivity and specificity for buried free flap despite positive findings in less than 60% of take backs. Monitoring the artery is preferable to the vein, but clinical exam remains the gold standard for flap monitoring.

A Review of Current Clinical Applications of Three-Dimensional Printing in Spine Surgery

PubMed Central

Job, Alan Varkey; Chen, Jing; Baek, Jung Hwan

2018-01-01

Three-dimensional (3D) printing is a transformative technology with a potentially wide range of applications in the field of orthopaedic spine surgery. This article aims to review the current applications, limitations, and future developments of 3D printing technology in orthopaedic spine surgery. Current preoperative applications of 3D printing include construction of complex 3D anatomic models for improved visual understanding, preoperative surgical planning, and surgical simulations for resident education. Intraoperatively, 3D printers have been successfully used in surgical guidance systems and in the creation of patient specific implantable devices. Furthermore, 3D printing is revolutionizing the field of regenerative medicine and tissue engineering, allowing construction of biocompatible scaffolds suitable for cell growth and vasculature. Advances in printing technology and evidence of positive clinical outcomes are needed before there is an expansion of 3D printing applied to the clinical setting. PMID:29503698

A Review of Current Clinical Applications of Three-Dimensional Printing in Spine Surgery.

PubMed

Cho, Woojin; Job, Alan Varkey; Chen, Jing; Baek, Jung Hwan

2018-02-01

Three-dimensional (3D) printing is a transformative technology with a potentially wide range of applications in the field of orthopaedic spine surgery. This article aims to review the current applications, limitations, and future developments of 3D printing technology in orthopaedic spine surgery. Current preoperative applications of 3D printing include construction of complex 3D anatomic models for improved visual understanding, preoperative surgical planning, and surgical simulations for resident education. Intraoperatively, 3D printers have been successfully used in surgical guidance systems and in the creation of patient specific implantable devices. Furthermore, 3D printing is revolutionizing the field of regenerative medicine and tissue engineering, allowing construction of biocompatible scaffolds suitable for cell growth and vasculature. Advances in printing technology and evidence of positive clinical outcomes are needed before there is an expansion of 3D printing applied to the clinical setting.

NIL fabrication of a polymer-based photonic sensor device in P3SENS project

NASA Astrophysics Data System (ADS)

Giannone, Domenico; Dortu, Fabian; Bernier, Damien; Johnson, Nigel P.; Sharp, Graham J.; Hou, Lianping; Khokhar, Ali Z.; Fürjes, Péter; Kurunczi, Sándor; Petrik, Peter; Horvath, Robert; Aalto, Timo; Kolari, Kai; Ylinen, Sami; Haatainen, Tomi; Egger, Holger

2012-06-01

We present the most recent results of EU funded project P3SENS (FP7-ICT-2009.3.8) aimed at the development of a low-cost and medium sensitivity polymer based photonic biosensor for point of care applications in proteomics. The fabrication of the polymer photonic chip (biosensor) using thermal nanoimprint lithography (NIL) is described. This technique offers the potential for very large production at reduced cost. However several technical challenges arise due to the properties of the used materials. We believe that, once the NIL technique has been optimised to the specific materials, it could be even transferred to a kind of roll-to-roll production for manufacturing a very large number of photonic devices at reduced cost.

Direct volumetric rendering based on point primitives in OpenGL.

PubMed

da Rosa, André Luiz Miranda; de Almeida Souza, Ilana; Yuuji Hira, Adilson; Zuffo, Marcelo Knörich

2006-01-01

The aim of this project is to present a renderization by software algorithm of acquired volumetric data. The algorithm was implemented in Java language and the LWJGL graphical library was used, allowing the volume renderization by software and thus preventing the necessity to acquire specific graphical boards for the 3D reconstruction. The considered algorithm creates a model in OpenGL, through point primitives, where each voxel becomes a point with the color values related to this pixel position in the corresponding images.

Semantic memory: a feature-based analysis and new norms for Italian.

PubMed

Montefinese, Maria; Ambrosini, Ettore; Fairfield, Beth; Mammarella, Nicola

2013-06-01

Semantic norms for properties produced by native speakers are valuable tools for researchers interested in the structure of semantic memory and in category-specific semantic deficits in individuals following brain damage. The aims of this study were threefold. First, we sought to extend existing semantic norms by adopting an empirical approach to category (Exp. 1) and concept (Exp. 2) selection, in order to obtain a more representative set of semantic memory features. Second, we extensively outlined a new set of semantic production norms collected from Italian native speakers for 120 artifactual and natural basic-level concepts, using numerous measures and statistics following a feature-listing task (Exp. 3b). Finally, we aimed to create a new publicly accessible database, since only a few existing databases are publicly available online.

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab.

PubMed

Hattori, Yosuke; Kojima, Toshihisa; Kaneko, Atsushi; Kida, Daihei; Hirano, Yuji; Fujibayashi, Takayoshi; Yabe, Yuichiro; Oguchi, Takeshi; Kanayama, Yasuhide; Miyake, Hiroyuki; Kato, Takefumi; Takagi, Hideki; Hayashi, Masatoshi; Ito, Takayasu; Shioura, Tomone; Takahashi, Nobunori; Ishikawa, Hisato; Funahashi, Koji; Ishiguro, Naoki

2018-01-01

This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA). Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis. DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively. Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

Validation of the Pediatric NEXUS II Head CT Decision Instrument for Selective Imaging of Pediatric Patients with Blunt Head Trauma.

PubMed

Gupta, Malkeet; Mower, William R; Rodriguez, Robert M; Hendey, Gregory W

2018-04-17

Data suggests that clinicians, when evaluating pediatric patients with blunt head trauma, may be over-ordering head computed tomography. Prior decision instruments aimed at aiding clinicians in safely forgoing CTs may be paradoxically increasing CT utilization. This study evaluated a novel decision instrument that aims for high sensitivity while also improving specificity over prior instruments. We conducted a planned secondary analysis of the NEXUS Head CT decision instrument (DI) among patients less than 18 years old. The rule required patients satisfy seven criteria to achieve "low-risk" classification. Patients were assigned "high risk" status if they fail to meet one or more criteria. Our primary outcome was the ability of the rule to identify all patients requiring neurosurgical intervention. The study enrolled 1,018 blunt head injury pediatric patients. The DI assigned high-risk status to 27 of 27 patients requiring neurosurgical intervention (sensitivity, 100.0% [95% confidence interval [CI]: 87.2% - 100%]). The instrument assigned low-risk status to 330 of 991 patients who did not require neurosurgical intervention (specificity, 33.3% [95% CI: 30.3% - 36.3%]). None of the 991 low-risk patients required neurosurgical intervention (NPV, 100% [95% CI: 99.6% - 100%]). The DI correctly assigned high-risk status to 48 of the 49 patients with significant intracranial injuries, yielding a sensitivity of 98.0% (95% CI: 89.1% - 99.9%). The instrument assigned low-risk status to 329 of 969 patients who did not have significant injuries to yield a specificity of 34.0% (95% CI: 31.0% - 37.0%). Significant injuries were absent in 329 of the 330 patients assigned low-risk status to yield a NPV of 99.7% (95% CI: 98.3% - 100%). The Pediatric NEXUS Head CT DI reliably identifies blunt trauma patients who require head CT imaging, and could significantly reduce the use of CT imaging This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Global Learning in England: Baseline Analysis of the Global Learning Programme Whole School Audit 2013-14. Research Paper No. 15 for the Global Learning Programme

ERIC Educational Resources Information Center

Hunt, Frances; Cara, Olga

2015-01-01

The Global Learning Programme in England is an initiative aimed at supporting the teaching and learning of global learning in schools in England at Key Stage 2 and Key Stage 3. It is a five-year national programme of support to schools to enhance their provision of global learning. Specifically, the GLP-E works with teachers to enhance their…

Intra-Articular Therapeutic Delivery for Post-Traumatic Osteoarthritis

DTIC Science & Technology

2017-10-01

takes about 10 years to develop. The goals of this work are to test the ability of a novel therapeutic to slow the progression of post -traumatic...frequency of delivery in well- established small and large animal models of post -traumatic OA. These hypotheses will be tested via three Specific Aims...group) to conduct further contrast agent pilot testing on non-healthy joints. Animals were euthanized at 3 weeks post -MMT surgery, and all limbs fixed

Creating a normative database of age-specific 3D geometrical data, bone density, and bone thickness of the developing skull: a pilot study.

PubMed

Delye, Hans; Clijmans, Tim; Mommaerts, Maurice Yves; Sloten, Jos Vnder; Goffin, Jan

2015-12-01

Finite element models (FEMs) of the head are used to study the biomechanics of traumatic brain injury and depend heavily on the use of accurate material properties and head geometry. Any FEM aimed at investigating traumatic head injury in children should therefore use age-specific dimensions of the head, as well as age-specific material properties of the different tissues. In this study, the authors built a database of age-corrected skull geometry, skull thickness, and bone density of the developing skull to aid in the development of an age-specific FEM of a child's head. Such a database, containing age-corrected normative skull geometry data, can also be used for preoperative surgical planning and postoperative long-term follow-up of craniosynostosis surgery results. Computed tomography data were processed for 187 patients (age range 0-20 years old). A 3D surface model was calculated from segmented skull surfaces. Skull models, reference points, and sutures were processed into a MATLAB-supported database. This process included automatic calculation of 2D measurements as well as 3D measurements: length of the coronal suture, length of the lambdoid suture, and the 3D anterior-posterior length, defined as the sum of the metopic and sagittal suture. Skull thickness and skull bone density calculations were included. Cephalic length, cephalic width, intercoronal distance, lateral orbital distance, intertemporal distance, and 3D measurements were obtained, confirming the well-established general growth pattern of the skull. Skull thickness increases rapidly in the first year of life, slowing down during the second year of life, while skull density increases with a fast but steady pace during the first 3 years of life. Both skull thickness and density continue to increase up to adulthood. This is the first report of normative data on 2D and 3D measurements, skull bone thickness, and skull bone density for children aged 0-20 years. This database can help build an age-specific FEM of a child's head. It can also help to tailor preoperative virtual planning in craniosynostosis surgery toward patient-specific normative target values and to perform objective long-term follow-up in craniosynostosis surgery.

Prediction of venous wound healing with laser speckle imaging.

PubMed

van Vuuren, Timme Maj; Van Zandvoort, Carina; Doganci, Suat; Zwiers, Ineke; tenCate-Hoek, Arina J; Kurstjens, Ralph Lm; Wittens, Cees Ha

2017-12-01

Introduction Laser speckle imaging is used for noninvasive assessment of blood flow of cutaneous wounds. The aim of this study was to assess if laser speckle imaging can be used as a predictor of venous ulcer healing. Methods After generating the flux speckle images, three regions of interest (ROI) were identified to measure the flow. Sensitivity, specificity, negative predictive value, and positive predictive value for ulcer healing were calculated. Results In total, 17 limbs were included. A sensitivity of 92.3%, specificity of 75.0%, PPV of 80.0%, and NPV 75.0% were found in predicting wound healing based on laser speckle images. Mean flux values were lowest in the center (ROI I) and showed an increase at the wound edge (ROI II, p = 0.03). Conclusion Laser speckle imaging shows acceptable sensitivity and specificity rates in predicting venous ulcer healing. The wound edge proved to be the best probability for the prediction of wound healing.

Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction

PubMed Central

Kim, Dong Hun; Kim, Hyun-Wook; Choi, Seo-Won; Kim, Bo-Bae; Chung, Joong-Wha; Koh, Young-Youp; Chang, Kyong-Sig; Hong, Soon-Pyo

2014-01-01

Background/Aims The aim of the present study was to evaluate the relationship between thyroid hormone levels and infarct severity in patients with ST-elevation myocardial infarction (STEMI). Methods We retrospectively reviewed thyroid hormone levels, infarct severity, and the extent of transmurality in 40 STEMI patients evaluated via contrast-enhanced cardiac magnetic resonance imaging. Results The high triiodothyronine (T3) group (≥ 68.3 ng/dL) exhibited a significantly higher extent of transmural involvement (late transmural enhancement > 75% after administration of gadolinium contrast agent) than did the low T3 group (60% vs. 15%; p = 0.003). However, no significant difference was evident between the high- and low-thyroid-stimulating hormone/free thyroxine (FT4) groups. When the T3 cutoff level was set to 68.3 ng/dL using a receiver operating characteristic curve, the sensitivity was 80% and the specificity 68% in terms of differentiating between those with and without transmural involvement. Upon logistic regression analysis, high T3 level was an independent predictor of transmural involvement after adjustment for the presence of diabetes mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62; 95% confidence interval, 3.29 to 502; p = 0.004). Conclusions The T3 level predicted transmural involvement that was independent of glycoprotein IIb/IIIa inhibitor use and DM positivity. PMID:25045293

An Automated Micro-Total Immunoassay System for Measuring Cancer-Associated α2,3-linked Sialyl N-Glycan-Carrying Prostate-Specific Antigen May Improve the Accuracy of Prostate Cancer Diagnosis

PubMed Central

Ishikawa, Tomokazu; Yoneyama, Tohru; Tobisawa, Yuki; Hatakeyama, Shingo; Kurosawa, Tatsuo; Nakamura, Kenji; Narita, Shintaro; Mitsuzuka, Koji; Duivenvoorden, Wilhelmina; Pinthus, Jehonathan H.; Hashimoto, Yasuhiro; Koie, Takuya; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara

2017-01-01

The low specificity of the prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is a major issue worldwide. The aim of this study to examine whether the serum PCa-associated α2,3-linked sialyl N-glycan-carrying PSA (S2,3PSA) ratio measured by automated micro-total immunoassay systems (μTAS system) can be applied as a diagnostic marker of PCa. The μTAS system can utilize affinity-based separation involving noncovalent interaction between the immunocomplex of S2,3PSA and Maackia amurensis lectin to simultaneously determine concentrations of free PSA and S2,3PSA. To validate quantitative performance, both recombinant S2,3PSA and benign-associated α2,6-linked sialyl N-glycan-carrying PSA (S2,6PSA) purified from culture supernatant of PSA cDNA transiently-transfected Chinese hamster ovary (CHO)-K1 cells were used as standard protein. Between 2007 and 2016, fifty patients with biopsy-proven PCa were pair-matched for age and PSA levels, with the same number of benign prostatic hyperplasia (BPH) patients used to validate the diagnostic performance of serum S2,3PSA ratio. A recombinant S2,3PSA- and S2,6PSA-spiked sample was clearly discriminated by μTAS system. Limit of detection of S2,3PSA was 0.05 ng/mL and coefficient variation was less than 3.1%. The area under the curve (AUC) for detection of PCa for the S2,3PSA ratio (%S2,3PSA) with cutoff value 43.85% (AUC; 0.8340) was much superior to total PSA (AUC; 0.5062) using validation sample set. Although the present results are preliminary, the newly developed μTAS platform for measuring %S2,3PSA can achieve the required assay performance specifications for use in the practical and clinical setting and may improve the accuracy of PCa diagnosis. Additional validation studies are warranted. PMID:28241428

Early functional outcome after lateral UKA is sensitive to postoperative lower limb alignment.

PubMed

van der List, J P; Chawla, H; Villa, J C; Zuiderbaan, H A; Pearle, A D

2017-03-01

The predictive role of patient-specific characteristics and radiographic parameters on medial unicompartmental knee arthroplasty (UKA) outcomes is well known, but knowledge of these predictors is lacking in lateral UKA. Therefore, purpose of this study was to assess the predictive role of these parameters on short-term functional outcomes of lateral UKA. In this retrospective cohort study, Western Ontario and McMaster Universities Arthritis Index scores were collected at 2-year follow-up (median 2.2 years, range 2.0-4.0 years) in 39 patients who underwent lateral UKA. Patient-specific characteristics included age, BMI and gender, while radiographic parameters included osteoarthritis severity of all three compartments and both preoperative and postoperative hip-knee-ankle alignment. BMI, gender, age and preoperative valgus alignment were not correlated with functional outcomes, while postoperative valgus alignment was correlated with functional outcomes (0.561; p = 0.001). Postoperative valgus of 3°-7° was correlated with better outcomes than more neutral (-2° to 3° valgus) alignment (96.7 vs. 85.6; p = 0.011). Postoperative alignment was a predictor when corrected for patient-specific characteristics (regression coefficient 4.1; p < 0.001) and radiological parameters (regression coefficient 3.8; p = 0.002). Postoperative valgus alignment of 3°-7° was correlated with the best short-term functional outcomes in lateral UKA surgery, while patient-specific parameters and preoperative alignment were not correlated with functional outcomes. Based on these findings, a surgeon should aim for valgus alignment of 3°-7° when performing lateral UKA surgery for optimal functional outcomes. Prognostic study, Level II.

Simulated procedure rehearsal is more effective than a preoperative generic warm-up for endovascular procedures.

PubMed

Willaert, Willem I M; Aggarwal, Rajesh; Daruwalla, Farhad; Van Herzeele, Isabelle; Darzi, Ara W; Vermassen, Frank E; Cheshire, Nicholas J

2012-06-01

Patient-specific simulated rehearsal (PsR) of a carotid artery stenting procedure (CAS) enables the interventionalist to rehearse the case before performing the procedure on the actual patient by incorporating patient-specific computed tomographic data into the simulation software. This study aimed to evaluate whether PsR of a CAS procedure can enhance the operative performance versus a virtual reality (VR) generic CAS warm-up procedure or no preparation at all. During a 10-session cognitive/technical VR course, medical residents were trained in CAS. Thereafter, in a randomized crossover study, each participant performed a patient-specific CAS case 3 times on the simulator, preceded by 3 different tasks: a PsR, a generic case, or no preparation. Technical performances were assessed using simulator-based metrics and expert-based ratings. Twenty medical residents (surgery, cardiology, radiology) were recruited. Training plateaus were observed after 10 sessions for all participants. Performances were significantly better after PsR than after a generic warm-up or no warm-up for total procedure time (16.3 ± 0.6 vs 19.7 ± 1.0 vs 20.9 ± 1.1 minutes, P = 0.001) and fluoroscopy time (9.3 ± 0.1 vs 11.2 ± 0.6 vs 11.2 ± 0.5 minutes, P = 0.022) but did not influence contrast volume or number of roadmaps used during the "real" case. PsR significantly improved the quality of performance as measured by the expert-based ratings (scores 28 vs 25 vs 25, P = 0.020). Patient-specific simulated rehearsal of a CAS procedure significantly improves operative performance, compared to a generic VR warm-up or no warm-up. This technology requires further investigation with respect to improved outcomes on patients in the clinical setting.

Construction of New Campylobacter Cloning Vectors and a New Mutational Cat Cassette

DTIC Science & Technology

1993-01-01

mutational cat cassette PE - 61102A PR - 3M161102 6. AUTHOR(S) TA - BS13AK Yao R, Aim RA, Trust TJ, Guerry P WU- 1291 7. PERFORMING ORGANIZATION NAME(S) AND...mutational cat cassette %~ccesion For (Site-specific mutagenesis; recombinant DNA; multiple cloning site; PCR; shuttle vectors) NTIS CRA&I OTIC TAB E...campylobacter portion of these vectors, only three CAT , Cm acetyllraaseriase; car, gene encoding CAT , Cm, restriction sites in the IacZ MCS remain unique

The Role of Adenosine A2BR in Metastatic Melanoma

DTIC Science & Technology

2017-07-01

100% complete. ACURO approval to perform animal studies was obtained July 2016. Specific Aim 1, Subtask 2: 100% complete. Use CRISPR /Cas9 technology...immune cell interactions, the first objective was to use the CRISPR Cas9 system to knock out A2BR expression in melanoma cell lines. Melanoma cell lines...and sgRNA3 to work but sgRNA2 would not be as efficient. We considered commercially available constructs to potentially improve the CRISPR knock

The Asian American Network for Cancer Awareness, Research, and Training’s Role in Cancer Awareness, Research, and Training

PubMed Central

Chen, Moon S.

2006-01-01

Purpose The purpose of this paper is to describe the content for the Asian American Network for Cancer Awareness Research and Training (AANCART) with respect to Asian American demographic characteristics and their cancer burden, highlights of accomplishments in various AANCART regions, aspirations for AANCART, and an interim assessment of AANCART’s activities to date. Methods The author compiled literature and other data references to describe the context for Asian American demographic characteristics and their cancer burden. As the AANCART Principal Investigator, he collected data from internal AANCART reports to depict highlights of accomplishments in various AANCART regions and offer evidence that AANCART’s first two specific aims have been attained. Principal Findings With respect to our first specific aim, we have built an infrastructure for cancer awareness, research and training operationally at a Network-wide basis through program directors for biostatistics, community, clinical, and research and in our four original AANCART regions: New York, Seattle, San Francisco, and Los Angeles. With respect to our second specific aim, we have established partnerships as exemplified by working collaboratively with New York’s Charles B. Wang Community Health Center in securing external funding with them for a tobacco control initiative and nationally with the American Cancer Society. With respect to our third specific aim, we have been fortunate to assist at least eight junior investigators in receiving NCI-funded pilot studies. The most notable change was the transfer of AANCART’s national headquarters from Columbus, Ohio to Sacramento, California along with potentially an increased diversification of Asian American ethnic groups as well as an expansion to Hawaii and Houston. Conclusion As of the end of year 2 of AANCART, AANCART’s two specific aims have been achieved. We are focusing on our third specific aim. PMID:15352772

Deciphering the Sensitivity and Specificity of the Implantable Doppler Probe in Free Flap Monitoring.

PubMed

Chang, Edward I; Ibrahim, Amir; Zhang, Hong; Liu, Jun; Nguyen, Alexander T; Reece, Gregory P; Yu, Peirong

2016-03-01

The efficacy of implantable Doppler probes remains an area of considerable debate. This study aims to decipher its sensitivity and specificity for free flap monitoring. A retrospective review of all free flaps with an implantable Doppler probe was performed between 2000 and 2012. A Cook-Swartz implantable Doppler probe was used in 439 patients (head and neck, n = 364; breast, n = 53; extremity, n = 22), and demonstrated equivalent sensitivity and specificity between flap types. The overall sensitivity and specificity were 77.8 percent and 88.4 percent, respectively. The artery was monitored in 267 patients, compared to venous monitoring in 101 patients, and in 71 patients both the artery and vein were monitored. Arterial monitoring had significantly greater specificity than venous monitoring, (94.2 percent versus 74.0 percent; p < 0.001), but no benefit was found in monitoring both the artery and the vein. Venous monitoring was significantly associated with reoperation (OR, 3.17; 95 percent CI, 1.70 to 5.91; p = 0.0003). There were 284 flaps that had a monitoring segment in addition to the implantable Doppler probe that significantly increased overall specificity for microvascular complications (OR, 17.71; 95 percent CI, 3.39 to 92.23; p = 0.0006). The specificity (90.5 percent versus 84.8 percent) and sensitivity (80.0 percent versus 66.7 percent) were significantly higher for clinically monitored flaps. The take-back rate was 13.0 percent, with positive findings in 59.6 percent, and 5.2 percent total flap loss. The use of implantable Doppler probes has high sensitivity and specificity for buried free flaps despite positive findings in less than 60 percent of take-backs. Monitoring the artery is recommended, but clinical examination remains the gold standard for flap monitoring. Diagnostic, IV.

Diagnostic value of sputum adenosine deaminase (ADA) level in pulmonary tuberculosis.

PubMed

Binesh, Fariba; Jalali, Hadi; Zare, Mohammad Reza; Behravan, Farhad; Tafti, Arefeh Dehghani; Behnaz, Fatemah; Tabatabaee, Mohammad; Shahcheraghi, Seyed Hossein

2016-06-01

Tuberculosis is still a considerable health problem in many countries. Rapid diagnosis of this disease is important, and adenosine deaminase (ADA) has been used as a diagnostic test. The aim of this study was to assess the diagnostic value of ADA in the sputum of patients with pulmonary tuberculosis. The current study included 40 patients with pulmonary tuberculosis (culture positive, smear ±) and 42 patients with non tuberculosis pulmonary diseases (culture negative). ADA was measured on all of the samples. The median value of ADA in non-tuberculosis patients was 2.94 (4.2) U/L and 4.01 (6.54) U/L in tuberculosis patients, but this difference was not statistically significant (p=0.100). The cut-off point of 3.1 U/L had a sensitivity of 61% and a specificity of 53%, the cut-off point of 2.81 U/L had a sensitivity of 64% and a specificity of 50% and the cut-off point of 2.78 U/L had a sensitivity of 65% and a specificity of 48%. The positive predictive values for cut-off points of 3.1, 2.81 and 2.78 U/L were 55.7%, 57.44% and 69.23%, respectively. The negative predictive values for the abovementioned cut-off points were 56.75%, 57.14% and 55.88%, respectively. Our results showed that sputum ADA test is neither specific nor sensitive. Because of its low sensitivity and specificity, determination of sputum ADA for the diagnosis of pulmonary tuberculosis is not recommended.

Patient-specific three-dimensional printing for pre-surgical planning in hepatocellular carcinoma treatment.

PubMed

Perica, Elizabeth; Sun, Zhonghua

2017-12-01

Recently, three-dimensional (3D) printing has shown great interest in medicine, and 3D printed models may be rendered as part of the pre-surgical planning process in order to better understand the complexities of an individual's anatomy. The aim of this study is to investigate the feasibility of utilising 3D printed liver models as clinical tools in pre-operative planning for resectable hepatocellular carcinoma (HCC) lesions. High-resolution contrast-enhanced computed tomography (CT) images were acquired and utilized to generate a patient-specific 3D printed liver model. Hepatic structures were segmented and edited to produce a printable model delineating intrahepatic anatomy and a resectable HCC lesion. Quantitative assessment of 3D model accuracy compared measurements of critical anatomical landmarks acquired from the original CT images, standard tessellation language (STL) files, and the 3D printed liver model. Comparative analysis of surveys completed by two radiologists investigated the clinical value of 3D printed liver models in radiology. The application of utilizing 3D printed liver models as tools in surgical planning for resectable HCC lesions was evaluated through kappa analysis of questionnaires completed by two abdominal surgeons. A scaled down multi-material 3D liver model delineating patient-specific hepatic anatomy and pathology was produced, requiring a total production time of 25.25 hours and costing a total of AUD $1,250. A discrepancy was found in the total mean of measurements at each stage of production, with a total mean of 18.28±9.31 mm for measurements acquired from the original CT data, 15.63±8.06 mm for the STL files, and 14.47±7.71 mm for the 3D printed liver model. The 3D liver model did not enhance the radiologists' perception of patient-specific anatomy or pathology. Kappa analysis of the surgeon's responses to survey questions yielded a percentage agreement of 80%, and a κ value of 0.38 (P=0.24) indicating fair agreement. Study outcomes indicate that there is minimal value in utilizing the 3D printed models in diagnostic radiology. The potential usefulness of utilizing patient-specific 3D printed liver models as tools in surgical planning and intraoperative guidance for HCC treatment is verified. However, the feasibility of this application is currently challenged by identified limitations in 3D model production, including the cost and time required for model production, and inaccuracies potentially introduced at each stage of model fabrication.

Exploring Vocational Evaluation Practices following Traumatic Brain Injury.

PubMed

Dillahunt-Aspillaga, Christina; Jorgensen Smith, Tammy; Hanson, Ardis; Ehlke, Sarah; Stergiou-Kita, Mary; Dixon, Charlotte G; Quichocho, Davina

2015-01-01

Individuals with traumatic brain injury (TBI) face many challenges when attempting to return to work (RTW). Vocational evaluation (VE) is a systematic process that involves assessment and appraisal of an individual's current work-related characteristics and abilities. The aims of this study are to (1) examine demographic and employment characteristics of vocational rehabilitation providers (VRPs), (2) identify the specific evaluation methods that are used in the VE of individuals with TBI, and (3) examine the differences in assessment method practices based upon evaluator assessment preferences. This exploratory case study used a forty-six-item online survey which was distributed to VRPs. One hundred and nine VRPs accessed the survey. Of these, 74 completed the survey. A majority of respondents were female (79.7%), Caucasian (71.6%), and holding a master's degree (74.3%), and more than half (56.8%) were employed as state vocational rehabilitation counselors (VRCs). In addition, over two-thirds (67.6%) were certified rehabilitation counselors (CRCs). Respondents reported using several specific tools and assessments during the VE process. Study findings reveal differences in use of and rationales for specific assessments amongst VRPs. Understanding VRP assessment practices and use of an evidence-based framework for VE following TBI may inform and improve VE practice.

Designing a leadership development program for surgeons.

PubMed

Jaffe, Gregory A; Pradarelli, Jason C; Lemak, Christy Harris; Mulholland, Michael W; Dimick, Justin B

2016-01-01

Although numerous leadership development programs (LDPs) exist in health care, no programs have been specifically designed to meet the needs of surgeons. This study aimed to elicit practicing surgeons' motivations and desired goals for leadership training to design an evidence-based LDP in surgery. At a large academic health center, we conducted semistructured interviews with 24 surgical faculty members who voluntarily applied and were selected for participation in a newly created LDP. Transcriptions of the interviews were analyzed using analyst triangulation and thematic coding to extract major themes regarding surgeons' motivations and perceived needs for leadership knowledge and skills. Themes from interview responses were then used to design the program curriculum specifically to meet the leadership needs of surgical faculty. Three major themes emerged regarding surgeons' motivations for seeking leadership training: (1) Recognizing key gaps in their formal preparation for leadership roles; (2) Exhibiting an appetite for personal self-improvement; and (3) Seeking leadership guidance for career advancement. Participants' interviews revealed four specific domains of knowledge and skills that they indicated as desired takeaways from a LDP: (1) leadership and communication; (2) team building; (3) business acumen/finance; and (4) greater understanding of the health care context. Interviews with surgical faculty members identified gaps in prior leadership training and demonstrated concrete motivations and specific goals for participating in a formal leadership program. A LDP that is specifically tailored to address the needs of surgical faculty may benefit surgeons at a personal and institutional level. Copyright © 2016 Elsevier Inc. All rights reserved.

Downregulation of an Aim-1 Kinase Couples with Megakaryocytic Polyploidization of Human Hematopoietic Cells

PubMed Central

Kawasaki, Akira; Matsumura, Itaru; Miyagawa, Jun-ichiro; Ezoe, Sachiko; Tanaka, Hirokazu; Terada, Yasuhiko; Tatsuka, Masaaki; Machii, Takashi; Miyazaki, Hiroshi; Furukawa, Yusuke; Kanakura, Yuzuru

2001-01-01

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3–dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-rasG12V), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes. PMID:11266445

Structural and spectroscopic study of the europium complex with N-(diphenylphosphoryl)pyrazine-2-carboxamide

NASA Astrophysics Data System (ADS)

Pham, Y. H.; Trush, V. A.; Amirkhanov, V. M.; Gawryszewska, P.

2017-12-01

This work presents a study of the Eu3+ complex with N-(diphenylphosphoryl)pyrazine-2-carboxamide (HL) and diphenylphosphinate ions (Ph2POO-) as co-ligands with the aim of probing the specific energetic and structural characteristics that influence the ligand-to-metal energy transfer and luminescence efficiency. The compound [Eu2(L)2(μ-Ph2POO)2(κ-OP(O)Ph2)2(CH3OH)2] crystallizes as a dimer with the space group P 1 bar . Absorption and emission (295, 77 K) spectra as well as luminescence decay times were used to characterize the photophysical properties of the complex in the solid state. Very effective energy transfer from ligands to Eu3+ ion was demonstrated.

3D printing process of oxidized nanocellulose and gelatin scaffold.

PubMed

Xu, Xiaodong; Zhou, Jiping; Jiang, Yani; Zhang, Qi; Shi, Hongcan; Liu, Dongfang

2018-08-01

For tissue engineering applications tissue scaffolds need to have a porous structure to meet the needs of cell proliferation/differentiation, vascularisation and sufficient mechanical strength for the specific tissue. Here we report the results of a study of the 3D printing process for composite materials based on oxidized nanocellulose and gelatin, that was optimised through measuring rheological properties of different batches of materials after different crosslinking times, simulation of the pneumatic extrusion process and 3D scaffolds fabrication with Solidworks Flow Simulation, observation of its porous structure by SEM, measurement of pressure-pull performance, and experiments aimed at finding out the vitro cytotoxicity and cell morphology. The materials printed are highly porous scaffolds with good mechanical properties.

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.

PubMed

Wu, Dacheng; Wu, Keyan; Zhu, Qingtian; Xiao, Weiming; Shan, Qing; Yan, Zhigang; Wu, Jian; Deng, Bin; Xue, Yan; Gong, Weijuan; Lu, Guotao; Ding, Yanbing

2018-01-01

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF- α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1 β ) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

Bioprocess development workflow: Transferable physiological knowledge instead of technological correlations.

PubMed

Reichelt, Wieland N; Haas, Florian; Sagmeister, Patrick; Herwig, Christoph

2017-01-01

Microbial bioprocesses need to be designed to be transferable from lab scale to production scale as well as between setups. Although substantial effort is invested to control technological parameters, usually the only true constant parameter is the actual producer of the product: the cell. Hence, instead of solely controlling technological process parameters, the focus should be increasingly laid on physiological parameters. This contribution aims at illustrating a workflow of data life cycle management with special focus on physiology. Information processing condenses the data into physiological variables, while information mining condenses the variables further into physiological descriptors. This basis facilitates data analysis for a physiological explanation for observed phenomena in productivity. Targeting transferability, we demonstrate this workflow using an industrially relevant Escherichia coli process for recombinant protein production and substantiate the following three points: (1) The postinduction phase is independent in terms of productivity and physiology from the preinduction variables specific growth rate and biomass at induction. (2) The specific substrate uptake rate during induction phase was found to significantly impact the maximum specific product titer. (3) The time point of maximum specific titer can be predicted by an easy accessible physiological variable: while the maximum specific titers were reached at different time points (19.8 ± 7.6 h), those maxima were reached all within a very narrow window of cumulatively consumed substrate dSn (3.1 ± 0.3 g/g). Concluding, this contribution provides a workflow on how to gain a physiological view on the process and illustrates potential benefits. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:261-270, 2017. © 2016 American Institute of Chemical Engineers.

Crew awareness as key to optimizing habitability standards onboard naval platforms: A 'back-to-basics' approach.

PubMed

Neelakantan, Anand; Ilankumaran, Mookkiah; Ray, Sougat

2017-10-01

A healthy habitable environment onboard warships is vital to operational fleet efficiency and fit sea-warrier force. Unique man-machine-armament interface issues and consequent constraints on habitability necessitate a multi-disciplinary approach toward optimizing habitability standards. Study of the basic 'human factor', including crew awareness on what determines shipboard habitability, and its association with habitation specifications is an essential step in such an approach. The aim of this study was to assess crew awareness on shipboard habitability and the association between awareness and maintenance of optimal habitability as per specifications. A cross-sectional descriptive study was carried out among 552 naval personnel onboard warships in Mumbai. Data on crew awareness on habitability was collected using a standardized questionnaire, and correlated with basic habitability requirement specifications. Data was analyzed using Microsoft Excel, Epi-info, and SPSS version 17. Awareness level on basic habitability aspects was very good in 65.3% of crew. Area-specific awareness was maximum with respect to living area (95.3%). Knowledge levels on waste management were among the lowest (65.2%) in the category of aspect-wise awareness. Statistically significant association was found between awareness levels and habitability standards (OR = 7.27). The new benchmarks set in the form of high crew awareness levels on basic shipboard habitability specifications and its significant association with standards needs to be sustained. It entails re-iteration of healthy habitation essentials into training; and holds the key to a fit fighting force.

Serum IGF-1, IGFBP-3 and their ratio: Potential biochemical growth maturity indicators.

PubMed

Jain, Nimisha; Tripathi, Tulika; Gupta, S K; Rai, Priyank; Kanase, Anup; Kalra, Shilpa

2017-12-01

Determination of skeletal maturation and remaining growth potential is an essential part of treatment planning in orthodontics. The aim of our study was to determine the relationship between IGF-1 levels, IGFBP-3 levels with CVM staging to track the pre pubertal and pubertal growth spurts in female patients in North Indian population. This cross-sectional study was conducted on ninety female subjects in the age group of 8-20 years. Blood samples were collected and centrifuged and serum samples were then analysed by Human IGF-1 and IGFBP-3 enzyme-linked immunosorbent assay kits, specific for IGF-1 and IGFBP-3, respectively. CVM staging on lateral cephalometric radiograph was determined for all patients. Analysis of variance test followed by a post hoc test was used to compare mean IGF-1 and IGFBP-3 corresponding to six stages of cervical vertebrae maturation stages. Linear Pearson's correlations were performed to determine the trends of IGF-1, IGFBP-3, and its ratio relating to CVM stage. The kappa statistic was used to measure inter and intra examiner reliability. P value <0.05 was considered as statistically significant. Mean serum IGF-1 levels were found to be highest (403.3 ± 12.3 ng/ml) at CVMI3 stage of CVMI. The post-hoc test revealed a significant difference in IGF-1 levels between all stages of CVMI, thereby indicating a specific range of IGF-1 levels for a specific skeletal stage. Mean serum IGFBP-3 levels were found to be highest (5186.8 ± 1384.2 ng/ml) at CVMI4 stage of CVMI. The mean serum IGFBP-3 levels at CVMI4 were found to be significantly higher than the levels at all other CVMI stages except CVMI3 stage. IGF-1 and IGFBP-3 can serve as a potential biochemical indicator for assessment of skeletal maturity.

Janus-faced Acrolein prevents allergy but accelerates tumor growth by promoting immunoregulatory Foxp3+ cells: Mouse model for passive respiratory exposure.

PubMed

Roth-Walter, Franziska; Bergmayr, Cornelia; Meitz, Sarah; Buchleitner, Stefan; Stremnitzer, Caroline; Fazekas, Judit; Moskovskich, Anna; Müller, Mario A; Roth, Georg A; Manzano-Szalai, Krisztina; Dvorak, Zdenek; Neunkirchner, Alina; Jensen-Jarolim, Erika

2017-03-23

Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen. Moreover, grafted D2F2 tumor cells grew faster and intratumoral Foxp3+ cell accumulation was observed in these mice compared to sham-treated controls. Results from reporter cell lines suggested that acrolein acts via the aryl-hydrocarbon receptor which could be inhibited by resveratrol and 3'-methoxy-4'-nitroflavone Acrolein- stimulation of human PBMCs increased Foxp3+ expression by T cells which could be antagonized by resveratrol. Our mouse and human data thus revealed that acrolein exerts systemic immunosuppression by promoting Foxp3+ regulatory cells. This provides a novel explanation why smokers have a lower allergy, but higher cancer risk.

The value of routine blood pressure measurement in children presenting to the emergency department with nonurgent problems.

PubMed

Stewart, Jessica N; McGillivray, David; Sussman, John; Foster, Bethany

2008-10-01

Blood pressure (BP) is measured at triage in most emergency departments (EDs). We aimed to determine the value of triage BP in diagnosing hypotension and true hypertension in children age > or =3 years presenting with nonurgent problems. In this prospective study, eligible children underwent automated BP measurement at triage. If BP was elevated, then the measurement was repeated manually. Children with a high manual BP were followed. True hypertension was defined as a manual BP >95th percentile for sex, age, and height measured on 3 occasions. Automated triage BP was measured in 549 children (53.4% male; mean age, 9.4 +/- 4.3 years) and was found to be elevated in 144 of them (26%). No child was hypotensive. Among the 495 patients with complete follow-up, the specificity and positive predictive value (PPV) of elevated triage BP in diagnosing true hypertension were 81.8% and 0%, respectively. A sensitivity analysis including those with incomplete follow-up, in which the population prevalence of true hypertension was assumed to be 1% to 2%, resulted in a specificity of 74.5% to 75.3% and a PPV of 3.8% to 7.5%. The yield of measuring BP at triage in children with nonurgent problems appears to be extremely low.

Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas.

PubMed

Mohanty, Sambit K; Smith, Steven C; Chang, Elena; Luthringer, Daniel J; Gown, Allen M; Aron, Manju; Amin, Mahul B

2014-08-01

New immunohistochemical (IHC) markers of urothelial carcinoma (UCa) and prostatic adenocarcinoma (PCa) have emerged in recent years, yet comparative studies to establish markers remain lacking. We aimed to identify an effective but parsimonious approach for poorly differentiated bladder neck lesions, to establish a best practice panel approach in a setting simulating prospective use. We tested the performance of a panel of IHC markers on whole sections of a consecutive cohort of transurethral resection specimens of poorly differentiated, challenging bladder neck resections (n=36). In the setting of poorly differentiated bladder neck carcinomas, biomarker sensitivities for UCa were as follows: GATA3, 100%; S100P, 88%; p63, 75%; and cytokeratin (CK) 5/6, 56%; specificities of each were 100%. CK7 and CK20 showed sensitivities of 75% and 63%, though these were only 85% and 80% specific. For PCa markers, NKX3.1, p501S, prostate-specific membrane antigen, and androgen receptor (AR) each showed 100% sensitivity, outperforming ERG (35%) and prostate-specific antigen (PSA; 25%). All the prostate histogenesis markers were 100% specific, except for AR, which was positive in 13% of the UCa cases. Novel IHC markers show improved diagnostic performance that enables positive and negative support for identifying histogenesis with the use of as few as two markers for this critical therapeutic distinction. PSA underperforms newer markers. Copyright© by the American Society for Clinical Pathology.

Monosodium Luminol for Improving Brain Function in Gulf War Illness

DTIC Science & Technology

2016-10-01

Specific Aim 2 studies are focused on examining whether long - term administration of an apt dose of MSL-GVT would alleviate mood and memory dysfunction...and inflammation. 15. SUBJECT TERMS DEET, Gulf war illness, hippocampal neurogenesis, Memory dysfunction, Mood dysfunction, neuroinflammation...doses of MSL-GVT, in comparison to age-matched naive control rats. Thus, short - term (3 weeks of) MSL-GVT treatment is not efficacious for enhancing

Successful Strategies for Activity and Wellness after Spinal Cord Injury

DTIC Science & Technology

2016-10-01

Concurrent qualitative and quantitative methods (mixed methods approach) will be used to address Specific Aims 3 and 4. The types of assessment and...Beatrice Kiratli PhD RECIPIENT: Palo Alto Veterens Institute for Research Palo Alto, CA 94304 REPORT DATE: October 2016 TYPE OF REPORT...37/40) with 25% of transcript analysis accomplished. Staff training in qualitative research and use of mind mapping software has been completed with

Beta-1,3-1,6-glucan modulate the non-specific immune response to enhance the survival in the Vibrio alginolyticus infection of Taiwan abalone (Haliotis diversicolor supertexta).

PubMed

Wu, Yu-Sheng; Tseng, Tzu-Yu; Nan, Fan-Hua

2016-07-01

This research aims to investigate the non-specific immune response of Taiwan abalone (Haliotis diversicolor supertexta) which was treated with the beta-1,3-1,6-glucan to be observed in the survival impact after the Vibrio alginolyticus infection. The non-specific immune and physiological response of superoxide anion radical (O2(-)), phenoloxidase (PO), phagocytic index (PI), phagocytic rate (PR) and lucigenin-chemiluminescence for reactive oxygen intermediates (ROIs) were enhanced via in-vitro experiment. In the in-vivo experiment, the observed data presented that the haemolymph lysate supernatant (HLS), superoxide dismutase (SOD), glutamate oxalacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) were not significant enhanced, but the total haemocyte count (THC), O2(-), PO, phagocytic index (PI), phagocytic ratio (PR) and other parameters of immune were significantly promoted after treated with beta-1,3-1,6-glucan. In the challenge experiment, the survival rates of abalone in the 40 and 80 μl/ml groups of beta-1,3-1,6-glucan were observed from 6.67% up to 33.33% and 36.67% after injection with Vibrio alginolyticus, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.

PubMed

Potgieter, Danielle; Simmers, Dale; Ryan, Lisa; Biccard, Bruce M; Lurati-Buse, Giovanna A; Cardinale, Daniela M; Chong, Carol P W; Cnotliwy, Miloslaw; Farzi, Sylvia I; Jankovic, Radmilo J; Lim, Wen Kwang; Mahla, Elisabeth; Manikandan, Ramaswamy; Oscarsson, Anna; Phy, Michael P; Rajagopalan, Sriram; Van Gaal, William J; Waliszek, Marek; Rodseth, Reitze N

2015-08-01

N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Modified Daily Undulating Periodization Model Produces Greater Performance Than a Traditional Configuration in Powerlifters.

PubMed

Zourdos, Michael C; Jo, Edward; Khamoui, Andy V; Lee, Sang-Rok; Park, Bong-Sup; Ormsbee, Michael J; Panton, Lynn B; Contreras, Robert J; Kim, Jeong-Su

2016-03-01

The primary aim of this study was to compare 2 daily undulating periodization (DUP) models on one-repetition maximum (1RM) strength in the squat, bench press, deadlift, total volume (TV) lifted, and temporal hormone response. Eighteen male, college-aged (21.1 ± 1.9 years) powerlifters participated in this study and were assigned to one of 2 groups: (a) traditional DUP training with a weekly training order: hypertrophy-specific, strength-specific, and power-specific training (HSP, n = 9) or (b) modified DUP training with a weekly training order: hypertrophy-specific, power-specific, and strength-specific training (HPS, n = 9). Both groups trained 3 nonconsecutive days per week for 6 weeks and performed the squat, bench press, and deadlift exercises. During hypertrophy and power sessions, subjects performed a fixed number of sets and repetitions but performed repetitions until failure at a given percentage during strength sessions to compare TV. Testosterone and cortisol were measured at pretesting and posttesting and before each strength-specific day. Hypertrophy, power, and strength produced greater TV in squat and bench press (p ≤ 0.05) than HSP, but not for deadlift (p > 0.05). For squat and deadlift, there was no difference between groups for 1RM (p > 0.05); however, HPS exhibited greater increases in 1RM bench press than HSP (p ≤ 0.05). Effect sizes (ES) showed meaningful differences (ES > 0.50) in favor of HPS for squat and bench press 1RM. Testosterone decreased (p ≤ 0.05) at weeks 5 and 6 and cortisol decline at weeks 3 and 4. However, neither hormone was different at posttesting compared with pretesting (p > 0.05). Our findings suggest that an HPS configuration of DUP has enhanced performance benefits compared with HSP.

The characterization of Bordetella pertussis strains isolated in the Central-Western region of Brazil suggests the selection of a specific genetic profile during 2012-2014 outbreaks.

PubMed

Rocha, E L; Leite, D; Camargo, C H; Martins, L M; Silva, R S N; Martins, V P; Campos, T A

2017-05-01

Pertussis is a worldwide acute respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, the bacterium continues to circulate in populations and is still one of the most common vaccine-preventable diseases. In Brazil, pertussis incidence has presented a significant decrease since 1990 but since 2011 a sudden increase in incidence has been observed. Thus, the aim of this study was to perform a molecular epidemiological characterization of B. pertussis strains isolated in the Central-Western region (specifically in Distrito Federal) of Brazil from August 2012 to August 2014. During this period, 92 B. pertussis strains were isolated from the outbreaks. All strains were characterized by serotyping and XbaI pulsed-field gel electrophoresis profiles. From August to December 2012, the most prevalent serotype observed was 1,3 (13/17). During 2013 the prevalence of serotype 1,3 decreased (13/30) and from January 2014 to August 2014 the most prevalent serotype was 1,2 (33/45). Fourteen PFGE profiles were identified. Of these, BP-XbaI0039 prevalence increased from 3/17 in 2012 to 10/30 in 2013, and 35/45 in 2014. These results evidence the selection of a specific genetic profile during this period, suggesting the occurrence of a bacterial genomic profile with high circulation potential.

Status of internal quality control for thyroid hormones immunoassays from 2011 to 2016 in China.

PubMed

Zhang, Shishi; Wang, Wei; Zhao, Haijian; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

2018-01-01

Internal quality control (IQC) plays a key role in the evaluation of precision performance in clinical laboratories. This report aims to present precision status of thyroid hormones immunoassays from 2011 to 2016 in China. Through Clinet-EQA reporting system, IQC information of Triiodothyronine and Thyroxine in the form of free and total (FT3, TT3, FT4, TT4), as well as Thyroid Stimulating Hormone (TSH) were collected from participant laboratories submitting IQC data in February, 2011-2016. For each analyte, current CVs were compared among different years and measurement systems. Percentages of laboratories meeting five allowable imprecision specifications (pass rates) were also calculated. Analysis of IQC practice was conducted to constitute a complete report. Current CVs were decreasing significantly but pass rates increasing only for FT3 during 6 years. FT3, TT3, FT4, and TT4 had the highest pass rates comparing with 1/3TEa imprecision specification but TSH had this comparing with minimum imprecision specification derived from biological variation. Constituent ratios of four mainstream measurement systems changed insignificantly. In 2016, precision performance of Abbott and Roche systems were better than Beckman and Siemens systems for all analytes except FT3 had Siemens also better than Beckman. Analysis of IQC practice demonstrated wide variation and great progress in aspects of IQC rules and control frequency. With change of IQC practice, only FT3 had precision performance improved in 6 years. However, precision status of five analytes in China was still unsatisfying. Ongoing investigation and improvement of IQC have yet to be achieved. © 2017 Wiley Periodicals, Inc.

Lack of effect of reserpine-induced dopamine depletion on the binding of the dopamine-D3 selective radioligand, [11C]RGH-1756.

PubMed

Sóvágó, Judit; Farde, Lars; Halldin, Christer; Schukin, Evgenij; Schou, Magnus; Laszlovszky, István; Kiss, Béla; Gulyás, Balázs

2005-10-15

The effect of reserpine induced dopamine depletion on the binding of the putative dopamine-D3 receptor ligand, [(11)C]RGH-1756 was examined in the monkey brain with positron emission tomography (PET). In a previous series of experiments, we have made an attempt to selectively label D3 receptors in the monkey brain using [(11)C]RGH-1756. Despite high selectivity and affinity of RGH-1756 in vitro, [(11)C]RGH-1756 displayed only low specific binding to D3 receptors in vivo. The aim of the present study was to examine whether low specific binding of [(11)C]RGH-1756 is caused by insufficient in vivo affinity of the ligand, or by high physiological occupancy of D3 receptors by endogenous dopamine (DA). PET experiments were performed in three monkeys under baseline conditions and after administration of reserpine (0.5 mg/kg). The results of the baseline measurements corresponded well to our earlier observations with [(11)C]RGH-1756. Reserpine caused no evident change in the regional distribution of [(11)C]RGH-1756 in the monkey brain, and no conspicuous regional accumulation of activity could be observed. After reserpine treatment there was no evident increase of specific binding and binding potential (BP) of [(11)C]RGH-1756. The lack of increased [(11)C]RGH-1756 binding after reserpine treatment indicates that competition with endogenous DA is not the predominant reason for the failure of the radioligand to label D3 receptors. Therefore, the low binding of [(11)C]RGH-1756 could largely be explained by the need for very high affinity of radioligand for D3 receptors in vivo, to obtain a suitable signal for the minute densities of D3 receptors expressed in the primate brain.

Central auditory processing disorder (CAPD) in children with specific language impairment (SLI). Central auditory tests.

PubMed

Dlouha, Olga; Novak, Alexej; Vokral, Jan

2007-06-01

The aim of this project is to use central auditory tests for diagnosis of central auditory processing disorder (CAPD) in children with specific language impairment (SLI), in order to confirm relationship between speech-language impairment and central auditory processing. We attempted to establish special dichotic binaural tests in Czech language modified for younger children. Tests are based on behavioral audiometry using dichotic listening (different auditory stimuli that presented to each ear simultaneously). The experimental tasks consisted of three auditory measures (test 1-3)-dichotic listening of two-syllable words presented like binaural interaction tests. Children with SLI are unable to create simple sentences from two words that are heard separately but simultaneously. Results in our group of 90 pre-school children (6-7 years old) confirmed integration deficit and problems with quality of short-term memory. Average rate of success of children with specific language impairment was 56% in test 1, 64% in test 2 and 63% in test 3. Results of control group: 92% in test 1, 93% in test 2 and 92% in test 3 (p<0.001). Our results indicate the relationship between disorders of speech-language perception and central auditory processing disorders.

Early life lead exposure causes gender-specific changes in the DNA methylation profile of DNA extracted from dried blood spots

PubMed Central

Sen, Arko; Heredia, Nicole; Senut, Marie-Claude; Hess, Matthew; Land, Susan; Qu, Wen; Hollacher, Kurt; Dereski, Mary O; Ruden, Douglas M

2015-01-01

Aims In this paper, we tested the hypothesis that early life lead (Pb) exposure associated DNA methylation (5mC) changes are dependent on the sex of the child and can serve as biomarkers for Pb exposure. Methods In this pilot study, we measured the 5mC profiles of DNA extracted from dried blood spots (DBS) in a cohort of 43 children (25 males and 18 females; ages from 3 months to 5 years) from Detroit. Result & Discussion We found that the effect of Pb-exposure on the 5-mC profiles can be separated into three subtypes: affected methylation loci which are conserved irrespective of the sex of the child (conserved); affected methylation loci unique to males (male-specific); and affected methylation loci unique to females (female-specific). PMID:26077427

Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint

PubMed Central

Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

2017-01-01

A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted. PMID:28670465

Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint.

PubMed

Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

2017-06-01

A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted.

Evaluation of the importance of the serum levels of CA-125, CA15-3, CA-19-9, carcinoembryonic antigen and alpha fetoprotein for distinguishing benign and malignant adnexal masses and contribution of different test combinations to diagnostic accuracy.

PubMed

Bozkurt, M; Yumru, A E; Aral, I

2013-01-01

The aim of this study was to investigate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPPV) of the serum levels of CA-125, CA15-3, CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) in the differentiation of benign and malignant ovarian tumors histopathologically diagnosed in patients and to determine the effects of the different test combinations on diagnostic accuracy. One-hundred sixty-eight patients that had their preoperative CA-125, CA15-3, CA19-9, CEA, AFP levels assessed and that were subsequently surgically treated for adnexal masses, were included in the study. For each tumor markers in these patients with histopathologically-confirmed diagnosis, the sensitivity, specificity, PPV and NPV, and diagnostic accuracy, and odds ratio were calculated. The sensitivity, specificity, PPV, NPV of CA125 with cut-off 35 U/ml, were found to be 78.9%, 86.9%, 63.8%, and 93.3%, respectively. The diagnostic odds ratio of CA-125 with cut-off of 35 U/ml, was found to be 25. With cut-off65 U/ml, the sensitivity, specificity, PPV, NPV values were 65.7%, 95.3%, 80.6%, and 90.5%, respectively. The sensitivity, specificity, PPV, and NPV of CEA were 16%, 93%, 37%, and 83%, respectively. For AFP, the sensitivity, specificity, PPV and NPV were to be 2.6%, 98%, 33.3%, and 77.5%, respectively. For CA 15-3, the sensitivity, specificity, PPV and NPV were found to be 26.3% 96.1%, 66.6%, and 81.6%, respectively. Likelihood ratio tests: positive (LR+) = 6.83 and negative (LR-) = 0.76, with an odds ratio: 8.9. The risk of malignancy for adnexal masses with higher CA15-3 increased by approximately nine times. For CA19-9, the sensitivity, specificity, PPV and NPV value were found to be 18.4%, 93%, 43.7%, and 79.6%, respectively. CA19-9 was not statistically significant in the differentiation of benign and malignant of adnexal masses. Even the combinations of CA125 + CEA + CA19-9 and CA125 + CEA + CA19-9 +AFP and CA125 + CA15-3 made a small contribution (one, two, and four cases, respectively), but was not statistically significant. The levels of CA-125 and CA15-3 were found to be significant in order to distinguish benign and malign; CA 19-9, CEA, and AFP were not found to be significant. The different test combinations did not have contribution for diagnostic accuracy.

ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation

PubMed Central

Shan, Yuexin; Akram, Ali; Amatullah, Hajera; Zhou, Dun Yuan; Gali, Patricia L.; Maron-Gutierrez, Tatiana; González-López, Adrian; Zhou, Louis; Rocco, Patricia R.M.; Hwang, David; Albaiceta, Guillermo M.; Haitsma, Jack J.

2015-01-01

Abstract Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow (BM) transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine BM-derived macrophages from wild-type or ATF3-deficient mice. Results: Absence of ATF3 in myeloid-derived cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased exudative edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased paracellular leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 expression in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest that ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner, opening novel opportunities for cell specific therapy for ALI/VILI. Antioxid. Redox Signal. 22, 651–668. PMID:25401197

IR technology for enhanced force protection by AIM

NASA Astrophysics Data System (ADS)

Breiter, R.; Ihle, T.; Rode, W.; Wendler, J.; Rühlich, I.; Haiml, M.; Ziegler, J.

2008-04-01

In all recent missions our forces are faced with various types of asymmetric threads like snipers, IEDs, RPGs or MANPADS. 2 nd and 3 rd Gen IR technology is a backbone of modern force protection by providing situational awareness and accurate target engagement at day/night. 3 rd Gen sensors are developed for thread warning capabilities by use of spectral or spatial information. The progress on a dual-color IR module is discussed in a separate paper [1]. A 1024x256 SWIR array with flexure bearing compressor and pulse tube cold finger provides > 50,000h lifetime for space or airborne hyperspectral imaging in pushbroom geometry with 256 spectral channels for improved change detection and remote sensing of IEDs or chemical agents. Similar concepts are pursued in the LWIR with either spectroscopic imaging or a system of LWIR FPA combined with a cooled tunable Laser to do spectroscopy with stimulated absorption of specific wavelengths. AIM introduced the RangIR sight to match the requirements of sniper teams, AGLs and weapon stations, extending the outstanding optronic performance of the fielded HuntIR with position data of a target by a laser range finder (LRF), a 3 axis digital magnetic compass (DMC) and a ballistic computer for accurate engagement of remote targets. A version with flexure bearing cooler with >30,000h life time is being developed for continuous operation in e.g. gunfire detection systems. This paper gives an overview of AIM's technologies for enhanced force protection.

Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin.

PubMed

Ito, Yoshihiko; Kashiwabara, Michishi; Yoshida, Akira; Hikiyama, Eriko; Onoue, Satomi; Yamada, Shizuo

2016-01-01

Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine.

Seroprevalence study of Equine rhinitis B virus (ERBV) in Australian weanling horses using serotype-specific ERBV enzyme-linked immunosorbent assays.

PubMed

Horsington, Jacquelyn; Hartley, Carol A; Gilkerson, James R

2013-09-01

Respiratory infections are a major burden in the performance horse industry. Equine rhinitis B virus (ERBV) has been isolated from horses displaying clinical respiratory disease, and ERBV-neutralizing antibodies have been detected in 50-80% of horses in reported surveys. Current ERBV isolation and detection methods may underestimate the number of ERBV-positive animals and do not identify multiple serotype infections. The aim of the current study was to develop a serotyping ERBV antibody-detection enzyme-linked immunosorbent assay (ELISA) and examine the seroprevalence of ERBV in a group of Australian weanling horses. ELISAs with high sensitivity and specificity were developed. The seroprevalence of ERBV in the weanling horses was high (74-86%); ERBV-3 antibodies were most prevalent (58-62%) and ERBV-2 antibodies were least prevalent (10-16%). Many horses were seropositive to 2 or more serotypes. All 3 serotypes of ERBV were detected, and concurrent positivity to multiple serotypes was common.

The effect of air pollution and other environmental stressors on leaf fluctuating asymmetry and specific leaf area of Salix alba L.

PubMed

Wuytack, Tatiana; Wuyts, Karen; Van Dongen, Stefan; Baeten, Lander; Kardel, Fatemeh; Verheyen, Kris; Samson, Roeland

2011-10-01

We aimed at evaluating the effect of low-level air pollution on leaf area fluctuating asymmetry (FAA) and specific leaf area (SLA) of Salix alba L., taking into account other environmental factors. Cuttings were grown in standardized conditions in the near vicinity of air quality measuring stations in Belgium. Variability of SLA and FAA between measuring stations explained 83% and 7.26%, respectively, of the total variability. FAA was not influenced by air pollution or environmental factors such as shading, herbivory, air temperature and humidity. SLA was increased by an increase in shadow, while NO(x) and O(3) concentrations had only a marginal influence. The influence of SO(2) concentration was negligible. Although our data analysis suggests a relationship between SLA and NO(x)/O(3) concentration, the absence of a straightforward relationship between FAA and SLA and air pollution still questions the usefulness of these bio-indicators for monitoring air pollution. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Multifunctional Effects of Nobiletin and Its Metabolites In Vivo and In Vitro

PubMed Central

Li, Linfu; Shi, Weimei; Liu, Hai; Yang, Jianqiong

2016-01-01

Nobiletin (NOB) chemically known as 5,6,7,8,3′,4′-hexamethoxyflavone is a dietary polymethoxylated flavonoid found in Citrus fruits. Recent evidences show that NOB is a multifunctional pharmaceutical agent. The various pharmacological activities of NOB include neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation. These events may be underpinned by modulation of signaling cascades, including PKA/ERK/MEK/CREB, NF-κB, MAPK, Ca2+/CaMKII, PI3K/Akt1/2, HIF-1α, and TGFβ signaling pathways. The metabolites may exhibit stronger beneficial effects than NOB on diseases pathogenesis. The biological activities of NOB have been clarified on many systems. This review aims to discuss the pharmacological effects of NOB with specific mechanisms of actions. NOB may become a promising candidate for potential drug development. However, further investigations of NOB on specific intracellular targets and clinical trials are still needed, especially for in vivo medical applications. PMID:27761146

Disorder-Specific Alteration in White Matter Structural Property in Adults With Autism Spectrum Disorder Relative to Adults With ADHD and Adult Controls.

PubMed

Chiang, Huey-Ling; Chen, Yu-Jen; Lin, Hsiang-Yuan; Tseng, Wen-Yih Isaac; Gau, Susan Shur-Fen

2017-01-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are not only often comorbid but also overlapped in behavioral and cognitive abnormalities. Little is known about whether these shared phenotypes are based on common or different underlying neuropathologies. Therefore, this study aims to examine the disorder-specific alterations in white matter (WM) structural property. The three comparison groups included 23 male adults with ASD (21.4 ± 3.1 years), 32 male adults with ADHD (23.4 ± 3.3 years), and 29 age-matched healthy male controls (22.4 ± 3.3 years). After acquisition of the diffusion spectrum imaging (DSI), whole brain tractography was reconstructed by a tract-based automatic analysis. Generalized fractional anisotropy (GFA) values were computed to indicate tract-specific WM property with adjusted P value < 0.05 for false discovery rate correction. Post hoc analyses revealed that men with ASD exhibited significant lower GFA values than men with ADHD and male controls in six identified fiber tracts: the right arcuate fasciculus, right cingulum (hippocampal part), anterior commissure, and three callosal fibers (ventrolateral prefrontal cortex part, precentral part, superior temporal part). There was no significant difference in the GFA values of any of the fiber tracts between men with ADHD and controls. In men with ASD, the GFA values of the right arcuate fasciculus and right cingulum (hippocampal part) were negatively associated with autistic social-deficit symptoms, and the anterior commissure GFA value was positively correlated with intelligence. This study highlights the disorder-specific alteration of the microstructural property of WM tracts in male adults with ASD. Hum Brain Mapp 38:384-395, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

New Perspective on Dextran Sodium Sulfate Colitis: Antigen-Specific T Cell Development during Intestinal Inflammation

PubMed Central

Morgan, Mary E.; Zheng, Bin; Koelink, Pim J.; van de Kant, Hendrick J. G.; Haazen, Lizette C. J. M.; van Roest, Manon; Garssen, Johan; Folkerts, Gert; Kraneveld, Aletta D.

2013-01-01

CD4+ T cell responses against oral antigens can develop in inflammatory bowel disease (IBD) patients, which may modulate disease. Dextran sodium sulfate (DSS) colitis is commonly used to study IBD, however, it is not considered the best model in which to study T cell involvement in intestinal disease. Our aim was to determine if antigen-specific T cells could be induced during DSS colitis and if they could be detected after disease resolution. To induce antigen-specific T cells, the tracking antigen, ovalbumin (OVA), was administered orally during colitis initiation. Disease severity was monitored, and the antigen-reactivity of CD4+ T cells examined using CD69 expression. While OVA-directed, CD4+ Foxp3+ regulatory T cells could be detected in the spleens of both OVA-treated control and DSS mice, OVA-reactive, CD4+ Foxp3-T cells were only found in the OVA and DSS-treated mice. These results indicate that during DSS colitis T cells develop that are specific against oral antigens, and they are found systemically after colitis resolution. This gives added depth and utility to the DSS model as well as a way to track T cells that are primed against luminal antigens. PMID:23936123

[Assessment Method of Remnant α-1, 3-galactosyle Epitopes in Animal Tissue-derived Biomaterials].

PubMed

Shan, Yongqiang; Xu, Liming; Ke, Linnan; Lu, Yan; Shao, Anliang; Zhang, Na; Zeng, Bixin

2015-06-01

The aim of this study was to establish an assessment method for determining α-Gal (α-1, 3-galactosyle) epitopes contained in animal tissue or animal tissue-derived biological materials with ELISA inhibition assay. Firstly, a 96 well plate was coated with Gal α-1, 3-Gal/bovine serum albumin (BSA) as a solid phase antigen and meanwhile, the anti-α-Gal M86 was used to react with α-Gal antigens which contained in the test materials. Then, the residual antibodies (M86) in the supernatant of M86-Gal reaction mixture were measured using ELISA inhibition assay by the α-Gal coating plate. The inhibition curve of the ELISA inhibition assay, the R2 = 0.999, was well established. Checking using both α-Gal positive materials (rat liver tissues) and α-Gal negative materials (human placenta tissues) showed a good sensitivity and specificity. Based on the presently established method, the α-Gal expression profile of rat tissues, decellular animal tissue-derived biological materials and porcine dermal before and after decellular treatment were determined. The M86 ELISA inhibition assay method, which can quantitatively determine the α-Gal antigens contained in animal tissues or animal tissue-derived biomaterials, was refined. This M86 specific antibody based-ELISA inhibition assay established in the present study has good sensitivity and specificity, and could be a useful method for determining remnant α-1, 3Gal antigens in animal tissue-derived biomaterials.

Transmission of Cultural Specific Items into English Translation of "Dear Shameless Death" by Latife Tekin

ERIC Educational Resources Information Center

Öztemel, Figen; Kurt, Mustafa

2017-01-01

This article aims at demonstrating which translation strategies are preferred in order to deal with the translation of culture-specific items in Latife Tekin's Sevgili Arsiz Ölüm (1983) and its English translation entitled "Dear Shameless Death" (2001). To achieve this primary aim, a comparative analysis is carried out between Sevgili…

Differential Splicing of Oncogenes and Tumor Suppressor Genes in African- and Caucasian-American Populations: Contributing Factor in Prostate Cancer Disparities

DTIC Science & Technology

2015-10-01

signaling protein as defined by in vitro assays and mouse xenograft studies, ii) is associated with worse prognosis in patients, and iii) is resistant to...available. Specific Aim 2. To characterize oncogenic differences of splice variant pairs in vivo using xenograft animal models. Task 1. Validate...idelalisib as defined by in vitro assays and mouse xenograft models. In contrast, the corresponding EA isoform (PI3Kδ-L) encodes a less aggressive isoform

Radical prostatectomy--long-term oncological outcome from a community hospital.

PubMed

Tol-Fakkar, Maria; Hermansson, Carl Gustaf; Hugosson, Jonas; Pedersen, Knud; Aus, Gunnar

2003-01-01

Radical prostatectomy has recently been shown to prolong cancer-specific survival compared to watchful waiting in patients with localized prostate cancer. Most patients who seek medical advice for this disease are treated in hospitals in which the operation is performed relatively infrequently. The aim of this study is to report the oncological outcome at intermediate- to long-term follow-up after radical prostatectomy performed in a community hospital. A total of 148 patients underwent radical prostatectomy at Ryhov County Hospital between 1985 and 1997. Patients without T3 tumours, prostate-specific antigen (PSA) >10 ng/ml or poorly differentiated tumours were judged to be in a low-risk group, those with one risk factor to be in an intermediate group and those with two or more factors to be in a high-risk group. The projected biochemical disease free- and cancer-specific survival rates were compared between these risk groups. Median follow-up was 96 months for surviving patients. Patients in the low- and intermediate risk groups had equal 10-year PSA-free survival rates of 68.8%, while that in the high-risk group was only 19.3% (9-year data). Corresponding cancer-specific survival rates were 93% and 84%, respectively. The oncological outcome seems comparable to that reported in the literature, even when the operation is performed in a low-volume community-based setting.

Glove-derived foreign proteins induce allergen-specific IgE in a mouse model.

PubMed

Busch, Marion; Schröder, Claudia; Baron, Jens-Malte; Ott, Hagen; Bruckner, Thomas; Diepgen, Thomas L; Mahler, Vera

2008-04-01

Currently, most medical gloves are produced with a low content of natural rubber latex (NRL) protein. However, they may be substituted by proteins of foreign origin to maintain specific properties of the material. The aim of this study was to investigate the allergenicity and immunogenicity of unexpected proteins (i.e., soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All respective allergen sources (extracts from three brands of NRL gloves, soy, and casein) were able to induce significant allergen-specific IgE and IgG(1) responses. On average, the highest IgE induction occurred after immunization with NRL, followed by soy and casein. Certain individuals from each treatment group exhibited levels of specific IgE as high as due to NRL. To analyze further specific IgE responses on a single allergen level, we established a microarray based on recombinant allergens for allergen-specific murine IgE detection. Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against kappa-casein could be detected in mice immunized with NRL glove extract, indicating a sensitization potential of the contained foreign protein. The substitution of genuine latex proteins by proteins of foreign origin may lead to a shift and de novo increase in sensitization to the finished products.

Re and 99mTc Tricarbonyl Probes for Target-Specific Detection of Melanoma and Sentinel Lymph Node

NASA Astrophysics Data System (ADS)

Morais, Mauricio da Silva

The work described in this thesis aimed at the development of M(I) (M = 99mTc, Re) specific probes for the detection of malignant melanoma and sentinel lymph node (SLN) through the in vivo targeting of membrane receptors. In the former case we have designed M(CO)3-complexes stabilized by tridentate chelators containing a pyrazolyl-diamine chelating unit (N,N,N donor atom set) and pendant alpha-melanocyte-stimulating hormone (alpha-MSH) derivatives for targeting the melanocortin receptor 1 (MC1R), which is overexpressed in melanotic and amelanotic human melanoma cells. (Abstract shortened by ProQuest.). None None None None None None None None None None None None None None None None None

Injecting drug users and their health seeking behavior: a cross-sectional study in dhaka, bangladesh.

PubMed

Shariful Islam, Sheikh Mohammed; Biswas, Tuhin; Bhuiyan, Faiz Ahmed; Islam, Md Serajul; Rahman, Mohammad Mizanur; Nessa, Hurun

2015-01-01

Introduction and Aim. Injecting drug users (IDUs) are amongst the most vulnerable people to acquisition of HIV/AIDS. This study aims to collect information on IDUs and their health seeking behavior in Bangladesh. Design and Methods. A cross-sectional study was conducted among 120 IDUs attending a drug rehabilitation center in Dhaka, Bangladesh. Data were collected on sociodemographics, drug use, health seeking behavior, knowledge of injecting drugs, and sexual behavior. Results. The mean ± SD and median (IQR) age of the participants were 32.5 ± 21.3 and 33 (27-38) years, respectively, with only 9.2% females. Injection buprenorphine was the drug of choice for 40% of participants, and 58% of the participants first started drug use with smoking cannabis. 73.3% of participants shared needles sometimes and 57.5% were willing to use the needle exchange programs. 60% of the participants had no knowledge about the diseases spread by injection. Condom use during the last intercourse with regular partners was 11.7% and with any partners 15.8%. Conclusion. IDUs in Bangladesh are a high-risk group for HIV/AIDS due to lack of knowledge and risky behaviors. Education and interventions specifically aimed at IDUs are needed, because traditional education may not reach IDUs or influence their behavior.

Injecting Drug Users and Their Health Seeking Behavior: A Cross-Sectional Study in Dhaka, Bangladesh

PubMed Central

Biswas, Tuhin; Bhuiyan, Faiz Ahmed; Islam, Md. Serajul; Rahman, Mohammad Mizanur; Nessa, Hurun

2015-01-01

Introduction and Aim. Injecting drug users (IDUs) are amongst the most vulnerable people to acquisition of HIV/AIDS. This study aims to collect information on IDUs and their health seeking behavior in Bangladesh. Design and Methods. A cross-sectional study was conducted among 120 IDUs attending a drug rehabilitation center in Dhaka, Bangladesh. Data were collected on sociodemographics, drug use, health seeking behavior, knowledge of injecting drugs, and sexual behavior. Results. The mean ± SD and median (IQR) age of the participants were 32.5 ± 21.3 and 33 (27–38) years, respectively, with only 9.2% females. Injection buprenorphine was the drug of choice for 40% of participants, and 58% of the participants first started drug use with smoking cannabis. 73.3% of participants shared needles sometimes and 57.5% were willing to use the needle exchange programs. 60% of the participants had no knowledge about the diseases spread by injection. Condom use during the last intercourse with regular partners was 11.7% and with any partners 15.8%. Conclusion. IDUs in Bangladesh are a high-risk group for HIV/AIDS due to lack of knowledge and risky behaviors. Education and interventions specifically aimed at IDUs are needed, because traditional education may not reach IDUs or influence their behavior. PMID:25692067

Effects of active vs. passive recovery on repeated rugby-specific exercises.

PubMed

Jougla, A; Micallef, J P; Mottet, D

2010-05-01

The aim of this study was to determine the effects of active vs. passive recovery on performance of a rugby-specific intermittent test in rugby union players. Seven male rugby players (20.6+/-0.5 yrs; 181.9+/-10.0 cm; 94.5+/-12.8 kg) performed in random order, over two separate sessions, a specific repeated-sprint rugby test, the Narbonne test (6 x 4 consecutive actions: 1, scrummaging; 2, agility sprinting; 3, tackling; 4, straight sprinting) with 30s of passive or active recovery (running at 50% of maximal aerobic speed). The Narbonne tests were completed before (pre-test) and after (post-test) a 30-min rugby match. During the Narbonne test, scrum forces, agility and sprint times, heart rate and rate of perceived exertion were measured. Scrum forces were lower in active (74.9+/-13.4 kg) than in passive recovery (90.4+/-20.9 kg), only during the post-test (p<0.05). Fatigue index (%) (p<0.05) and total sprint time (s) (p<0.01) were significantly greater in active than in passive recovery, both during the pre-test (11.5+/-5.7% vs. 6.7+/-4.5% and 18.1+/-1.3s vs. 16.9+/-0.9s) and the post-test (7.3+/-3.3% vs. 4.3+/-1.5% and 18.3+/-1.6s vs. 16.9+/-1.1s). Consequently, the results indicated that passive recovery enabled better performance during the Narbonne test. However, it is obviously impractical to suggest that players should stand still during and following repeated-sprint bouts: the players have to move to ensure they have taken an optimal position. 2009 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Evaluation of 16S rRNA qPCR for detection of Mycobacterium leprae DNA in nasal secretion and skin biopsy samples from multibacillary and paucibacillary leprosy cases.

PubMed

Marques, Lívia Érika Carlos; Frota, Cristiane Cunha; Quetz, Josiane da Silva; Bindá, Alexandre Havt; Mota, Rosa Maria Salane; Pontes, Maria Araci de Andrade; Gonçalves, Heitor de Sá; Kendall, Carl; Kerr, Ligia Regina Franco Sansigolo

2017-12-26

Mycobacterium leprae bacilli are mainly transmitted by the dissemination of nasal aerosols from multibacillary (MB) patients to susceptible individuals through inhalation. The upper respiratory tract represents the main entry and exit routes of M. leprae. Therefore, this study aimed to evaluate the sensitivity and specificity of real-time quantitative polymerase chain reaction (qPCR) in detecting M. leprae in nasal secretion (NS) and skin biopsy (SB) samples from MB and paucibacillary (PB) cases. Fifty-four NS samples were obtained from leprosy patients at the Dona Libânia National Reference Centre for Sanitary Dermatology in Ceará, Brazil. Among them, 19 MB cases provided both NS and SB samples. Bacilloscopy index assays were conducted and qPCR amplification was performed using specific primers for M. leprae 16S rRNA gene, generating a 124-bp fragment. Primer specificity was verified by determining the amplicon melting temperature (T m  = 79.5 °C) and detection limit of qPCR was 20 fg of M. leprae DNA. Results were positive for 89.7 and 73.3% of NS samples from MB and PB cases, respectively. SB samples from MB patients were 100% positive. The number of bacilli detected in NS samples were 1.39 × 10 3 -8.02 × 10 5 , and in SB samples from MB patients were 1.87 × 10 3 -1.50 × 10 6 . Therefore, qPCR assays using SYBR Green targeting M. leprae 16S rRNA region can be employed in detecting M. leprae in nasal swabs from leprosy patients, validating this method for epidemiological studies aiming to identify healthy carriers among household contacts or within populations of an endemic area.

Safeguarding Stem Cell-Based Regenerative Therapy against Iatrogenic Cancerogenesis: Transgenic Expression of DNASE1, DNASE1L3, DNASE2, DFFB Controlled By POLA1 Promoter in Proliferating and Directed Differentiation Resisting Human Autologous Pluripotent Induced Stem Cells Leads to their Death

PubMed Central

Malecki, Marek; LaVanne, Christine; Alhambra, Dominique; Dodivenaka, Chaitanya; Nagel, Sarah; Malecki, Raf

2014-01-01

Introduction The worst possible complication of using stem cells for regenerative therapy is iatrogenic cancerogenesis. The ultimate goal of our work is to develop a self-triggering feedback mechanism aimed at causing death of all stem cells, which resist directed differentiation, keep proliferating, and can grow into tumors. Specific aim The specific aim was threefold: (1) to genetically engineer the DNA constructs for the human, recombinant DNASE1, DNASE1L3, DNASE2, DFFB controlled by POLA promoter; (2) to bioengineer anti-SSEA-4 antibody guided vectors delivering transgenes to human undifferentiated and proliferating pluripotent stem cells; (3) to cause death of proliferating and directed differentiation resisting stem cells by transgenic expression of the human recombinant the DNases (hrDNases). Methods The DNA constructs for the human, recombinant DNASE1, DNASE1L3, DNASE2, DFFB controlled by POLA promoter were genetically engineered. The vectors targeting specifically SSEA-4 expressing stem cells were bioengineered. The healthy volunteers’ bone marrow mononuclear cells (BMMCs) were induced into human, autologous, pluripotent stem cells with non-integrating plasmids. Directed differentiation of the induced stem cells into endothelial cells was accomplished with EGF and BMP. The anti-SSEA 4 antibodies’ guided DNA vectors delivered the transgenes for the human recombinant DNases’ into proliferating stem cells. Results Differentiation of the pluripotent induced stem cells into the endothelial cells was verified by highlighting formation of tight and adherens junctions through transgenic expression of recombinant fluorescent fusion proteins: VE cadherin, claudin, zona occludens 1, and catenin. Proliferation of the stem cells was determined through highlighting transgenic expression of recombinant fluorescent proteins controlled by POLA promoter, while also reporting expression of the transgenes for the hrDNases. Expression of the transgenes for the DNases resulted in complete collapse of the chromatin architecture and degradation of the proliferating cells’ genomic DNA. The proliferating stem cells, but not the differentiating ones, were effectively induced to die. Conclusion Herein, we describe attaining the proof-of-concept for the strategy, whereby transgenic expression of the genetically engineered human recombinant DNases in proliferating and directed differentiation resisting stem cells leads to their death. This novel strategy reduces the risk of iatrogenic neoplasms in stem cell therapy. PMID:25045589

Sex-specific lean body mass predictive equations are accurate in the obese paediatric population

PubMed Central

Jackson, Lanier B.; Henshaw, Melissa H.; Carter, Janet; Chowdhury, Shahryar M.

2015-01-01

Background The clinical assessment of lean body mass (LBM) is challenging in obese children. A sex-specific predictive equation for LBM derived from anthropometric data was recently validated in children. Aim The purpose of this study was to independently validate these predictive equations in the obese paediatric population. Subjects and methods Obese subjects aged 4–21 were analysed retrospectively. Predicted LBM (LBMp) was calculated using equations previously developed in children. Measured LBM (LBMm) was derived from dual-energy x-ray absorptiometry. Agreement was expressed as [(LBMm-LBMp)/LBMm] with 95% limits of agreement. Results Of 310 enrolled patients, 195 (63%) were females. The mean age was 11.8 ± 3.4 years and mean BMI Z-score was 2.3 ± 0.4. The average difference between LBMm and LBMp was −0.6% (−17.0%, 15.8%). Pearson’s correlation revealed a strong linear relationship between LBMm and LBMp (r=0.97, p<0.01). Conclusion This study validates the use of these clinically-derived sex-specific LBM predictive equations in the obese paediatric population. Future studies should use these equations to improve the ability to accurately classify LBM in obese children. PMID:26287383

Care Planning for Prostate Cancer Patients on Active Surveillance

DTIC Science & Technology

2016-10-01

intervention (PCPEP) for prostate cancer patients on active surveillance ( Study Specific Aim 1). As part of the adoption process, we will: (Aim 1a...evaluate the acceptability and feasibility of the program with prostate cancer patients on active surveillance in a small pilot study ( Study Specific...to a poster depicting the study finding on “Treatment 4 Decision-making and Adherence to Active Surveillance in Prostate Cancer Patients” presented

Diagnostic performance of the "MESACUP anti-Skin profile TEST".

PubMed

Horváth, Orsolya N; Varga, Rita; Kaneda, Makoto; Schmidt, Enno; Ruzicka, Thomas; Sárdy, Miklós

2016-01-01

The "MESACUP anti-Skin profile TEST" is a new, commercially available ELISA kit to detect circulating IgG autoantibodies against desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen, both simultaneously and more rapidly than previous assays. The aim of this study was to evaluate the diagnostic accuracy of this kit for the diagnosis of pemphigus foliaceus, pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita. Dual-centre retrospective study in which 138 patients with autoimmune blistering diseases were compared to 40 controls Using the MESACUP anti-Skin profile TEST, both sensitivities and specificities for desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen autoantibodies were similar to those obtained using previous, specific ELISA systems and 88% of the results were concordant without any significant difference. The MESACUP anti-Skin profile TEST had a similar performance to previously produced ELISA systems. The novel kit can be used for rapid diagnosis of most common autoimmune blistering diseases and is especially suitable for identifying overlapping disorders.

Determination of some pure compound ideal-gas enthalpies of formation

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

Steele, W. V.; Chirico, R. D.; Nguyen, A.

1989-06-01

The results of a study aimed at improvement of group-additivity methodology for estimation of thermodynamic properties of organic substances are reported. Specific weaknesses where ring corrections were unknown or next-nearest-neighbor interactions were only estimated because of lack of experimental data are addressed by experimental studies of enthalpies of combustion in the condensed- phase and vapor pressure measurements. Ideal-gas enthalpies of formation are reported for acrylamide, succinimide, ..gamma..-butyrolactone, 2-pyrrolidone, 2,3-dihydrofuran, 3,4-dihydro-2H-pyran, 1,3-cyclohexadiene, 1,4-cyclohexadiene, and 1-methyl-1-phenylhydrazine. Ring corrections, group terms, and next-nearest-neighbor interaction terms useful in the application of group additivity correlations are derived. 44 refs., 2 figs., 59 tabs.

The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

PubMed Central

Kadayifci, Abdurrahman; Al-Haddad, Mohammad; Atar, Mustafa; Dewitt, John M.; Forcione, David G.; Sherman, Stuart; Casey, Brenna W.; Fernandez-del Castillo, Carlos; Schmidt, C. Max; Pitman, Martha B.; Brugge, William R.

2016-01-01

Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use. PMID:27092317

Using component technologies for web based wavelet enhanced mammographic image visualization.

PubMed

Sakellaropoulos, P; Costaridou, L; Panayiotakis, G

2000-01-01

The poor contrast detectability of mammography can be dealt with by domain specific software visualization tools. Remote desktop client access and time performance limitations of a previously reported visualization tool are addressed, aiming at more efficient visualization of mammographic image resources existing in web or PACS image servers. This effort is also motivated by the fact that at present, web browsers do not support domain-specific medical image visualization. To deal with desktop client access the tool was redesigned by exploring component technologies, enabling the integration of stand alone domain specific mammographic image functionality in a web browsing environment (web adaptation). The integration method is based on ActiveX Document Server technology. ActiveX Document is a part of Object Linking and Embedding (OLE) extensible systems object technology, offering new services in existing applications. The standard DICOM 3.0 part 10 compatible image-format specification Papyrus 3.0 is supported, in addition to standard digitization formats such as TIFF. The visualization functionality of the tool has been enhanced by including a fast wavelet transform implementation, which allows for real time wavelet based contrast enhancement and denoising operations. Initial use of the tool with mammograms of various breast structures demonstrated its potential in improving visualization of diagnostic mammographic features. Web adaptation and real time wavelet processing enhance the potential of the previously reported tool in remote diagnosis and education in mammography.

EXECUTIVE FUNCTION PROFILES IN CHILDREN WITH AND WITHOUT SPECIFIC LANGUAGE IMPAIRMENT

PubMed Central

Marton, Klara; Campanelli, Luca; Scheuer, Jessica; Yoon, Jungmee; Eichorn, Naomi

2013-01-01

We present findings from a study that focused on specific executive functions (EF) in children with and without specific language impairment (SLI). We analyzed performance patterns and EF profiles (spatial working memory, inhibition control, and sustained attention) in school-age SLI children and two control groups: age-matched and language matched. Our main research goal was to identify those EFs that show a weakness in children with SLI. Our specific aims were to: (1) examine whether the EF problems in children with SLI are domain-general; (2) examine whether deficits in EF in children with SLI can be explained by the general slowness hypothesis or by an overall delay in development; (3) compare EF profiles to examine whether children with SLI show a distinct pattern of performance from their peers. Our findings showed different EF profiles for the groups. We observed differences in performance patterns related to age (e.g., reaction time in response inhibition) and differences related to language status (e.g., sensitivity to interference). The findings show interesting associations in EFs that play a crucial role in language processing. PMID:25302062

The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass.

PubMed

Rom, Oren; Reznick, Abraham Z

2016-09-01

The ubiquitin-proteasome system (UPS) is the main regulatory mechanism of protein degradation in skeletal muscle. The ubiquitin-ligase enzymes (E3s) have a central role in determining the selectivity and specificity of the UPS. Since their identification in 2001, the muscle specific E3s, muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx), have been shown to be implicated in the regulation of skeletal muscle atrophy in various pathological and physiological conditions. This review aims to explore the involvement of MuRF-1 and MAFbx in catabolism of skeletal muscle during various pathologies, such as cancer cachexia, sarcopenia of aging, chronic kidney disease (CKD), diabetes, and chronic obstructive pulmonary disease (COPD). In addition, the effects of various lifestyle and modifiable factors (e.g. nutrition, exercise, cigarette smoking, and alcohol) on MuRF-1 and MAFbx regulation will be discussed. Finally, evidence of potential strategies to protect against skeletal muscle wasting through inhibition of MuRF-1 and MAFbx expression will be explored. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural characterization of the Man5 glycoform of human IgG3 Fc

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

Shah, Ishan S.; Lovell, Scott; Mehzabeen, Nurjahan

Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined themore » crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8 Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure provides a template for further studies aimed at engineering the Fc for specific gain of function.« less

Therapists' self-reported drift from dialectical behavior therapy techniques for eating disorders.

PubMed

Wisniewski, Lucene; Hernandez Hernandez, Maria Elena; Waller, Glenn

2018-01-01

Research has shown that clinicians underuse or omit techniques that constitute an essential part of evidence-based therapies. However, it is not known whether this is the case in DBT for eating disorders. The aims of this study were; 1) exploring the extent to which DBT techniques were used by self-identified DBT clinicians treating eating disorders; 2) determining whether therapists fell into distinct groups, based on their usage of DBT techniques; and 3) examining whether clinician characteristics were related to the use of such techniques. Seventy-three clinicians offering DBT for eating disorders completed an online survey about their use of specific DBT techniques. They also completed measures of personality and intolerance of uncertainty. In relation to the first aim, the pattern of use of DBT techniques showed a bimodal distribution - most were used either a lot or a little. Considering the second aim, clinicians fell into two groups according to the techniques that they delivered - one characterized by a higher use of DBT techniques and the other by a higher use of techniques that were specific to the treatment of eating disorders, rather than DBT methods. Finally, more experienced clinicians were more likely to be in the 'DBT technique-focused' group. DBT clinicians are encouraged to implement both sets of techniques (DBT techniques and standard techniques for the treatment of eating disorders) in an integrated way. Training, supervision and the use of manuals are recommended to decrease therapist drift in DBT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study.

PubMed

Martín-Gandul, Cecilia; Pérez-Romero, Pilar; Mena-Romo, Damián; Molina-Ortega, Alejandro; González-Roncero, Francisco M; Suñer, Marta; Bernal, Gabriel; Cordero, Elisa

2018-03-23

Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8 + CD69 + INF-γ + T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8 + CD69 + INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunohistochemical identification of varicella-zoster virus gene 63-encoded protein (IE63) and late (gE) protein on smears and cutaneous biopsies: implications for diagnostic use.

PubMed

Nikkels, A F; Debrus, S; Sadzot-Delvaux, C; Piette, J; Rentier, B; Piérard, G E

1995-12-01

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51). Microscopic examinations of Tzanck smears and skin sections yielded a diagnostic accuracy of Herpesviridae infections in 66.7% (10/15) and 92.3% (12/13) of varicella, and 74.4% (29/39) and 87.8% (43/49) of herpes zoster, respectively. Immunohistochemistry applied to varicella provided a type-specific virus diagnostic accuracy of 86.7% (13/15; IE63) and 100% (15/15; gE) on smears, and of 92.3% for both VZV proteins on skin sections. In herpes zoster, the diagnostic accuracy of immunohistochemistry reached 92.3% (36/39; IE63) and 94.9% (37/39; gE) on smears, and 91.7% (44/48; IE63) and 91.8% (45/49; gE) on skin sections. These findings indicate that the immunohistochemical detection of IE63 and gE on both smears and skin sections yields a higher specificity and sensitivity than standard microscopic assessments.

Genomic profiling of human penile carcinoma predicts worse prognosis and survival.

PubMed

Busso-Lopes, Ariane F; Marchi, Fábio A; Kuasne, Hellen; Scapulatempo-Neto, Cristovam; Trindade-Filho, José Carlos S; de Jesus, Carlos Márcio N; Lopes, Ademar; Guimarães, Gustavo C; Rogatto, Silvia R

2015-02-01

The molecular mechanisms underlying penile carcinoma are still poorly understood, and the detection of genetic markers would be of great benefit for these patients. In this study, we assessed the genomic profile aiming at identifying potential prognostic biomarkers in penile carcinoma. Globally, 46 penile carcinoma samples were considered to evaluate DNA copy-number alterations via array comparative genomic hybridization (aCGH) combined with human papillomavirus (HPV) genotyping. Specific genes were investigated by using qPCR, FISH, and RT-qPCR. Genomic alterations mapped at 3p and 8p were related to worse prognostic features, including advanced T and clinical stage, recurrence and death from the disease. Losses of 3p21.1-p14.3 and gains of 3q25.31-q29 were associated with reduced cancer-specific and disease-free survival. Genomic alterations detected for chromosome 3 (LAMP3, PPARG, TNFSF10 genes) and 8 (DLC1) were evaluated by qPCR. DLC1 and PPARG losses were associated with poor prognosis characteristics. Losses of DLC1 were an independent risk factor for recurrence on multivariate analysis. The gene-expression analysis showed downexpression of DLC1 and PPARG and overexpression of LAMP3 and TNFSF10 genes. Chromosome Y losses and MYC gene (8q24) gains were confirmed by FISH. HPV infection was detected in 34.8% of the samples, and 19 differential genomic regions were obtained related to viral status. At first time, we described recurrent copy-number alterations and its potential prognostic value in penile carcinomas. We also showed a specific genomic profile according to HPV infection, supporting the hypothesis that penile tumors present distinct etiologies according to virus status. ©2014 American Association for Cancer Research.

Quantitation of specific binding ratio in 123I-FP-CIT SPECT: accurate processing strategy for cerebral ventricular enlargement with use of 3D-striatal digital brain phantom.

PubMed

Furuta, Akihiro; Onishi, Hideo; Amijima, Hizuru

2018-06-01

This study aimed to evaluate the effect of ventricular enlargement on the specific binding ratio (SBR) and to validate the cerebrospinal fluid (CSF)-Mask algorithm for quantitative SBR assessment of 123 I-FP-CIT single-photon emission computed tomography (SPECT) images with the use of a 3D-striatum digital brain (SDB) phantom. Ventricular enlargement was simulated by three-dimensional extensions in a 3D-SDB phantom comprising segments representing the striatum, ventricle, brain parenchyma, and skull bone. The Evans Index (EI) was measured in 3D-SDB phantom images of an enlarged ventricle. Projection data sets were generated from the 3D-SDB phantoms with blurring, scatter, and attenuation. Images were reconstructed using the ordered subset expectation maximization (OSEM) algorithm and corrected for attenuation, scatter, and resolution recovery. We bundled DaTView (Southampton method) with the CSF-Mask processing software for SBR. We assessed SBR with the use of various coefficients (f factor) of the CSF-Mask. Specific binding ratios of 1, 2, 3, 4, and 5 corresponded to SDB phantom simulations with true values. Measured SBRs > 50% that were underestimated with EI increased compared with the true SBR and this trend was outstanding at low SBR. The CSF-Mask improved 20% underestimates and brought the measured SBR closer to the true values at an f factor of 1.0 despite an increase in EI. We connected the linear regression function (y = - 3.53x + 1.95; r = 0.95) with the EI and f factor using root-mean-square error. Processing with CSF-Mask generates accurate quantitative SBR from dopamine transporter SPECT images of patients with ventricular enlargement.

Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells*

PubMed Central

Li, Ying Hui; Choi, Dae Hee; Lee, Eun Hye; Seo, Su Ryeon; Lee, Seungkoo

2016-01-01

Sirtuin 3 (SIRT3) is an NAD+-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro. In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment. PMID:26912655

Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells.

PubMed

Li, Ying Hui; Choi, Dae Hee; Lee, Eun Hye; Seo, Su Ryeon; Lee, Seungkoo; Cho, Eun-Hee

2016-05-06

Sirtuin 3 (SIRT3) is an NAD(+)-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Patterns of aeroallergen sensitization predicting risk for asthma in preschool children with atopic dermatitis.

PubMed

Calamelli, Elisabetta; Ricci, Giampaolo; Neri, Iria; Ricci, Lorenza; Rondelli, Roberto; Pession, Andrea; Patrizi, Annalisa

2015-06-01

Atopic dermatitis (AD) is a chronic inflammatory skin disorder mostly affecting young children. Although several studies aimed to identify the risk factors for asthma in AD children, many aspects still need to be clarified. The aim of this study was to investigate the possible risk factors for asthma at school age in 99 children with early-onset and IgE-mediated AD. All children performed clinical evaluation and total and specific IgE assay for a panel of inhalant and food allergens at two different times (t1 and t2) during preschool, and asthma diagnosis was assessed at one follow-up visit (t3) at school age. At t3, 39% of children had developed asthma. Of the variables compared, the sensitization to more than one class of inhalant allergens at t2 (mean age = 30 months) was associated with asthma, with grass (OR = 3.24, p = 0.020) and cat sensitization (OR = 2.74, p = 0.043) as independent risk factors. The sensitization pattern of a child with early-onset AD, also within the first 2-3 years of life, can reflect his risk to develop asthma. Therefore, testing these children for the more common allergens during this time frame should be recommended to predict the evolution of atopic diseases.

Dual modality virtual colonoscopy workstation: design, implementation, and preliminary evaluation

NASA Astrophysics Data System (ADS)

Chen, Dongqing; Meissner, Michael

2006-03-01

The aim of this study is to develop a virtual colonoscopy (VC) workstation that supports both CT (computed tomography) and MR (magnetic resonance) imaging procedures. The workflow should be optimized and be able to take advantage of both image modalities. The technological break through is at the real-time volume rendering of spatial-intensity-inhomogeneous MR images to achieve high quality 3D endoluminal view. VC aims at visualizing CT or MR tomography images for detection of colonic polyp and lesion. It is also called as CT/MR colonography based on the imaging modality that is employed. The published results of large scale clinical trial demonstrated more than 90% of sensitivity on polyp detection for certain CT colonography (CTC) workstation. A drawback of the CT colonoscopy is the radiation exposure. MR colonography (MRC) is free from the X-ray radiation. It achieved almost 100% specificity for polyp detection in published trials. The better tissue contrast in MR image allows the accurate diagnosis of inflammatory bowel disease also, which is usually difficult in CTC. At present, most of the VC workstations are designed for CT examination. They are not able to display multi-sequence MR series concurrently in a single application. The automatic correlation between 2D and 3D view is not available due to the difficulty of 3D model building for MR images. This study aims at enhancing a commercial VC product that was successfully used for CTC to equally support dark-lumen protocol MR procedure also.

Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas.

PubMed

Loussouarn, Delphine; Le Loupp, Anne-Gaëlle; Frenel, Jean-Sébastien; Leclair, François; Von Deimling, Andreas; Aumont, Maud; Martin, Stéphane; Campone, Mario; Denis, Marc G

2012-06-01

Previous studies have identified mutations of the isocitrate dehydrogenase 1 (IDH1) gene in more than 70% of World Health Organization (WHO) grade II and III gliomas. The most frequent mutation leads to a specific amino acid change from arginine to histidine at codon 132 (c.395G>A, p.R132H). IDH1 mutated tumors have a better prognosis than IDH1 non-mutated tumors. The aim of our study was to evaluate and compare the methods of mIDH1 R132H immunohistochemistry, allele-specific PCR and DNA sequencing for determination of IDH1 status. We performed a retrospective study of 91 patients with WHO grade II (n=43) and III (n=48) oligodendrogliomas. A fragment of exon 4 spanning the sequence encoding the catalytic domain of IDH1, including codon 132, was amplified and sequenced using standard conditions. Allele-specific amplification was performed using two forward primers with variations in their 3' nucleotides such that each was specific for the wild-type or the mutated variant, and one reverse primer. Immunohistochemistry was performed with mouse monoclonal mIDH1 R132H. DNA was extracted from FFPE sections following macrodissection. IDH1 mutations were found in 55/90 patients (61.1%) by direct sequencing. R132H mutations were found in 47/55 patients (85.4%). The results of the allele-specific PCR positively correlated with those from DNA sequencing. Other mutations (p.R132C, p.R132S and pR132G) were found by DNA sequencing in 3, 3 and 2 tumors, respectively (8/55 patients, 14.6%). mIDH1 R132H immunostaining was found in the 47 patients presenting the R132H mutation (sensitivity 47/47, 100% for this mutation). None of the tumors presenting a wild-type IDH1 gene were stained (specificity 35/35, 100%). Our results demonstrate that immunohistochemistry using the mIDH1 R132H antibody and allele-specific amplification are highly sensitive techniques to detect the most frequent mutation of the IDH1 gene.

Linking Investigations in Trauma and Emergency Services (LITES)

DTIC Science & Technology

2017-10-01

observational cohort that will have a limited data set from trauma registry data and electronic health records. Specific Aim one is to characterize the...epidemiology of moderate and severe physical injury in the U.S. and across the LITES network and investigate regional variations of presenting...observational cohort that will have a limited data set from trauma registry data and electronic health records. Specific Aim one is to characterize the

Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine

PubMed Central

Jakab, Robert L.; Collaco, Anne M.

2012-01-01

Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO3−-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane (BBM) recruitment of CFTR in crypts and villi. In villus enterocytes, CFTR recruitment was coincident with internalization of BBM NHE3 and basolateral membrane recruitment of the bicarbonate transporter NBCe1. Both cAMP and carbachol recruited NKCC1 to the basolateral membrane of enterocytes, while luminal acid or HCO3− retained NKCC1 in intracellular vesicles. Luminal acid resulted in robust recruitment of CFTR and NBCe1 to their respective enterocyte membrane domains in the upper third of the villi; luminal HCO3− induced similar membrane changes lower in the villi. These findings indicate that each stimulus promotes a specific transporter trafficking response along the crypt-villus axis. This is the first demonstration that physiologically relevant secretory stimuli exert their actions in villus enterocytes by membrane recruitment of CFTR and NBCe1 in tandem with NHE3 internalization. PMID:22936272

Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine.

PubMed

Jakab, Robert L; Collaco, Anne M; Ameen, Nadia A

2012-10-15

Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO(3)(-)-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane (BBM) recruitment of CFTR in crypts and villi. In villus enterocytes, CFTR recruitment was coincident with internalization of BBM NHE3 and basolateral membrane recruitment of the bicarbonate transporter NBCe1. Both cAMP and carbachol recruited NKCC1 to the basolateral membrane of enterocytes, while luminal acid or HCO(3)(-) retained NKCC1 in intracellular vesicles. Luminal acid resulted in robust recruitment of CFTR and NBCe1 to their respective enterocyte membrane domains in the upper third of the villi; luminal HCO(3)(-) induced similar membrane changes lower in the villi. These findings indicate that each stimulus promotes a specific transporter trafficking response along the crypt-villus axis. This is the first demonstration that physiologically relevant secretory stimuli exert their actions in villus enterocytes by membrane recruitment of CFTR and NBCe1 in tandem with NHE3 internalization.

Ageing opioid users' increased risk of methadone-specific death in the UK.

PubMed

Pierce, Matthias; Millar, Tim; Robertson, J Roy; Bird, Sheila M

2018-05-01

The first evidence that the hazard ratio (HR) for methadone-specific death rises more steeply with age-group than for all drug-related deaths (DRDs) came from Scotland's cohort of 33,000 methadone-prescription clients. We aim to examine, for England, whether illicit opioid users' risk of methadone-specific death increases with age; and to pool age-related HRs for methadone-specific deaths with those for Scotland's methadone-prescription clients. The setting is all services in England that provide publicly-funded, structured treatment for illicit opioid users, the methodology linkage of the English National Drug Treatment Monitoring System and mortality database, and key measurements are DRDs, methadone-specific DRDs, or heroin-specific DRDs, by age-group and gender, with proportional hazards adjustment for substances used, injecting status and periods in/out of treatment. Linkage was achieved for 129,979 adults receiving prescribing treatment modalities for opioid dependence during April 2005 to March 2009 and followed-up for 378,009 person-years (pys). There were 1,266 DRDs: 271 methadone-specific (7 per 10,000 pys: irrespective of gender) and 473 heroin-specific (15 per 10,000 pys for males, 7 for females). Methadone-specific DRD-rate per 10,000 person-years was 3.5 (95% CI: 2.7-4.4) at 18-34 years, 8.9 (CI: 7.3-10.5) at 35-44 years and 18 (CI: 13.8-21.2) at 45+ years; heroin-specific DRD-rate was unchanged with age. Relative to 25-34 years, pooled HRs for UK clients' methadone-specific deaths were: 0.87 at <25 years (95% CI: 0.56-1.35); 2.14 at 35-44 years (95% CI: 1.76-2.60); 3.75 at 45+ years (95% CI: 2.99-4.70). International testing and explanation are needed of UK's sharp age-related increase in the risk of methadone-specific death. Clients should be alerted that their risk of methadone-specific death increases as they age. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Mumps serum antibody levels before and after an outbreak to assess infection and immunity in vaccinated students.

PubMed

Gouma, Sigrid; Schurink-Van't Klooster, Tessa M; de Melker, Hester E; Kerkhof, Jeroen; Smits, Gaby P; Hahné, Susan J M; van Els, Cécile A C M; Boland, Greet J; Vossen, Ann C T M; Goswami, Pulak R; Koopmans, Marion P G; van Binnendijk, Rob S

2014-12-01

Since 2009, various mumps outbreaks have occurred in the Netherlands, affecting mostly young adults vaccinated against mumps. In this retrospective study, we estimated attack rates for symptomatic and asymptomatic mumps virus infection based on mumps-specific immunoglobulin (Ig)G concentrations in paired blood samples obtained before and after the mumps outbreaks, collected in 2 university cities. We aimed to identify a serological correlate of immune protection and risk factors for mumps virus infection. Mumps-specific IgG levels were measured by Luminex technology in paired pre- and post-outbreak samples from students from Leiden (n = 135) and Utrecht (n = 619). Persons with a 4-fold increase in mumps IgG concentrations or mumps IgG concentrations >1500 RU/mL were assumed to have had a mumps virus infection. Attack rates for symptomatic and asymptomatic mumps virus infection were 2.0% and 3.8%, respectively. Pre-outbreak mumps-specific IgG concentrations were lower among cases than among noncases (P = .005) despite vaccination history, but no serological cutoff for immune protection could be established. Mumps among housemates was significantly associated with serological evidence for mumps virus infection (odds ratio, 7.25 [95% confidence interval, 3.20-16.40]; P < .001). Symptomatic and asymptomatic mumps virus infections in vaccinated persons can be identified by retrospective assessment of mumps-specific IgG antibodies in blood samples.

Speech Perception and Phonological Short-Term Memory Capacity in Language Impairment: Preliminary Evidence from Adolescents with Specific Language Impairment (SLI) and Autism Spectrum Disorders (ASD)

ERIC Educational Resources Information Center

Loucas, Tom; Riches, Nick Greatorex; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Baird, Gillian

2010-01-01

Background: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. Aims: This study aimed to investigate the…

Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector.

PubMed

Liu, Quan; Yang, Yijun; Tan, Xuefang; Tao, Zhu; Adah, Dickson; Yu, Songlin; Lu, Junnan; Zhao, Siting; Qin, Limei; Qin, Li; Chen, Xiaoping

2017-04-11

We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y) expressing murine glypican-3 (GPC3) protein (P.y-GPC3), and examined its therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response were assessed after P.y-based immunization, which included obviously increased concentrations of T helper cell type 1 (Th1)-associated cytokines, such as IL-2, IFN-γ and TNF-α, in serum and preferential expansion of the CD8α+ dendritic cell (DC) subset with higher expression of CD80 and CD86 molecules. Compared with uninfected and wild-type P.y-infected mice, a significant GPC3-specific cytotoxic T lymphocyte (CTL) response was detected in P.y-GPC3 vaccinated mice. Furthermore, P.y-GPC3-based vaccination dramatically inhibited Hepa1-6-induced tumor growth in the implanted HCC and prolonged the survival of tumor-bearing mice. We concluded that a Plasmodium-based vector is highly efficient in inducing tumor antigen-specific T cell-mediated immunity and protection against tumor cells. More broadly, this strategy supported our hypothesis that Plasmodium parasites, as novel therapeutic antigen vectors, may be applicable to tumor immunotherapy for patients with HCC.

Systematic Review of Patient-Specific Surgical Simulation: Toward Advancing Medical Education.

PubMed

Ryu, Won Hyung A; Dharampal, Navjit; Mostafa, Ahmed E; Sharlin, Ehud; Kopp, Gail; Jacobs, William Bradley; Hurlbert, Robin John; Chan, Sonny; Sutherland, Garnette R

Simulation-based education has been shown to be an effective tool to teach foundational technical skills in various surgical specialties. However, most of the current simulations are limited to generic scenarios and do not allow continuation of the learning curve beyond basic technical skills to prepare for more advanced expertise, such as patient-specific surgical planning. The objective of this study was to evaluate the current medical literature with respect to the utilization and educational value of patient-specific simulations for surgical training. We performed a systematic review of the literature using Pubmed, Embase, and Scopus focusing on themes of simulation, patient-specific, surgical procedure, and education. The study included randomized controlled trials, cohort studies, and case-control studies published between 2005 and 2016. Two independent reviewers (W.H.R. and N.D) conducted the study appraisal, data abstraction, and quality assessment of the studies. The search identified 13 studies that met the inclusion criteria; 7 studies employed computer simulations and 6 studies used 3-dimensional (3D) synthetic models. A number of surgical specialties evaluated patient-specific simulation, including neurosurgery, vascular surgery, orthopedic surgery, and interventional radiology. However, most studies were small in size and primarily aimed at feasibility assessments and early validation. Early evidence has shown feasibility and utility of patient-specific simulation for surgical education. With further development of this technology, simulation-based education may be able to support training of higher-level competencies outside the clinical settingto aid learners in their development of surgical skills. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNFα enhances GPR84 expression in adipocytes.

PubMed

Nagasaki, Hiroshi; Kondo, Takaaki; Fuchigami, Masahiro; Hashimoto, Hiroyuki; Sugimura, Yoshihisa; Ozaki, Nobuaki; Arima, Hiroshi; Ota, Akira; Oiso, Yutaka; Hamada, Yoji

2012-02-17

In this study we aimed to identify the physiological roles of G protein-coupled receptor 84 (GPR84) in adipose tissue, together with medium-chain fatty acids (MCFAs), the specific ligands for GPR84. In mice, high-fat diet up-regulated GPR84 expression in fat pads. In 3T3-L1 adipocytes, co-culture with a macrophage cell line, RAW264, or TNFα remarkably enhanced GPR84 expression. In the presence of TNFα, MCFAs down-regulated adiponectin mRNA expression in 3T3-L1 adipocytes. Taken together, our results suggest that GPR84 emerges in adipocytes in response to TNFα from infiltrating macrophages and exacerbates the vicious cycle between adiposity and diabesity. Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

PubMed Central

Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid

2016-01-01

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428

Health-related quality of life questionnaires in lung cancer trials: a systematic literature review

PubMed Central

2013-01-01

Background Lung cancer is one of the leading causes of cancer deaths. Treatment goals are the relief of symptoms and the increase of overall survival. With the rising number of treatment alternatives, the need for comparable assessments of health-related quality of life (HRQoL) parameters grows. The aim of this paper was to identify and describe measurement instruments applied in lung cancer patients under drug therapy. Methods We conducted a systematic literature review at the beginning of 2011 using the electronic database Pubmed. Results A total of 43 studies were included in the review. About 17 different measurement instruments were identified, including 5 generic, 5 cancer-specific, 4 lung cancer-specific and 3 symptom-specific questionnaires. In 29 studies at least 2 instruments were used. In most cases these were cancer and lung cancer-specific ones. The most frequently used instruments are the EORTC QLQ-C30 and its lung cancer modules LC13 or LC17. Only 5 studies combined (lung) cancer-specific questionnaires with generic instruments. Conclusions The EORTC-C30 and EORTC-LC13 are the most frequently used health-related quality of life measurement instruments in pharmacological lung cancer trials. PMID:23680096

Validation of a Screening Questionnaire for Chronic Leg Ulcers.

PubMed

Zarchi, Kian; Theut Riis, Peter; Graversgaard, Christine; Miller, Iben M; Heidenheim, Michael; Jemec, Gregor B E

2016-12-01

The use of a validated screening questionnaire to identify individuals with chronic leg ulcers allows large-scale population-based studies to be conducted that measure and monitor the prevalence of the disease. The aim of this study was to design and validate such a screening questionnaire to identify patients with chronic leg ulcers. A simple 3-item questionnaire was developed at the Department of Dermatology, University Hospital of Zealand, Denmark. In total, 90 patients attending the department's outpatient clinic for dermatological diseases and chronic wounds were included in this study. All included participants completed the questionnaire and were subsequently examined by dermatologists. We found that the constructed 3-item questionnaire in this study had a sensitivity and specificity of 95% and 93% and a positive predictive value and negative predictive value of 78% and 95%, respectively. Moreover, we found that the use of the 3-item questionnaire, as compared with a single question, in which the participants were asked whether they currently have a leg ulcer, resulted in significantly higher positive predictive value (+11.6%, P = .035) and specificity (+5.6%, P = .046) of the diagnostic test. Future studies are merited to investigate the diagnostic accuracy of the questionnaire in other populations and settings.

Cardiac Parasympathetic Reactivation in Elite Soccer Players During Different Types of Traditional High-Intensity Training Exercise Modes and Specific Tests: Interests and Limits

PubMed Central

Dellal, Alexandre; Casamichana, David; Castellano, Julen; Haddad, Monoem; Moalla, Wassim; Chamari, Karim

2015-01-01

Background: The cardiac parasympathetic reactivation is currently used in soccer with a daily or weekly monitoring. However, previous studies have not investigated how this cardiac parasympathetic reactivation is in elite soccer players along different types of traditional high-intensity training exercise and specific tests. In this context, the present study aim to analyse it and to determine the interests and limits of this type of physiological information. Objectives: The present study aims to examine how different traditional training exercise modes affect the cardiac parasympathetic reactivation function in elite soccer players. Materials and Methods: Twenty-two international soccer players participating in UEFA Champion’s League took part in this study (age: 24.3 ± 4.2 years; height: 178.1 ± 6.2 cm; body mass: 80.3 ± 5.7 kg). Players performed different training methods including: short-duration intermittent exercises (INT) in-line and with changes of direction (COD) (10 - 10 seconds, 15 - 15 seconds, 30 - 30 seconds, e.g. an alternance of 10 - 10 seconds is 10 seconds of running according to the maximal aerobic speed (MAS) and 10-sec of recovery), INT including agility and technical skills (8 - 24-seconds), small-sided-games (SSGs) with and without goalkeepers (2 vs. 2, 3 vs. 3, 4 vs. 4), and repeated sprint ability (RSA) efforts (10 × 20 m, 10 × 30 m, 15 × 20 m). Heart rate (HR) decline was recorded 3 minutes after each exercise. Results: HR declines were greater after the RSA compared to SSGs (P < 0.001) and INT (P < 0.01), especially at 1 min post-exercise. In addition, when the analysis focused on each type of exercise, greater HR declines were observed in on-field players at 1 minute when there was: inclusion of goalkeepers in SSGs (for 2 vs. 2 and 3 vs. 3, P < 0.01); increase of sprint distances or number of sprint repetitions in RSA (P < 0.01); increase of intensity (% of maximal aerobic speed), and the use of COD or inclusion of technical skills during INT, especially for the 30 - 30-seconds. Conclusions: This study revealed that cardiac parasympathetic reactivation function varied after INT, RSA and SSG, but also according to the rules manipulation. Therefore, this study provides interesting information for the training monitoring and players’ recovery profile, with the aim of facilitating a more efficient planning and manipulation of training recovery strategies according to their fitness markers. PMID:26715972

Characterisation of myosin heavy chain gene variants in the fast and slow muscle fibres of gammarid amphipods.

PubMed

Whiteley, N M; Magnay, J L; McCleary, S J; Nia, S Khazraee; El Haj, A J; Rock, J

2010-10-01

Recent molecular work has revealed a large diversity of myosin heavy chain (MyHC) gene variants in the abdominal musculature of gammarid amphipods. An unusual truncated MyHC transcript from the loop 1 region (Variant A(3)) was consistently observed in multiple species and populations. The current study aimed to determine whether this MyHC variant is specific to a particular muscle fibre type, as a change in net charge to the loop 1 region of Variant A(3) could be functionally significant. The localisation of different fibre types within the abdominal musculature of several gammarid species revealed that the deep flexor and extensor muscles are fast-twitch muscle fibres. The dorsal superficial muscles were identified as slow fibres and the muscles extrinsic to the pleopods were identified as intermediate fibres. Amplification of loop 1 region mRNA from isolated superficial extensor and deep flexor muscles, and subsequent liquid chromatography and sequence analysis revealed that Variant A(3) was the primary MyHC variant in slow muscles, and the conserved A(1) sequence was the primary variant in fast muscles. The specific role of Variant A(3) in the slow muscles remains to be investigated. 2010 Elsevier Inc. All rights reserved.

A full Monte Carlo simulation of the YAP-PEM prototype for breast tumor detection

NASA Astrophysics Data System (ADS)

Motta, A.; Righi, S.; Del Guerra, A.; Belcari, N.; Vaiano, A.; De Domenico, G.; Zavattini, G.; Campanini, R.; Lanconelli, N.; Riccardi, A.

2004-07-01

A prototype for Positron Emission Mammography, the YAP-PEM, is under development within a collaboration of the Italian Universities of Pisa, Ferrara, and Bologna. The aim is to detect breast lesions, with dimensions of 5 mm in diameter, and with a specific activity ratio of 10:1 between the cancer and breast tissue. The YAP-PEM is composed of two stationary detection heads of 6×6 cm 2, composed of a matrix of 30×30 YAP:Ce finger crystals of 2×2×30 mm 3 each. The EGSnrc Monte Carlo code has been used to simulate several characteristics of the prototype. A fast EM algorithm has been adapted to reconstruct all of the collected lines of flight, also at large incidence angles, by achieving 3D positioning capability of the lesion in the FOV. The role of the breast compression has been studied. The performed study shows that a 5 mm diameter tumor of 37 kBq/cm 3 (1 μCi/cm 3), embedded in active breast tissue with 10:1 tumor/background specific activity ratio, is detected in 10 min with a Signal-to-Noise Ratio of 8.7±1.0. Two hot lesions in the active breast phantom are clearly visible in the reconstructed image.

BATTLE: Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination

DTIC Science & Technology

2007-04-01

localization, which • The combination of erlotinib and Ad-dnIGF-1R synergistically inhibits the growth of tumors in xenograft mouse models . able outcomes...of erlotinib and Ad-dnIGF-1R synergistically inhibits the growth of tumors in xenograft mouse models . Specific Aim 2.3: To investigate the...biomarkers and adaptive randomization via hierarchical Bayes modeling . 2) To study the molecular mechanisms of response and resistance to targeted

Robust Routing Protocol For Digital Messages

NASA Technical Reports Server (NTRS)

Marvit, Maclen

1994-01-01

Refinement of ditigal-message-routing protocol increases fault tolerance of polled networks. AbNET-3 is latest of generic AbNET protocols for transmission of messages among computing nodes. AbNET concept described in "Multiple-Ring Digital Communication Network" (NPO-18133). Specifically aimed at increasing fault tolerance of network in broadcast mode, in which one node broadcasts message to and receives responses from all other nodes. Communication in network of computers maintained even when links fail.

Siah1/2 Ubiquitin Ligases in ER Stress Signaling in Melanoma

DTIC Science & Technology

2015-10-01

expression of RTK including EGFR, PDGFR and AXL , which were shown to be important in melanoma resistance phenotypes. This study was published few months ago...year will establish novel therapeutic modality for treatment of cancer, focused on melanoma. Major Task 3: Determine the effect of Siah1/2 and ER...foundation for novel stratification methods and therapeutic modalities for BCa. Specific Aims: (1) Identify RNF5-dependent and -independent

Tumorigenic Potential of Transit Amplifying Prostate Cells

DTIC Science & Technology

2012-06-01

by ChIP-Seq showed that in both the human prostate cell line LNCaP and in mouse prostate, NKX3.1 bound DNA fragments are significantly enriched in...progression. Cancer Cell. 2010;17(5):443–454. 29. Steadman DJ, Giuffrida D, Gelmann EP. DNA - binding sequence of the human prostate-specific...bind nucleosomal DNA and destabilize nucleosomes thereby allowing other transcription factors to access their sites (7),(8). BODY Aim 1: To

Effects of Early Acute Care on Autonomic Outcomes in SCI: Bedside to Bench and Back

DTIC Science & Technology

2016-10-01

Journal of Neurotrauma (Hawlryluk GWH, Whetstone W, Saigal R, Ferguson AR, Talbott JF, Bresnahan JC, Dhall SS...Other 2 Blunt Injury 26 ISS on Arrival (N=19) 29.6 (10-75) Central Cord 13 History of Hypertension 10 Hospital Stay Transport Time (N...Specific Aim 3: Determine the effects of episodes of hypotension and hypertension on the recovery of locomotor and bladder and bowel function

Sulforaphane Treatment of Children with Autism Spectrum Disorder

DTIC Science & Technology

2016-07-01

aims of the study are: (1) to determine if there are measurable effects on social responsiveness and problem behaviors during treatment with orally...Analyses and assessments will be done at several specific points over the course of the study . To date, the Pilot trial of 10 children has been...crosses the blood brain barrier and is bioavailable orally. The study will enroll 50 children with moderate to severe autism, between 3 and 12 years

Validation of Smartphone Based Retinal Photography for Diabetic Retinopathy Screening

PubMed Central

Rajalakshmi, Ramachandran; Arulmalar, Subramanian; Usha, Manoharan; Prathiba, Vijayaraghavan; Kareemuddin, Khaji Syed; Anjana, Ranjit Mohan; Mohan, Viswanathan

2015-01-01

Aim To evaluate the sensitivity and specificity of “fundus on phone’ (FOP) camera, a smartphone based retinal imaging system, as a screening tool for diabetic retinopathy (DR) detection and DR severity in comparison with 7-standard field digital retinal photography. Design Single-site, prospective, comparative, instrument validation study. Methods 301 patients (602 eyes) with type 2 diabetes underwent standard seven-field digital fundus photography with both Carl Zeiss fundus camera and indigenous FOP at a tertiary care diabetes centre in South India. Grading of DR was performed by two independent retina specialists using modified Early Treatment of Diabetic Retinopathy Study grading system. Sight threatening DR (STDR) was defined by the presence of proliferative DR(PDR) or diabetic macular edema. The sensitivity, specificity and image quality were assessed. Results The mean age of the participants was 53.5 ±9.6 years and mean duration of diabetes 12.5±7.3 years. The Zeiss camera showed that 43.9% had non-proliferative DR(NPDR) and 15.3% had PDR while the FOP camera showed that 40.2% had NPDR and 15.3% had PDR. The sensitivity and specificity for detecting any DR by FOP was 92.7% (95%CI 87.8–96.1) and 98.4% (95%CI 94.3–99.8) respectively and the kappa (ĸ) agreement was 0.90 (95%CI-0.85–0.95 p<0.001) while for STDR, the sensitivity was 87.9% (95%CI 83.2–92.9), specificity 94.9% (95%CI 89.7–98.2) and ĸ agreement was 0.80 (95%CI 0.71–0.89 p<0.001), compared to conventional photography. Conclusion Retinal photography using FOP camera is effective for screening and diagnosis of DR and STDR with high sensitivity and specificity and has substantial agreement with conventional retinal photography. PMID:26401839

Patch testing and allergen-specific serum IgE and IgG antibodies in the diagnosis of canine adverse food reactions.

PubMed

Bethlehem, Simone; Bexley, Jennifer; Mueller, Ralf S

2012-02-15

Adverse food reaction (AFR) is a common differential diagnosis for pruritic dogs. The only way to diagnose AFR is an elimination diet of 6-8 weeks with a protein and a carbohydrate source not previously fed. In humans, patch testing has been shown to be a useful tool to diagnose food allergies. In veterinary medicine, serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for such diets. The aim of this study was to determine sensitivity, specificity, negative and positive predictability of patch testing with and serum antibody testing for a variety of common food stuffs. Twenty-five allergic dogs underwent an elimination diet and individual rechallenge with selected food stuffs, food patch testing and serum testing for food-antigen specific IgE and IgG. Eleven clinically normal control dogs only were subjected to patch and serum testing. The sensitivity and specificity of the patch test were 96.7 and 89.0% respectively, negative and positive predictability were 99.3 and 63.0%. For IgE and IgG the sensitivity was 6.7 and 26.7%, specificity were 91.4 and 88.3%, the negative predictive values 80.7 and 83.7% and the positive predictive values were 15.4 and 34.8%. Based on these results, a positive reaction of a dog on these tests is not very helpful, but a negative result indicates that this antigen is tolerated well. We conclude that patch testing (and to a lesser degree serum testing) can be helpful in choosing ingredients for an elimination diet in a dog with suspected AFR. Copyright © 2012. Published by Elsevier B.V.

Modulators of 14-3-3 Protein–Protein Interactions

PubMed Central

2017-01-01

Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein–protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as “undruggable” targets, the last two decades have seen an increasing number of successful examples of PPI modulators, resulting in growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This perspective focuses on the hub-protein 14-3-3, which has several hundred identified protein interaction partners, and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide mimetics, and natural products. PMID:28968506

H-Ransac a Hybrid Point Cloud Segmentation Combining 2d and 3d Data

NASA Astrophysics Data System (ADS)

Adam, A.; Chatzilari, E.; Nikolopoulos, S.; Kompatsiaris, I.

2018-05-01

In this paper, we present a novel 3D segmentation approach operating on point clouds generated from overlapping images. The aim of the proposed hybrid approach is to effectively segment co-planar objects, by leveraging the structural information originating from the 3D point cloud and the visual information from the 2D images, without resorting to learning based procedures. More specifically, the proposed hybrid approach, H-RANSAC, is an extension of the well-known RANSAC plane-fitting algorithm, incorporating an additional consistency criterion based on the results of 2D segmentation. Our expectation that the integration of 2D data into 3D segmentation will achieve more accurate results, is validated experimentally in the domain of 3D city models. Results show that HRANSAC can successfully delineate building components like main facades and windows, and provide more accurate segmentation results compared to the typical RANSAC plane-fitting algorithm.

Development and application of the RE-AIM QuEST mixed methods framework for program evaluation.

PubMed

Forman, Jane; Heisler, Michele; Damschroder, Laura J; Kaselitz, Elizabeth; Kerr, Eve A

2017-06-01

To increase the likelihood of successful implementation of interventions and promote dissemination across real-world settings, it is essential to evaluate outcomes related to dimensions other than Effectiveness alone. Glasgow and colleagues' RE-AIM framework specifies four additional types of outcomes that are important to decision-makers: Reach, Adoption, Implementation (including cost), and Maintenance. To further strengthen RE-AIM, we propose integrating qualitative assessments in an expanded framework: RE-AIM Qualitative Evaluation for Systematic Translation (RE-AIM QuEST), a mixed methods framework. RE-AIM QuEST guides formative evaluation to identify real-time implementation barriers and explain how implementation context may influence translation to additional settings. RE-AIM QuEST was used to evaluate a pharmacist-led hypertension management intervention at 3 VA facilities in 2008-2009. We systematically reviewed each of the five RE-AIM dimensions and created open-ended companion questions to quantitative measures and identified qualitative and quantitative data sources, measures, and analyses. To illustrate use of the RE-AIM QuEST framework, we provide examples of real-time, coordinated use of quantitative process measures and qualitative methods to identify site-specific issues, and retrospective use of these data sources and analyses to understand variation across sites and explain outcomes. For example, in the Reach dimension, we conducted real-time measurement of enrollment across sites and used qualitative data to better understand and address barriers at a low-enrollment site. The RE-AIM QuEST framework may be a useful tool for improving interventions in real-time, for understanding retrospectively why an intervention did or did not work, and for enhancing its sustainability and translation to other settings.

Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study.

PubMed

Blanchard, Valentin; Ramin-Mangata, Stéphane; Billon-Crossouard, Stéphanie; Aguesse, Audrey; Durand, Manon; Chemello, Kevin; Nativel, Brice; Flet, Laurent; Chétiveaux, Maud; Jacobi, David; Bard, Jean-Marie; Ouguerram, Khadija; Lambert, Gilles; Krempf, Michel; Croyal, Mikaël

2018-05-01

Human apoE exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the APOE gene. Total plasma apoE concentrations are closely related to these isoforms, but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used LC-MS/MS to discriminate between isoforms by identifying specific peptide sequences in subjects (three E2/E3, three E3/E3, and three E3/E4 phenotypes) who received a primed constant infusion of 2 H 3 -leucine for 14 h. apoE concentrations and leucine enrichments were measured hourly in plasma. Concentrations of apoE2 were higher than apoE3, and concentrations of apoE4 were lower than apoE3. There was no difference between apoE3 and apoE4 catabolic rates and between apoE2 and apoE3 production rates (PRs), but apoE2 catabolic rates and apoE4 PRs were lower. The mechanisms leading to the difference in total plasma apoE concentrations are therefore related to contrasted kinetics of the isoforms. Production or catabolic rates are differently affected according to the specific isoforms. On these grounds, studies on the regulation of the involved biochemical pathways and the impact of pathological environments are now warranted. Copyright © 2018 Blanchard et al.

Differential Association of the Na+/H+ Exchanger Regulatory Factor (NHERF) Family of Adaptor Proteins with the Raft-and the Non-Raft Brush Border Membrane Fractions of NHE3

PubMed Central

Sultan, Ayesha; Luo, Min; Yu, Qin; Riederer, Brigitte; Xia, Weiliang; Chen, Mingmin; Lissner, Simone; Gessner, Johannes E.; Donowitz, Mark; Yun, C. Chris; deJonge, Hugo; Lamprecht, Georg; Seidler, Ursula

2014-01-01

Background/Aims Trafficking, brush border membrane (BBM) retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adaptor proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of these NHERFs. Thus, we studied the association of NHE3, NHERF1 (EBP50), NHERF2 (E3KARP), and NHERF3 (PDZK1) with lipid rafts in murine small intestinal BBM. Methods Detergent resistant membranes (“lipid rafts”) were isolated by floatation of Triton X-incubated small intestinal BBM from a variety of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3 activity was measured fluorometrically in BCECF-loaded microdissected villi, or by assessment of CO2/HCO3− mediated increase in fluid absorption in perfused jejunal loops of anethetized mice. Results NHE3 was found to partially associate with lipid rafts in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase-deficient mice, which have altered membrane lipid as well as lipid raft composition, allowed us to test the validity of the lipid raft concept in vivo. Conclusions The differential association of the NHERFs with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is one component of the differential and signal-specific NHE3 regulation by the different NHERFs. PMID:24297041

Oncolytic Viruses-Interaction of Virus and Tumor Cells in the Battle to Eliminate Cancer.

PubMed

Howells, Anwen; Marelli, Giulia; Lemoine, Nicholas R; Wang, Yaohe

2017-01-01

Oncolytic viruses (OVs) are an emerging treatment option for many cancer types and have recently been the focus of extensive research aiming to develop their therapeutic potential. The ultimate aim is to design a virus which can effectively replicate within the host, specifically target and lyse tumor cells and induce robust, long lasting tumor-specific immunity. There are a number of viruses which are either naturally tumor-selective or can be modified to specifically target and eliminate tumor cells. This means they are able to infect only tumor cells and healthy tissue remains unharmed. This specificity is imperative in order to reduce the side effects of oncolytic virotherapy. These viruses can also be modified by various methods including insertion and deletion of specific genes with the aim of improving their efficacy and safety profiles. In this review, we have provided an overview of the various virus species currently being investigated for their oncolytic potential and the positive and negative effects of a multitude of modifications used to increase their infectivity, anti-tumor immunity, and treatment safety, in particular focusing on the interaction of tumor cells and OVs.

Assessment of the best N(3-) donors in preparation of [M(N)(PNP)]-based (M=(99m)Tc-; (188)Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ).

PubMed

Carta, Davide; Jentschel, Christian; Thieme, Stefan; Salvarese, Nicola; Morellato, Nicolò; Refosco, Fiorenzo; Ruzza, Paolo; Bergmann, Ralf; Pietzsch, Hans-Jurgen; Bolzati, Cristina

2014-08-01

Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]-complexes (M=(99m)Tc and (188)Re). This study aims to compare the capability and the efficiency of these three N(3-) group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M=(99m)Tc, (188)Re; PNP=aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO2C-PEG600-DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys~)(PNP3)](0/+) complexes (cys~=cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(~cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N(3-) donors and of the exchanging ligand, was determined. For (99m)Tc, data clearly show that HDTCZ is the most efficient donor of N(3-); however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [(99m)Tc(N)(PNP)]-based target-specific agents with high specific activity. When HO2C-PEG600-DTCZ or HDTCZ are used in N(3-) donation, high amounts of the exchanging ligand (10(-4)M) were required for the formation of the final complex in acceptable yield. The possibility to use microgram amounts of HDTCZ also in [(188)Re(N)] preparation (0.050mg) reduces its ability to compete in ligand exchange reactions, minimizing the quantity of chelators required to obtain the final complex in high yield. This finding can be exploit for increasing the radiolabeling efficiency in [(188)Re(N)]-radiopharmaceutical preparations compared to the previously reported HDTCZ-based procedure, notwithstanding a purification process could be necessary to improve the specific activity of the complexes. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

PubMed

Hiramine, Yasushi; Tanabe, Toshizumi

2011-06-01

Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

PubMed Central

Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

2017-01-01

ABSTRACT Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). Conclusions: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants. PMID:28059609

Memory Alteration Test to Detect Amnestic Mild Cognitive Impairment and Early Alzheimer's Dementia in Population with Low Educational Level.

PubMed

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Montesinos, Rosa; Castro-Suarez, Sheila; Cuenca-Alfaro, José; Valeriano-Lorenzo, Lucía

2017-01-01

Background/Aims : Short tests to early detection of the cognitive impairment are necessary in primary care setting, particularly in populations with low educational level. The aim of this study was to assess the performance of Memory Alteration Test (M@T) to discriminate controls, patients with amnestic Mild Cognitive Impairment (aMCI) and patients with early Alzheimer's Dementia (AD) in a sample of individuals with low level of education. Methods : Cross-sectional study to assess the performance of the M@T (study test), compared to the neuropsychological evaluation (gold standard test) scores in 247 elderly subjects with low education level from Lima-Peru. The cognitive evaluation included three sequential stages: (1) screening (to detect cases with cognitive impairment); (2) nosological diagnosis (to determinate specific disease); and (3) classification (to differentiate disease subtypes). The subjects with negative results for all stages were considered as cognitively normal (controls). The test performance was assessed by means of area under the receiver operating characteristic (ROC) curve. We calculated validity measures (sensitivity, specificity and correctly classified percentage), the internal consistency (Cronbach's alpha coefficient), and concurrent validity (Pearson's ratio coefficient between the M@T and Clinical Dementia Rating (CDR) scores). Results : The Cronbach's alpha coefficient was 0.79 and Pearson's ratio coefficient was 0.79 ( p < 0.01). The AUC of M@T to discriminate between early AD and aMCI was 99.60% (sensitivity = 100.00%, specificity = 97.53% and correctly classified = 98.41%) and to discriminate between aMCI and controls was 99.56% (sensitivity = 99.17%, specificity = 91.11%, and correctly classified = 96.99%). Conclusions : The M@T is a short test with a good performance to discriminate controls, aMCI and early AD in individuals with low level of education from urban settings.

Laws, causation and dynamics at different levels.

PubMed

Butterfield, Jeremy

2012-02-06

I have two main aims. The first is general, and more philosophical (§2). The second is specific, and more closely related to physics (§§3 and 4). The first aim is to state my general views about laws and causation at different 'levels'. The main task is to understand how the higher levels sustain notions of law and causation that 'ride free' of reductions to the lower level or levels. I endeavour to relate my views to those of other symposiasts. The second aim is to give a framework for describing dynamics at different levels, emphasizing how the various levels' dynamics can mesh or fail to mesh. This framework is essentially that of elementary dynamical systems theory. The main idea will be, for simplicity, to work with just two levels, dubbed 'micro' and 'macro', which are related by coarse-graining. I use this framework to describe, in part, the first four of Ellis' five types of top-down causation.

Virtual 3D planning of tracheostomy placement and clinical applicability of 3D cannula design: a three-step study.

PubMed

de Kleijn, Bertram J; Kraeima, Joep; Wachters, Jasper E; van der Laan, Bernard F A M; Wedman, Jan; Witjes, M J H; Halmos, Gyorgy B

2018-02-01

We aimed to investigate the potential of 3D virtual planning of tracheostomy tube placement and 3D cannula design to prevent tracheostomy complications due to inadequate cannula position. 3D models of commercially available cannula were positioned in 3D models of the airway. In study (1), a cohort that underwent tracheostomy between 2013 and 2015 was selected (n = 26). The cannula was virtually placed in the airway in the pre-operative CT scan and its position was compared to the cannula position on post-operative CT scans. In study (2), a cohort with neuromuscular disease (n = 14) was analyzed. Virtual cannula placing was performed in CT scans and tested if problems could be anticipated. Finally (3), for a patient with Duchenne muscular dystrophy and complications of conventional tracheostomy cannula, a patient-specific cannula was 3D designed, fabricated, and placed. (1) The 3D planned and post-operative tracheostomy position differed significantly. (2) Three groups of patients were identified: (A) normal anatomy; (B) abnormal anatomy, commercially available cannula fits; and (C) abnormal anatomy, custom-made cannula, may be necessary. (3) The position of the custom-designed cannula was optimal and the trachea healed. Virtual planning of the tracheostomy did not correlate with actual cannula position. Identifying patients with abnormal airway anatomy in whom commercially available cannula cannot be optimally positioned is advantageous. Patient-specific cannula design based on 3D virtualization of the airway was beneficial in a patient with abnormal airway anatomy.

Targeted delivery of doxorubicin into tumor cells by nanostructured lipid carriers conjugated to anti-EGFRvIII monoclonal antibody.

PubMed

Abdolahpour, Saeideh; Toliyat, Tayebeh; Omidfar, Kobra; Modjtahedi, Helmout; Wong, Albert J; Rasaee, Mohammad Javad; Kashanian, Susan; Paknejad, Maliheh

2018-02-01

Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the EGF receptor in many human tumors. This variant is tumor specific and highly immunogenic, thus, it can be used as a target for targeted drug delivery toward tumor cells. The major aim of this study was to develop an EGFRvIII-mediated drug delivery system by anti-EGFRvIII monoclonal antibody (MAb) conjugated to doxorubicin (Dox)-loaded nanostructured lipid carriers (NLC) to enhance the targeting specificity and cytotoxic effect of Dox on EGFRvIII-overexpressing cell line. In our study, Dox was chosen as a hydrophobic cytotoxic drug and drug-loaded nanostructured lipid carriers (Dox-NLC) was prepared by solvent emulsification/evaporation method. In order to conjugate anti-EGFRvIII MAb to Dox-NLC, DSPE-PEG2000-NHS (1,2-distearoylphosphatidylethanolamine-polyethylene glycol 2000-NHS) was used as a linker. Physicochemical characteristics of antibody conjugated Dox-NLC (MAb-Dox-NLC), including particle size, zeta potential, entrapment efficiency and in vitro Dox release were investigated. Cytotoxicity of MAb-Dox-NLC against NIH-3T3 and HC2 20d2/c (EGFRvIII-transfected NIH-3T3) cell lines was evaluated. The MAb-Dox-NLC appeared to enhance the cytotoxic activity of targeted NLC against HC2 20d2/c cells. The cellular uptake percentage of targeted NLC by HC2 20d2/c cells was higher than that of NIH-3T3 cells, indicating that EGFRvIII can specifically target HC2 20d2/c cells. In conclusion, anti-EGFRvIII MAb-targeted NLC may be considered as an effective nanocarrier for targeted drug delivery.

The Ottawa ankle rules for the use of diagnostic X-ray in after hours medical centres in New Zealand.

PubMed

Wynn-Thomas, Simon; Love, Tom; McLeod, Deborah; Vernall, Sue; Kljakovic, Marjan; Dowell, Antony; Durham, John

2002-09-27

The aims of this study were to measure baseline use of Ottawa ankle rules (OAR), validate the OAR and, if appropriate, explore the impact of implementing the Rules on X-ray rates in a primary care, after hours medical centre setting. General practitioners (GPs) were surveyed to find their awareness of ankle injury guidelines. Data concerning diagnosis and X-ray utilisation were collected prospectively for patients presenting with ankle injuries to two after hours medical centres. The OAR were applied retrospectively, and the sensitivity and specificity of the OAR were compared with GPs clinical judgement in ordering X-rays. The outcome measures were X-ray utilisation and diagnosis of fracture. Awareness of the OAR was low. The sensitivity of the OAR for diagnosis of fractures was 100% (95% CI: 75.3 - 100) and the specificity was 47% (95% CI: 40.5 - 54.5). The sensitivity of GPs clinical judgement was 100% (95% CI: 75.3 - 100) and the specificity was 37% (95% CI: 30.2 - 44.2). Implementing the OAR would reduce X-ray utilisation by 16% (95% CI: approx 10.8 - 21.3). The OAR are valid in a New Zealand primary care setting. Further implementation of the rules would result in some reduction of X-rays ordered for ankle injuries, but less than the reduction found in previous studies.

CD4+ T-cell engagement by both wild-type and variant HCV peptides modulates the conversion of viral clearing helper T cells to Tregs

PubMed Central

Cusick, Matthew F; Libbey, Jane E; Cox Gill, Joan; Fujinami, Robert S; Eckels, David D

2013-01-01

Aim To determine whether modulation of T-cell responses by naturally occurring viral variants caused an increase in numbers of Tregs in HCV-infected patients. Patients, materials & methods Human peripheral blood mononuclear cells, having proliferative responses to a wild-type HCV-specific CD4+ T-cell epitope, were used to quantify, via proliferative assays, flow cytometry and class II tetramers, the effects of naturally occurring viral variants arising in the immunodominant epitope. Results In combination, the wild-type and variant peptides led to enhanced suppression of an anti-HCV T-cell response. The variant had a lower avidity for the wild-type-specific CD4+ T cell. Variant-stimulated CD4+ T cells had increased Foxp3, compared with wild-type-stimulated cells. Conclusion A stable viral variant from a chronic HCV subject was able to induce Tregs in multiple individuals that responded to the wild-type HCV-specific CD4+ T-cell epitope. PMID:24421862

How Does Attention Relate to the Ability-Specific and Position-Specific Components of Reasoning Measured by APM?

ERIC Educational Resources Information Center

Ren, Xuezhu; Goldhammer, Frank; Moosbrugger, Helfried; Schweizer, Karl

2012-01-01

The aim of the present study was to clarify the nature of the ability-specific and position-specific components of Raven's Advanced Progressive Matrices (APM) by relating them to a number of types of attention. The ability-specific component represents the constant part of cognitive performance whereas the position-specific component reflects the…

Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

PubMed

Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

2016-07-01

The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

Age of majority assessment in Dutch individuals based on Cameriere's third molar maturity index.

PubMed

Boyacıoğlu Doğru, Hatice; Gulsahi, Ayşe; Çehreli, Sevi Burçak; Galić, Ivan; van der Stelt, Paul; Cameriere, Roberto

2018-01-01

Radiological examination of the third molar is done in living individuals for estimation of chronological age, especially in the late adolescence. The aim of this study was to assess the application of Cameriere's third molar maturity index (I 3M ) to determine whether an individual is 18 years or older (adult) or younger than 18 years (minor) in a sample of Dutch individuals. The sample consisted of panoramic images of 360 individuals aged between 14 and 22 years old. Three observers performed the measurements. Gender was not statistically significant in discriminating adults and minors. The highest value of the Youden index of the receiver operating curve analysis was for the value of I 3M <0.08 in discriminating individuals as minor or adult. The specificity (Sp) and sensitivity (Se) results for females were 96.3% and 72.7% respectively. The Sp and Se for males were 95.0% and 84.0% respectively. The probabilities of correctly classified individuals were 83.3% and 88.9%, and Bayes post-test probability was 96.3% and 95.7% in females and males respectively. Obtained results showed that the specific cut-off point of I 3M <0.08 may be a useful and reliable method for adult age assessment in a Dutch population. Copyright © 2017 Elsevier B.V. All rights reserved.

Can paediatric early warning scores (PEWS) be used to guide the need for hospital admission and predict significant illness in children presenting to the emergency department? An assessment of PEWS diagnostic accuracy using sensitivity and specificity.

PubMed

Lillitos, Peter J; Hadley, Graeme; Maconochie, Ian

2016-05-01

Designed to detect early deterioration of the hospitalised child, paediatric early warning scores (PEWS) validity in the emergency department (ED) is less validated. We aimed to evaluate sensitivity and specificity of two commonly used PEWS (Brighton and COAST) in predicting hospital admission and, for the first time, significant illness. Retrospective analysis of PEWS data for paediatric ED attendances at St Mary's Hospital, London, UK, in November 2012. Patients with missing data were excluded. Diagnoses were grouped: medical and surgical. To classify diagnoses as significant, established guidelines were used and, where not available, common agreement between three acute paediatricians. 1921 patients were analysed. There were 211 admissions (11%). 1630 attendances were medical (86%) and 273 (14%) surgical. Brighton and COAST PEWS performed similarly. hospital admission: PEWS of ≥3 was specific (93%) but poorly sensitive (32%). The area under the receiver operating curve (AUC) was low at 0.690. Significant illness: for medical illness, PEWS ≥3 was highly specific (96%) but poorly sensitive (44%). The AUC was 0.754 and 0.755 for Brighton and COAST PEWS, respectively. Both scores performed poorly for predicting significant surgical illness (AUC 0.642). PEWS ≥3 performed well in predicting significant respiratory illness: sensitivity 75%, specificity 91%. Both Brighton and COAST PEWS scores performed similarly. A score of ≥3 has good specificity but poor sensitivity for predicting hospital admission and significant illness. Therefore, a high PEWS should be taken seriously but a low score is poor at ruling out the requirement for admission or serious underlying illness. PEWS was better at detecting significant medical illness compared with detecting the need for admission. PEWS performed poorly in detecting significant surgical illness. PEWS may be particularly useful in evaluating respiratory illness in a paediatric ED. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Context-specific Factors and Contraceptive Use: A Mixed Method Study among Women, Men and Health Providers in a Rural Ghanaian District.

PubMed

Ayanore, Martin Amogre; Pavlova, Milena; Groot, Wim

2017-06-01

Suitable options for improving women's access to effective, safe and context-specific contraceptive methods must be explored to curtail rising unmet needs for contraceptive use in rural Ghana. The study aimed to outline context-specific factors associated with contraceptive use, access on demand and future use intentions among women in one district of Ghana. Using mixed method approach, quantitative data (n=720) was collected among women aged 18-28. Focus group discussions and in-depth interviews were also conducted among women (n=30) aged 18-49 and men (n=10) respectively. IDIs were conducted among 3 midwives. Women who received focused counseling on contraceptive use were twice likely to have ever used (OR=2 95% CI 1.163-3.467) or be current users (OR=2, 95% CI 1.146-4.010) of contraceptives. Male partner support can drive cultural sensitivities towards accepting use of contraception (OR=34.5, CI% 19.01-64.22). Covert use is still preferred by most in the study. Services delivered on good provider-relational grounds and convenient clinic hours encourage contraceptive use among women. Male targeting for improving contraceptive service use must first identify context-specific preferences of the woman, since covert use is highly valued. Ascertaining the prevalence of covert use and how community systems can address this for improved contraceptive uptake is further recommended.

Is the standard SF-12 health survey valid and equivalent for a Chinese population?

PubMed

Lam, Cindy L K; Tse, Eileen Y Y; Gandek, Barbara

2005-03-01

Chinese is the world's largest ethnic group but few health-related quality of life (HRQoL) measures have been tested on them. The aim of this study was to determine if the standard SF-12 was valid and equivalent for a Chinese population. The SF-36 data of 2410 Chinese adults randomly selected from the general population of Hong Kong (HK) were analysed. The Chinese (HK) specific SF-12 items and scoring algorithm were derived from the HK Chinese population data by multiple regressions. The SF-36 PCS and MCS scores were used as criteria to assess the content and criterion validity of the SF-12. The standard and Chinese (HK) specific SF-12 PCS and MCS scores were compared for equivalence. The standard SF-12 explained 82% and 89% of the variance of the SF-36 PCS and MCS scores, respectively, and the effect size differences between the standard SF-36 and SF-12 scores were less than 0.3. Six of the Chinese (HK) specific SF-12 items were different from those of the standard SF-12, but the effect size differences between the Chinese (HK) specific and standard SF-12 scores were mostly less than 0.3. The standard SF-12 was valid and equivalent for the Chinese, which would enable more Chinese to be included in clinical trials that measure HRQoL.

The resistance mutation R155K in the NS3/4A protease of hepatitis C virus also leads the virus to escape from HLA-A*68-restricted CD8 T cells.

PubMed

Salloum, Shadi; Kluge, Silvia F; Kim, Arthur Y; Roggendorf, Michael; Timm, Joerg

2010-08-01

The NS3/4A serine protease of the hepatitis C virus (HCV) is one of the most attractive targets for specific antiviral agents. However, mutations conferring resistance may decrease the efficacy of these drugs. Although the level of resistance associated with specific mutations differs between different compounds, substitutions R155K and A156T reduce susceptibility to all protease inhibitors published so far. Interestingly, variants harboring the resistant mutation R155K were also detected as the predominant quasispecies in some treatment-naïve patients. Of note, key positions for resistance overlap with the HLA-A*68-restricted epitope HAVGIFRAAV(1175-1184). The aim of our study was to analyze the impact of protease inhibitor resistance mutations on the replication level and the antiviral CD8 T cell response against this HCV epitope. Our findings suggest that the R155K variant is associated with a relatively high replication level and with a substantial loss of cross-recognition by specific CD8 T cells targeting the epitope HAVGIFRAAV(1175-1184), providing a possible explanation for its existence in the absence of drug selection pressure. Copyright 2010 Elsevier B.V. All rights reserved.

Assessment of Myometrial Invasion in Premenopausal Grade 1 Endometrial Carcinoma: Is Magnetic Resonance Imaging a Reliable Tool in Selecting Patients for Fertility-Preserving Therapy?

PubMed

Sakane, Makoto; Hori, Masatoshi; Onishi, Hiromitsu; Tsuboyama, Takahiro; Ota, Takashi; Tatsumi, Mitsuaki; Ueda, Yutaka; Kimura, Toshihiro; Kimura, Tadashi; Tomiyama, Noriyuki

The aim of this study was to evaluate the diagnostic ability of magnetic resonance imaging (MRI) in premenopausal women with G1 endometrial carcinoma. Twenty-six patients underwent T2W, diffusion weighted, and dynamic contrast-enhanced 3-T MRI. The degree of myometrial invasion was pathologically classified into no invasion, shallow (3 mm or less), and more. Two radiologists assessed myometrial invasion on MRI. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values, AUC, and interobserver agreement were analyzed. For assessing myometrial invasion, mean accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and AUC, respectively, were as follows: 63%, 42%, 85%, 79%, 47%, and 0.75. Mean interobserver agreement was fair (k = 0.36). Shallow invasions were underestimated as no invasion on MRI in all 6 cases. Magnetic resonance imaging produced false-negative result on half of patients. The misjudgments tended to happen in patients with shallow invasion.

Designing a Leadership Development Program for Surgeons

PubMed Central

Jaffe, Gregory A.; Pradarelli, Jason C.; Lemak, Christy Harris; Mulholland, Michael W.; Dimick, Justin B.

2015-01-01

Background Although numerous leadership development programs exist in healthcare, no programs have been specifically designed to meet the needs of surgeons. This study aimed to elicit practicing surgeons’ motivations and desired goals for leadership training in order to design an evidence-based Leadership Development Program (LDP) in surgery. Materials and Methods At a large academic health center, we conducted semi-structured interviews with 24 surgical faculty members who voluntarily applied and were selected for participation in a newly created LDP. Transcriptions of the interviews were analyzed using analyst triangulation and thematic coding in order to extract major themes regarding surgeons’ motivations and perceived needs for leadership knowledge and skills. Themes from interview responses were then used to design the program curriculum specifically to meet the leadership needs of surgical faculty. Results Three major themes emerged regarding surgeons’ motivations for seeking leadership training: 1) Recognizing key gaps in their formal preparation for leadership roles; 2) Exhibiting an appetite for personal self-improvement; and 3) Seeking leadership guidance for career advancement. Participants’ interviews revealed four specific domains of knowledge and skills that they indicated as desired takeaways from a leadership development program: 1) leadership and communication; 2) team building; 3) business acumen/finance; and 4) greater understanding of the healthcare context. Conclusions Interviews with surgical faculty members identified gaps in prior leadership training and demonstrated concrete motivations and specific goals for participating in a formal leadership program. A Leadership Development Program that is specifically tailored to address the needs of surgical faculty may benefit surgeons at a personal and institutional level. PMID:26323368

Rapid and sensitive detection of human astrovirus in water samples by loop-mediated isothermal amplification with hydroxynaphthol blue dye.

PubMed

Yang, Bo-Yun; Liu, Xiao-Lu; Wei, Yu-Mei; Wang, Jing-Qi; He, Xiao-Qing; Jin, Yi; Wang, Zi-Jian

2014-02-14

The aim of this paper was to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, sensitive and inexpensive detection of astrovirus. The detection limit of LAMP using in vitro RNA transcripts was 3.6 × 10 copies·μL⁻¹, which is as sensitive as the presently used PCR assays. However, the LAMP products could be identified as different colors with the naked eye following staining with hydroxynaphthol blue dye (HNB). No cross-reactivity with other gastroenteric viruses (rotavirus and norovirus) was observed, indicating the relatively high specificity of LAMP. The RT-LAMP method with HNB was used to effectively detect astrovirus in reclaimed water samples. The LAMP technique described in this study is a cheap, sensitive, specific and rapid method for the detection of astrovirus. The RT-LAMP method can be simply applied for the specific detection of astrovirus and has the potential to be utilized in the field as a screening test.

Disentangling the Dyadic Dance: Theoretical, Methodological and Outcomes Systematic Review of Mother-Infant Dyadic Processes.

PubMed

Provenzi, Livio; Scotto di Minico, Giunia; Giusti, Lorenzo; Guida, Elena; Müller, Mitho

2018-01-01

Background: During the last decades, the research on mother-infant dyad has produced a great amount of data, methods and theories, which largely contributed to set a revolution in the way we look at developmental changes during infancy and childhood. Very different constructs depict the different aspects of the "dyadic dance" occurring between a mother and her infant; nonetheless, a comprehensive and consistent systematization of these concepts in a coherent theoretical landscape is still lacking. Aim: In the present work, we aim at disentangling the different theoretical and methodological definitions of 9 dyadic constructs and we highlight their effects on infants' and children developmental outcomes. Methods: A literature search has been conducted on three databases-PubMed, Scopus, Web of Science. Three different reviews are reported here: (1) a review on the theoretical definitions of dyadic constructs; (2) a review of operational definitions, settings and methods of dyadic processes; (3) a systematic review of dyadic processes' outcomes for infants' and children developmental trajectories. Results: Two constructs emerged as wide meta-theoretical concepts (reciprocity and mutuality) and seven described specific processes (attunement, contingency, coordination, matching, mirroring, reparation, synchrony). A global model resuming the relationships among different processes is reported, which highlights the emergence of two specific cycles of dyadic functioning (i.e., matching-mismatching-reparation-synchrony; contingency, coordination, attunement, mirroring). A comprehensive review of the adopted measures is also provided. Finally, all the processes provided significant contributions to infants' behavioral, cognitive, and socio-emotional development during the first 3 years of age, but limited research has been conducted on specific processes (e.g. reparation and mirroring). Conclusion: The present study provides an original research-grounded framework to consider the different nature of mother-infant dyadic processes within a unified dyadic eco-system. Different levels of evidence emerged for the role of diverse mother-infant dyadic processes on infants' and children development. Open questions and future research directions are highlighted.

Disentangling the Dyadic Dance: Theoretical, Methodological and Outcomes Systematic Review of Mother-Infant Dyadic Processes

PubMed Central

Provenzi, Livio; Scotto di Minico, Giunia; Giusti, Lorenzo; Guida, Elena; Müller, Mitho

2018-01-01

Background: During the last decades, the research on mother-infant dyad has produced a great amount of data, methods and theories, which largely contributed to set a revolution in the way we look at developmental changes during infancy and childhood. Very different constructs depict the different aspects of the “dyadic dance” occurring between a mother and her infant; nonetheless, a comprehensive and consistent systematization of these concepts in a coherent theoretical landscape is still lacking. Aim: In the present work, we aim at disentangling the different theoretical and methodological definitions of 9 dyadic constructs and we highlight their effects on infants' and children developmental outcomes. Methods: A literature search has been conducted on three databases—PubMed, Scopus, Web of Science. Three different reviews are reported here: (1) a review on the theoretical definitions of dyadic constructs; (2) a review of operational definitions, settings and methods of dyadic processes; (3) a systematic review of dyadic processes' outcomes for infants' and children developmental trajectories. Results: Two constructs emerged as wide meta-theoretical concepts (reciprocity and mutuality) and seven described specific processes (attunement, contingency, coordination, matching, mirroring, reparation, synchrony). A global model resuming the relationships among different processes is reported, which highlights the emergence of two specific cycles of dyadic functioning (i.e., matching-mismatching-reparation-synchrony; contingency, coordination, attunement, mirroring). A comprehensive review of the adopted measures is also provided. Finally, all the processes provided significant contributions to infants' behavioral, cognitive, and socio-emotional development during the first 3 years of age, but limited research has been conducted on specific processes (e.g. reparation and mirroring). Conclusion: The present study provides an original research-grounded framework to consider the different nature of mother-infant dyadic processes within a unified dyadic eco-system. Different levels of evidence emerged for the role of diverse mother-infant dyadic processes on infants' and children development. Open questions and future research directions are highlighted. PMID:29615947

A Genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Screen Identifies NEK7 as an Essential Component of NLRP3 Inflammasome Activation.

PubMed

Schmid-Burgk, Jonathan L; Chauhan, Dhruv; Schmidt, Tobias; Ebert, Thomas S; Reinhardt, Julia; Endl, Elmar; Hornung, Veit

2016-01-01

Inflammasomes are high molecular weight protein complexes that assemble in the cytosol upon pathogen encounter. This results in caspase-1-dependent pro-inflammatory cytokine maturation, as well as a special type of cell death, known as pyroptosis. The Nlrp3 inflammasome plays a pivotal role in pathogen defense, but at the same time, its activity has also been implicated in many common sterile inflammatory conditions. To this effect, several studies have identified Nlrp3 inflammasome engagement in a number of common human diseases such as atherosclerosis, type 2 diabetes, Alzheimer disease, or gout. Although it has been shown that known Nlrp3 stimuli converge on potassium ion efflux upstream of Nlrp3 activation, the exact molecular mechanism of Nlrp3 activation remains elusive. Here, we describe a genome-wide CRISPR/Cas9 screen in immortalized mouse macrophages aiming at the unbiased identification of gene products involved in Nlrp3 inflammasome activation. We employed a FACS-based screen for Nlrp3-dependent cell death, using the ionophoric compound nigericin as a potassium efflux-inducing stimulus. Using a genome-wide guide RNA (gRNA) library, we found that targeting Nek7 rescued macrophages from nigericin-induced lethality. Subsequent studies revealed that murine macrophages deficient in Nek7 displayed a largely blunted Nlrp3 inflammasome response, whereas Aim2-mediated inflammasome activation proved to be fully intact. Although the mechanism of Nek7 functioning upstream of Nlrp3 yet remains elusive, these studies provide a first genetic handle of a component that specifically functions upstream of Nlrp3. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Potential of Past Tense Marking in Oral Reading as a Clinical Marker of Specific Language Impairment in School-Age Children

ERIC Educational Resources Information Center

Werfel, Krystal L.; Hendricks, Alison Eisel; Schuele, C. Melanie

2017-01-01

Purpose: The purpose of this study was twofold. The first aim was to explore differences in profiles of past tense marking in oral reading of school-age children with specific language impairment (SLI). The second aim was to explore the potential of past tense marking in oral reading as a clinical marker of SLI in school-age children. Method: This…

The association of weight percentile and motor vehicle crash injury among 3 to 8 year old children.

PubMed

Zonfrillo, Mark R; Nelson, Kyle A; Durbin, Dennis R; Kallan, Michael J

2010-01-01

The use of age-appropriate child restraint systems significantly reduces injury and death associated with motor vehicle crashes (MVCs). Pediatric obesity has become a global epidemic. Although recent evidence suggests a possible association between pediatric obesity and MVC-related injury, there are potential misclassifications of body mass index from under-estimated height in younger children. Given this limitation, age- and sex-specific weight percentiles can be used as a proxy of weight status. The specific aim of this study was to determine the association between weight percentile and the risk of significant injury for children 3-8 years in MVCs. This was a cross-sectional study of children aged 3-8 years in MVCs in 16 US states, with data collected via insurance claims records and a telephone survey from 12/1/98-11/30/07. Parent-reported injuries with an abbreviated Injury Scale (AIS) score of 2+ indicated a clinically significant injury. Age- and sex-specific weight percentiles were calculated using pediatric norms. The study sample included 9,327 children aged 3-8 years (weighted to represent 157,878 children), of which 0.96% sustained clinically significant injuries. There was no association between weight percentiles and overall injury when adjusting for restraint type (p=0.71). However, increasing weight percentiles were associated with lower extremity injuries at a level that approached significance (p=0.053). Further research is necessary to describe mechanisms for weight-related differences in injury risk. Parents should continue to properly restrain their children in accordance with published guidelines.

Forensic discrimination of vaginal epithelia by DNA methylation analysis through pyrosequencing.

PubMed

Antunes, Joana; Silva, Deborah S B S; Balamurugan, Kuppareddi; Duncan, George; Alho, Clarice S; McCord, Bruce

2016-10-01

The accurate identification of body fluids from crime scenes can aid in the discrimination between criminal and innocent intent. This research aimed to determine if the levels of DNA methylation in the locus PFN3A could be used to discriminate vaginal epithelia from other body fluids. In this work we bisulfite-modified and amplified DNA samples from blood, saliva, semen, and vaginal epithelia using primers for PFN3A. Through pyrosequencing we were able to show that vaginal epithelia present distinct methylation levels when compared to other body fluids. Mixtures of different body fluids present methylation values that correlate with single-source body fluid samples and the primers for PFN3A are specific for primates. This report successfully demonstrated that the analysis of methylation in the PFN3A locus can be used for vaginal epithelia discrimination in forensic samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitivity and specificity of mammographic screening as practised in Vermont and Norway

PubMed Central

Hofvind, S; Geller, B M; Skelly, J; Vacek, P M

2012-01-01

Objective The aim of this study was to examine the sensitivity and specificity of screening mammography as performed in Vermont, USA, and Norway. Methods Incident screening data from 1997 to 2003 for female patients aged 50–69 years from the Vermont Breast Cancer Surveillance System (116 996 subsequent screening examinations) and the Norwegian Breast Cancer Screening Program (360 872 subsequent screening examinations) were compared. Sensitivity and specificity estimates for the initial (based on screening mammogram only) and final (screening mammogram plus any further diagnostic imaging) interpretations were directly adjusted for age using 5-year age intervals for the combined Vermont and Norway population, and computed for 1 and 2 years of follow-up, which ended at the time of the next screening mammogram. Results For the 1-year follow-up, sensitivities for initial assessments were 82.0%, 88.2% and 92.5% for 1-, 2- and >2-year screening intervals, respectively, in Vermont (p=0.022). For final assessments, the values were 73.6%, 83.3% and 81.2% (p=0.047), respectively. For Norway, sensitivities for initial assessments were 91.0% and 91.3% (p=0.529) for 2- and >2-year intervals, and 90.7% and 91.3%, respectively, for final assessments (p=0.630). Specificity was lower in Vermont than in Norway for each screening interval and for all screening intervals combined, for both initial (90.6% vs 97.8% for all intervals; p<0.001) and final (98.8% vs 99.5% for all intervals; p<0.001) assessments. Conclusion Our study showed higher sensitivity and specificity in a biennial screening programme with an independent double reading than in a predominantly annual screening program with a single reading. Advances in knowledge This study demonstrates that higher recall rates and lower specificity are not always associated with higher sensitivity of screening mammography. Differences in the screening processes in Norway and Vermont suggest potential areas for improvement in the latter. PMID:22993383

Diagnostic value of serum galactomannan, (1-3)-β-D-glucan, and Aspergillus fumigatus-specific IgA and IgG assays for invasive pulmonary aspergillosis in non-neutropenic patients.

PubMed

Dobias, R; Jaworska, P; Tomaskova, H; Kanova, M; Lyskova, P; Vrba, Z; Holub, C; Svobodová, L; Hamal, P; Raska, M

2018-03-25

Detection of serum galactomannan (GM) and (1-3)-β-D-glucan (BG) is considered useful for non-culture diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Only few studies evaluated these seromarkers in non-neutropenic patients suspected of having IPA. The aim of this study was to evaluate both tests together with the Aspergillus fumigatus-specific serum IgG and IgA (IgAG) test for serological IPA diagnosis in non-neutropenic patients.Sera from 87 patients suspected of having IPA were retrospectively analyzed. Patients were categorized into groups of proven IPA (n=10), putative IPA (n=31), and non-IPA colonization (n=46). When the GM, BG, and IgAG assays were used for patients included in the study, the sensitivity/specificity / positive predictive value (PPV) / negative predictive value (NPV) were 48.8%/91.3%/83.3%/66.7%, 82.9%/73.9%/73.9%/82.9%, and 75.6%/95.7%/93.9%/81.5%, respectively. Thus, the highest specificity and PPV were confirmed for the IgAG assay. Improvements in the sensitivity and NPV were achieved by "at least one positive" analysis with the GM and BG assays, with the sensitivity/specificity/PPV/NPV values being 85.0%/69.6%/71.4%/84.2%. Nevertheless, the highest sensitivity and NPV were achieved by the "at least one positive" analysis combining the GM, BG, and IgAG tests (97.6% and 96.8%, respectively).The involvement of the IgAG assay could improve IPA diagnosis in non-neutropenic patients by increasing the sensitivity and NPV when combined with the GM or BG assays. Further improvement was achieved by combining the GM, BG, and IgAG assays using the "at least one positive test" strategy, especially if doubt exists. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Validation of a field test for the non-invasive determination of badminton specific aerobic performance

PubMed Central

Wonisch, M; Hofmann, P; Schwaberger, G; von Duvillard, S P; Klein, W

2003-01-01

Aim: To develop a badminton specific test to determine on court aerobic and anaerobic performance. Method: The test was evaluated by using a lactate steady state test. Seventeen male competitive badminton players (mean (SD) age 26 (8) years, weight 74 (10) kg, height 179 (7) cm) performed an incremental field test on the badminton court to assess the heart rate turn point (HRTP) and the individual physical working capacity (PWCi) at 90% of measured maximal heart rate (HRmax). All subjects performed a 20 minute steady state test at a workload just below the PWCi. Results: Significant correlations (p<0.05) for Pearson's product moment coefficient were found between the two methods for HR (r = 0.78) and velocity (r = 0.93). The HR at the PWCi (176 (5.5) beats/min) was significantly lower than the HRTP (179 (5.5) beats/min), but no significant difference was found for velocity (1.44 (0.3) m/s, 1.38 (0.4) m/s). The constant exercise test showed steady state conditions for both HR (175 (9) beats/min) and blood lactate concentration (3.1 (1.2) mmol/l). Conclusion: The data indicate that a valid determination of specific aerobic and anaerobic exercise performance for the sport of badminton is possible without HRTP determination. PMID:12663351

Dual-Affinity Re-Targeting proteins direct T cell–mediated cytolysis of latently HIV-infected cells

PubMed Central

Sung, Julia A.M.; Pickeral, Joy; Liu, Liqin; Stanfield-Oakley, Sherry A.; Lam, Chia-Ying Kao; Garrido, Carolina; Pollara, Justin; LaBranche, Celia; Bonsignori, Mattia; Moody, M. Anthony; Yang, Yinhua; Parks, Robert; Archin, Nancie; Allard, Brigitte; Kirchherr, Jennifer; Kuruc, JoAnn D.; Gay, Cynthia L.; Cohen, Myron S.; Ochsenbauer, Christina; Soderberg, Kelly; Liao, Hua-Xin; Montefiori, David; Moore, Paul; Johnson, Syd; Koenig, Scott; Haynes, Barton F.; Nordstrom, Jeffrey L.; Margolis, David M.; Ferrari, Guido

2015-01-01

Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell–mediated clearance of HIV-1–infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity–mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected–patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals. PMID:26413868

The cut-off values of anthropometric variables for predicting mild cognitive impairment in Malaysian older adults: a large population based cross-sectional study.

PubMed

Won, Huiloo; Abdul, Manaf Zahara; Mat Ludin, Arimi Fitri; Omar, Mohd Azahadi; Razali, Rosdinom; Shahar, Suzana

2017-01-01

Older adults are at risk of mild cognitive impairment (MCI), and simple anthropometric measurements can be used to screen for this condition. Thus, the aim of this study was to explore the cut-off values of body mass index (BMI) and waist circumference (WC) for predicting the risk of MCI in older Malaysian adults. A total of 2,240 Malaysian older adults aged ≥60 years were recruited using multistage random sampling in a population based cross-sectional study. Receiver operating characteristic (ROC) curve was used to determine the cut-off values of BMI and WC with optimum sensitivity and specificity for the detection of MCI. Age, gender, years of education, smoking habit, alcohol consumption, depression, and medical conditions were used as confounding factors in this analysis. A BMI cut-off value of 26 kg/m 2 (area under the receiver operating characteristic curve [AUC] 0.725; sensitivity 90.5%; specificity 38.8%) was appropriate in identifying the risk of getting MCI in both men and women. The optimum WC cut-offs for likelihood of MCI were 90 cm (AUC 0.745; sensitivity 78.0%; specificity 59.8%) for men and 82 cm (AUC 0.714; sensitivity 84.3%; specificity 49.7%) for women. The optimum calf circumference (CC) cut-off values for identifying MCI were 29 cm (AUC 0.731; sensitivity 72.6%; specificity 61.1%) for men and 26 cm (AUC 0.598; sensitivity 79.1%; specificity 45.3%) for women. The cut-off values could be advocated and used as part of the screening of MCI among older Malaysian adults. There is a need to further determine the predictive values of these cut-off points on outcomes through longitudinal study design.

Evaluation of In-House and Commercial Serological Tests for Diagnosis of Human Tularemia

PubMed Central

Yanes, Hadjila; Hennebique, Aurélie; Pelloux, Isabelle; Boisset, Sandrine; Bicout, Dominique J.; Caspar, Yvan

2017-01-01

ABSTRACT Tularemia is a zoonosis caused by the bacterium Francisella tularensis. Its specific diagnosis remains based on serological methods, while F. tularensis is rarely detected in clinical samples by culture or PCR. The aim of the present study was to evaluate the performance of the Serion enzyme-linked immunosorbent assay (ELISA) classic Francisella tularensis IgG and IgM tests (Virion/Serion GmbH Institute, Würzburg, Germany) and the VIRapid tularemia immunochromatographic test (ICT) (Vircell, Granada, Spain) compared to that of the in-house microagglutination test (MAT) and indirect immunofluorescence assay (IFA) currently used at the French National Reference Center for Francisella. We evaluated 256 consecutive sera from 208 patients, including 51 confirmed and 23 probable tularemia cases, and 134 control patients not infected with F. tularensis. The IFA tests displayed 72.5% sensitivity for IgM (cutoff titer ≥80) and 74.5% for IgG (cutoff titer ≥160), and 99.3% specificity for both IgM and IgG. Using cutoffs advocated by the manufacturer, the Serion ELISAs displayed 88.2% sensitivity for IgM and 86.3% for IgG antibodies; specificity was 94.8% for IgM and 95.5% for IgG. Compared to MAT and IFA tests, the Serion ELISAs allowed earlier detection of specific antibodies (1 to 2 weeks versus 2 to 3 weeks after the onset of symptoms). The ICT sensitivity and specificity were 90% and 83.6%, respectively, when considering the cutoff advocated by the manufacturer. In conclusion, the Serion ELISAs are useful as screening tests for tularemia diagnosis, but additional confirmatory tests (such as MAT and IFA) are needed, especially in areas of low endemicity. PMID:29118164

Evaluation of IgY Antibody as a Polyspecific Coombs-Reagent.

PubMed

Calzado, Esteban Justo Gutiérrez; Heredia, Marlene Toledano; Duharte, Jeorge Fernadez; Zarnani, Amir-Hassan

2017-01-01

During the last twenty years, the extraction of specific egg yolk (IgY) antibodies from the immunized chickens has been accepted as a useful alternative to the immunization of mammals. The aim of the present study was immunizing the chickens with Human Umbilical Cord Serum (HUCS) and the extraction of specific anti-human globulins (IgG, C3b, and C3d) antibodies from egg yolk in order to obtain polyspecific Coombs reagent. The novelty of this work was the achievement of a polyclonal reagent through a very cheap alternative method in accordance with all ethical regulations required for obtaining it. Three Leghorn hens (21 weeks old) were immunized four times for a period of 66 days with 20uL of HUCS mixed with PBS/FCA or FIA each time. The extraction of IgY antibodies was performed according to the method of lipid precipitation of yolk and using water soluble fraction as the reagent material. The resulting IgY antibody was characterized by SDS-PAGE and immunoelectrophoresis and tested for the presence of hetero-agglutinins by means of direct agglutination using human erythrocytes of all blood groups treated with 0.1% papain and for indirect Coombs-test to evaluate its specificity to fractions (C3b, C3d, C4d) of human complement and human IgG, respectively. Our findings show, that, the reagent obtained contains IgY and other 3 proteins (SDS-PAGE), and reacts specifically with plasma proteins, that migrate in β and ϒ regions. In immunoelectrophoresis, in addition, there is the presence of low hetero-agglutinins levels in IgY-preparation (3 lots), and the possibility to produce high amount (more than 500 ml/egg ) of polyspecific Coombs-reagent in chickens is also discussed. IgY-preparation (3 lots), and the possibility to produce high amount (more than 500 ml/egg ) of polyspecific Coombs-reagent in chickens with the originality to achieve a polyclonal reagent through a very cheap alternative method in accordance with all ethical regulations required for obtaining it, was also discussed.

Evaluation of IgY Antibody as a Polyspecific Coombs-Reagent

PubMed Central

Calzado, Esteban Justo Gutiérrez; Heredia, Marlene Toledano; Duharte, Jeorge Fernadez; Zarnani, Amir-Hassan

2017-01-01

Background: During the last twenty years, the extraction of specific egg yolk (IgY) antibodies from the immunized chickens has been accepted as a useful alternative to the immunization of mammals. The aim of the present study was immunizing the chickens with Human Umbilical Cord Serum (HUCS) and the extraction of specific anti-human globulins (IgG, C3b, and C3d) antibodies from egg yolk in order to obtain polyspecific Coombs reagent. Methods: The novelty of this work was the achievement of a polyclonal reagent through a very cheap alternative method in accordance with all ethical regulations required for obtaining it. Three Leghorn hens (21 weeks old) were immunized four times for a period of 66 days with 20uL of HUCS mixed with PBS/FCA or FIA each time. The extraction of IgY antibodies was performed according to the method of lipid precipitation of yolk and using water soluble fraction as the reagent material. The resulting IgY antibody was characterized by SDS-PAGE and immunoelectrophoresis and tested for the presence of hetero-agglutinins by means of direct agglutination using human erythrocytes of all blood groups treated with 0.1% papain and for indirect Coombs-test to evaluate its specificity to fractions (C3b, C3d, C4d) of human complement and human IgG, respectively. Results: Our findings show, that, the reagent obtained contains IgY and other 3 proteins (SDS-PAGE), and reacts specifically with plasma proteins, that migrate in β and ϒ regions. In immunoelectrophoresis, in addition, there is the presence of low hetero-agglutinins levels in IgY-preparation (3 lots), and the possibility to produce high amount (more than 500 ml/egg) of polyspecific Coombs-reagent in chickens is also discussed. Conclusion: IgY-preparation (3 lots), and the possibility to produce high amount (more than 500 ml/egg) of polyspecific Coombs-reagent in chickens with the originality to achieve a polyclonal reagent through a very cheap alternative method in accordance with all ethical regulations required for obtaining it, was also discussed. PMID:28496948

Adverse Psychosexual Impact Related to the Treatment of Genital Warts and Cervical Intraepithelial Neoplasia

PubMed Central

Campaner, Adriana Bittencourt; Vespa Junior, Nelson; Giraldo, Paulo César; Leal Passos, Mauro Romero

2013-01-01

Objective. To compare the psychosexual impact related to the treatment of genital warts and cervical intraepithelial neoplasia (CIN) in women. Methods. 75 patients presenting with HPV-induced genital lesions, belonging to one of two patient groups, were included in the study: 29 individuals with genital warts (GWs) and 46 individuals with CIN grades 2 or 3 (CIN 2/3). Initially, medical charts of each woman were examined for extraction of data on the type of HPV-induced infection and treatment administered. Subjects were interviewed to collect sociodemographic data as well as personal, gynecologic, obstetric, and sexual history. After this initial anamnesis, the Sexual Quotient-Female Version (SQ-F) questionnaire was applied to assess sexual function. After application of the questionnaire, patients answered specific questions produced by the researchers, aimed at assessing the impact of the disease and its treatment on their sexual lives. Results. It is noteworthy that patients with CIN 2/3 had statistically similar classification of sexual quotient to patients with GWs (P = 0.115). However, patients with GWs more frequently gave positive answers to the specific questions compared to patients with CIN 2/3. Conclusion. Based on these findings, it is clear that GWs have a greater impact on sexual behavior compared to CIN 2/3. PMID:26316956

K(v) channel interacting protein 3 expression and regulation by haloperidol in midbrain dopaminergic neurons.

PubMed

Duncan, Carlotta E; Schofield, Peter R; Weickert, Cynthia Shannon

2009-12-22

Antipsychotic drugs are the main treatment for schizophrenia, despite their adverse side effects and uncertain mode of action. Gene expression studies in the brains of rodents treated with antipsychotic drugs aim to uncover this mechanism and elucidate more specific targets for schizophrenia treatment. Previous expression profiling analyses showed that K(v) channel interacting protein 3 (KChIP3) was down-regulated in the mouse brain following treatment with multiple antipsychotic drugs. In this study, we used in situ hybridization to anatomically define the expression of KChIP3 mRNA in the mouse brain and to quantify its regulation by 7-day haloperidol treatment. We used immunohistochemistry to localize KChIP3 protein expression in the midbrain, dorsal and ventral striatum and the prefrontal cortex. We found KChIP3 mRNA throughout the grey matter of the brain, with high expression in the hippocampus, specific thalamic nuclei, deeper cortical layers and in the midbrain. KChIP3 mRNA was significantly down-regulated in the dorsal striatum and the ventral tegmental area following haloperidol treatment. KChIP3 protein is expressed in the neuropil in the cortex and striatum, as well as in the soma of deeper layer cortical and striatal neurons. This study, for the first time, also localized KChIP3 protein in the cell bodies and processes of dopaminergic neurons in the midbrain. These findings indicate that regulation of KChIP3, particularly in mesocortical dopamine neurons, may be part of the action of antipsychotic drugs and that prolonged and more specific targeting of ion channel subunits may enhance the therapeutic effects of antipsychotic drugs.

Frequency of Specific Cardiovascular Disease Risk Factors among Cameroonian Patients on Dialysis: The Cases of Anaemia, Inflammation, Phosphate, and Calcium

PubMed Central

Pancha Mbouemboue, Olivier; Danbe, Olivier Djile; Tangyi Tamanji, Marcel; Ngoufack, Jacques Olivier

2016-01-01

Specific cardiovascular risk factors are known to contribute to increasing cardiovascular mortality in patients with chronic renal disease. However, little is known about their distribution in our population. This study aimed at determining the prevalence of anaemia, inflammation, and phosphocalcium disorders in Cameroonian patients on dialysis. Thirty-five participants with stage V chronic kidney disease (defined by glomerular filtration rate, GFR < 15 mL/1.73 m3) of age at least 20 years on haemodialysis were randomly recruited. A control group composed of persons without a history of renal or cardiovascular disease was also recruited. Haemoglobin concentration, serum phosphate concentration, serum calcium concentration, and CRP status as a marker of inflammation were determined for all participants. Anaemia, phosphocalcium metabolic disorders, and a positive CRP result among haemodialysed patients were estimated at 94.3%, 61.6%, and 77.1%, respectively. Anaemia was diagnosed in all female patients compared to 92% in males, while a positive CRP result was recorded in 90% of females and 72% of males. No significant differences were observed on the distribution of studied specific cardiovascular risk factors with duration of dialysis. Among the factors studied, anaemia was the most encountered. PMID:27313944

Spring assisted cranioplasty: A patient specific computational model.

PubMed

Borghi, Alessandro; Rodriguez-Florez, Naiara; Rodgers, Will; James, Gregory; Hayward, Richard; Dunaway, David; Jeelani, Owase; Schievano, Silvia

2018-03-01

Implantation of spring-like distractors in the treatment of sagittal craniosynostosis is a novel technique that has proven functionally and aesthetically effective in correcting skull deformities; however, final shape outcomes remain moderately unpredictable due to an incomplete understanding of the skull-distractor interaction. The aim of this study was to create a patient specific computational model of spring assisted cranioplasty (SAC) that can help predict the individual overall final head shape. Pre-operative computed tomography images of a SAC patient were processed to extract a 3D model of the infant skull anatomy and simulate spring implantation. The distractors were modeled based on mechanical experimental data. Viscoelastic bone properties from the literature were tuned using the specific patient procedural information recorded during surgery and from x-ray measurements at follow-up. The model accurately captured spring expansion on-table (within 9% of the measured values), as well as at first and second follow-ups (within 8% of the measured values). Comparison between immediate post-operative 3D head scanning and numerical results for this patient proved that the model could successfully predict the final overall head shape. This preliminary work showed the potential application of computational modeling to study SAC, to support pre-operative planning and guide novel distractor design. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

A Concise and Practical Framework for the Development and Usability Evaluation of Patient Information Websites

PubMed Central

Knijnenburg, S.L.; Kremer, L.C.; Jaspers, M.W.M.

2015-01-01

Summary Background The Website Developmental Model for the Healthcare Consumer (WDMHC) is an extensive and successfully evaluated framework that incorporates user-centered design principles. However, due to its extensiveness its application is limited. In the current study we apply a subset of the WDMHC framework in a case study concerning the development and evaluation of a website aimed at childhood cancer survivors (CCS). Objective To assess whether the implementation of a limited subset of the WDMHC-framework is sufficient to deliver a high-quality website with few usability problems, aimed at a specific patient population. Methods The website was developed using a six-step approach divided into three phases derived from the WDMHC: 1) information needs analysis, mock-up creation and focus group discussion; 2) website prototype development; and 3) heuristic evaluation (HE) and think aloud analysis (TA). The HE was performed by three double experts (knowledgeable both in usability engineering and childhood cancer survivorship), who assessed the site using the Nielsen heuristics. Eight end-users were invited to complete three scenarios covering all functionality of the website by TA. Results The HE and TA were performed concurrently on the website prototype. The HE resulted in 29 unique usability issues; the end-users performing the TA encountered eleven unique problems. Four issues specifically revealed by HE concerned cosmetic design flaws, whereas two problems revealed by TA were related to website content. Conclusion Based on the subset of the WDMHC framework we were able to deliver a website that closely matched the expectancy of the end-users and resulted in relatively few usability problems during end-user testing. With the successful application of this subset of the WDMHC, we provide developers with a clear and easily applicable framework for the development of healthcare websites with high usability aimed at specific medical populations. PMID:26171083

Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract.

PubMed

Abe, Masayuki; Ito, Yoshihiko; Oyunzul, Luvsandorj; Oki-Fujino, Tomomi; Yamada, Shizuo

2009-04-01

Saw palmetto extract (SPE), used widely for the treatment of benign prostatic hyperplasia (BPH) has been shown to bind alpha(1)-adrenergic, muscarinic and 1,4-dihydropyridine (1,4-DHP) calcium channel antagonist receptors. Major constituents of SPE are lauric acid, oleic acid, myristic acid, palmitic acid and linoleic acid. The aim of this study was to investigate binding affinities of these fatty acids for pharmacologically relevant (alpha(1)-adrenergic, muscarinic and 1,4-DHP) receptors. The fatty acids inhibited specific [(3)H]prazosin binding in rat brain in a concentration-dependent manner with IC(50) values of 23.8 to 136 microg/ml, and specific (+)-[(3)H]PN 200-110 binding with IC(50) values of 24.5 to 79.5 microg/ml. Also, lauric acid, oleic acid, myristic acid and linoleic acid inhibited specific [(3)H]N-methylscopolamine ([(3)H]NMS) binding in rat brain with IC(50) values of 56.4 to 169 microg/ml. Palmitic acid had no effect on specific [(3)H]NMS binding. The affinity of oleic acid, myristic acid and linoleic acid for each receptor was greater than the affinity of SPE. Scatchard analysis revealed that oleic acid and lauric acid caused a significant decrease in the maximal number of binding sites (B(max)) for [(3)H]prazosin, [(3)H]NMS and (+)-[(3)H]PN 200-110. The results suggest that lauric acid and oleic acid bind noncompetitively to alpha(1)-adrenergic, muscarinic and 1,4-DHP calcium channel antagonist receptors. We developed a novel and convenient method of determining 5alpha-reductase activity using LC/MS. With this method, SPE was shown to inhibit 5alpha-reductase activity in rat liver with an IC(50) of 101 microg/ml. Similarly, all the fatty acids except palmitic acid inhibited 5alpha-reductase activity, with IC(50) values of 42.1 to 67.6 microg/ml. In conclusion, lauric acid, oleic acid, myristic acid, and linoleic acid, major constituents of SPE, exerted binding activities of alpha(1)-adrenergic, muscarinic and 1,4-DHP receptors and inhibited 5alpha-reductase activity.

Detection of Antibodies against Epidermodysplasia Verruciformis-Associated Canine Papillomavirus 3 in Sera of Dogs from Europe and Africa by Enzyme-Linked Immunosorbent Assay▿ †

PubMed Central

Lange, C. E.; Tobler, K.; Favrot, C.; Müller, M.; Nöthling, J. O.; Ackermann, M.

2009-01-01

The role of papillomaviruses (PVs) in the development of canine cancers is controversial. However, recently a novel canine PV (CPV3) was detected in a dog affected with a condition reminiscent of epidermodysplasia verruciformis (EV). The aim of the present study was to investigate the seroprevalence of CPV3 by using generic enzyme-linked immunosorbent assays (ELISAs) for the detection of antibodies against either canine oral PV (COPV) or CPV3. Therefore, the capsid proteins of both PV types were expressed as glutathione S-transferase fusion protein antigens and adsorbed to glutathione-casein-coated ELISA plates. After showing that PV type-specific antibodies could be detected in the sera from dogs with confirmed COPV or CPV3 infection, CPV3- and COPV-seropositive samples were detected in two sets of canine sera collected in Switzerland and South Africa, respectively. We found specific antibodies against COPV and CPV3 among the tested sera and also a large number that were positive for both antigens. The seroprevalences of PV antibodies of 21.9% (COPV) and 26.9% (CPV3) among the tested dogs from South Africa were higher than those among the dogs from Switzerland at 10.5% (COPV) and 1.3% (CPV3). Our data suggest a need for further CPV-related seroepidemiological surveys in different countries, especially in the context of clinical manifestations and possible breed predispositions. For this purpose, the newly developed ELISAs can be a useful tool. PMID:19038784

Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine

PubMed Central

Chen, Mingmin; Sultan, Ayesha; Cinar, Ayhan; Yeruva, Sunil; Riederer, Brigitte; Singh, Anurag Kumar; Li, Junhua; Bonhagen, Janina; Chen, Gang; Yun, Chris; Donowitz, Mark; Hogema, Boris; deJonge, Hugo; Seidler, Ursula

2010-01-01

Trafficking and regulation of the epithelial brush border membrane (BBM) Na+/H+ exchanger 3 (NHE3) in the intestine involves interaction with four different members of the NHERF family in a signal-dependent and possibly segment-specific fashion. The aim of this research was to study the role of NHERF2 (E3KARP) in intestinal NHE3 BBM localization and second messenger-mediated and receptor-mediated inhibition of NHE3. Immunolocalization of NHE3 in WT mice revealed predominant microvillar localization in jejunum and colon, a mixed distribution in the proximal ileum but localization near the terminal web in the distal ileum. The terminal web localization of NHE3 in the distal ileum correlated with reduced acid-activated NHE3 activity (fluorometrically assessed). NHERF2 ablation resulted in a shift of NHE3 to the microvilli and higher basal fluid absorption rates in the ileum, but no change in overall NHE3 protein or mRNA expression. Forskolin-induced NHE3 inhibition was preserved in the absence of NHERF2, whereas Ca2+ ionophore- or carbachol-mediated inhibition was abolished. Likewise, Escherichia coli heat stable enterotoxin peptide (STp) lost its inhibitory effect on intestinal NHE3. It is concluded that in native murine intestine, the NHE3 adaptor protein NHERF2 plays important roles in tethering NHE3 to a position near the terminal web and in second messenger inhibition of NHE3 in a signal- and segment-specific fashion, and is therefore an important regulator of intestinal fluid transport. PMID:20962002

Bone-specific alkaline phosphatase - a potential biomarker for skeletal growth assessment.

PubMed

Tripathi, Tulika; Gupta, Prateek; Sharma, Jitender; Rai, Priyank; Gupta, Vinod Kumar; Singh, Navneet

2018-03-01

The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages. Cross-sectional study. Maulana Azad Institute of Dental Sciences, New Delhi, India. 150 subjects (75 males and 75 females) in the age group of 8-20 years. Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann-Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages. Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p < .01). BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.

Immunogenicity of Phleum pratense depigmented allergoid vaccines: experimental study in rabbits.

PubMed

Iraola, V; Gallego, M T; López-Matas, M A; Morales, M; Bel, I; García, N; Carnés, J

2012-01-01

Immunogenicity studies are based on accurate preclinical and clinical assessment of pharmaceutical products. The immunogenicity of modified allergen vaccines has not been fully elucidated, and the mechanisms involved are not well understood. Animal and human models have recently shown that depigmented allergoids induce specific immunoglobulin (Ig) G against individual allergens, thus supporting the clinical efficacy of these vaccines. The aim of this study was to investigate the production of specific IgG against individual antigens and their isoforms in rabbits injected with depigmented allergoid extracts of Phleum pratense pollen. Two New Zealand rabbits were immunized with depigmented-polymerized extracts adsorbed onto aluminum hydroxide (Depigoid) of P pratense. Rabbits were injected 3 times (35 microg Phl p 5). Specific IgG titers against native, depigmented, and depigmented-polymerized extracts and individual allergens (rPhl p 1 and rPhl p 5a) were analyzed by direct enzyme-linked immunosorbent assay. The capacity of these synthesized antibodies to recognize individual native and depigmented allergens and different isoforms was evaluated by immunoblot and 2-D analysis. All rabbits produced high titers of specific IgG against the 3 extracts. Rabbits injected with depigmented allergoids produced similar specific antibody titers against native, depigmented, and depigmented-polymerized extracts. Serum samples recognized individual allergens and their isoforms in the nonmodified extracts. Vaccines containing depigmented allergoid extracts of P pratense induce immunogenicity in vivo. The antibodies produced after injection of these extracts clearly recognized allergens and different isoforms in their native configuration.

[Study of compatibility of psychiatric diagnoses with ICD-10 diagnostic criteria using the SCAN questionnaire].

PubMed

Adamowski, Tomasz; Kiejna, Andrzej; Hadryś, Tomasz

2006-01-01

Authors aimed at testing whether psychiatrists in their diagnostic process obeyed strict ICD-10 diagnostic criteria. Diagnoses made by psychiatrists at discharge were compared with those of SCAN ver.2.1 on admission. Diagnoses obtained by SCAN I-Shell program were compared with clinical diagnoses obtained by psychiatrists in the psychiatric wards according to ICD-10 criteria on 3 levels: diagnostic group (Fc), diagnostic class (Fcc), and diagnostic category (Fcc.c). Validity assessment was obtained with Cohen's Kappa coefficient, sensitivity, specificity and Yule's Y coefficient. On the diagnostic group level, Cohen's kappa was 0.14-0.65, Yule's Y 0.57-0.71. Sensitivity 0.69-0.95 and specificity 0.41-0.94. In psychotic disorders group F2 kappa was 0.65, Yule's Y 0.71, sensitivity 0.69, specificity 0.94. In affective disorders group F3 kappa was 0.31, Yule's Y 0.57, sensitivity 0.95, specificity 0.41. In neurotic disorders group F4 kappa was low 0.14, Yule's Y 0.62, sensitivity 0.95, specificity 0.50. The study showed a higher level of agreement between SCAN and clinical diagnoses in the group of psychotic disorders with exception of schizoaffective disorders, and lower agreement rates in the group of affective and neurotic disorders where the number of SCAN diagnoses outweighed that of the clinical ones. It could be the result of systematic faults in the coding of diagnoses.

The influence of a real job on upper limb performance in motor skill tests: which abilities are transferred?

PubMed

Giangiardi, Vivian Farahte; Alouche, Sandra Regina; de Freitas, Sandra Maria Sbeghen Ferreira; Pires, Raquel Simoni; Padula, Rosimeire Simprini

2018-06-01

To investigate whether the specificities of real jobs create distinctions in the performance of workers in different motor tests for the upper limbs, 24 participants were divided into two groups according to their specific job: fine and repetitive tasks and general tasks. Both groups reproduced tasks related to aiming movements, handling and strength of the upper limbs. There were no significant differences between groups in the dexterity and performance of aiming movements. However, the general tasks group had higher grip strength than the repetitive tasks group, demonstrating differences according to job specificity. The results suggest that a particular motor skill in a specific job cannot improve performance in other tasks with the same motor requirements. The transfer of the fine and gross motor skills from previous experience in a job-specific task is the basis for allocating training and guidance to workers.

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway

PubMed Central

Wu, Dacheng; Wu, Keyan; Zhu, Qingtian; Xiao, Weiming; Shan, Qing; Yan, Zhigang; Wu, Jian; Deng, Bin; Xue, Yan; Gong, Weijuan

2018-01-01

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation. PMID:29507526

3T MRI evaluation of large nerve perineural spread of head and neck cancers.

PubMed

Baulch, Justin; Gandhi, Mitesh; Sommerville, Jennifer; Panizza, Ben

2015-10-01

Accurate definition of the presence and extent of large nerve perineural spread (PNS) is a vital component in planning appropriate surgery and radiotherapy for head and neck cancers. Our research aimed to define the sensitivity and specificity of 3T MRI in detecting the presence and extent of large nerve PNS, compared with histologic evaluation. Retrospective review of surgically proven cases of large nerve PNS in patients with preoperative 3T MRI performed as high resolution neurogram. 3T MRI had a sensitivity of 95% and a specificity of 84%, detecting PNS in 36 of 38 nerves and correctly identifying uninvolved nerves in 16 of 19 cases. It correctly identified the zonal extent of spread in 32 of 36 cases (89%), underestimating the extent in three cases and overestimating the extent in one case. Targeted 3T MRI is highly accurate in defining the presence and extent of large nerve PNS in head and neck cancers. However, there is still a tendency to undercall the zonal extent due to microscopic, radiologically occult involvement. Superficial large nerve involvement also remains a difficult area of detection for radiologists and should be included as a 'check area' for review. Further research is required to define the role radiation-induced neuritis plays in the presence of false-positive PNS on MRI. © 2015 The Royal Australian and New Zealand College of Radiologists.

Prostate-Specific Natural Health Products (Dietary Supplements) Radiosensitize Normal Prostate Cells

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

Hasan, Yasmin; Schoenherr, Diane; Martinez, Alvaro A.

Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity wasmore » assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH2AX. Results: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2mug/mL], Trinovin [10mug/mL], and Prostate Rx [50 mug/mL]). However, both Trinovin (10mug/mL) and Prostate Rx (6mug/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.« less

3M™ Molecular detection system versus MALDI-TOF mass spectrometry and molecular techniques for the identification of Escherichia coli 0157:H7, Salmonella spp. &Listeria spp.

PubMed

Loff, Marché; Mare, Louise; de Kwaadsteniet, Michele; Khan, Wesaal

2014-06-01

The aim of this study was to compare standard selective plating, conventional PCR (16S rRNA and species specific primers), MALDI-TOF MS and the 3M™ Molecular Detection System for the routine detection of the pathogens Listeria, Salmonella and Escherichia coli 0157:H7 in wastewater and river water samples. MALDI-TOF MS was able to positively identify 20/21 (95%) of the E. coli isolates obtained at genus and species level, while 16S rRNA sequencing only correctly identified 6/21 (28%) as E. coli strains. None of the presumptive positive Listeria spp. and Salmonella spp. isolates obtained by culturing on selective media were positively identified by MALDI-TOF and 16S rRNA analysis. The species-specific E. coli 0157:H7 PCR described in this present study, was not able to detect any E. coli 0157:H7 strains in the wastewater and river water samples analysed. However, E. coli strains, Listeria spp., L. monocytogenes and Salmonella spp. were detected using species specific PCR. Escherichia coli 0157:H7, Listeria spp. and Salmonella spp. were also sporadically detected throughout the sampling period in the wastewater and river water samples analysed by the 3M™ Molecular Detection System. MALDI-TOF MS, which is a simple, accurate and cost-effective detection method, efficiently identified the culturable organisms, while in the current study both species specific PCR (Listeria spp. and Salmonella spp.) and 3M™ Molecular Detection System could be utilised for the direct routine analysis of pathogens in water sources. Copyright © 2014 Elsevier B.V. All rights reserved.

Sex-specific quantitative trait loci contribute to normal variation in bone structure at the proximal femur in men

PubMed Central

Peacock, Munro; Koller, Daniel L.; Lai, Dongbing; Hui, Siu; Foroud, Tatiana; Econs, Michael J.

2006-01-01

Bone structure is an important determinant of osteoporotic fracture. In women bone structure is highly heritable and several quantitative trait loci (QTL) have been reported. There are few comparable data in men. This study in men aimed at establishing the heritability of bone structure at the proximal femur, identifying QTL contributing to normal variation in bone structure, and determining which QTL might be sex-specific. Bone structure at the proximal femur was measured in 205 pairs of brothers age 18–61. Heritability was calculated and linkage analysis performed on phenotypes at the proximal femur. Heritability estimates ranged from 0.99 to 0.39. A genome wide scan identified suggestive QTL (LOD>2.2) for femoral shaft width on chromosome 14q (LOD=2.69 at position 99cM), calcar femorale at chromosome 2p (LOD= 3.97 at position 194cM) and at the X chromosome (LOD= 3.01 at position 77cM), femoral neck width on chromosome 5p (LOD=2.28 at position 0 cM), femoral head width on chromosome 11q (LOD=2.30 at position 131 cM) and 15q (LOD=3.11 at position 90 cM), and pelvic axis length on chromosome 4q (LOD= 4.16 at 99cM) and 17q (LOD=2.80 at position 112 cM). Comparison with published data in 437 pairs of premenopausal sisters from the same geographical region suggested that 3 of the 7 autosomal QTL were male-specific. This study demonstrates that bone structure at the proximal femur in healthy men is highly heritable. The occurrence of sex-specific genes in humans for bone structure has important implications for the pathogenesis and treatment of osteoporosis. PMID:16046210

Tropheryma whipplei endocarditis in Spain

PubMed Central

García-Álvarez, Lara; Sanz, María Mercedes; Marín, Mercedes; Fariñas, MªCarmen; Montejo, Miguel; Goikoetxea, Josune; Rodríguez García, Raquel; de Alarcón, Arístides; Almela, Manuel; Fernández-Hidalgo, Núria; Alonso Socas, María del Mar; Goenaga, Miguel Ángel; Navas, Enrique; Vicioso, Luis; Oteo, José Antonio

2016-01-01

Abstract Tropheryma whipplei endocarditis is an uncommon condition with very few series and <90 cases reported in the literature. The aim of the study was to analyze the epidemiological, clinical, and outcome characteristics of 17 cases of T. whipplei endocarditis recruited in our country from a multicentric cohort from 25 Spanish hospitals from the Spanish Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España. From a total of 3165 cases included in the cohort, 14.2% were diagnosed of blood culture negative endocarditis (BCNE) and 3.5% of these had T. whipplei endocarditis. This condition was more frequent in men. The average age was 60.3 years. Previous cardiac condition was present in 35.3% of the cases. The main clinical manifestation was cardiac failure (76.5%) while fever was only present in the 35.3%. Ecocardiography showed vegetations in 64.7% of patients. Surgery was performed in all but 1 cases and it allowed the diagnosis when molecular assays were performed. A broad range rRNA 16S polymerase chain reaction was used for first instance in all laboratories and different specific targets for T. whipplei were employed for confirmation. A concomitant Whipple disease was diagnosed in 11.9% of patients. All patients received specific antimicrobial treatment for at least 1 year, with no relapse and complete recovery. T. whipplei endocarditis is an uncommon condition with an atypical presentation that must be considered in the diagnosis of BCNE. The prognosis is very good when an appropriate surgical management and antimicrobial-specific treatment is given. PMID:27368042

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Risk-based screening combined with a PCR-based test for group B streptococci diminishes the use of antibiotics in laboring women.

PubMed

Khalil, Mohammed R; Uldbjerg, Niels; Thorsen, Poul B; Henriksen, Birgitte; Møller, Jens K

2017-08-01

To assess the performance of a polymerase chain reaction - group B streptococci test (PCR-GBS test) - in deciding antibiotic prophylaxis in term laboring women. In this observational study, we enrolled 902 unselected Danish term pregnant women. During labor, midwives obtained vaginal swabs that were used for both GBS cultures (reference standard) and for the PCR-GBS test. Furthermore, we recorded the presence of risk factors for EOGBS (Early Onset Group B Streptococcal disease): (1) Bacteriuria during current pregnancy, (2) Prior infant with EOGBS (3) Temperature above 38.0°C during labor, and (4) Rupture of membranes ≥18h. The prevalence of GBS carriers was 12% (104 of 902), the sensitivity of the PCR-GBS test 83% (86 of 104), and the specificity 97% (774 of 798). Among the 108 with one or more EOGBS-risk factors, GBS was present in 23% (25 of 108), the sensitivity 92% (23 of 25), and the specificity 89% (74 of 83). In programs that aim to treat all laboring women with vaginal GBS-colonization (12% in the present study) with penicillin, the PCR-GBS will perform well (sensitivity 83% and specificity 97%). In programs aiming to treat only GBS-carriers among those with risk factors of EOGBS, a reduction of penicillin usage by two-thirds from 12% to 4% may be possible. Copyright © 2017 Elsevier B.V. All rights reserved.

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.

PubMed

Gandomkar, Mostafa; Najafi, Reza; Shafiei, Mohammad; Mazidi, Mohammad; Ebrahimi, Sayed Esmaeil Sadat

2007-08-01

Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.

Surgical approach to TIR3 cytology class A prospective evaluation.

PubMed

D'Alessandro, Nicola; Fasano, Giovanni Michele; Gilio, Francesco; Iside, Giovanni; Izzo, Maria Lucia; Loffredo, Andrea; Pinto, Margherita; Tramontano, Salvatore; Tramutola, Giuseppe; Citro, Giuseppe

2014-01-01

Fine-needle aspiration (FNA) has proven to be a safe and reliable method of investigation of thyroid lesions. Referencing to European classification, the associated risk of malignancy for TIR3, category reserved for aspirates that contain architectural and/or nuclear atypia, is variable in such studies. Aims of study were evaluating safety of surgical approach, assessing perioperative parameters surgically related, and estimating neoplastic rate for TIR3 group. A prospective evaluation of all TIR3 submitted to thyroidectomy was conducted by assessing histopatohologic results between January 2005 and December 2012, considering two categories, positive (neoplastic) and negative (not neoplastic) group. Intraoperative and complication rate was analyzed on TIR3 population. A total of 1514 total thyroidectomy was performed from 2005 to 2012: a total of 148 cases was considered on TIR3 group. Positive cases amounted to 64 (43.2%), 29 of which were carcinoma (19.6% of total population) and 35 of which were adenoma, while negative cases amounted to 84 (56.8%). Sensitivity and specificity of TIR3 as neoplastic screening was 43.2% and 82.1%. A total of 32 linfectomies was performed (21.6% of group). Positive group presented a significant lower mean age than negative group (42.1 vs 56.2 years) TIR3 group represents a various category, with probably different malignancy risk. Our results and neoplasms rate confirmed that surgical option should be gold standard, in order to define atypical pattern and reduce delayed diagnoses. Choice of a second FNA or a imaging monitoring should be adopted for specific condition. Fine-needle aspiration, Thyroidectomy, TIR3, Thyroid cancer.

Proceedings of a Workshop on Assessment of Techniques for Measuring Tropospheric N sub x O sub y

NASA Technical Reports Server (NTRS)

1983-01-01

Human impact on the troposphere, particularly on the regional to global scale is assessed. One area of required research is instrumentation development, which is aimed at improving the capability to measure important trace gases and aerosols which are key species in the major atmospheric biogeochemical cycles. To focus on specific needs, the Instrumentation Workshop for NxOy Tropospheric Species was conducted. The workshop discussed measurement needs and instrument capabilities for NxOy species, including NO, NO2, HNO3, HNO2, PAN, and NO3 aerosols. The status and measurement capabilities of various techniques (operational as well as conceptual) were discussed, along with future instrument and technology needs.

Exploring Vocational Evaluation Practices following Traumatic Brain Injury

PubMed Central

Dillahunt-Aspillaga, Christina; Jorgensen Smith, Tammy; Hanson, Ardis; Ehlke, Sarah; Stergiou-Kita, Mary; Dixon, Charlotte G.; Quichocho, Davina

2015-01-01

Background. Individuals with traumatic brain injury (TBI) face many challenges when attempting to return to work (RTW). Vocational evaluation (VE) is a systematic process that involves assessment and appraisal of an individual's current work-related characteristics and abilities. Objective. The aims of this study are to (1) examine demographic and employment characteristics of vocational rehabilitation providers (VRPs), (2) identify the specific evaluation methods that are used in the VE of individuals with TBI, and (3) examine the differences in assessment method practices based upon evaluator assessment preferences. Methods. This exploratory case study used a forty-six-item online survey which was distributed to VRPs. Results. One hundred and nine VRPs accessed the survey. Of these, 74 completed the survey. A majority of respondents were female (79.7%), Caucasian (71.6%), and holding a master's degree (74.3%), and more than half (56.8%) were employed as state vocational rehabilitation counselors (VRCs). In addition, over two-thirds (67.6%) were certified rehabilitation counselors (CRCs). Respondents reported using several specific tools and assessments during the VE process. Conclusions. Study findings reveal differences in use of and rationales for specific assessments amongst VRPs. Understanding VRP assessment practices and use of an evidence-based framework for VE following TBI may inform and improve VE practice. PMID:26494945

A Comparison between Decision Tree and Random Forest in Determining the Risk Factors Associated with Type 2 Diabetes.

PubMed

Esmaily, Habibollah; Tayefi, Maryam; Doosti, Hassan; Ghayour-Mobarhan, Majid; Nezami, Hossein; Amirabadizadeh, Alireza

2018-04-24

We aimed to identify the associated risk factors of type 2 diabetes mellitus (T2DM) using data mining approach, decision tree and random forest techniques using the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) Study program. A cross-sectional study. The MASHAD study started in 2010 and will continue until 2020. Two data mining tools, namely decision trees, and random forests, are used for predicting T2DM when some other characteristics are observed on 9528 subjects recruited from MASHAD database. This paper makes a comparison between these two models in terms of accuracy, sensitivity, specificity and the area under ROC curve. The prevalence rate of T2DM was 14% among these subjects. The decision tree model has 64.9% accuracy, 64.5% sensitivity, 66.8% specificity, and area under the ROC curve measuring 68.6%, while the random forest model has 71.1% accuracy, 71.3% sensitivity, 69.9% specificity, and area under the ROC curve measuring 77.3% respectively. The random forest model, when used with demographic, clinical, and anthropometric and biochemical measurements, can provide a simple tool to identify associated risk factors for type 2 diabetes. Such identification can substantially use for managing the health policy to reduce the number of subjects with T2DM .

MRI and Additive Manufacturing of Nasal Alar Constructs for Patient-specific Reconstruction.

PubMed

Visscher, Dafydd O; van Eijnatten, Maureen; Liberton, Niels P T J; Wolff, Jan; Hofman, Mark B M; Helder, Marco N; Don Griot, J Peter W; Zuijlen, Paul P M van

2017-08-30

Surgical reconstruction of cartilaginous defects remains a major challenge. In the current study, we aimed to identify an imaging strategy for the development of patient-specific constructs that aid in the reconstruction of nasal deformities. Magnetic Resonance Imaging (MRI) was performed on a human cadaver head to find the optimal MRI sequence for nasal cartilage. This sequence was subsequently used on a volunteer. Images of both were assessed by three independent researchers to determine measurement error and total segmentation time. Three dimensionally (3D) reconstructed alar cartilage was then additively manufactured. Validity was assessed by comparing manually segmented MR images to the gold standard (micro-CT). Manual segmentation allowed delineation of the nasal cartilages. Inter- and intra-observer agreement was acceptable in the cadaver (coefficient of variation 4.6-12.5%), but less in the volunteer (coefficient of variation 0.6-21.9%). Segmentation times did not differ between observers (cadaver P = 0.36; volunteer P = 0.6). The lateral crus of the alar cartilage was consistently identified by all observers, whereas part of the medial crus was consistently missed. This study suggests that MRI is a feasible imaging modality for the development of 3D alar constructs for patient-specific reconstruction.

Reaching the grassroots: publishing methodologies for development organizations.

PubMed

Zielinski, C

1987-01-01

There are 3 major distinctions between the traditional form of academic publishing and publishing for the grassroots as a development-organization activity, particularly in developing countries. Whereas academic publishing seeks to cover the target audience in its entirety, grassroots publishing can only cover a sampling. Academic publishing fulfills a need, while grassroots publishing demonstrates a need and a way to fulfill it. Finally, whereas academic publishing is largely a support activity aimed at facilitating the dissemination of information as a relatively minor part of a technical program, grassroots publishing is a more substantive activity aimed at producing a catalytic effect. Publication for the grassroots further calls for a different methodological approach. Given the constraint of numbers, publications aimed at the grassroots can only be examples or prototypes. The function of a prototype is to serve both as a basis for translation, adaptation, and replication and as a model end result. The approach to the use and promotion of prototypes differs according to the specific country situation. In countries with a heterogenous culture or several different languages, 2 items should be produced: a prototype of the complete text, which should be pretested and evaluated, and a prototype adaptation kit stripped of cultural and social biases. Promotion of the translation and replication of a publication can be achieved by involving officials at the various levels of government, interesting international and voluntary funding agencies, and stimulating indigenous printing capacities at the community level. The most important factors are the appropriateness of the publication in solving specific priority problems and the interest and involvement of national and state authorities at all stages of the project.

Haptic computer-assisted patient-specific preoperative planning for orthopedic fractures surgery.

PubMed

Kovler, I; Joskowicz, L; Weil, Y A; Khoury, A; Kronman, A; Mosheiff, R; Liebergall, M; Salavarrieta, J

2015-10-01

The aim of orthopedic trauma surgery is to restore the anatomy and function of displaced bone fragments to support osteosynthesis. For complex cases, including pelvic bone and multi-fragment femoral neck and distal radius fractures, preoperative planning with a CT scan is indicated. The planning consists of (1) fracture reduction-determining the locations and anatomical sites of origin of the fractured bone fragments and (2) fracture fixation-selecting and placing fixation screws and plates. The current bone fragment manipulation, hardware selection, and positioning processes based on 2D slices and a computer mouse are time-consuming and require a technician. We present a novel 3D haptic-based system for patient-specific preoperative planning of orthopedic fracture surgery based on CT scans. The system provides the surgeon with an interactive, intuitive, and comprehensive, planning tool that supports fracture reduction and fixation. Its unique features include: (1) two-hand haptic manipulation of 3D bone fragments and fixation hardware models; (2) 3D stereoscopic visualization and multiple viewing modes; (3) ligaments and pivot motion constraints to facilitate fracture reduction; (4) semiautomatic and automatic fracture reduction modes; and (5) interactive custom fixation plate creation to fit the bone morphology. We evaluate our system with two experimental studies: (1) accuracy and repeatability of manual fracture reduction and (2) accuracy of our automatic virtual bone fracture reduction method. The surgeons achieved a mean accuracy of less than 1 mm for the manual reduction and 1.8 mm (std [Formula: see text] 1.1 mm) for the automatic reduction. 3D haptic-based patient-specific preoperative planning of orthopedic fracture surgery from CT scans is useful and accurate and may have significant advantages for evaluating and planning complex fractures surgery.

Application of Sal classification to parotid gland fine-needle aspiration cytology: 10-year retrospective analysis of 312 patients.

PubMed

Kilavuz, Ahmet Erdem; Songu, Murat; İmre, Abdulkadir; Arslanoğlu, Secil; Özkul, Yilmaz; Pinar, Ercan; Ateş, Düzgün

2018-05-01

The accuracy of fine-needle aspiration biopsy (FNAB) is controversial in parotid tumors. We aimed to compare FNAB results with the final histopathological diagnosis and to apply the "Sal classification" to our data and discuss its results and its place in parotid gland cytology. The FNAB cytological findings and final histological diagnosis were assessed retrospectively in 2 different scenarios based on the distribution of nondefinitive cytology, and we applied the Sal classification and determined malignancy rate, sensitivity, and specificity for each category. In 2 different scenarios FNAB sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were found to be 81%, 87%, 54.7%, and 96.1%; and 65.3%, 100%, 100%, and 96.1%, respectively. The malignancy rates and sensitivity and specificity were also calculated and discussed for each Sal category. We believe that the Sal classification has a great potential to be a useful tool in classification of parotid gland cytology. © 2018 Wiley Periodicals, Inc.

A specific and sensitive HPLC-MS/MS micromethod for milrinone plasma levels determination after inhalation in cardiac patients.

PubMed

Gavra, Paul; Nguyen, Anne Q-N; Theoret, Yves; Litalien, Catherine; Denault, André Y; Varin, France

2014-10-01

Milrinone administered through inhalation is an emerging method aimed at specifically reducing pulmonary hypertension without affecting systemic pressures. Its administration has been shown to be useful both in patients undergoing cardiac surgery and for persistent pulmonary hypertension of the newborn. These populations are prone to receive many concomitant medications and/or blood sampling may require a low volume quantification method. To address these issues in view of pharmacokinetic studies, this article aims to develop and validate a specific and sensitive analytical assay using high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) detection for the quantification of milrinone plasma concentrations after inhalation in patients undergoing cardiac surgery. Plasma samples (50 μL) were extracted using ethyl acetate. Milrinone was separated on a C18 analytical column at 50°C. The mobile phase consisted of methanol and 10 mM ammonium acetate (45:55 vol/vol). The electrospray was operated in the negative ionization mode and monitored the following mass transitions: m/z 212.1 → 140.0 at 36 eV for milrinone and m/z 252.1 → 156.1 at 32 eV for olprinone. Calibration curves followed a quadratic regression in the concentration range of 0.3125-640 ng/mL. The lower limit of quantification is 0.3125 ng/mL and is based on a low plasma volume of 50 μL. Mean drug recovery and accuracy were ≥72.3% and 96.0%, respectively. Intraday and interday precision coefficient of variation (%) was ≤7.4% and ≤11.5%, respectively. The specificity allowed milrinone quantification in the multidrug administration conditions of cardiopulmonary bypass. This validated micromethod proved to be highly sensitive and specific while using a low volume of plasma. Its low volume and its lower limit of quantification indicate that this approach is suitable for further characterization of milrinone pharmacokinetics in both adults (inhalation) and neonates.

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus

PubMed Central

van den Akker, Guus G. H.; Surtel, Don A. M.; Cremers, Andy; Richardson, Stephen M.; Hoyland, Judith A.; van Rhijn, Lodewijk W.

2016-01-01

Introduction Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Methods Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). Results The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. Conclusion We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair. PMID:26794306

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus.

PubMed

van den Akker, Guus G H; Surtel, Don A M; Cremers, Andy; Richardson, Stephen M; Hoyland, Judith A; van Rhijn, Lodewijk W; Voncken, Jan Willem; Welting, Tim J M

2016-01-01

Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair.

Organ-specific antibodies in LADA patients for the prediction of insulin dependence.

PubMed

Delitala, Alessandro P; Pes, Giovanni M; Fanciulli, Giuseppe; Maioli, Margherita; Secchi, Giannina; Sanciu, Franca; Delitala, Giuseppe; Manetti, Roberto

2016-08-01

The aim of the present study was to define the frequency of organ-specific and non-organ-specific autoantibodies in a cohort of Latent Autoimmune Diabetes in Adults (LADA) patients and to test whether multiple antibodies positivity could be a predictor of early insulin dependence. We enrolled 210 LADA and 210 type 2 diabetes mellitus (T2D) patients. In all subjects anti-islet antigen-2 (IA-2Ab), anti-thyroperoxidase (TPOAb), anti-zinc transporter 8 (ZnT8Ab), anti-nuclear (ANA), anti-parietal cell (APCA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-liver kidney microsomes (LKM), and anti-reticulin (ARA) circulating antibodies were assessed. The frequency of TPOAb, ZnT8Ab, APCA, and IA-2Ab positivity was, respectively, detected in 40.0%, 32.4%, 24.7%, and 9.5% of LADA patients, whereas their frequency was significantly lower in T2D patients (11.4%, 1.9%, 9.5%, and 0.0%, respectively, p < 0.001). The frequency of ANA was the same in both groups whereas the frequency of ASMA, ARA, AMA, and LKM was very low (range 0.0-3.3%). The presence of TPOAb associated with ZnT8Ab, IA-2Ab, or APCA allows one to predict the progression of disease with a high specificity but low sensibility. LADA patients show an increased frequency of organ- and non-organ-specific antibodies. Consequently, a screening is worthwhile in these patients. The simultaneous presence of TPOAb with ZnT8, IA-2Ab, or APCA may help differentiate clinical phenotypes and predict faster insulin dependence in LADA patients.

FOXP3 gene variations and susceptibility to autism: A case-control study.

PubMed

Safari, Mohammad Reza; Ghafouri-Fard, Soudeh; Noroozi, Rezvan; Sayad, Arezou; Omrani, Mir Davood; Komaki, Alireza; Eftekharian, Mohammad Mahdi; Taheri, Mohammad

2017-01-05

Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental disorders associated with immune system dysregulation. There are supporting evidences for the role of Forkhead Box P3 (FOXP3) gene as a lineage specification factor of regulatory T cells in the pathogenesis of ASD. The aim of this study was to explore possible relationship between genetic variants rs2232365 and rs3761548 of FOXP3 and ASD in 523 ASD patients versus 472 control individuals. Allele frequency analyses showed significant overpresentation of rs2232365-G allele in cases versus controls. In addition, rs2232365 GG genotype was associated with ASD in dominant inheritance model. Haplotype analysis revealed no significant association of any estimated block of rs2232365/rs3761548 with ASD. Our study indicated that rs2232365 is associated with ASD. Copyright © 2016 Elsevier B.V. All rights reserved.

An immunomagnetic separation-real-time PCR system for the detection of Alicyclobacillus acidoterrestris in fruit products.

PubMed

Wang, Zhouli; Cai, Rui; Yuan, Yahong; Niu, Chen; Hu, Zhongqiu; Yue, Tianli

2014-04-03

Alicyclobacillus acidoterrestris is the most important spoilage species within the Alicyclobacillus genus and has become a major issue in the pasteurized fruit juice industry. The aim of this study was to develop a method combining immunomagnetic separation (IMS) with real-time PCR system (IMS-PCR) for rapid and specific detection of A. acidoterrestris in fruit products. A real-time PCR with the TaqMan system was designed to target the 16S rDNA genes with specific primer and probe set. The specificity of the assay was confirmed using 9 A. acidoterrestris strains and 21 non-A. acidoterrestris strains. The results indicated that no combination of the designed primers and probe was found in any Alicyclobacillus genus except A. acidoterrestris. The detection limit of the established IMS-PCR was less than 10CFU/mL and the testing process was accomplished in 2-3h. For the three types of samples (sterile water, apple juice and kiwi juice), the correlation coefficient of standard curves was greater than 0.991, and the calculated PCR efficiencies were from 108% to 109%. As compared with the standard culture method performed concurrently on the same set of samples, the sensitivity, specificity and accuracy of IMS-PCR for 196 naturally contaminated fruit products were 90.0%, 98.3% and 97.5%, respectively. The results exhibited that the proposed IMS-PCR method was effective for the rapid detection of A. acidoterrestris in fruit products. Copyright © 2014. Published by Elsevier B.V.

Patient-specific dosimetry calculations using mathematic models of different anatomic sizes during therapy with 111In-DTPA-D-Phe1-octreotide infusions after catheterization of the hepatic artery.

PubMed

Kontogeorgakos, Dimitrios K; Dimitriou, Panagiotis A; Limouris, Georgios S; Vlahos, Lambros J

2006-09-01

The aim of the study was to provide dosimetric data on intrahepatic (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide therapy for neuroendocrine tumors with overexpression of somatostatin receptors. A dosimetric protocol was designed to estimate the absorbed dose to the tumor and healthy tissue in a course of 48 treatments for 12 patients, who received a mean activity of 5.4 +/- 1.7 GBq per session. The patient-specific dosimetry calculations, based on quantitative biplanar whole-body scintigrams, were performed using a Monte Carlo simulation program for 3 male and 3 female mathematic models of different anatomic sizes. Thirty minutes and 2, 6, 24, and 48 h after the radionuclide infusion, blood-sample data were collected for estimation of the red marrow radiation burden. The mean absorbed doses per administered activity (mGy/MBq) by the critical organs liver, spleen, kidneys, bladder wall, and bone marrow were 0.14 +/- 0.04, 1.4 +/- 0.6, 0.41 +/- 0.08, 0.094 +/- 0.013, and (3.5 +/- 0.8) x 10(-3), respectively; the tumor absorbed dose ranged from 2.2 to 19.6 mGy/MBq, strongly depending on the lesion size and tissue type. The results of the present study quantitatively confirm the therapeutic efficacy of transhepatic administration; the tumor-to-healthy-tissue uptake ratio was enhanced, compared with the results after antecubital infusions. Planning of treatment was also optimized by use of the patient-specific dosimetric protocol.

JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma.

PubMed

Maia, Lucas de Lima; Peterle, Gabriela Tonini; Dos Santos, Marcelo; Trivilin, Leonardo Oliveira; Mendes, Suzanny Oliveira; de Oliveira, Mayara Mota; Dos Santos, Joaquim Gasparini; Stur, Elaine; Agostini, Lidiane Pignaton; Couto, Cinthia Vidal Monteiro da Silva; Dalbó, Juliana; de Assis, Aricia Leone Evangelista Monteiro; Archanjo, Anderson Barros; Mercante, Ana Maria Da Cunha; Lopez, Rossana Veronica Mendoza; Nunes, Fábio Daumas; de Carvalho, Marcos Brasilino; Tajara, Eloiza Helena; Louro, Iúri Drumond; Álvares-da-Silva, Adriana Madeira

2018-01-01

Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.

Identifying Aboriginal-specific AUDIT-C and AUDIT-3 cutoff scores for at-risk, high-risk, and likely dependent drinkers using measures of agreement with the 10-item Alcohol Use Disorders Identification Test.

PubMed

Calabria, Bianca; Clifford, Anton; Shakeshaft, Anthony P; Conigrave, Katherine M; Simpson, Lynette; Bliss, Donna; Allan, Julaine

2014-09-01

The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item alcohol screener that has been recommended for use in Aboriginal primary health care settings. The time it takes respondents to complete AUDIT, however, has proven to be a barrier to its routine delivery. Two shorter versions, AUDIT-C and AUDIT-3, have been used as screening instruments in primary health care. This paper aims to identify the AUDIT-C and AUDIT-3 cutoff scores that most closely identify individuals classified as being at-risk drinkers, high-risk drinkers, or likely alcohol dependent by the 10-item AUDIT. Two cross-sectional surveys were conducted from June 2009 to May 2010 and from July 2010 to June 2011. Aboriginal Australian participants (N = 156) were recruited through an Aboriginal Community Controlled Health Service, and a community-based drug and alcohol treatment agency in rural New South Wales (NSW), and through community-based Aboriginal groups in Sydney NSW. Sensitivity, specificity, and positive and negative predictive values of each score on the AUDIT-C and AUDIT-3 were calculated, relative to cutoff scores on the 10-item AUDIT for at-risk, high-risk, and likely dependent drinkers. Receiver operating characteristic (ROC) curve analyses were conducted to measure the detection characteristics of AUDIT-C and AUDIT-3 for the three categories of risk. The areas under the receiver operating characteristic (AUROC) curves were high for drinkers classified as being at-risk, high-risk, and likely dependent. Recommended cutoff scores for Aboriginal Australians are as follows: at-risk drinkers AUDIT-C ≥ 5, AUDIT-3 ≥ 1; high-risk drinkers AUDIT-C ≥ 6, AUDIT-3 ≥ 2; and likely dependent drinkers AUDIT-C ≥ 9, AUDIT-3 ≥ 3. Adequate sensitivity and specificity were achieved for recommended cutoff scores. AUROC curves were above 0.90.

Tripeptide inhibitors of dengue and West Nile virus NS2B-NS3 protease.

PubMed

Schüller, Andreas; Yin, Zheng; Brian Chia, C S; Doan, Danny N P; Kim, Hyeong-Kyu; Shang, Luqing; Loh, Teck Peng; Hill, Jeffery; Vasudevan, Subhash G

2011-10-01

A series of tripeptide aldehyde inhibitors were synthesized and their inhibitory effect against dengue virus type 2 (DENV2) and West Nile virus (WNV) NS3 protease was evaluated side by side with the aim to discover potent flaviviral protease inhibitors and to examine differences in specificity of the two proteases. The synthesized inhibitors feature a varied N-terminal cap group and side chain modifications of a P2-lysine residue. In general a much stronger inhibitory effect of the tripeptide inhibitors was observed toward WNV protease. The inhibitory concentrations against DENV2 protease were in the micromolar range while they were submicromolar against WNV. The data suggest that a P2-arginine shifts the specificity toward DENV2 protease while WNV protease favors a lysine in the P2 position. Peptides with an extended P2-lysine failed to inhibit DENV2 protease suggesting a size-constrained S2 pocket. Our results generally encourage the investigation of di- and tripeptide aldehydes as inhibitors of DENV and WNV protease. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of PCR protocols for specific identification of Clostridium spiroforme and detection of sas and sbs genes.

PubMed

Drigo, Ilenia; Bacchin, Cosetta; Cocchi, Monia; Bano, Luca; Agnoletti, Fabrizio

2008-10-15

Rabbit diarrhoea caused by toxigenic Clostridium spiroforme is responsible for significant losses in commercial rabbitries but the accurate identification of this micro-organism is difficult due to the absence of both a commercial biochemical panel and biomolecular methods. The aim of this study was therefore to develop PCR protocols for specific detection of C. spiroforme and its binary toxin encoding genes. The C. spiroforme specie-specific primers were designed based on its 16S rDNA published sequences and the specificity of these primers was tested with DNA extracted from closely related Clostridium species. The sa/bs_F and sa/bs _R C. spiroforme binary toxin specific primers were designed to be complementary, respectively, to a sequence of 21 bases on the 3' and of sas gene and on the 5' of the sbs gene. The detection limits of in house developed PCR protocols were 25CFU/ml of bacterial suspension and 1.38x10(4)CFU/g of caecal content for specie-specific primers and 80CFU/ml of bacterial suspension and 2.8x10(4)CFU/g of caecal content in case of sa/bs primers. These results indicated that the described PCR assays enable specific identification of C. spiroforme and its binary toxin genes and can therefore be considered a rapid, reliable tool for the diagnosis of C. spiroforme-related enterotoxaemia.

Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

PubMed Central

Calvert, Melanie; Kyte, Derek; Duffy, Helen; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; Ives, Jonathan; Draper, Heather; Brundage, Michael; Blazeby, Jane; King, Madeleine

2014-01-01

Background Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers. Methods and Findings We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency. Conclusions PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care. PMID:25333995

Evaluation of a rapid IgM detection test for diagnosis of acute leptospirosis in dogs.

PubMed

Lizer, J; Grahlmann, M; Hapke, H; Velineni, S; Lin, D; Kohn, B

2017-05-27

Recently, a lateral flow assay (LFA) for detection of Leptospira -specific IgM in canine sera became commercially available in Europe. The present study aims to evaluate the diagnostic performance of this assay using canine sera from a collection of diagnostic accessions. Diagnostic sensitivity was assessed by testing 37 acute-phase and 9 corresponding convalescent-phase sera from dogs with a confirmed diagnosis of leptospirosis. Specificity was determined by testing sera from sick dogs with non-leptospiral infections (n=15) and healthy dogs with incomplete history of vaccination (n=45). During acute phase of illness, LFA scored positive for 28/37 sera with a sensitivity of 75.7 per cent while only 9/37 (24.3 per cent) samples were positive on microscopic agglutination test. The specificity of the LFA was 98.3 per cent (59/60). This test showed 89.7 and 100 per cent overall agreements with clinical diagnosis for acute-phase and convalescent-phase sera, respectively. The impact of vaccination on the LFA was also determined and vaccine-stimulated IgM responses were negative in 19/25 (76 per cent) dogs at 12 weeks post vaccination. In conclusion, the LFA is a rapid and reliable test for early detection of Leptospira -specific IgM during acute phase of canine leptospirosis. However, interpretation of a positive result must be made in the context of clinical signs and vaccination history. British Veterinary Association.

Diagnostic and Prognostic Significance of Serum and Tissue Galectin 3 Expression in Patients with Carcinoma of the Bladder

PubMed Central

Gendy, Hoda El; Madkour, Bothina; Abdelaty, Sara; Essawy, Fayza; Khattab, Dina; Hammam, Olfat; Nour, Hani H.

2014-01-01

Background Galectins are group of proteins found in the cytoplasm, nucleus, cell surface and extracellular matrix. Galectin 3 (Gal-3) displays pathological expression in a variety of processes such as tumorigenesis. Patients and Method 70 patients classified into the control group, cystitis group, transitional cell carcinoma group, and squamous cell carcinoma group were enrolled in this study which aimed to detect the serum level and the intensity of tissue expression of Gal-3. Results Both serum level and tissue expression of Gal-3 were statistically higher in bladder cancer patients compared to the other groups. Gal-3 level expression increased from low to high grade urothelial tumors, with a statistically significant increase of its level and expression between muscle invasive and non-muscle invasive Ta urothelial tumors. Conclusion The serum Gal-3 level is sensitive and specific for the diagnosis of bladder cancer. The prognostic significance of tissue expression is to be confirmed. PMID:26195948

Extreme divergence in floral scent among woodland star species (Lithophragma spp.) pollinated by floral parasites

PubMed Central

Friberg, Magne; Schwind, Christopher; Raguso, Robert A.; Thompson, John N.

2013-01-01

Backgrounds and Aims A current challenge in coevolutionary biology is to understand how suites of traits vary as coevolving lineages diverge. Floral scent is often a complex, variable trait that attracts a suite of generalized pollinators, but may be highly specific in plants specialized on attracting coevolved pollinating floral parasites. In this study, floral scent variation was investigated in four species of woodland stars (Lithophragma spp.) that share the same major pollinator (the moth Greya politella, a floral parasite). Three specific hypotheses were tested: (1) sharing the same specific major pollinator favours conservation of floral scent among close relatives; (2) selection favours ‘private channels’ of rare compounds particularly aimed at the specialist pollinator; or (3) selection from rare, less-specialized co-pollinators mitigates the conservation of floral scent and occurrence of private channels. Methods Dynamic headspace sampling and solid-phase microextraction were applied to greenhouse-grown plants from a common garden as well as to field samples from natural populations in a series of experiments aiming to disentangle the genetic and environmental basis of floral scent variation. Key Results Striking floral scent divergence was discovered among species. Only one of 69 compounds was shared among all four species. Scent variation was largely genetically based, because it was consistent across field and greenhouse treatments, and was not affected by visits from the pollinating floral parasite. Conclusions The strong divergence in floral scents among Lithophragma species contrasts with the pattern of conserved floral scent composition found in other plant genera involved in mutualisms with pollinating floral parasites. Unlike some of these other obligate pollination mutualisms, Lithophragma plants in some populations are occasionally visited by generalist pollinators from other insect taxa. This additional complexity may contribute to the diversification in floral scent found among the Lithophragma species pollinated by Greya moths. PMID:23365407