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Sample records for terms random peptide

  1. Novel Zn2+-chelating peptides selected from a fimbria-displayed random peptide library

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Schembri, Mark; Klemm, Per

    2001-01-01

    The display of peptide sequences on the surface of bacteria is a technology that offers exciting applications in biotechnology and medical research. Type 1 fimbriae are surface organelles of Escherichia coli which mediate D-mannose-sensitive binding to different host surfaces by virtue of the Fim......H adhesin. FimH is a component of the fimbrial organelle that can accommodate and display a diverse range of peptide sequences on the E. coli cell surface. In this study we have constructed a random peptide library in FimH. The library, consisting of similar to 40 million individual clones, was screened...

  2. Phage display peptide libraries: deviations from randomness and correctives

    Science.gov (United States)

    Ryvkin, Arie; Ashkenazy, Haim; Weiss-Ottolenghi, Yael; Piller, Chen; Pupko, Tal; Gershoni, Jonathan M

    2018-01-01

    Abstract Peptide-expressing phage display libraries are widely used for the interrogation of antibodies. Affinity selected peptides are then analyzed to discover epitope mimetics, or are subjected to computational algorithms for epitope prediction. A critical assumption for these applications is the random representation of amino acids in the initial naïve peptide library. In a previous study, we implemented next generation sequencing to evaluate a naïve library and discovered severe deviations from randomness in UAG codon over-representation as well as in high G phosphoramidite abundance causing amino acid distribution biases. In this study, we demonstrate that the UAG over-representation can be attributed to the burden imposed on the phage upon the assembly of the recombinant Protein 8 subunits. This was corrected by constructing the libraries using supE44-containing bacteria which suppress the UAG driven abortive termination. We also demonstrate that the overabundance of G stems from variant synthesis-efficiency and can be corrected using compensating oligonucleotide-mixtures calibrated by mass spectroscopy. Construction of libraries implementing these correctives results in markedly improved libraries that display random distribution of amino acids, thus ensuring that enriched peptides obtained in biopanning represent a genuine selection event, a fundamental assumption for phage display applications. PMID:29420788

  3. Random walk term weighting for information retrieval

    DEFF Research Database (Denmark)

    Blanco, R.; Lioma, Christina

    2007-01-01

    We present a way of estimating term weights for Information Retrieval (IR), using term co-occurrence as a measure of dependency between terms.We use the random walk graph-based ranking algorithm on a graph that encodes terms and co-occurrence dependencies in text, from which we derive term weights...

  4. Human milk peptides differentiate between the preterm and term infant and across varying lactational stages.

    Science.gov (United States)

    Dingess, Kelly A; de Waard, Marita; Boeren, Sjef; Vervoort, Jacques; Lambers, Tim T; van Goudoever, Johannes B; Hettinga, Kasper

    2017-10-18

    Variations in endogenous peptide profiles, functionality, and the enzymes responsible for the formation of these peptides in human milk are understudied. Additionally, there is a lack of knowledge regarding peptides in donor human milk, which is used to feed preterm infants when mother's own milk is not (sufficiently) available. To assess this, 29 human milk samples from the Dutch Human Milk Bank were analyzed as three groups, preterm late lactation stage (LS) (n = 12), term early (n = 8) and term late LS (n = 9). Gestational age (GA) groups were defined as preterm (24-36 weeks) and term (≥37 weeks). LS was determined as days postpartum as early (16-36 days) or late (55-88 days). Peptides, analyzed by LC-MS/MS, and parent proteins (proteins from matched peptide sequences) were identified and quantified, after which peptide functionality and the enzymes responsible for protein cleavage were determined. A total of 16 different parent proteins were identified from human milk, with no differences by GA or LS. We identified 1104 endogenous peptides, of which, the majority were from the parent proteins β-casein, polymeric immunoglobulin receptor, α s1 -casein, osteopontin, and κ-casein. The absolute number of peptides differed by GA and LS with 30 and 41 differing sequences respectively (p milk peptides. These results explain some of the variation in endogenous peptides in human milk, leading to future targets that may be studied for functionality.

  5. GuiTope: an application for mapping random-sequence peptides to protein sequences.

    Science.gov (United States)

    Halperin, Rebecca F; Stafford, Phillip; Emery, Jack S; Navalkar, Krupa Arun; Johnston, Stephen Albert

    2012-01-03

    Random-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules. It is often of interest to compare the selected peptide sequences to the natural protein binding partners to infer the exact binding site or the importance of particular residues. The ability to search a set of sequences for similarity to a set of peptides may sometimes enable the prediction of an antibody epitope or a novel binding partner. We have developed a software application designed specifically for this task. GuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the amino acid frequency in the peptide library; these frequencies often differ significantly from those assumed by popular alignment programs. It also includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. Finally, GuiTope can randomly select peptides from a given library to estimate a null distribution of scores and calculate statistical significance. GuiTope provides a convenient method for comparing selected peptide sequences to protein sequences, including flexible alignment parameters, novel alignment features, ability to search a database, and statistical significance of results. The software is available as an executable (for PC) at http://www.immunosignature.com/software and ongoing updates and source code will be available at sourceforge.net.

  6. GuiTope: an application for mapping random-sequence peptides to protein sequences

    Directory of Open Access Journals (Sweden)

    Halperin Rebecca F

    2012-01-01

    Full Text Available Abstract Background Random-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules. It is often of interest to compare the selected peptide sequences to the natural protein binding partners to infer the exact binding site or the importance of particular residues. The ability to search a set of sequences for similarity to a set of peptides may sometimes enable the prediction of an antibody epitope or a novel binding partner. We have developed a software application designed specifically for this task. Results GuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the amino acid frequency in the peptide library; these frequencies often differ significantly from those assumed by popular alignment programs. It also includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. Finally, GuiTope can randomly select peptides from a given library to estimate a null distribution of scores and calculate statistical significance. Conclusions GuiTope provides a convenient method for comparing selected peptide sequences to protein sequences, including flexible alignment parameters, novel alignment features, ability to search a database, and statistical significance of results. The software is available as an executable (for PC at http://www.immunosignature.com/software and ongoing updates and source code will be available at sourceforge.net.

  7. Biopanning and characterization of peptides with Fe3O4 nanoparticles-binding capability via phage display random peptide library technique.

    Science.gov (United States)

    You, Fei; Yin, Guangfu; Pu, Ximing; Li, Yucan; Hu, Yang; Huang, Zhongbin; Liao, Xiaoming; Yao, Yadong; Chen, Xianchun

    2016-05-01

    Functionalization of inorganic nanoparticles (NPs) play an important role in biomedical applications. A proper functionalization of NPs can improve biocompatibility, avoid a loss of bioactivity, and further endow NPs with unique performances. Modification with vairous specific binding biomolecules from random biological libraries has been explored. In this work, two 7-mer peptides with sequences of HYIDFRW and TVNFKLY were selected from a phage display random peptide library by using ferromagnetic NPs as targets, and were verified to display strong binding affinity to Fe3O4 NPs. Fourier transform infrared spectrometry, fluorescence microscopy, thermal analysis and X-ray photoelectron spectroscopy confirmed the presence of peptides on the surface of Fe3O4 NPs. Sequence analyses revealed that the probable binding mechanism between the peptide and Fe3O4 NPs might be driven by Pearson hard acid-hard base specific interaction and hydrogen bonds, accompanied with hydrophilic interactions and non-specific electrostatic attractions. The cell viability assay indicated a good cytocompatibility of peptide-bound Fe3O4 NPs. Furthermore, TVNFKLY peptide and an ovarian tumor cell A2780 specific binding peptide (QQTNWSL) were conjugated to afford a liner 14-mer peptide (QQTNWSLTVNFKLY). The binding and targeting studies showed that 14-mer peptide was able to retain both the strong binding ability to Fe3O4 NPs and the specific binding ability to A2780 cells. The results suggested that the Fe3O4-binding peptides would be of great potential in the functionalization of Fe3O4 NPs for the tumor-targeted drug delivery and magnetic hyperthermia. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Triiodothyronine and brain natriuretic peptide: similar long-term prognostic values for chronic heart failure.

    Science.gov (United States)

    Kozdag, Guliz; Ertas, Gokhan; Kilic, Teoman; Acar, Eser; Sahin, Tayfun; Ural, Dilek

    2010-01-01

    Although low levels of free triiodothyronine and high levels of brain natriuretic peptide have been shown as independent predictors of death in chronic heart failure patients, few studies have compared their prognostic values. The aim of this prospective study was to measure free triiodothyronine and brain natriuretic peptide levels and to compare their prognostic values among such patients.A total of 334 patients (mean age, 62 ± 13 yr; 218 men) with ischemic and nonischemic dilated cardiomyopathy were included in the study. The primary endpoint was a major cardiac event.During the follow-up period, 92 patients (28%) experienced a major cardiac event. Mean free triiodothyronine levels were lower and median brain natriuretic peptide levels were higher in patients with major cardiac events than in those without. A significant negative correlation was found between free triiodothyronine and brain natriuretic peptide levels. Receiver operating characteristic curve analysis showed that the predictive cutoff values were triiodothyronine and > 686 pg/mL for brain natriuretic peptide. Cumulative survival was significantly lower among patients with free triiodothyronine 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide.In the present study, free triiodothyronine and brain natriuretic peptide had similar prognostic values for predicting long-term prognosis in chronic heart failure patients. These results also suggested that combining these biomarkers may provide an important risk indicator for patients with heart failure.

  9. Handling a tricycle: Orthogonal versus random oxidation of the tricyclic inhibitor cystine knotted peptide gurmarin

    DEFF Research Database (Denmark)

    Eliasen, Rasmus; Andresen, Thomas L.; Conde-Frieboes, Kilian W.

    2012-01-01

    random oxidation strategy. We compared two oxidation procedures to form the three disulfide bridges. In the first, based on random oxidation, reduced gurmarin was synthesized using trityl for cysteine protection, and oxidized for 48h in a Tris–HCl buffer containing cystamine and reduced glutathione...... to facilitate disulfide scrambling. The second was based on step-wise deprotection followed by oxidation in which the cysteine pairs are orthogonally protected with tert-Butylthio, trityl and acetamidomethyl. To verify that the native gurmarin oxidation product was obtained, thermolysin cleavage was used...... UPLC. It was found that the random oxidation procedure leads to native gurmarin in high yield. Thus, the synthetic route was simple and significantly more efficient than previously reported syntheses of gurmarin and other cysteine rich peptides. Importantly, native gurmarin was obtained by random...

  10. Short term aerobic exercise training increases postprandial pancreatic polypeptide but not peptide YY concentrations in obese individuals

    OpenAIRE

    Kanaley, Jill A.; Heden, Timothy D.; Liu, Ying; Whaley-Connell, Adam T.; Chockalingam, Anand; Dellsperger, Kevin C.; Fairchild, Timothy J.

    2013-01-01

    Objective Short-term exercise training improves glycemic control, but the effect of short-term training on postprandial satiety peptide responses or perceived satiety remains unknown. We tested the hypothesis that short-term aerobic exercise training (15 days) would alter postprandial pancreatic and gut peptide [pancreatic polypeptide (PP) and peptide YY (PYY)] responses and perceived appetite and satiety in obese individuals. Subjects Thirteen healthy obese men and women (age: 42±2 y; BMI: 3...

  11. A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

    National Research Council Canada - National Science Library

    Carraway, Kermit

    1998-01-01

    .... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

  12. A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

    National Research Council Canada - National Science Library

    Carraway, Kermit

    1999-01-01

    .... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

  13. Development and validation of novel AAV2 random libraries displaying peptides of diverse lengths and at diverse capsid positions.

    Science.gov (United States)

    Naumer, Matthias; Ying, Ying; Michelfelder, Stefan; Reuter, Antje; Trepel, Martin; Müller, Oliver J; Kleinschmidt, Jürgen A

    2012-05-01

    Libraries based on the insertion of random peptide ligands into the capsid of adeno-associated virus type 2 (AAV2) have been widely used to improve the efficiency and selectivity of the AAV vector system. However, so far only libraries of 7-mer peptide ligands have been inserted at one well-characterized capsid position. Here, we expanded the combinatorial AAV2 display system to a panel of novel AAV libraries, displaying peptides of 5, 7, 12, 19, or 26 amino acids in length at capsid position 588 or displaying 7-mer peptides at position 453, the most prominently exposed region of the viral capsid. Library selections on two unrelated cell types-human coronary artery endothelial cells and rat cardiomyoblasts-revealed the isolation of cell type-characteristic peptides of different lengths mediating strongly improved target-cell transduction, except for the 26-mer peptide ligands. Characterization of vector selectivity by transduction of nontarget cells and comparative gene-transduction analysis using a panel of 44 human tumor cell lines revealed that insertion of different-length peptides allows targeting of distinct cellular receptors for cell entry with similar efficiency, but with different selectivity. The application of such novel AAV2 libraries broadens the spectrum of targetable receptors by capsid-modified AAV vectors and provides the opportunity to choose the best suited targeting ligand for a certain application from a number of different candidates.

  14. Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion.

    Science.gov (United States)

    Deglaire, Amélie; De Oliveira, Samira C; Jardin, Julien; Briard-Bion, Valérie; Emily, Mathieu; Ménard, Olivia; Bourlieu, Claire; Dupont, Didier

    2016-07-01

    Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization × Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with β-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial

    DEFF Research Database (Denmark)

    Connor, Kathryn M; Aurora, Sheena K; Loeys, Tom

    2011-01-01

    To evaluate the long-term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine....

  16. Human milk peptides differentiate between the preterm and term infant and across varying lactational stages

    NARCIS (Netherlands)

    Dingess, Kelly A.; de Waard, Marita; Boeren, Sjef; Vervoort, Jacques; Lambers, Tim T.; van Goudoever, Johannes B.; Hettinga, Kasper

    2017-01-01

    Variations in endogenous peptide profiles, functionality, and the enzymes responsible for the formation of these peptides in human milk are understudied. Additionally, there is a lack of knowledge regarding peptides in donor human milk, which is used to feed preterm infants when mother's own milk is

  17. Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management.

    Directory of Open Access Journals (Sweden)

    Gergana Galabova

    Full Text Available Low Density Lipoprotein (LDL hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9 to modulate circulating LDL cholesterol (LDLc concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models.PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt mice, Ldlr+/- mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested.Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans.

  18. Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

    Science.gov (United States)

    Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

    2007-10-01

    In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

  19. Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Peabody, David S.; Chackerian, Bryce; Ashley, Carlee; Carnes, Eric; Negrete, Oscar

    2017-01-24

    The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referred to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.

  20. Short-term effects of beta-amyloid25-35 peptide aggregates on transmitter release in neuromuscular synapses.

    Science.gov (United States)

    Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Tomàs, Josep

    2008-03-01

    The beta-amyloid (AB) peptide25-35 contains the functional domain of the AB precursor protein that is both required for neurotrophic effects in normal neural tissues and is involved in the neurotoxic effects in Alzheimer disease. We demonstrated the presence of the amyloid precursor protein/AB peptide in intramuscular axons, presynaptic motor nerve terminals, terminal and myelinating Schwann cells, and the postsynaptic and subsarcolemmal region in the Levator auris longus muscle of adult rats by immunocytochemistry. Using intracellular recording, we investigated possible short-term functional effects of the AB fragment (0.1-10 micromol/L) on acetylcholine release in adult and newborn motor end plates. We found no change in evoked, spontaneous transmitter release or resting membrane potential of the muscle cells. A previous block of the presynaptic muscarinic receptor subtypes and a previous block or stimulation of protein kinase C revealed no masked effect of the peptide on the regulation of transmitter release. The aggregated form of AB peptide25-35, however, interfered acutely with acetylcholine release (quantal content reduction) when synaptic activity was maintained by electric stimulation. The possible relevance of this inhibition of neurotransmission by AB peptide25-35 to the pathogenesis of Alzheimer remains to be determined.

  1. The physics of randomness and regularities for languages (lifetimes, family trees, and the second languages); in terms of random matrices

    OpenAIRE

    Tuncay, Caglar

    2007-01-01

    The physics of randomness and regularities for languages (mother tongues) and their lifetimes and family trees and for the second languages are studied in terms of two opposite processes; random multiplicative noise [1], and fragmentation [2], where the original model is given in the matrix format. We start with a random initial world, and come out with the regularities, which mimic various empirical data [3] for the present languages.

  2. Antibiotic prophylaxis for term or near-term premature rupture of membranes: metaanalysis of randomized trials.

    Science.gov (United States)

    Saccone, Gabriele; Berghella, Vincenzo

    2015-05-01

    The objective of the study was to evaluate the efficacy of antibiotic prophylaxis in women with term or near-term premature rupture of membranes. Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, ScienceDirect.com, MEDSCAPE, and the Cochrane Central Register of Controlled Trials with the use of a combination of key words and text words related to antibiotics, premature rupture of membranes, term, and trials from inception of each database to September 2014. We included all randomized trials of singleton gestations with premature rupture of membranes at 36 weeks or more, who were randomized to antibiotic prophylaxis or control (either placebo or no treatment). The primary outcomes included maternal chorioamnionitis and neonatal sepsis. A subgroup analysis on studies with latency more than 12 hours was planned. Before data extraction, the review was registered with the PROSPERO International Prospective Register of Systematic Reviews (registration number CRD42014013928). The metaanalysis was performed following the Preferred Reporting Item for Systematic Reviews and Meta-analyses statement. Women who received antibiotics had the same rate of chorioamnionitis (2.7% vs 3.7%; relative risk [RR], 0.73, 95% confidence interval [CI], 0.48-1.12), endometritis (0.4% vs 0.9%; RR, 0.44, 95% CI, 0.18-1.10), maternal infection (3.1% vs 4.6%; RR, 0.48, 95% CI, 0.19-1.21), and neonatal sepsis (1.0% vs 1.4%; RR, 0.69, 95% CI, 0.34-1.39). In the planned subgroup analysis, women with latency longer than 12 hours, who received antibiotics, had a lower rate of chorioamnionitis (2.9% vs 6.1%; RR, 0.49, 95% CI, 0.27-0.91) and endometritis (0% vs 2.2%; RR, 0.12, 95% CI, 0.02-0.62) compared with the control group. Antibiotic prophylaxis for term or near-term premature rupture of membranes is not associated with any benefits in either maternal or neonatal outcomes. In women with latency longer

  3. Screening and identification of RhD antigen mimic epitopes from a phage display random peptide library for the serodiagnosis of haemolytic disease of the foetus and newborn.

    Science.gov (United States)

    Wang, Jiao; Song, Jingjing; Zhou, Shuimei; Fu, Yourong; Bailey, Jeffrey A; Shen, Changxin

    2018-01-16

    Identification of RhD antigen epitopes is a key component in understanding the pathogenesis of haemolytic disease of the foetus and newborn. Research has indicated that phage display libraries are useful tools for identifying novel mimic epitopes (mimotopes) which may help to determine antigen specificity. We selected the mimotopes of blood group RhD antigen by affinity panning a phage display library using monoclonal anti-D. After three rounds of biopanning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and then sent for sequencing and peptides synthesis. Next, competitive ELISA and erythrocyte haemagglutination inhibition tests were carried out to confirm the inhibitory activity of the synthetic peptide. To evaluate the diagnostic performance of the synthetic peptide, a diagnostic ELISA was examined. Fourteen of 35 phage clones that were chosen randomly from the titering plate were considered to be positive. Following DNA sequencing and translation, 11 phage clones were found to represent the same peptide - RMKMLMMLMRRK (P4) - whereas each of the other three clones represented a unique peptide. Through the competitive ELISA and erythrocyte haemagglutination inhibition tests, the peptide (P4) was verified to have the ability to mimic the RhD antigen. The diagnostic ELISA for P4 proved to be sensitive (82.61%) and specific (88.57%). This study reveals that the P4 peptide can mimic RhD antigen and paves the way for the development of promising targeted diagnostic and therapeutic platforms for haemolytic disease of the foetus and newborn.

  4. A randomized placebo-controlled phase Ia malaria vaccine trial of two virosome-formulated synthetic peptides in healthy adult volunteers.

    Directory of Open Access Journals (Sweden)

    Blaise Genton

    2007-10-01

    Full Text Available Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof the concept that virosomes can also be used to elicit high titers of antibodies against synthetic peptides. The specific objective was to demonstrate the safety and immunogenicity of two virosome-formulated P. falciparum protein derived synthetic peptide antigens given in two different doses alone or in combination.The design was a single blind, randomized, placebo controlled, dose-escalating study involving 46 healthy Caucasian volunteers aged 18-45 years. Five groups of 8 subjects received virosomal formulations containing 10 microg or 50 microg of AMA 49-CPE, an apical membrane antigen-1 (AMA-1 derived synthetic phospatidylethanolamine (PE-peptide conjugate or 10 ug or 50 ug of UK39, a circumsporozoite protein (CSP derived synthetic PE-peptide conjugate or 50 ug of both antigens each. A control group of 6 subjects received unmodified virosomes. Virosomal formulations of the antigens (designated PEV301 and PEV302 for the AMA-1 and the CSP virosomal vaccine, respectively or unmodified virosomes were injected i. m. on days 0, 60 and 180. In terms of safety, no serious or severe adverse events (AEs related to the vaccine were observed. 11/46 study participants reported 16 vaccine related local AEs. Of these 16 events, all being pain, 4 occurred after the 1(st, 7 after the 2(nd and 5 after the 3(rd vaccination. 6 systemic AEs probably related to the study vaccine were reported after the 1(st injection, 10 after the 2(nd and 6 after the 3(rd. Generally, no difference in the distribution of the systemic AEs between either the doses applied (10 respectively 50 microg or the synthetic antigen vaccines (PEV301 and PEV302 used for immunization was found. In terms of immunogenicity, both PEV301 and PEV302 elicited already after two injections a synthetic peptide

  5. Random sequences are an abundant source of bioactive RNAs or peptides

    DEFF Research Database (Denmark)

    Neme, Rafik; Amador, Cristina; Yildirim, Burcin

    2017-01-01

    It is generally assumed that new genes arise through duplication and/or recombination of existing genes. The probability that a new functional gene could arise out of random non-coding DNA is so far considered to be negligible, as it seems unlikely that such an RNA or protein sequence could have ...

  6. Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program.

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Gorgels, W.J.M.J.; Mol, A.J.J.; Balkom, A.J.L.M. van; Mulder, J.; Lisdonk, E.H. van de; Breteler, M.H.M.; Zitman, F.G.

    2006-01-01

    OBJECTIVE: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. METHOD: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in

  7. Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Gorgels, W.J.M.J.; Mol, A.J.J.; Balkom, A.J.L.M. van; Mulder, J.; Lisdonk, E.H. van de; Breteler, M.H.M.; Zitman, F.G.

    2006-01-01

    Objective: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. Method: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in

  8. Monomeric Aβ1–40 and Aβ1–42 Peptides in Solution Adopt Very Similar Ramachandran Map Distributions That Closely Resemble Random Coil

    Science.gov (United States)

    2016-01-01

    The pathogenesis of Alzheimer’s disease is characterized by the aggregation and fibrillation of amyloid peptides Aβ1–40 and Aβ1–42 into amyloid plaques. Despite strong potential therapeutic interest, the structural pathways associated with the conversion of monomeric Aβ peptides into oligomeric species remain largely unknown. In particular, the higher aggregation propensity and associated toxicity of Aβ1–42 compared to that of Aβ1–40 are poorly understood. To explore in detail the structural propensity of the monomeric Aβ1–40 and Aβ1–42 peptides in solution, we recorded a large set of nuclear magnetic resonance (NMR) parameters, including chemical shifts, nuclear Overhauser effects (NOEs), and J couplings. Systematic comparisons show that at neutral pH the Aβ1–40 and Aβ1–42 peptides populate almost indistinguishable coil-like conformations. Nuclear Overhauser effect spectra collected at very high resolution remove assignment ambiguities and show no long-range NOE contacts. Six sets of backbone J couplings (3JHNHα, 3JC′C′, 3JC′Hα, 1JHαCα, 2JNCα, and 1JNCα) recorded for Aβ1–40 were used as input for the recently developed MERA Ramachandran map analysis, yielding residue-specific backbone ϕ/ψ torsion angle distributions that closely resemble random coil distributions, the absence of a significantly elevated propensity for β-conformations in the C-terminal region of the peptide, and a small but distinct propensity for αL at K28. Our results suggest that the self-association of Aβ peptides into toxic oligomers is not driven by elevated propensities of the monomeric species to adopt β-strand-like conformations. Instead, the accelerated disappearance of Aβ NMR signals in D2O over H2O, particularly pronounced for Aβ1–42, suggests that intermolecular interactions between the hydrophobic regions of the peptide dominate the aggregation process. PMID:26780756

  9. Monomeric Aβ(1-40) and Aβ(1-42) Peptides in Solution Adopt Very Similar Ramachandran Map Distributions That Closely Resemble Random Coil.

    Science.gov (United States)

    Roche, Julien; Shen, Yang; Lee, Jung Ho; Ying, Jinfa; Bax, Ad

    2016-02-09

    The pathogenesis of Alzheimer's disease is characterized by the aggregation and fibrillation of amyloid peptides Aβ(1-40) and Aβ(1-42) into amyloid plaques. Despite strong potential therapeutic interest, the structural pathways associated with the conversion of monomeric Aβ peptides into oligomeric species remain largely unknown. In particular, the higher aggregation propensity and associated toxicity of Aβ(1-42) compared to that of Aβ(1-40) are poorly understood. To explore in detail the structural propensity of the monomeric Aβ(1-40) and Aβ(1-42) peptides in solution, we recorded a large set of nuclear magnetic resonance (NMR) parameters, including chemical shifts, nuclear Overhauser effects (NOEs), and J couplings. Systematic comparisons show that at neutral pH the Aβ(1-40) and Aβ(1-42) peptides populate almost indistinguishable coil-like conformations. Nuclear Overhauser effect spectra collected at very high resolution remove assignment ambiguities and show no long-range NOE contacts. Six sets of backbone J couplings ((3)JHNHα, (3)JC'C', (3)JC'Hα, (1)JHαCα, (2)JNCα, and (1)JNCα) recorded for Aβ(1-40) were used as input for the recently developed MERA Ramachandran map analysis, yielding residue-specific backbone ϕ/ψ torsion angle distributions that closely resemble random coil distributions, the absence of a significantly elevated propensity for β-conformations in the C-terminal region of the peptide, and a small but distinct propensity for αL at K28. Our results suggest that the self-association of Aβ peptides into toxic oligomers is not driven by elevated propensities of the monomeric species to adopt β-strand-like conformations. Instead, the accelerated disappearance of Aβ NMR signals in D2O over H2O, particularly pronounced for Aβ(1-42), suggests that intermolecular interactions between the hydrophobic regions of the peptide dominate the aggregation process.

  10. IDENTIFICATION OF THE CORE RESIDUES OF THE EPITOPE OF A MONOCLONAL-ANTIBODY RAISED AGAINST GLYCOPROTEIN-D OF HERPES-SIMPLEX VIRUS TYPE-1 BY SCREENING OF A RANDOM PEPTIDE LIBRARY

    NARCIS (Netherlands)

    SCHELLEKENS, GA; LASONDER, E; FEIJLBRIEF, M; KOEDIJK, DGAM; DRIJFHOUT, JW; SCHEFFER, AJ; WELLINGWESTER, S; WELLING, GW

    1994-01-01

    Random peptide libraries (RPL) displayed on the surface of a filamentous bacteriophage can be used to identify peptide ligands that interact with target molecules. We have used a 15-amino acid residue RPL displayed on bacteriophage M13 to identify the core residues within the epitope of a monoclonal

  11. Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

    Science.gov (United States)

    Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

    2017-07-19

    High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory. SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

  12. Involvement of insulin-like peptide in long-term synaptic plasticity and long-term memory of the pond snail Lymnaea stagnalis.

    Science.gov (United States)

    Murakami, Jun; Okada, Ryuichi; Sadamoto, Hisayo; Kobayashi, Suguru; Mita, Koichi; Sakamoto, Yuki; Yamagishi, Miki; Hatakeyama, Dai; Otsuka, Emi; Okuta, Akiko; Sunada, Hiroshi; Takigami, Satoshi; Sakakibara, Manabu; Fujito, Yutaka; Awaji, Masahiko; Moriyama, Shunsuke; Lukowiak, Ken; Ito, Etsuro

    2013-01-02

    The pond snail Lymnaea stagnalis is capable of learning taste aversion and consolidating this learning into long-term memory (LTM) that is called conditioned taste aversion (CTA). Previous studies showed that some molluscan insulin-related peptides (MIPs) were upregulated in snails exhibiting CTA. We thus hypothesized that MIPs play an important role in neurons underlying the CTA-LTM consolidation process. To examine this hypothesis, we first observed the distribution of MIP II, a major peptide of MIPs, and MIP receptor and determined the amounts of their mRNAs in the CNS. MIP II was only observed in the light green cells in the cerebral ganglia, but the MIP receptor was distributed throughout the entire CNS, including the buccal ganglia. Next, when we applied exogenous mammalian insulin, secretions from MIP-containing cells or partially purified MIPs, to the isolated CNS, we observed a long-term change in synaptic efficacy (i.e., enhancement) of the synaptic connection between the cerebral giant cell (a key interneuron for CTA) and the B1 motor neuron (a buccal motor neuron). This synaptic enhancement was blocked by application of an insulin receptor antibody to the isolated CNS. Finally, injection of the insulin receptor antibody into the snail before CTA training, while not blocking the acquisition of taste aversion learning, blocked the memory consolidation process; thus, LTM was not observed. These data suggest that MIPs trigger changes in synaptic connectivity that may be correlated with the consolidation of taste aversion learning into CTA-LTM in the Lymnaea CNS.

  13. Screening of random peptide library of hemagglutinin from pandemic 2009 A(H1N1 influenza virus reveals unexpected antigenically important regions.

    Directory of Open Access Journals (Sweden)

    Wanghui Xu

    Full Text Available The antigenic structure of the membrane protein hemagglutinin (HA from the 2009 A(H1N1 influenza virus was dissected with a high-throughput screening method using complex antisera. The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS against antisera from mouse, goat and human, respectively. The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify "hot spots" or antigenically important regions. Unexpectedly, different antigenic structures were seen for different antisera. Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion. Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region. The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein. The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins.

  14. Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects.

    Science.gov (United States)

    Couroux, P; Patel, D; Armstrong, K; Larché, M; Hafner, R P

    2015-05-01

    Cat-PAD, the first in a new class of synthetic peptide immuno-regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment. To evaluate the long-term effects of Cat-PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment. In a randomized, double-blind, placebo-controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat-PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3-month period. In this follow-up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment. The primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat-PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat-PAD compared to placebo between the 2 and 3 h time points on days 1-4 of EEC challenge at 2 years (P Cat-PAD. This study is the first to provide evidence of a long-term therapeutic effect with this new class of SPIREs. © 2015 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

  15. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

    Directory of Open Access Journals (Sweden)

    Roman Pfister

    2011-10-01

    Full Text Available Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP levels in blood and risk of type 2 diabetes (T2D, but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36% decreased risk of incident T2D per one standard deviation (SD higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97 was similar to that expected (0.96, 0.93-0.98 based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90 and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29 per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies

  16. The anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model: a prospective randomized study

    Science.gov (United States)

    2013-01-01

    Introduction Increasing rates of multi-resistant bacteria are a major problem in the treatment of critically ill patients. Furthermore, conventional antibiotics lead to the release of bacterial derived membrane parts initiating pro-inflammatory cascades with potential harm to the patient. Antimicrobial peptides (AMP) may kill bacteria without releasing pro-inflammatory factors. Thus, we compared three newly developed synthetic anti-lipopolysaccharide peptides (SALPs) with a broader range of efficacy to suppress cytokine release in plasma and CD14 mRNA expression in organ tissue in a murine, polymicrobial sepsis model. Methods A randomized, experimental trial was conducted in an animal research facility. Male NMRI mice (n = 90; 8- to 12-weeks old) were randomized to the following six groups: (i) sham operation and parenteral vehicle (NaCl 0.9%) administration (sham); (ii) cecal ligation and puncture (CLP) and vehicle infusion (sepsis-control), (iii) CLP and polymyxin B infusion (polyB), or (iv to vi) CLP and infusion of three different synthetic antimicrobial peptides Peptide 19-2.5 (Pep2.5), Peptide 19-4 (Pep4) or Peptide 19-8 (Pep8). All animals underwent arterial and venous catheterization for hemodynamic monitoring 48 hours prior to CLP or sham-operation. Physical appearance and behavior (activity), plasma cytokine levels, and CD14 mRNA expression in heart, lung, liver, spleen and kidney tissue were determined 24 hours after CLP or sham operation. Results Only Pep2.5 significantly enhanced the activity after CLP, whereas none of the therapeutic regimens elevated the mean arterial pressure or heart rate. The strongly elevated IL-6, IL-10 and monocyte chemoattractant protein serum levels in septic animals were significantly reduced after Pep2.5 administration (P < 0.001, P < 0.001, and P < 0.001, respectively). Similarly, Pep2.5 significantly reduced the sepsis-induced CD14 mRNA expression in heart (P = 0.003), lung (P = 0.008), and spleen tissue (P = 0.009) but

  17. Effect of Probiotics on Serum Bilirubin Level in Term Neonates with Jaundice; A Randomized Clinical Trial

    OpenAIRE

    Yadollah Zahed Pasha; Mousa Ahmadpour-kacho; Abes Ahmadi Jazi; Hemmat Gholinia

    2017-01-01

    Background In recent years, tendency to use drugs has been increasing in the treatment of neonatal jaundice. Several drugs have been used since then, but the effect of probiotics on serum bilirubin level (SBL) is not so clear. This study was conducted to evaluate the effect of probiotics on SBL and the duration of phototherapy in term neonates with hyperbilirubinemia. Materials and Methods: In this randomized clinical trial, we studied 150 term neonate with jaundice hospitalized for photother...

  18. The invariant measure of random walks in the quarter-plane: respresentation in geometric terms

    NARCIS (Netherlands)

    Chen, Y.; Boucherie, Richardus J.; Goseling, Jasper

    We consider the invariant measure of homogeneous random walks in the quarter-plane. In particular, we consider measures that can be expressed as a finite linear combination of geometric terms and present conditions on the structure of these linear combinations such that the resulting measure may

  19. Management of prelabor rupture of membranes at term. A randomized study

    DEFF Research Database (Denmark)

    Sperling, Lene; Schantz, A L; Wåhlin, A

    1993-01-01

    OBJECTIVE: To compare the rate of obstetric interventions, length of labor, and maternal morbidity in pregnancies with prelabor rupture of membranes at term after either early or late induction of labor in both primiparous and pluriparous women. DESIGN: Prospective, randomized study. SUBJECTS: 362...... primiparous and pluriparous (p rupture of membranes to delivery increased...

  20. Long-term stability assessment of AlGaN/GaN field effect transistors modified with peptides: Device characteristics vs. surface properties

    Energy Technology Data Exchange (ETDEWEB)

    Rohrbaugh, Nathaniel; Bryan, Isaac; Bryan, Zachary; Collazo, Ramon; Ivanisevic, Albena, E-mail: ivanisevic@ncsu.edu [Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC 27695 (United States)

    2015-09-15

    AlGaN/GaN Field Effect Transistors (FETs) are promising biosensing devices. Functionalization of these devices is explored in this study using an in situ approach with phosphoric acid etchant and a phosphonic acid derivative. Devices are terminated on peptides and soaked in water for up to 168 hrs to examine FETs for both device responses and surface chemistry changes. Measurements demonstrated threshold voltage shifting after the functionalization and soaking processes, but demonstrated stable FET behavior throughout. X-ray photoelectron spectroscopy and atomic force microscopy confirmed peptides attachment to device surfaces before and after water soaking. Results of this work point to the stability of peptide coated functionalized AlGaN/GaN devices in solution and support further research of these devices as disposable, long term, in situ biosensors.

  1. LONG-TERM OUTCOMES OF RETINAL DEGENERATIVE DISORDER TREATMENT WITH PEPTIDE BIOREGULATORS

    Directory of Open Access Journals (Sweden)

    M. I. Razumovskiy

    2015-01-01

    Full Text Available Aim. To analyze long-term outcomes and efficacy of retinal degeneration treatment with Retinalamin.Patients and methods. Group I included 20 patients (40 eyes with pigmentary retinal dystrophy (15 patients, 30 eyes and retinal abiotrophy (5 patients, 10 eyes who received treatment with Retinalamin for 5‑7 years. Group II included 11 patients (22 eyes with pigmentary retinal dystrophy (9 patients, 18 eyes and retinal abiotrophy (2 patients, 4 eyes who received treatment with Retinalamin for 23‑25 years. Group III (controls included 15 patients (30 eyes with pigmentary retinal dystrophy (11 patients, 22 eyes and retinal abiotrophy (4 patients, 8 eyes who received traditional treatment (vasodilators, angioprotectors, antisclerotic agents, vitamins for 25 years. Standard ophthalmological examination, i.e., visual acuity measurement, visual field test, refractometry, biomicroscopy, ophthalmoscopy, was performed.Results. First course of treatment with Retinalamin improved vision in 58.1 % of retinal degeneration patients. Visual fields improved in 64.5 % of cases. Repeated treatment courses (1‑2 times a year for 23‑25 years preserved residual vision in 55.6 % of patients and object vision in 11.1 % of cases. In retinal abiotrophy patients, residual vision preserved in 100 % of cases.Conclusions. In retinal degenerations, Retinalamin improves vision and visual fields and decreases total area of absolute scotomas even after the first treatment course as well as preserves vision in prolonged use. 

  2. Short-term glucagon stimulation test of C-peptide effect on glucose utilization in patients with type 1 diabetes mellitus.

    Science.gov (United States)

    Mojto, Viliam; Rausova, Zuzana; Chrenova, Jana; Dedik, Ladislav

    2015-12-01

    This work aimed to evaluate the use of a four-point glucagon stimulation test of C-peptide effect on glucose utilization in type 1 diabetic patients using a new mathematical model. A group of 32 type 1 diabetic patients and a group of 10 healthy control subjects underwent a four-point glucagon stimulation test with blood sampling at 0, 6, 15 and 30 min after 1 mg glucagon bolus intravenous administration. Pharmacokinetic and pharmacokinetic/pharmacodynamic models of C-peptide effect on glucose utilization versus area under curve (AUC) were used. A two-sample t test and ANOVA with Bonferroni correction were used to test the significance of differences between parameters. A significant difference between control and patient groups regarding the coefficient of whole-body glucose utilization and AUC C-peptide/AUC glucose ratio (p ≪ 0.001 and p = 0.002, respectively) was observed. The high correlation (r = 0.97) between modeled coefficient of whole-body glucose utilization and numerically calculated AUC C-peptide/AUC glucose ratio related to entire cohort indicated the stability of used method. The short-term four-point glucagon stimulation test allows the numerically calculated AUC C-peptide/AUC glucose ratio and/or the coefficient of whole-body glucose utilization calculated from model to be used to diagnostically identify type 1 diabetic patients.

  3. The effect of physical exercise on orexigenic and anorexigenic peptides and its role on long-term feeding control.

    Science.gov (United States)

    Benite-Ribeiro, Sandra Aparecida; Putt, David A; Santos, Júlia Matzenbacher

    2016-08-01

    Over the past decades, life-styles changing have led to exacerbated food and caloric intake and a reduction in energy expenditure. Obesity, main outcome of these changes, increases the risk for developing type 2 diabetes, cardiovascular disease and metabolic syndrome, the leading cause of death in adult and middle age population. Body weight and energy homeostasis are maintained via complex interactions between orexigenic and anorexigenic neuropeptides that take place predominantly in the hypothalamus. Overeating may disrupt the mechanisms of feeding control, by decreasing the expression of proopiomelanocortin (POMC) and α-melanocyte stimulating hormone (α-MSH) and increasing orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP), which leads to a disturbance in appetite control and energy balance. Studies have shown that regular physical exercise might decrease body-weight, food intake and improve the metabolic profile, however until the currently there is no consensus about its effects on the expression of orexigenic/anorexigenic neuropeptides expression. Therefore, we propose that the type and length of physical exercise affect POMC/αMSH and NPY/AgRP systems differently and plays an important role in feeding behavior. Moreover, based on the present reports, we hypothesize that increased POMC/αMSH overcome NPY/AgRP expression decreasing food intake in long term physical exercise and that results in amelioration of several conditions related to overweight and obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Novel β-lactamase-random peptide fusion libraries for phage display selection of cancer cell-targeting agents suitable for enzyme prodrug therapy

    Science.gov (United States)

    Shukla, Girja S.; Krag, David N.

    2010-01-01

    Novel phage-displayed random linear dodecapeptide (X12) and cysteine-constrained decapeptide (CX10C) libraries constructed in fusion to the amino-terminus of P99 β-lactamase molecules were used for identifying β-lactamase-linked cancer cell-specific ligands. The size and quality of both libraries were comparable to the standards of other reported phage display systems. Using the single-round panning method based on phage DNA recovery, we identified severalβ-lactamase fusion peptides that specifically bind to live human breast cancer MDA-MB-361 cells. The β-lactamase fusion to the peptides helped in conducting the enzyme activity-based clone normalization and cell-binding screening in a very time- and cost-efficient manner. The methods were suitable for 96-well readout as well as microscopic imaging. The success of the biopanning was indicated by the presence of ~40% cancer cell-specific clones among recovered phages. One of the binding clones appeared multiple times. The cancer cell-binding fusion peptides also shared several significant motifs. This opens a new way of preparing and selecting phage display libraries. The cancer cell-specific β-lactamase-linked affinity reagents selected from these libraries can be used for any application that requires a reporter for tracking the ligand molecules. Furthermore, these affinity reagents have also a potential for their direct use in the targeted enzyme prodrug therapy of cancer. PMID:19751096

  5. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Kupchak Brian R

    2009-07-01

    Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

  6. An adaptive random search for short term generation scheduling with network constraints.

    Directory of Open Access Journals (Sweden)

    J A Marmolejo

    Full Text Available This paper presents an adaptive random search approach to address a short term generation scheduling with network constraints, which determines the startup and shutdown schedules of thermal units over a given planning horizon. In this model, we consider the transmission network through capacity limits and line losses. The mathematical model is stated in the form of a Mixed Integer Non Linear Problem with binary variables. The proposed heuristic is a population-based method that generates a set of new potential solutions via a random search strategy. The random search is based on the Markov Chain Monte Carlo method. The main key of the proposed method is that the noise level of the random search is adaptively controlled in order to exploring and exploiting the entire search space. In order to improve the solutions, we consider coupling a local search into random search process. Several test systems are presented to evaluate the performance of the proposed heuristic. We use a commercial optimizer to compare the quality of the solutions provided by the proposed method. The solution of the proposed algorithm showed a significant reduction in computational effort with respect to the full-scale outer approximation commercial solver. Numerical results show the potential and robustness of our approach.

  7. Necessary conditions for the invariant measure of a random walk to be a sum of geometric terms

    NARCIS (Netherlands)

    Chen, Y.; Boucherie, Richardus J.; Goseling, Jasper

    We consider the invariant measure of homogeneous random walks in the quarter-plane. In particular, we consider measures that can be expressed as an infinite sum of geometric terms. We present necessary conditions for the invariant measure of a random walk to be a sum of geometric terms. We

  8. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek

    2015-01-01

    neurolide-1 effects on short- and long-term social and spatial memory in social recognition, Morris water-maze, and Y-maze tests. We found that subcutaneous neurolide-1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK-801. It counteracted MK-801-induced memory deficit...... in the water-maze and Y-maze tests after long-term treatment (24 h and 1-2 h before the test), but not after short-term exposure (1-2 h). Long-term exposure to neurolide-1 also facilitated social recognition memory. In addition, neurolide-1-induced phosphorylation of the NMDA receptor NR1 subunit on a site...... receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide-1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide-1 on long-term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK-801. Finally, we investigated...

  9. Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

    Science.gov (United States)

    Felker, G Michael; Anstrom, Kevin J; Adams, Kirkwood F; Ezekowitz, Justin A; Fiuzat, Mona; Houston-Miller, Nancy; Januzzi, James L; Mark, Daniel B; Piña, Ileana L; Passmore, Gayle; Whellan, David J; Yang, Hongqiu; Cooper, Lawton S; Leifer, Eric S; Desvigne-Nickens, Patrice; O'Connor, Christopher M

    2017-08-22

    The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with

  10. Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials.

    Directory of Open Access Journals (Sweden)

    Gianluigi Savarese

    Full Text Available BACKGROUND: The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF. METHODOLOGY/PRINCIPAL FINDINGS: MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005 and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000, but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077. When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007 and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003, but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438, whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371, HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142 or all-cause hospitalization (OR:0.726; CI:0.509 to 1.035; p = 0.077. [corrected]. CONCLUSIONS/SIGNIFICANCE: Use of cardiac peptides to guide

  11. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with {sup 177}Lu-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [Charite, University Medicine Berlin, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Berlin (Germany); Nagarajah, James [University Hospital, Department of Nuclear Medicine, Essen (Germany)

    2014-03-15

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with {sup 177}Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by {sup 99m}Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m{sup 2} per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m{sup 2} per year) and 16 patients (22 %) a significant (>10 ml/min/m{sup 2} per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m{sup 2} per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of

  12. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate

    International Nuclear Information System (INIS)

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer; Pape, Ulrich-Frank; Nagarajah, James

    2014-01-01

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using 99m Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with 177 Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by 99m Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m 2 per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m 2 per year) and 16 patients (22 %) a significant (>10 ml/min/m 2 per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m 2 per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of patients. None of the investigated

  13. Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Denise L Faustman

    Full Text Available No targeted immunotherapies reverse type 1 diabetes in humans. However, in a rodent model of type 1 diabetes, Bacillus Calmette-Guerin (BCG reverses disease by restoring insulin secretion. Specifically, it stimulates innate immunity by inducing the host to produce tumor necrosis factor (TNF, which, in turn, kills disease-causing autoimmune cells and restores pancreatic beta-cell function through regeneration.Translating these findings to humans, we administered BCG, a generic vaccine, in a proof-of-principle, double-blind, placebo-controlled trial of adults with long-term type 1 diabetes (mean: 15.3 years at one clinical center in North America. Six subjects were randomly assigned to BCG or placebo and compared to self, healthy paired controls (n = 6 or reference subjects with (n = 57 or without (n = 16 type 1 diabetes, depending upon the outcome measure. We monitored weekly blood samples for 20 weeks for insulin-autoreactive T cells, regulatory T cells (Tregs, glutamic acid decarboxylase (GAD and other autoantibodies, and C-peptide, a marker of insulin secretion. BCG-treated patients and one placebo-treated patient who, after enrollment, unexpectedly developed acute Epstein-Barr virus infection, a known TNF inducer, exclusively showed increases in dead insulin-autoreactive T cells and induction of Tregs. C-peptide levels (pmol/L significantly rose transiently in two BCG-treated subjects (means: 3.49 pmol/L [95% CI 2.95-3.8], 2.57 [95% CI 1.65-3.49] and the EBV-infected subject (3.16 [95% CI 2.54-3.69] vs.1.65 [95% CI 1.55-3.2] in reference diabetic subjects. BCG-treated subjects each had more than 50% of their C-peptide values above the 95(th percentile of the reference subjects. The EBV-infected subject had 18% of C-peptide values above this level.We conclude that BCG treatment or EBV infection transiently modified the autoimmunity that underlies type 1 diabetes by stimulating the host innate immune response. This suggests that BCG or other

  14. EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

    Science.gov (United States)

    Dines, M; Lamprecht, R

    2014-09-30

    Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

  15. Steps to Health employee weight management randomized control trial: short-term follow-up results.

    Science.gov (United States)

    Østbye, Truls; Stroo, Marissa; Brouwer, Rebecca J N; Peterson, Bercedis L; Eisenstein, Eric L; Fuemmeler, Bernard F; Joyner, Julie; Gulley, Libby; Dement, John M

    2015-02-01

    To present the short-term follow-up findings of the Steps to Health study, a randomized trial to evaluate the effectiveness of two employee weight management programs offered within Duke University and the Health System. A total of 550 obese (body mass index, ≥30 kg/m2) employees were randomized 1:1 between January 2011 and June 2012 to the education-based Weight Management (WM) or the WM+ arm, which focused on behavior modification. Employees were contacted to complete a follow-up visit approximately 14 months after baseline. There were no clinically, or statistically, meaningful differences between arms, but there were modest reductions in body mass index, and positive, meaningful changes in diet and physical activity for both arms. The modest positive effects observed in this study may suggest that to achieve weight loss through the workplace more intensive interventions may be required.

  16. Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

    Science.gov (United States)

    Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Zhang-Jin; Chan, Wai-Chi; Zhang, Shi-Ping; Ng, Roger Man-Kin; Chan, Connie Lai-Wah; Ho, Lai-Ming; Yu, Yee-Man; Lao, Li-Xing

    2017-03-31

    Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. ClinicalTrials.gov NCT02475538 .

  17. The Neural Cell Adhesion Molecule-Derived Peptide FGL Facilitates Long-Term Plasticity in the Dentate Gyrus in Vivo

    Science.gov (United States)

    Dallerac, Glenn; Zerwas, Meike; Novikova, Tatiana; Callu, Delphine; Leblanc-Veyrac, Pascale; Bock, Elisabeth; Berezin, Vladimir; Rampon, Claire; Doyere, Valerie

    2011-01-01

    The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as…

  18. Ranked solutions to a class of combinatorial optimizations—with applications in mass spectrometry based peptide sequencing and a variant of directed paths in random media

    Science.gov (United States)

    Doerr, Timothy P.; Alves, Gelio; Yu, Yi-Kuo

    2005-08-01

    Typical combinatorial optimizations are NP-hard; however, for a particular class of cost functions the corresponding combinatorial optimizations can be solved in polynomial time using the transfer matrix technique or, equivalently, the dynamic programming approach. This suggests a way to efficiently find approximate solutions-find a transformation that makes the cost function as similar as possible to that of the solvable class. After keeping many high-ranking solutions using the approximate cost function, one may then re-assess these solutions with the full cost function to find the best approximate solution. Under this approach, it is important to be able to assess the quality of the solutions obtained, e.g., by finding the true ranking of the kth best approximate solution when all possible solutions are considered exhaustively. To tackle this statistical issue, we provide a systematic method starting with a scaling function generated from the finite number of high-ranking solutions followed by a convergent iterative mapping. This method, useful in a variant of the directed paths in random media problem proposed here, can also provide a statistical significance assessment for one of the most important proteomic tasks-peptide sequencing using tandem mass spectrometry data. For directed paths in random media, the scaling function depends on the particular realization of randomness; in the mass spectrometry case, the scaling function is spectrum-specific.

  19. Dynamical system modeling to simulate donor T cell response to whole exome sequencing-derived recipient peptides: Understanding randomness in alloreactivity incidence following stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Vishal Koparde

    Full Text Available Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA and graft versus host disease (GVHD pathophysiology in stem cell transplant (SCT donor-recipient pairs (DRP is not established. In order to elucidate this relationship, whole exome sequencing (WES was performed on 27 HLA matched related (MRD, & 50 unrelated donors (URD, to identify nonsynonymous single nucleotide polymorphisms (SNPs. An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0.01; resulting peptide antigens that may be presented on HLA class I molecules in each DRP were derived in silico (NetMHCpan ver2.0 and the tissue expression of proteins these were derived from determined (GTex. MRD DRP had an average 3,670 HLA-binding-alloreactive peptides, putative mHA (pmHA with an IC50 of <500 nM, and URD, had 5,386 (p<0.01. To simulate an alloreactive donor cytotoxic T cell response, the array of pmHA in each patient was considered as an operator matrix modifying a hypothetical cytotoxic T cell clonal vector matrix; each responding T cell clone's proliferation was determined by the logistic equation of growth, accounting for HLA binding affinity and tissue expression of each alloreactive peptide. The resulting simulated organ-specific alloreactive T cell clonal growth revealed marked variability, with the T cell count differences spanning orders of magnitude between different DRP. Despite an estimated, uniform set of constants used in the model for all DRP, and a heterogeneously treated group of patients, higher total and organ-specific T cell counts were associated with cumulative incidence of moderate to severe GVHD in recipients. In conclusion, exome wide sequence differences and the variable alloreactive peptide binding to HLA in each DRP yields a large range of possible alloreactive donor T cell responses. Our findings also help understand the apparent randomness observed in the development of alloimmune responses.

  20. Randomized trial of plastic bags to prevent term neonatal hypothermia in a resource-poor setting.

    Science.gov (United States)

    Belsches, Theodore C; Tilly, Alyssa E; Miller, Tonya R; Kambeyanda, Rohan H; Leadford, Alicia; Manasyan, Albert; Chomba, Elwyn; Ramani, Manimaran; Ambalavanan, Namasivayam; Carlo, Waldemar A

    2013-09-01

    Term infants in resource-poor settings frequently develop hypothermia during the first hours after birth. Plastic bags or wraps are a low-cost intervention for the prevention of hypothermia in preterm and low birth weight infants that may also be effective in term infants. Our objective was to test the hypothesis that placement of term neonates in plastic bags at birth reduces hypothermia at 1 hour after birth in a resource-poor hospital. This parallel-group randomized controlled trial was conducted at University Teaching Hospital, the tertiary referral center in Zambia. Inborn neonates with both a gestational age ≥37 weeks and a birth weight ≥2500 g were randomized 1:1 to either a standard thermoregulation protocol or to a standard thermoregulation protocol with placement of the torso and lower extremities inside a plastic bag within 10 minutes after birth. The primary outcome was hypothermia (plastic bag (n = 135) or to standard thermoregulation care (n = 136) had similar baseline characteristics (birth weight, gestational age, gender, and baseline temperature). Neonates in the plastic bag group had a lower rate of hypothermia (60% vs 73%, risk ratio 0.76, confidence interval 0.60-0.96, P = .026) and a higher axillary temperature (36.4 ± 0.5°C vs 36.2 ± 0.7°C, P plastic bag at birth reduced the incidence of hypothermia at 1 hour after birth in term neonates born in a resource-poor setting, but most neonates remained hypothermic.

  1. Random fractional ultrapulsed CO2 resurfacing of photodamaged facial skin: long-term evaluation.

    Science.gov (United States)

    Tretti Clementoni, Matteo; Galimberti, Michela; Tourlaki, Athanasia; Catenacci, Maximilian; Lavagno, Rosalia; Bencini, Pier Luca

    2013-02-01

    Although numerous papers have recently been published on ablative fractional resurfacing, there is a lack of information in literature on very long-term results. The aim of this retrospective study is to evaluate the efficacy, adverse side effects, and long-term results of a random fractional ultrapulsed CO2 laser on a large population with photodamaged facial skin. Three hundred twelve patients with facial photodamaged skin were enrolled and underwent a single full-face treatment. Six aspects of photodamaged skin were recorded using a 5 point scale at 3, 6, and 24 months after the treatment. The results were compared with a non-parametric statistical test, the Wilcoxon's exact test. Three hundred one patients completed the study. All analyzed features showed a significant statistical improvement 3 months after the procedure. Three months later all features, except for pigmentations, once again showed a significant statistical improvement. Results after 24 months were similar to those assessed 18 months before. No long-term or other serious complications were observed. From the significant number of patients analyzed, long-term results demonstrate not only how fractional ultrapulsed CO2 resurfacing can achieve good results on photodamaged facial skin but also how these results can be considered stable 2 years after the procedure.

  2. Virosome-formulated Plasmodium falciparum AMA-1 & CSP derived peptides as malaria vaccine: randomized phase 1b trial in semi-immune adults & children.

    Directory of Open Access Journals (Sweden)

    Patrick Georges Cech

    Full Text Available This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.No serious or severe adverse events (AEs related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014. In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02.These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.ClinicalTrials.gov NCT00513669.

  3. The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo

    DEFF Research Database (Denmark)

    Dallérac, Glenn; Zerwas, Meike; Novikova, Tatiana

    2011-01-01

    The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have...... a beneficial impact on normal memory functioning, as well as to rescue some pathological cognitive impairments. Whether its facilitating impact may be mediated through promoting neuronal plasticity is not known. The present study was therefore designed to test whether FGL modulates the induction...

  4. Effect of Probiotics on Serum Bilirubin Level in Term Neonates with Jaundice; A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Yadollah Zahed Pasha

    2017-10-01

    Full Text Available Background In recent years, tendency to use drugs has been increasing in the treatment of neonatal jaundice. Several drugs have been used since then, but the effect of probiotics on serum bilirubin level (SBL is not so clear. This study was conducted to evaluate the effect of probiotics on SBL and the duration of phototherapy in term neonates with hyperbilirubinemia. Materials and Methods: In this randomized clinical trial, we studied 150 term neonate with jaundice hospitalized for phototherapy in Amirkola Children’s Hospital, Babol- Iran, during October 5, 2016 till May 19, 2017. Eligible neonates were randomly divided into two; intervention (n=75, and control (n=75 groups. Both groups received standard conventional phototherapy, but the intervention group received 10 drop/day of probiotics (Pedilact Zisttakhmir. Co. Iran, until hospital discharge. The outcome variables were SBL and the duration of phototherapy. The data was analyzed by SPSS 22.0 and   the P 0.05.After 24, 48 and 72hours it decreased to 13.73±1.72, 10.92±1.87 and 10.25±1.32 in the intervention and 13.66±1.91, 11.01±1.69 and10.09 ±1.38 in the control groups, respectively but comparison of the amount of SBL reduction  between the two groups was not significant (P>0.05. The duration of phototherapy in the intervention group and the control group was 3.61±1.17 days and 3.72±1.18 days respectively (P>0.05. Conclusion Oral probiotics in neonates with jaundice has no significant effect on SBL and the duration of phototherapy. Further studies are needed to with longer time follow-up.

  5. Foley Catheter for Induction of Labor at Term: An Open-Label, Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Ning Gu

    Full Text Available This study aimed to determine the optimal Foley catheter balloon volume (30-mL vs. 80-mL and the maximum time for cervical ripening (12 hours vs. 24 hours to improve vaginal delivery rate within 24 hours of induction.We conducted an open-label, randomized controlled trial in a teaching hospital in China. Women with a term singleton pregnancy, cephalic presentation, intact membrane and an unfavorable cervix (Bishop score <6 were randomly allocated, in 1:1:1:1 ratio, to receive either one of the four treatments: (1 30-mL balloon for a maximum of 12 hours, (2 30-mL balloon for a maximum of 24 hours, (3 80-mL balloon for a maximum of 12 hours, and (4 80-mL balloon for a maximum of 24 hours. The primary outcome was vaginal delivery within 24 hours. Secondary outcomes included cesarean section rate and maternal/neonatal morbidity. Data were analyzed on a per-protocol basis.Five hundred and four women were recruited and randomized (126 women in each group; nine women did not receive the assigned intervention. More women achieved vaginal delivery within 24 hours in 12-hour Foley catheter groups than in the 24-hour Foley catheter groups (30-mL/12 hours: 54.5%, 30-mL/24 hours: 33.1%, 80-mL/12 hours: 46.4%, 80-mL/24 hours: 24.0%, p < 0.001. Cesarean section rates and the incidence of chorioaminonitis were comparable among four groups. After adjustment for confounding factors, both ripening time and balloon size did not affect the proportion of women delivered vaginally within 24 hours of induction.For women with an unfavorable cervix at term, induction of labor with a Foley catheter is safe and effective. Higher balloon volume (80-mL vs. 30-mL and longer ripening time (24 hours vs. 12 hours would not shorten induction to delivery interval or reduce cesarean section rate.Chinese Clinical trial registry (ChiCTR-TRC-13003044.

  6. Long-term weight-loss maintenance in obese patients with knee osteoarthritis: a randomized trial.

    Science.gov (United States)

    Christensen, Pia; Henriksen, Marius; Bartels, Else M; Leeds, Anthony R; Meinert Larsen, Thomas; Gudbergsen, Henrik; Riecke, Birgit F; Astrup, Arne; Heitmann, Berit L; Boesen, Mikael; Christensen, Robin; Bliddal, Henning

    2017-09-01

    Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear. Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight-loss maintenance and number of knee replacements over 3 y. Design: The design was a randomized trial with participants aged >50 y who had knee osteoarthritis and a body mass index [BMI (in kg/m 2 )] ≥30. Participants were recruited from the osteoarthritis outpatient clinic at Copenhagen University Hospital in Frederiksberg, Denmark; they had previously completed a 68-wk lifestyle intervention trial and achieved an average weight loss of 10.5 kg (10% of initial body weight). Participants were randomly assigned to either the intermittent treatment (IN) group with LED for 5 wk every 4 mo for 3 y or to daily meal replacements of 1-2 meals for 3 y [regular (RE) group]. Attention by dietitians and the amount of formula products were similar. Primary outcomes were changes in body weight and proportion of participants receiving knee replacements. Outcomes were analyzed on the intention-to-treat-population with the use of baseline-carried-forward imputation for missing data. Results: A total of 153 participants (means ± SDs: BMI: 33.3 ± 4.6; age: 63.8 ± 6.3 y; 83% women) were recruited between June and December 2009 and randomly assigned to the IN ( n = 76) or RE ( n = 77) group. A total of 53 and 56 participants, respectively, completed the trial. Weight increased by 0.68 and 1.75 kg in the IN and RE groups, respectively (mean difference: -1.06 kg; 95% CI: -2.75, 0.63 kg; P = 0.22). Alloplasty rates were low and did not differ (IN group: 8 of 76 participants; RE group: 12 of 77 participants; P = 0.35). Conclusions: After a mean 10% weight-loss and 1-y maintenance, additional use of daily meal replacements or intermittent LED resulted in weight-loss maintenance for 3 y. These

  7. Long-term indoor air conditioner filtration and cardiovascular health: A randomized crossover intervention study.

    Science.gov (United States)

    Chuang, Hsiao-Chi; Ho, Kin-Fai; Lin, Lian-Yu; Chang, Ta-Yuan; Hong, Gui-Bing; Ma, Chi-Ming; Liu, I-Jung; Chuang, Kai-Jen

    2017-09-01

    The association of short-term air pollution filtration with cardiovascular health has been documented. However, the effect of long-term indoor air conditioner filtration on the association between air pollution and cardiovascular health is still unclear. We recruited 200 homemakers from Taipei and randomly assigned 100 of them to air filtration or control intervention; six home visits were conducted per year from 2013 to 2014. The participants under air filtration intervention during 2013 were reassigned to control intervention in 2014. The air pollution measurements consisted of particulate matter less than or equal to 2.5μm in diameter (PM 2.5 ) and total volatile organic compounds (VOCs); blood pressure was monitored for each participant during each visit. The following morning, blood samples were collected after air pollution monitoring. The blood samples were used to analyze biological markers, including high sensitivity-C-reactive protein (hs-CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and fibrinogen. Household information, including cleaning, cooking, and air conditioning, was collected by a questionnaire. Mixed-effects models were used to investigate the associations among air pollution measurements, blood pressure and biological markers. The results showed that increased levels of PM 2.5 and total VOCs were associated with increased hs-CRP, 8-OHdG and blood pressure. The health variables were higher among participants in the control intervention phase than among those in the air filtration intervention phase. We concluded that air pollution exposure was associated with systemic inflammation, oxidative stress and elevated blood pressure. The long-term filtration of air pollution with an air conditioner filter was associated with cardiovascular health of adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Ligand-regulated peptide aptamers.

    Science.gov (United States)

    Miller, Russell A

    2009-01-01

    The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

  9. Post-Exercise Protein Trial: Interactions between Diet and Exercise (PEPTIDE): study protocol for randomized controlled trial.

    Science.gov (United States)

    Alghannam, Abdullah F; Tsintzas, Kostas; Thompson, Dylan; Bilzon, James; Betts, James A

    2014-11-24

    Performing regular exercise is known to manifest a number of health benefits that mainly relate to cardiovascular and muscular adaptations to allow for greater oxygen extraction and utilization. There is increasing evidence that nutrient intake can affect the adaptive response to a single exercise bout, and that protein feeding is important to facilitate this process. Thus, the exercise-nutrient interaction may potentially lead to a greater response to training. The role of post-exercise protein ingestion in enhancing the effects of running-based endurance exercise training relative to energy-matched carbohydrate intervention remains to be established. Additionally, the influence of immediate versus overnight protein ingestion in mediating these training effects is currently unknown. The current protocol aims to establish whether post-exercise nutrient intake and timing would influence the magnitude of improvements during a prescribed endurance training program. The project involves two phases with each involving two treatment arms applied in a randomized investigator-participant double-blind parallel group design. For each treatment, participants will be required to undergo six weeks of running-based endurance training. Immediately post-exercise, participants will be prescribed solutions providing 0.4 grams per kilogram of body mass (g · kg(-1)) of whey protein hydrolysate plus 0.4 g · kg(-1) sucrose, relative to an isocaloric sucrose control (0.8 g · kg(-1); Phase I). In Phase II, identical protein supplements will be provided (0.4 + 0.4 g · kg(-1) · h(-1) of whey protein hydrolysate and sucrose, respectively), with the timing of ingestion manipulated to compare immediate versus overnight recovery feedings. Anthropometric, expired gas, venous blood and muscle biopsy samples will be obtained at baseline and following the six-week training period. By investigating the role of nutrition in enhancing the effects of endurance exercise training, we will provide

  10. The Effects of Wenxin Keli on Left Ventricular Ejection Fraction and Brain Natriuretic Peptide in Patients with Heart Failure: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Yu Chen

    2014-01-01

    Full Text Available Objective. To evaluate the beneficial and adverse effects of Wenxin Keli (WXKL, either alone or in combination with Western medicine, on the left ventricular ejection fraction (LVEF and plasma brain natriuretic peptide (BNP in the treatment of heart failure (HF. Methods. Seven major electronic databases were searched to retrieve potential randomized controlled trials (RCTs designed to evaluate the clinical effectiveness of WXKL, either alone or in combination with Western medicine, for HF, with the LVEF or BNP after eight weeks of treatment as main outcome measures. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook for Systematic Review of Interventions, Version 5.1.0, and analyzed using RevMan 5.1.0 software. Results. Eleven RCTs of WXKL were included. The methodological quality of the trials was generally evaluated as low. The risk of bias was high. The results of the meta-analysis showed that WXKL, either alone or in combination with Western medicine, was more effective in LVEF and BNP, compared with no medicine or Western medicine alone, in patients with HF or HF complicated by other diseases. Five of the trials reported adverse events, while the others did not mention them, indicating that the safety of WXKL remains uncertain. Conclusions. WXKL, either alone or in combination with Western medicine, appears to be more effective in improving the LVEF and BNP in patients with HF and HF complications.

  11. Tai Chi for treating knee osteoarthritis: Designing a long-term follow up randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Rones Ramel

    2008-07-01

    Full Text Available Abstract Background Knee Osteoarthritis (KOA is a major cause of pain and functional impairment among elders. Currently, there are neither feasible preventive intervention strategies nor effective medical remedies for the management of KOA. Tai Chi, an ancient Chinese mind-body exercise that is reported to enhance muscle function, balance and flexibility, and to reduce pain, depression and anxiety, may safely and effectively be used to treat KOA. However, current evidence is inconclusive. Our study examines the effects of a 12-week Tai Chi program compared with an attention control (wellness education and stretching on pain, functional capacity, psychosocial variables, joint proprioception and health status in elderly people with KOA. The study will be completed by July 2009. Methods/Design Forty eligible patients, age > 55 yr, BMI ≤ 40 kg/m2 with tibiofemoral osteoarthritis (American College of Rheumatology criteria are identified and randomly allocated to either Tai Chi (10 modified forms from classical Yang style Tai Chi or attention control (wellness education and stretching. The 60-minute intervention sessions take place twice weekly for 12 weeks. The study is conducted at an urban tertiary medical center in Boston, Massachusetts. The primary outcome measure is the Western Ontario and McMaster Universities (WOMAC pain subscale at 12 weeks. Secondary outcomes include weekly WOMAC pain, function and stiffness scores, patient and physician global assessments, lower-extremity function, knee proprioception, depression, self-efficacy, social support, health-related quality of life, adherence and occurrence of adverse events after 12, 24 and 48 weeks. Discussion In this article, we present the challenges of designing a randomized controlled trial with long-term follow up. The challenges encountered in this design are: strategies for recruitment, avoidance of selection bias, the actual practice of Tai Chi, and the maximization of adherence

  12. Human papillomavirus-based cervical cancer prevention: long-term results of a randomized screening trial.

    Science.gov (United States)

    Denny, Lynette; Kuhn, Louise; Hu, Chih-Chi; Tsai, Wei-Yann; Wright, Thomas C

    2010-10-20

    Screen-and-treat approaches to cervical cancer prevention are an attractive option for low-resource settings, but data on their long-term efficacy are lacking. We evaluated the efficacy of two screen-and-treat approaches through 36 months of follow-up in a randomized trial. A total of 6637 unscreened South African women aged 35-65 years who were tested for the presence of high-risk human papillomavirus (HPV) DNA in cervical samples underwent visual inspection of the cervix using acetic acid staining and HIV serotesting. Of these, 6555 were randomly assigned to three study arms: 1) HPV-and-treat, in which all women with a positive HPV DNA test result underwent cryotherapy; 2) visual inspection-and-treat, in which all women with a positive visual inspection test result underwent cryotherapy; or 3) control, in which further evaluation or treatment was delayed for 6 months. All women underwent colposcopy with biopsy at 6 months. All women who were HPV DNA- or visual inspection-positive at enrollment, and a subset of all other women had extended follow-up to 36 months (n = 3639) with yearly colposcopy. The endpoint-cervical intraepithelial neoplasia grade 2 or worse (CIN2+)-was analyzed using actuarial life-table methods. All statistical tests were two-sided. After 36 months, there was a sustained statistically significant decrease in the cumulative detection of CIN2+ in the HPV-and-treat arm compared with the control arm (1.5% vs 5.6%, difference = 4.1%, 95% confidence interval [CI] = 2.8% to 5.3%, P cryotherapy.

  13. Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Hong Qin

    2010-01-01

    Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

  14. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  15. The synthetic Plasmodium falciparum circumsporozoite peptide PfCS102 as a malaria vaccine candidate: a randomized controlled phase I trial.

    Directory of Open Access Journals (Sweden)

    Régine Audran

    Full Text Available BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102 in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity was based on the frequency of adverse events (AE and of abnormal biological safety tests; secondary-end point (immunogenicity on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema. After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+ T cell responses. Responses were only marginally boosted after the 3(rd vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential

  16. Influence of Random Inclusion of Coconut Fibres on the Short term Strength of Highly Compressible Clay

    Science.gov (United States)

    Ramani Sujatha, Evangelin; SaiSree, S.; Prabalini, C.; Aysha Farsana, Z.

    2017-07-01

    The choice of natural fibres for soil stabilization provides an economic, safe and eco-friendly alternative to improve the properties of soil. They are an important step forward toward sustainable development. An attempt was made to study the influence of the random addition of untreated coconut fibres on the short term strength of soil, its stress-strain behavior, compaction characteristics and index properties. The soil selected for the study is a highly compressible clay sample with a liquid limit of 52.5 % and plasticity index of 38 %. The soil has no organic content. The study reveals that the compaction curves tend to shift to the right side, indicating more plastic behavior with the addition of fibres. The addition of fibres also reorient the soil structure to a more dispersed fashion. A significant increase in the unconfined compressive strength is also observed. An increase of nearly 51 % in the unconfined compressive strength is observed at 0.75 % coir inclusion. The stress-strain behavior of the soil shows a shift toward more plastic behavior. The mode of failure of the soil specimen is by cracking and with fibre inclusion, length of the failure cracks is restrained as the fibre tends to hold the cracks together, resulting in shorter cracks, with significant bulging of the specimen at failure.

  17. Randomized comparison of oral misoprostol and oxytocin for labor induction in term prelabor membrane rupture.

    Science.gov (United States)

    Butt, K D; Bennett, K A; Crane, J M; Hutchens, D; Young, D C

    1999-12-01

    To compare labor induction intervals between oral misoprostol and intravenous oxytocin in women who present at term with premature rupture of membranes. One hundred eight women were randomly assigned to misoprostol 50 microg orally every 4 hours as needed or intravenous oxytocin. The primary outcome measure was time from induction to vaginal delivery. Sample size was calculated using a two-tailed alpha of 0.05 and power of 80%. Baseline demographic data, including maternal age, gestation, parity, Bishop score, birth weight, and group B streptococcal status, were similar. The mean time +/-standard deviation to vaginal birth with oral misoprostol was 720+/-382 minutes compared with 501+/-389 minutes with oxytocin (P = .007). The durations of the first, second, and third stages of labor were similar. There were no differences in maternal secondary outcomes, including cesarean birth (eight and seven, respectively), infection, maternal satisfaction with labor, epidural use, perineal trauma, manual placental removal, or gastrointestinal side effects. Neonatal outcomes including cord pH, Apgar scores, infection, and admission to neonatal intensive care unit were not different. Although labor induction with oral misoprostol was effective, oxytocin resulted in a shorter induction-to-delivery interval. Active labor intervals and other maternal and neonatal outcomes were similar.

  18. Using Random Forests to Select Optimal Input Variables for Short-Term Wind Speed Forecasting Models

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2017-10-01

    Full Text Available Achieving relatively high-accuracy short-term wind speed forecasting estimates is a precondition for the construction and grid-connected operation of wind power forecasting systems for wind farms. Currently, most research is focused on the structure of forecasting models and does not consider the selection of input variables, which can have significant impacts on forecasting performance. This paper presents an input variable selection method for wind speed forecasting models. The candidate input variables for various leading periods are selected and random forests (RF is employed to evaluate the importance of all variable as features. The feature subset with the best evaluation performance is selected as the optimal feature set. Then, kernel-based extreme learning machine is constructed to evaluate the performance of input variables selection based on RF. The results of the case study show that by removing the uncorrelated and redundant features, RF effectively extracts the most strongly correlated set of features from the candidate input variables. By finding the optimal feature combination to represent the original information, RF simplifies the structure of the wind speed forecasting model, shortens the training time required, and substantially improves the model’s accuracy and generalization ability, demonstrating that the input variables selected by RF are effective.

  19. Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse.

    Science.gov (United States)

    Alba, Maria; Fintini, Danilo; Bowers, Cyril Y; Parlow, A F; Salvatori, Roberto

    2005-11-01

    Growth hormone (GH) secretagogues (GHS) stimulate GH secretion in vivo in humans and in animals. They act on the ghrelin receptor, expressed in both the hypothalamus and the pituitary. It is unknown whether GHSs act predominantly by increasing the release of hypothalamic GH-releasing hormone (GHRH) or by acting directly on the somatotroph cells. We studied whether a potent GHS could stimulate growth in the absence of endogenous GHRH. To this end, we used GHRH knockout (GHRH-KO) mice. These animals have proportionate dwarfism due to severe GH deficiency (GHD) and pituitary hypoplasia due to reduced somatotroph cell mass. We treated male GHRH-KO mice for 6 wk (from week 1 to week 7 of age) with GH-releasing peptide-2 (GHRP-2, 10 microg s.c. twice a day). Chronic treatment with GHRP-2 failed to stimulate somatotroph cell proliferation and GH secretion and to promote longitudinal growth. GHRP-2-treated mice showed an increase in total body weight compared with placebo-treated animals, due to worsening of the body composition alterations typical of GHD animals. These data demonstrate that GHRP-2 failed to reverse the severe GHD caused by lack of GHRH.

  20. Fluorescent CdSe/ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and nuclear targeting in living cells

    International Nuclear Information System (INIS)

    Chen, Fanqing; Gerion, Daniele

    2004-01-01

    One of the biggest challenges in cell biology is the imaging of living cells. For this purpose, the most commonly used visualization tool is fluorescent markers. However, conventional labels, such as organic fluorescent dyes or green fluorescent proteins (GFP), lack the photostability to allow the tracking of cellular events that happen over minutes to days. In addition, they are either toxic to cells (dyes), or difficult to construct and manipulate (GFP). We report here the use of a new class of fluorescent labels, silanized CdSe/ZnS nanocrystal-peptide conjugates, for imaging the nuclei of living cells. CdSe/ZnS nanocrystals, or so called quantum dots (qdots), are extremely photostable, and have been used extensively in cellular imaging of fixed cells. However, most of the studies about living cells so far have been concerned only with particle entry into the cytoplasm or the localization of receptors on the cell membrane. Specific targeting of qdots to the nucleus of living cells ha s not been reported in previous studies, due to the lack of a targeting mechanism and proper particle size. Here we demonstrate for the first time the construction of a CdSe/ZnS nanocrystal-peptide conjugate that carries the SV40 large T antigen nuclear localization signal (NLS), and the transfection of the complex into living cells. By a novel adaptation of commonly used cell transfection techniques for qdots, we were able to introduce and retain the NLS-qdots conjugate in living cells for up to a week without detectable negative cellular effects. Moreover, we can visualize the movement of the CdSe/ZnS nanocrystal-peptide conjugates from cytoplasm to the nucleus, and the accumulation of the complex in the cell nucleus, over a long observation time period. This report opens the door for using qdots to visualize long-term biological events that happen in the cell nucleus, and provides a new nontoxic, long-term imaging platform for cell nuclear processes

  1. Visual discrimination and short-term memory for random patterns in patients with a focal cortical lesion

    NARCIS (Netherlands)

    Greenlee, MW; Koessler, M; Cornelissen, FW; Mergner, T

    1997-01-01

    Visual discrimination and short-term recognition memory for computer-generated random patterns were explored in 23 patients with a postsurgical lesion in one of the cortical hemispheres. Their results are compared with those of 23 age-matched volunteers. In a same-different forced-choice

  2. Long-term effects of a weight loss intervention with or without exercise component in postmenopausal women : A randomized trial

    NARCIS (Netherlands)

    de Roon, Martijn; van Gemert, Willemijn A; Peeters, Petra H; Schuit, A.J.; Monninkhof, Evelyn M

    2017-01-01

    The aim of this study was to determine the long-term effects of a weight loss intervention with or without an exercise component on body weight and physical activity. Women were randomized to diet (n = 97) or exercise (N = 98) for 16 weeks. During the intervention, both groups had achieved the set

  3. Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial

    DEFF Research Database (Denmark)

    Maggio, Aurelio; Vitrano, Angela; Capra, Marcello

    2009-01-01

    A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8-1...

  4. Self-assembling peptide matrix for the prevention of esophageal stricture after endoscopic resection: a randomized controlled trial in a porcine model.

    Science.gov (United States)

    Barret, M; Bordaçahar, B; Beuvon, F; Terris, B; Camus, M; Coriat, R; Chaussade, S; Batteux, F; Prat, F

    2017-05-01

    Esophageal stricture formation after extensive endoscopic resection remains a major limitation of endoscopic therapy for early esophageal neoplasia. This study assessed a recently developed self-assembling peptide (SAP) matrix as a wound dressing after endoscopic resection for the prevention of esophageal stricture. Ten pigs were randomly assigned to the SAP or the control group after undergoing a 5-cm-long circumferential endoscopic submucosal dissection of the lower esophagus. Esophageal diameter on endoscopy and esophagogram, weight variation, and histological measurements of fibrosis, granulation tissue, and neoepithelium were assessed in each animal. The rate of esophageal stricture at day 14 was 40% in the SAP-treated group versus 100% in the control group (P = 0.2). Median interquartile range (IQR) esophageal diameter at day 14 was 8 mm (2.5-9) in the SAP-treated group versus 4 mm (3-4) in the control group (P = 0.13). The median (IQR) stricture indexes on esophagograms at day 14 were 0.32 (0.14-0.48) and 0.26 (0.14-0.33) in the SAP-treated and control groups, respectively (P = 0.42). Median (IQR) weight variation during the study was +0.2 (-7.4; +1.8) and -3.8 (-5.4; +0.6) in the SAP-treated and control groups, respectively (P = 0.9). Fibrosis, granulation tissue, and neoepithelium were not significantly different between the groups. The application of SAP matrix on esophageal wounds after a circumferential endoscopic submucosal dissection delayed the onset of esophageal stricture in a porcine model. © International Society for Diseases of the Esophagus 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke: A Randomized Controlled Trial.

    Science.gov (United States)

    Bunketorp-Käll, Lina; Lundgren-Nilsson, Åsa; Samuelsson, Hans; Pekny, Tulen; Blomvé, Karin; Pekna, Marcela; Pekny, Milos; Blomstrand, Christian; Nilsson, Michael

    2017-07-01

    Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke. Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants' perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up. One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79-9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00-13.66]), compared with controls (-0.5 [-3.20 to 2.28]); P =0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes. Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke. URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059. © 2017 American Heart Association, Inc.

  6. N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease

    DEFF Research Database (Denmark)

    Kragelund, Charlotte; Grønning, Bjørn; Køber, Lars

    2005-01-01

    quartile was 2.4 (95 percent confidence interval, 1.5 to 4.0; Pfamily history with respect to ischemic heart disease; the presence or absence of a history......-term mortality in patients with stable coronary disease and provides prognostic information above and beyond that provided by conventional cardiovascular risk factors and the degree of left ventricular systolic dysfunction....

  7. Randomized controlled trial evaluating the temporal effects of high-intensity exercise on learning, short-term and long-term memory, and prospective memory.

    Science.gov (United States)

    Frith, Emily; Sng, Eveleen; Loprinzi, Paul D

    2017-11-01

    The broader purpose of this study was to examine the temporal effects of high-intensity exercise on learning, short-term and long-term retrospective memory and prospective memory. Among a sample of 88 young adult participants, 22 were randomized into one of four different groups: exercise before learning, control group, exercise during learning, and exercise after learning. The retrospective assessments (learning, short-term and long-term memory) were assessed using the Rey Auditory Verbal Learning Test. Long-term memory including a 20-min and 24-hr follow-up assessment. Prospective memory was assessed using a time-based procedure by having participants contact (via phone) the researchers at a follow-up time period. The exercise stimulus included a 15-min bout of progressive maximal exertion treadmill exercise. High-intensity exercise prior to memory encoding (vs. exercise during memory encoding or consolidation) was effective in enhancing long-term memory (for both 20-min and 24-h follow-up assessments). We did not observe a differential temporal effect of high-intensity exercise on short-term memory (immediate post-memory encoding), learning or prospective memory. The timing of high-intensity exercise may play an important role in facilitating long-term memory. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

    Science.gov (United States)

    Wu, Xin; Zhang, Jie-Ting; Liu, Jue; Yang, Si; Chen, Tao; Chen, Jian-Guo; Wang, Fang

    2015-11-01

    Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting long-term potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 μM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist (CGRP8-37 ), N-methyl-d-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-d-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Calcitonin gene-related peptide (CGRP) plays an essential role in synaptic plasticity in the amygdala and fear memory. We found that CGRP-induced chemical long-term potentiation (LTP) in a dose-dependent way in the BLA-CeA (basolateral and central nucleus of amygdala, respectively) pathway and enhanced fear memory extinction in rats through a protein kinase A (PKA)-dependent postsynaptic mechanism that involved NMDA receptors. These results support a pivotal role of CGRP in amygdala. © 2015 International

  9. Patterns of Change in Interpersonal Problems During and After Short-term and Long-term Psychodynamic Group Therapy: A Randomized Clinical Trial.

    Science.gov (United States)

    Fjeldstad, Anette; Høglend, Per; Lorentzen, Steinar

    2017-05-01

    In this study, we compared the patterns of change in interpersonal problems between short-term and long-term psychodynamic group therapy. A total of 167 outpatients with mixed diagnoses were randomized to 20 or 80 weekly sessions of group therapy. Interpersonal problems were assessed with the Inventory of Interpersonal Problems at six time points during the 3-year study period. Using linear mixed models, change was linearly modelled in two steps. Earlier (within the first 6 months) and later (during the last 2.5 years) changes in five subscales were estimated. Contrary to what we expected, short-term therapy induced a significantly larger early change than long-term therapy on the cold subscale and there was a trend on the socially avoidant subscale, using a Bonferroni-adjusted alpha. There was no significant difference between short-term and long-term group therapy for improving problems in the areas cold, socially avoidant, nonassertive, exploitable, and overly nurturant over the 3 years.

  10. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Directory of Open Access Journals (Sweden)

    Geert Leroux-Roels

    Full Text Available Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101. Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1.ClinicalTrials.gov NCT01084343.

  11. Recurrent Neural Network Model for Constructive Peptide Design.

    Science.gov (United States)

    Müller, Alex T; Hiss, Jan A; Schneider, Gisbert

    2018-02-26

    We present a generative long short-term memory (LSTM) recurrent neural network (RNN) for combinatorial de novo peptide design. RNN models capture patterns in sequential data and generate new data instances from the learned context. Amino acid sequences represent a suitable input for these machine-learning models. Generative models trained on peptide sequences could therefore facilitate the design of bespoke peptide libraries. We trained RNNs with LSTM units on pattern recognition of helical antimicrobial peptides and used the resulting model for de novo sequence generation. Of these sequences, 82% were predicted to be active antimicrobial peptides compared to 65% of randomly sampled sequences with the same amino acid distribution as the training set. The generated sequences also lie closer to the training data than manually designed amphipathic helices. The results of this study showcase the ability of LSTM RNNs to construct new amino acid sequences within the applicability domain of the model and motivate their prospective application to peptide and protein design without the need for the exhaustive enumeration of sequence libraries.

  12. Effect of short-term vs. long-term elevation of dietary protein intake on responsiveness of rat thick ascending limbs to peptide hormones.

    Science.gov (United States)

    Goldstein, David L; Plaga, Kimberly

    2002-10-01

    We compared the renal responses of rats on three diet regimens. Rats received either 8% protein food (low-protein, LP) for 10 weeks following weaning, 8% protein for 9 weeks followed by 1 week on 30% protein (short-term high-protein, SHP), or 30% protein for 10 weeks (high-protein, HP). Kidneys from HP rats were enlarged by approximately 50%, or 20% when corrected for body mass. Most of this hypertrophy resulted from enlargement of the inner stripe of the outer medulla, site of the thick ascending limbs (TAL), and TAL from HP rats were larger in diameter. SHP rats had TAL diameters similar to HP rats, but changes in renal mass or height of renal zones did not reach statistical significance. The activity of adenylyl cyclase (AC) in TAL, measured from the accumulation of cAMP in isolated tubules, increased with dose of both arginine vasopressin (AVP) and glucagon in all rats. However, HP rats had significantly higher hormone-induced AC activity than LP or SHP rats, which were not different from each other. Our results suggest that tubule hypertrophy may precede up-regulation of hormone-sensitive AC activity during the progression of renal response to elevated dietary protein.

  13. Prognostic value of N-terminal prohormone brain natriuretic peptide for in-hospital and long-term outcomes in patients with infective endocarditis.

    Science.gov (United States)

    Wei, Xue-Biao; Liu, Yuan-Hui; He, Peng-Cheng; Yu, Dan-Qing; Zhou, Ying-Ling; Tan, Ning; Chen, Ji-Yan

    2017-05-01

    Background Limited research studies with a large sample size were performed to evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for in-hospital or long-term poor outcomes in patients with infective endocarditis. Methods A total of 703 patients with infective endocarditis were enrolled and divided into four groups according to admission NT-pro-BNP (pg/mL) quartiles: Q1 (3522). Multivariate regression was used to determine independent risk of NT-proBNP for in-hospital and one-year death. Results In-hospital death occurred in 9.0% of patients. The in-hospital mortality was increased from the lowest to the highest NT-proBNP quartiles (1.1%, 3.4%, 9.1% and 22.3%, P  2260 pg/mL had 76.2% sensitivity and 69.1% specificity for predicting in-hospital death. Kaplan-Meier analysis showed that patients with NT-proBNP > 2260 pg/ml had a worse prognosis than those without (log-rank test 18.84, P endocarditis.

  14. Long-term Diet and Biomarker Changes after a Short-term Intervention among Hispanic Breast Cancer Survivors: The ¡Cocinar Para Su Salud! Randomized Controlled Trial.

    Science.gov (United States)

    Greenlee, Heather; Ogden Gaffney, Ann; Aycinena, A Corina; Koch, Pam; Contento, Isobel; Karmally, Wahida; Richardson, John M; Shi, Zaixing; Lim, Emerson; Tsai, Wei-Yann; Santella, Regina M; Blaner, William S; Clugston, Robin D; Cremers, Serge; Pollak, Susan; Sirosh, Iryna; Crew, Katherine D; Maurer, Matthew; Kalinsky, Kevin; Hershman, Dawn L

    2016-11-01

    Among Hispanic breast cancer survivors, we examined the long-term effects of a short-term culturally based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat, and changing biomarkers associated with breast cancer recurrence risk. Spanish-speaking women (n = 70) with a history of stage 0-III breast cancer who completed treatment were randomized to ¡Cocinar Para Su Salud! (n = 34), a culturally based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n = 36, written dietary recommendations for breast cancer survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months. We report changes between groups at 12 months in dietary intake and biomarkers using 2-sample Wilcoxon t tests and generalized estimating equation (GEE) models. At 12 months, the intervention group compared with the control group reported higher increases in mean daily F/V servings (total: +2.0 vs. -0.4; P Salud! program was effective at increasing long-term F/V intake in Hispanic breast cancer survivors and changed biomarkers associated with breast cancer recurrence risk. It is possible for short-term behavioral interventions to have long-term effects on behaviors and biomarkers in minority cancer patient populations. Results can inform future study designs. Cancer Epidemiol Biomarkers Prev; 25(11); 1491-502. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Fermi sea term in the relativistic linear muffin-tin-orbital transport theory for random alloys

    Czech Academy of Sciences Publication Activity Database

    Turek, Ilja; Kudrnovský, Josef; Drchal, Václav

    2014-01-01

    Roč. 89, č. 6 (2014), 064405 ISSN 1098-0121 R&D Projects: GA ČR(CZ) GAP204/11/1228 Institutional support: RVO:68081723 ; RVO:68378271 Keywords : electron transport * anomalous Hall effect * random alloys Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.736, year: 2014

  16. Inhomogeneous Linear Random Differential Equations with Mutual Correlations between Multiplicative, Additive and Initial-Value Terms

    NARCIS (Netherlands)

    Roerdink, J.B.T.M.

    1981-01-01

    The cumulant expansion for linear stochastic differential equations is extended to the general case in which the coefficient matrix, the inhomogeneous part and the initial condition are all random and, moreover, statistically interdependent. The expansion now involves not only the autocorrelation

  17. InfAcrOnt: calculating cross-ontology term similarities using information flow by a random walk.

    Science.gov (United States)

    Cheng, Liang; Jiang, Yue; Ju, Hong; Sun, Jie; Peng, Jiajie; Zhou, Meng; Hu, Yang

    2018-01-19

    Since the establishment of the first biomedical ontology Gene Ontology (GO), the number of biomedical ontology has increased dramatically. Nowadays over 300 ontologies have been built including extensively used Disease Ontology (DO) and Human Phenotype Ontology (HPO). Because of the advantage of identifying novel relationships between terms, calculating similarity between ontology terms is one of the major tasks in this research area. Though similarities between terms within each ontology have been studied with in silico methods, term similarities across different ontologies were not investigated as deeply. The latest method took advantage of gene functional interaction network (GFIN) to explore such inter-ontology similarities of terms. However, it only used gene interactions and failed to make full use of the connectivity among gene nodes of the network. In addition, all existent methods are particularly designed for GO and their performances on the extended ontology community remain unknown. We proposed a method InfAcrOnt to infer similarities between terms across ontologies utilizing the entire GFIN. InfAcrOnt builds a term-gene-gene network which comprised ontology annotations and GFIN, and acquires similarities between terms across ontologies through modeling the information flow within the network by random walk. In our benchmark experiments on sub-ontologies of GO, InfAcrOnt achieves a high average area under the receiver operating characteristic curve (AUC) (0.9322 and 0.9309) and low standard deviations (1.8746e-6 and 3.0977e-6) in both human and yeast benchmark datasets exhibiting superior performance. Meanwhile, comparisons of InfAcrOnt results and prior knowledge on pair-wise DO-HPO terms and pair-wise DO-GO terms show high correlations. The experiment results show that InfAcrOnt significantly improves the performance of inferring similarities between terms across ontologies in benchmark set.

  18. Calcitonin gene-related peptide antagonism and cluster headache

    DEFF Research Database (Denmark)

    Ashina, Håkan; Newman, Lawrence; Ashina, Sait

    2017-01-01

    Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact...... role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov . The search term used was "cluster headache and calcitonin gene related peptide......" and "primary headaches and calcitonin gene related peptide." Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play...

  19. Mild erythrocytopenia is the most frequent long-term sequel after peptide receptor radionuclide Therapy: Results of long-term follow-up in more than 500 Patients from a single centre

    International Nuclear Information System (INIS)

    Schmidt, J.; Kulkami, H.R.; Baum, R.P.; Menghui, Y.

    2015-01-01

    Full text of publication follows. Aim: Peptide receptor radionuclide therapy (PRRT) is highly effective in well differentiated neuroendocrine neoplasms (NENs) and lends a benefit in overall survival of several years. Renal toxicity is a well-known adverse effect of PRRNT. Hematological toxicity as possible long-term sequel has been hardly examined. Therefore we investigated the effect of PRRT on the hematological status (erythrocytes, leukocytes, thrombocytes) of patients who received individualized therapy at our centre. Materials and Methods: Out of over 500 patients, 59 chemotherapy naive patients with well-differentiated NENs who were treated with at least 3 cycles of PRRT with 177 Lu- and/or 90 Y- labeled DOTATATE/DOTATOC and long-term follow-up were selected for this analysis. Blood counts were documented before the first cycle and repeated at monthly intervals between further cycles and during re-staging examinations after PRRT for many years. Comparisons were done between the hematological status before the first cycle and the one 3 years after the last cycle of PRRT. Results: All 3 cell lines were significantly decreased 3 years after the last radionuclide therapy (erythrocytes, leukocytes: p=0,000; thrombocytes: p=0,002; confidence interval 95%). But only erythrocytes showed a significant decrement, i.e., below the reference level of our in-house laboratory (mean value ± standard deviation: (4.07 ± 0.69)/l; reference level: 4.1-5.4/l). Conclusions: Mild erythrocytopenia is the most frequent long-term sequel after PRRT. Although it has to be considered that repeated cycles probably cause impoverishment in bone marrow reserve (or red cell precursors), PRRT achieves both significant improvement in clinical symptoms and excellent palliation. Thus it remains a safe procedure if performed at specialized centres with interdisciplinary and long-term care. (authors)

  20. The effects of long- and short-term interdisciplinary treatment approaches in women with fibromyalgia: a randomized controlled trial.

    Science.gov (United States)

    Saral, Ilknur; Sindel, Dilsad; Esmaeilzadeh, Sina; Sertel-Berk, Hanife Ozlem; Oral, Aydan

    2016-10-01

    We investigated the effects of long- and short-term interdisciplinary treatment approaches for reducing symptoms and improving health-related quality of life (HRQoL) and physical functions of patients with fibromyalgia and compared the effects of two different interdisciplinary treatment approaches. We conducted a prospective, randomized, controlled trial involving 66 women with fibromyalgia eligible for the study at a university hospital setting. The patients were randomized into three groups (allocation ratio 1:1:1) using a computer-generated random numbers: a long-term interdisciplinary treatment group (LG, n = 22) that participated in 10 sessions (3-h once-weekly session for 10 weeks) of cognitive behavioral therapy (CBT) together with exercise training and other fibromyalgia related educational programs (two full days); a short-term interdisciplinary treatment group (SG, n = 22) that received two full days of educational, exercise, and CBT programs; and a control group (CG, n = 22). The patients were evaluated at baseline and 6 months after treatment using the visual analog scale (pain, fatigue, and sleep), Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Short Form-36, tender point numbers, and pressure algometry as primary outcomes. The statistical analysis was confined to the 'per-protocol' set. No blinding was performed. The number of patients analyzed was 21 in the LG, 19 in the SG, and 19 in the CG. The intensity of pain (p treatment approaches when compared with controls; the long-term treatment was found more effective in reducing pain than the short-term. Both, long- and short-term interdisciplinary treatments were effective in reducing the severity of some symptoms and disease activity in patients with fibromyalgia. The short-term program well meets the needs of women with fibromyalgia particularly in relation to pain and health status as measured using FIQ; however, a long-term program may be beneficial in reducing fatigue and

  1. Characterisation of random Gaussian and non-Gaussian stress processes in terms of extreme responses

    Directory of Open Access Journals (Sweden)

    Colin Bruno

    2015-01-01

    Full Text Available In the field of military land vehicles, random vibration processes generated by all-terrain wheeled vehicles in motion are not classical stochastic processes with a stationary and Gaussian nature. Non-stationarity of processes induced by the variability of the vehicle speed does not form a major difficulty because the designer can have good control over the vehicle speed by characterising the histogram of instantaneous speed of the vehicle during an operational situation. Beyond this non-stationarity problem, the hard point clearly lies in the fact that the random processes are not Gaussian and are generated mainly by the non-linear behaviour of the undercarriage and the strong occurrence of shocks generated by roughness of the terrain. This non-Gaussian nature is expressed particularly by very high flattening levels that can affect the design of structures under extreme stresses conventionally acquired by spectral approaches, inherent to Gaussian processes and based essentially on spectral moments of stress processes. Due to these technical considerations, techniques for characterisation of random excitation processes generated by this type of carrier need to be changed, by proposing innovative characterisation methods based on time domain approaches as described in the body of the text rather than spectral domain approaches.

  2. A Logistic Regression Model with a Hierarchical Random Error Term for Analyzing the Utilization of Public Transport

    Directory of Open Access Journals (Sweden)

    Chong Wei

    2015-01-01

    Full Text Available Logistic regression models have been widely used in previous studies to analyze public transport utilization. These studies have shown travel time to be an indispensable variable for such analysis and usually consider it to be a deterministic variable. This formulation does not allow us to capture travelers’ perception error regarding travel time, and recent studies have indicated that this error can have a significant effect on modal choice behavior. In this study, we propose a logistic regression model with a hierarchical random error term. The proposed model adds a new random error term for the travel time variable. This term structure enables us to investigate travelers’ perception error regarding travel time from a given choice behavior dataset. We also propose an extended model that allows constraining the sign of this error in the model. We develop two Gibbs samplers to estimate the basic hierarchical model and the extended model. The performance of the proposed models is examined using a well-known dataset.

  3. Usefulness of repeated N-terminal pro-B-type natriuretic peptide measurements as incremental predictor for long-term cardiovascular outcome after vascular surgery.

    Science.gov (United States)

    Goei, Dustin; van Kuijk, Jan-Peter; Flu, Willem-Jan; Hoeks, Sanne E; Chonchol, Michel; Verhagen, Hence J M; Bax, Jeroen J; Poldermans, Don

    2011-02-15

    Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels improve preoperative cardiac risk stratification in vascular surgery patients. However, single preoperative measurements of NT-pro-BNP cannot take into account the hemodynamic stress caused by anesthesia and surgery. Therefore, the aim of the present study was to assess the incremental predictive value of changes in NT-pro-BNP during the perioperative period for long-term cardiac mortality. Detailed cardiac histories, rest left ventricular echocardiography, and NT-pro-BNP levels were obtained in 144 patients before vascular surgery and before discharge. The study end point was the occurrence of cardiovascular death during a median follow-up period of 13 months (interquartile range 5 to 20). Preoperatively, the median NT-pro-BNP level in the study population was 314 pg/ml (interquartile range 136 to 1,351), which increased to a median level of 1,505 pg/ml (interquartile range 404 to 6,453) before discharge. During the follow-up period, 29 patients (20%) died, 27 (93%) from cardiovascular causes. The median difference in NT-pro-BNP in the survivors was 665 pg/ml, compared to 5,336 pg/ml in the patients who died (p = 0.01). Multivariate Cox regression analyses, adjusted for cardiac history and cardiovascular risk factors (age, angina pectoris, myocardial infarction, stroke, diabetes mellitus, renal dysfunction, body mass index, type of surgery and the left ventricular ejection fraction), demonstrated that the difference in NT-pro-BNP level between pre- and postoperative measurement was the strongest independent predictor of cardiac outcome (hazard ratio 3.06, 95% confidence interval 1.36 to 6.91). In conclusion, the change in NT-pro-BNP, indicated by repeated measurements before surgery and before discharge is the strongest predictor of cardiac outcomes in patients who undergo vascular surgery. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Cluster Randomized Controlled Trial: Clinical and Cost-Effectiveness of a System of Longer-Term Stroke Care.

    Science.gov (United States)

    Forster, Anne; Young, John; Chapman, Katie; Nixon, Jane; Patel, Anita; Holloway, Ivana; Mellish, Kirste; Anwar, Shamaila; Breen, Rachel; Knapp, Martin; Murray, Jenni; Farrin, Amanda

    2015-08-01

    We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was -0.6 points (95% confidence interval, -1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305. © 2015 Bradford Teaching Hospitals NHS Foundation Trust.

  5. Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: a randomized, placebo-controlled study

    NARCIS (Netherlands)

    Smit, J. W. A.; Eustatia-Rutten, C. F. A.; Corssmit, E. P. M.; Pereira, A. M.; Frölich, M.; Bleeker, G. B.; Holman, E. R.; van der Wall, E. E.; Romijn, J. A.; Bax, J. J.

    2005-01-01

    Subclinical hyperthyroidism has been reported to affect systolic and diastolic cardiac function. However, the reversibility of these effects is not well established. Our objective was to investigate the presence and reversibility of cardiac abnormalities in patients with long-term exogenous

  6. Beating the random walk: a performance assessment of long-term interest rate forecasts

    NARCIS (Netherlands)

    den Butter, F.A.G.; Jansen, P.W.

    2013-01-01

    This article assesses the performance of a number of long-term interest rate forecast approaches, namely time series models, structural economic models, expert forecasts and combinations thereof. The predictive performance of these approaches is compared using outside sample forecast errors, where a

  7. Physical activity after commitment lotteries: examining long-term results in a cluster randomized trial.

    Science.gov (United States)

    van der Swaluw, Koen; Lambooij, Mattijs S; Mathijssen, Jolanda J P; Schipper, Maarten; Zeelenberg, Marcel; Berkhout, Stef; Polder, Johan J; Prast, Henriëtte M

    2018-02-26

    To overcome self-control difficulties, people can commit to their health goals by voluntarily accepting deadlines with consequences. In a commitment lottery, the winners are drawn from all participants, but can only claim their prize if they also attained their gym-attendance goals. In a 52-week, three-arm trial across six company gyms, we tested if commitment lotteries with behavioral economic underpinnings would promote physical activity among overweight adults. In previous work, we presented an effective 26-week intervention. In the present paper we analyzed maintenance of goal attainment at 52-week follow-up and the development of weight over time. We compared weight and goal attainment (gym attendance ≥ 2 per week) between three arms that-in the intervention period- consisted of (I) weekly short-term lotteries for 13 weeks; (II) the same short-term lotteries in combination with an additional long-term lottery after 26 weeks; and (III) a control arm without lottery-deadlines. After a successful 26-week intervention, goal attainment declined between weeks 27 and 52 in the long-term lottery arm, but remained higher than in the control group. Goal attainment did not differ between the short-term lottery arm and control arm. Weight declined slightly in all arms in the first 13 weeks of the trial and remained stable from there on. Commitment lotteries can support regular gym attendance up to 52 weeks, but more research is needed to achieve higher levels of maintenance and weight loss.

  8. Pro B-type natriuretic peptide plasma value: a new criterion for the prediction of short- and long-term outcomes after transcatheter aortic valve implantation.

    Science.gov (United States)

    López-Otero, Diego; Trillo-Nouche, Ramiro; Gude, Francisco; Cid-Álvarez, Belen; Ocaranza-Sanchez, Raimundo; Alvarez, Melisa Santas; Lear, Pamela V; Gonzalez-Juanatey, José R

    2013-09-30

    To determine the prognostic value of pro B-type natriuretic peptide (pro-BNP) to predict mortality after transcatheter aortic valve implantation (TAVI). Logistic EuroSCORE (LES) overestimates observed mortality after TAVI. A new risk score specific to TAVI is needed to accurately assess mortality and outcome. Eighty-five patients were included. Indications for TAVI were nonoperable or surgically high-risk patients (LES>20%). Pro-BNP was measured 24h before the procedure. Cox proportional hazards model was used to evaluate clinical factors. The predictive accuracy of these Cox models was determined by using time-dependent receiver operating characteristic (ROC) curves. Pro-BNP levels (log-transformed) were significantly higher in non-survivors than in survivors at 30 days (3.36 ± 0.43 vs. 3.81 ± 0.43, p<0.004) and at the end of follow-up (3.34 ± 0.42 vs. 3.63 ± 0.48, p<0.011). Multivariate analysis revealed that only increased log pro-BNP levels were associated with higher mortality rate at short [hazard ratio (HR) (95% confidence intervals (CI)]=5.35 (1.74-16.5), p=0.003] and long-term follow-ups [HR=11 (CI: 1.51-81.3), p=0.018]. LES was not associated with increased mortality at either time point [HR=1.03 (CI: 0.95-1.10), p=0.483 and HR=1.03 (CI: 0.98-1.07), p=0.230, respectively]. At 30, 90, 180, and 365 days, the c-index was 0.72 for log pro-BNP and 0.63 for LES (p=0.044). Pre-procedure log transform of plasma pro-BNP levels are an independent and strong predictor of short- and long-term outcomes after TAVI and are more discriminatory than LES. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2017-11-01

    cellular proliferation, differentiation, apoptosis, organ development, and sex determination , the protein is processed by the proteasome and the derived...peptide). Vaccine:  2/3 CD8+  4/8 CD4+ Control:  0/4 CD8+  1/8 CD4+ Injection site reactions were common, mild, and self -limited...the ASCO Annual Meeting 2016. 3 Abstract Purpose: Determine the 1-year progression-free survival (PFS) among patients with malignant pleural

  10. Immunoglobulins in Neonates with Rhesus Hemolytic Disease of the Fetus and Newborn: Long-Term Outcome in a Randomized Trial.

    Science.gov (United States)

    van Klink, Jeanine M M; van Veen, Suzanne J; Smits-Wintjens, Vivianne E H J; Lindenburg, Irene T M; Rijken, Monique; Oepkes, Dick; Lopriore, Enrico

    2016-01-01

    Prophylactic intravenous immunoglobulin (IVIg) does neither reduce the need for exchange transfusion nor the rates of other adverse neonatal outcomes in neonates with rhesus hemolytic disease of the fetus and newborn (rhesus HDFN) according to our randomized controlled trial analysis. Our objective was to assess the long-term neurodevelopmental outcome in the children included in the trial and treated with either IVIg or placebo. All families of the children included in the trial were asked to participate in this follow-up study. The long-term neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests. The primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe cognitive and/or motor developmental delay (with a test score of less than -2 SD), bilateral deafness or blindness. Sixty-six of the 80 children (82.5%) who had been recruited to the initial randomized controlled trial participated in the follow-up study. The children were assessed at a median age of 4 years (range 2-7). The median cognitive score was 96 (range 68-118) in the IVIg group and 97 (range 66-118) in the placebo group (p = 0.79). There was no difference in the rate of neurodevelopmental impairment between the IVIg and the placebo group [3% (1/34) vs. 3% (1/32); p = 1.00]. The long-term neurodevelopmental outcome in children treated with IVIg was not different from that in children treated with placebo. Standardized long-term follow-up studies with large enough case series and sufficient power are needed to replicate these findings. © 2015 S. Karger AG, Basel.

  11. Effectiveness and short-term safety of modified sodium hyaluronic acid-carboxymethylcellulose at cesarean delivery: a randomized trial.

    Science.gov (United States)

    Kiefer, Daniel G; Muscat, Jolene C; Santorelli, Jarrett; Chavez, Martin R; Ananth, Cande V; Smulian, John C; Vintzileos, Anthony M

    2016-03-01

    The rising cesarean birth rate has drawn attention to risks associated with repeat cesarean birth. Prevention of adhesions with adhesion barriers has been promoted as a way to decrease operative difficulty. However, robust data demonstrating effectiveness of such interventions are lacking. We report data from a multicenter trial designed to evaluate the short-term safety and effectiveness of a modified sodium hyaluronic acid (HA)-carboxymethylcellulose (CMC) absorbable adhesion barrier for reduction of adhesions following cesarean delivery. Patients who underwent primary or repeat cesarean delivery were included in this multicenter, single-blinded (patient), randomized controlled trial. Patients were randomized into either HA-CMC (N = 380) or no treatment (N = 373). No other modifications to their treatment were part of the protocol. Short-term safety data were collected following randomization. The location and density of adhesions (primary outcome) were assessed at their subsequent delivery using a validated tool, which can also be used to derive an adhesion score that ranges from 0-12. No differences in baseline characteristics, postoperative course, or incidence of complications between the groups following randomization were noted. Eighty patients from the HA-CMC group and 92 controls returned for subsequent deliveries. Adhesions in any location were reported in 75.6% of the HA-CMC group and 75.9% of the controls (P = .99). There was no significant difference in the median adhesion score; 2 (range 0-10) for the HA-CMC group vs 2 (range 0-8) for the control group (P = .65). One third of the HA-CMC patients met the definition for severe adhesions (adhesion score >4) compared to 15.5% in the control group (P = .052). There were no significant differences in the time from incision to delivery (P = .56). Uterine dehiscence in the next pregnancy was reported in 2 patients in HA-CMC group vs 1 in the control group (P = .60). Although we did not identify any short-term

  12. Dor Vs Toupet Fundoplication After Laparoscopic Heller Myotomy: Long-Term Randomized Controlled Trial Evaluated by High-Resolution Manometry.

    Science.gov (United States)

    Torres-Villalobos, Gonzalo; Coss-Adame, Enrique; Furuzawa-Carballeda, Janette; Romero-Hernández, Fernanda; Blancas-Breña, Blanca; Torres-Landa, Samuel; Palacios-Ramírez, Axel; Alejandro-Medrano, Edgar; Hernández-Ávila, Axel; Flores-Najera, Athenea; Ávila Escobedo, Lourdes Margarita; Ramírez Angulo, Cecilia; Rodríguez-Garcés, Angélica; Valdovinos, Miguel Ángel

    2018-01-01

    Laparoscopic Heller myotomy (LHM) with partial fundoplication is an effective treatment for achalasia. However, the type of fundoplication is still a subject of debate. The aim of the study is to identify which partial fundoplication leads to better control of acid exposure, manometric parameters, and symptoms scores. A randomized controlled trial was performed to compare Dor vs Toupet fundoplication after LHM. The preoperative diagnosis was made by high-resolution manometry (HRM), upper endoscopy, and barium esophagogram. Preoperative and postoperative symptoms were evaluated with Eckardt, GERD-HRQL, and EAT-10 questionnaires. Seventy-three patients were randomized, 38 underwent Dor and 35 Toupet. Baseline characteristics were similar between groups. Postoperative HRM showed that the integrated relaxation pressure (IRP) and basal lower esophageal sphincter (LES) pressure were similar at 6 and 24 months. The number of patients with abnormal acid exposure was significantly lower for Dor (6.9%) than that of Toupet (34.0%) at 6 months, but it was not different at 12 or 24 months. No differences were found in postoperative symptom scores at 1, 6, or 24 months. There were no differences in symptom scores or HRM between fundoplications in the long term. A higher percentage of abnormal 24-h pH test were found for the Toupet group, with no difference in the long term.

  13. Short-term results of a prospective randomized evaluator blinded multicenter study comparing TVT and TVT-Secur.

    Science.gov (United States)

    Andrada Hamer, Maria; Larsson, Per-Göran; Teleman, Pia; Etén-Bergqvist, Christina; Persson, Jan

    2011-07-01

    The aim of this prospective randomized multicenter study was to compare TVT (tension-free vaginal tape) with TVT-Secur in terms of efficacy and safety. We set out to enrol 280 stress incontinent women with a half time interim analysis of short-term cure and a continuous registration of adverse events. Of 133 randomized women, 126 were operated and 123 (TVT n = 62, TVT-Secur n = 61) available for 2 months follow-up. No significant differences were found between groups regarding demographics or grade of incontinence. At 2 months follow-up, subjective cure rate following TVT-Secur was significantly lower than for TVT (72% and 92%, respectively, p = 0.01). Three major complications occurred in the TVT-Secur group: tape erosion into the urethra, a tape inadvertently placed inside the bladder, and an immediate postoperative bleeding from the corona mortis. No major complications occurred in the TVT group. No significant differences were found between groups regarding perioperative bleeding, hospital stay, urge symptoms, or postoperative urinary tract infections. Median time for surgery was 13 and 22 min for TVT-Secur and TVT, respectively (p TVT-Secur procedure had a significantly lower subjective cure rate than the retropubic TVT procedure. Due to this, in addition to three serious complications in the TVT-Secur group, we decided to stop further enrolment after the interim analysis. We discourage from further use of the TVT-Secur.

  14. Proteome Analysis of Thyroid Cancer Cells After Long-Term Exposure to a Random Positioning Machine

    Science.gov (United States)

    Pietsch, Jessica; Bauer, Johann; Weber, Gerhard; Nissum, Mikkel; Westphal, Kriss; Egli, Marcel; Grosse, Jirka; Schönberger, Johann; Eilles, Christoph; Infanger, Manfred; Grimm, Daniela

    2011-11-01

    Annulling gravity during cell culturing triggers various types of cells to change their protein expression in a time dependent manner. We therefore decided to determine gravity sensitive proteins and their period of sensitivity to the effects of gravity. In this study, thyroid cancer cells of the ML-1 cell line were cultured under normal gravity (1 g) or in a random positioning machine (RPM), which simulated near weightlessness for 7 and 11 days. Cells were then sonicated and proteins released into the supernatant were separated from those that remained attached to the cell fragments. Subsequently, both types of proteins were fractionated by free-flow isoelectric focussing (FF-IEF). The fractions obtained were further separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) to which comparable FF-IEF fractions derived from cells cultured either under 1 g or on the RPM had been applied side by side. The separation resulted in pairs of lanes, on which a number of identical bands were observed. Selected gel pieces were excised and their proteins determined by mass spectrometry. Equal proteins from cells cultured under normal gravity and the RPM, respectively, were detected in comparable gel pieces. However, many of these proteins had received different Mascot scores. Quantifying heat shock cognate 71 kDa protein, glutathione S-transferase P, nucleoside diphosphate kinase A and annexin-2 by Western blotting using whole cell lysates indicated usefulness of Mascot scores for selecting the most efficient antibodies.

  15. Gemfibrozil in late preterm and term neonates with moderate jaundice: a randomized controlled trial.

    Science.gov (United States)

    Jaikrishan; Kumar, Praveen; Narang, Anil

    2009-12-01

    To determine, if oral Gemfibrozil is effective in decreasing the duration of phototherapy by at least 24 hours in neonates >34 weeks gestation with non-hemolytic jaundice, as compared to placebo. Double blind placebo controlled randomized controlled trial. Tertiary care neonatal unit in north India. Ninety seven neonates >34 weeks gestation with non-hemolytic jaundice within first 7 days of life requiring phototherapy. Two doses of Gemfibrozil (60 mg/kg/dose) or placebo, 12 hours apart. Babies were treated with single surface special blue light phototherapy. Serum total bilirubin (STB) was measured 8 hourly. Phototherapy was stopped if two consecutive STB values were below phototherapy zone. Duration of phototherapy. The median (IQR) duration of phototherapy was 40 (30, 60) hours in Gemfibrozil and 36 (19, 55) hours in the placebo group (P=0.13). The peak STB levels were 16.8 +/- 2.7 mg/dL and 16.3 +/- 2.3 mg/dL in Gemfibrozil and placebo groups, respectively. No side effect of the drug or placebo was noticed. Two doses of gemfibrozil (60 mg/kg/dose) given 12 hours apart were not able to reduce the duration of phototherapy, or peak bilirubin level in babies > 34 weeks gestation with non-hemolytic jaundice in the first week of life. Gemfibrozil was not associated with any side effects.

  16. Prevention of fall-related injuries in long-term care: a randomized controlled trial of staff education.

    Science.gov (United States)

    Ray, Wayne A; Taylor, Jo A; Brown, Anne K; Gideon, Patricia; Hall, Kathi; Arbogast, Patrick; Meredith, Sarah

    2005-10-24

    Fall-related injuries, a major public health problem in long-term care, may be reduced by interventions that improve safety practices. Previous studies have shown that safety practice interventions can reduce falls; however, in long-term care these have relied heavily on external funding and staff. The aim of this study was to test whether a training program in safety practices for staff could reduce fall-related injuries in long-term care facilities. A cluster randomization clinical trial with 112 qualifying facilities and 10,558 study residents 65 years or older and not bedridden. The intervention was an intensive 2-day safety training program with 12-month follow-up. The training program targeted living space and personal safety; wheelchairs, canes, and walkers; psychotropic medication use; and transferring and ambulation. The main outcome measure was serious fall-related injuries during the follow-up period. There was no difference in injury occurrence between the intervention and control facilities (adjusted rate ratio, 0.98; 95% confidence interval, 0.83-1.16). For residents with a prior fall in facilities with the best program compliance, there was a nonsignificant trend toward fewer injuries in the intervention group (adjusted rate ratio, 0.79; 95% confidence interval, 0.57-1.10). More intensive interventions are required to prevent fall-related injuries in long-term care facilities.

  17. Short- and long-term forecast for chaotic and random systems (50 years after Lorenz's paper)

    International Nuclear Information System (INIS)

    Bunimovich, Leonid A

    2014-01-01

    We briefly review a history of the impact of the famous 1963 paper by E Lorenz on hydrodynamics, physics and mathematics communities on both sides of the iron curtain. This paper was an attempt to apply the ideas and methods of dynamical systems theory to the problem of weather forecast. Its major discovery was the phenomenon of chaos in dissipative dynamical systems which makes such forecasts rather problematic, if at all possible. In this connection we present some recent results which demonstrate that both a short-term and a long-term forecast are actually possible for the most chaotic dynamical (as well as for the most random, like IID and Markov chain) systems. Moreover, there is a sharp transition between the time interval where one may use a short-term forecast and the times where a long-term forecast is applicable. Finally we discuss how these findings could be incorporated into the forecast strategy outlined in the Lorenz's paper. (invited article)

  18. External cephalic version for breech presentation with or without spinal analgesia in nulliparous women at term: a randomized controlled trial.

    Science.gov (United States)

    Weiniger, Carolyn F; Ginosar, Yehuda; Elchalal, Uriel; Sharon, Einav; Nokrian, Malka; Ezra, Yossef

    2007-12-01

    To compare the success of external cephalic version using spinal analgesia with no analgesia among nulliparas. A prospective randomized controlled trial was performed in a tertiary referral center delivery suite. Nulliparous women at term requesting external cephalic version for breech presentation were randomized to receive spinal analgesia (7.5 mg bupivacaine) or no analgesia before the external cephalic version. An experienced obstetrician performed the external cephalic version. Primary outcome was successful conversion to vertex presentation. Seventy-four women were enrolled, and 70 analyzed (36 spinal, 34 no analgesia). Successful external cephalic version occurred among 24 of 36 (66.7%) women randomized to receive spinal analgesia compared with 11 of 34 (32.4%) without, P=.004 (95% confidence interval [CI] of the difference: 0.0954-0.5513). External cephalic version with spinal analgesia resulted in a lower visual analog pain score, 1.76+/-2.74 compared with 6.84+/-3.08 without, Pexternal cephalic version success was 4.0-fold higher when performed with spinal analgesia P=.02 (95% CI, odds ratio [OR] 1.2-12.9). Complete breech presentation before attempting external cephalic version increased the odds of success 8.2-fold, P=.001 (95% CI, OR 2.2-30.3). Placental position, estimated fetal weight, and maternal weight did not contribute to the success rate when spinal analgesia was used. There were no cases of placental abruption or fetal distress. Administration of spinal analgesia significantly increases the success rate of external cephalic version among nulliparous women at term, which allows possible normal vaginal delivery. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00119184 I.

  19. Long-term follow-up of a randomized study of support group intervention in women with primary breast cancer.

    Science.gov (United States)

    Björneklett, Helena Granstam; Rosenblad, Andreas; Lindemalm, Christina; Ojutkangas, Marja-Leena; Letocha, Henry; Strang, Peter; Bergkvist, Leif

    2013-04-01

    Despite a fairly good prognosis, many breast-cancer patients suffer from symptoms such as anxiety, depression and fatigue, which may affect health-related quality of life and may persist for several years. The aim of the present study was to perform a long-term follow-up of a randomized study of support group intervention in women after primary breast cancer treatment. Three hundred and eighty two women with primary breast cancer were randomized to support group intervention or control group, 181 in each group. Women in the intervention group participated in 1 week of intervention followed by 4 days of follow-up 2 months later. This is a long-term follow-up undertaken, in average, 6.5 years after randomization. Patients answered the questionnaires the European Organisation for Research and Treatment of Cancer, quality of life questionnaire (EORTC QLQ-C30) and the breast cancer module questionnaire (BR 23), the hospital anxiety and depression scale (HAD) and the Norwegian version of the fatigue scale (FQ). After adjusting for treatment with chemotherapy, age, marriage, education and children at home, there was a significant improvement in physical, mental and total fatigue (FQ), cognitive function, body image and future perspective (EORTC QLQ C30 and BR23) in the intervention group compared with controls. The proportion of women affected by high anxiety and depression scores were not significantly different between the groups. Support intervention significantly improved cognitive function, body image, future perspective and fatigue, compared with to the findings in the control group. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino.

    Science.gov (United States)

    Wu, Bo; Lu, Peijuan; Cloer, Caryn; Shaban, Mona; Grewal, Snimar; Milazi, Stephanie; Shah, Sapana N; Moulton, Hong M; Lu, Qi Long

    2012-08-01

    Exon skipping is capable of correcting frameshift and nonsense mutations in Duchenne muscular dystrophy. Phase 2 clinical trials in the United Kingdom and the Netherlands have reported induction of dystrophin expression in muscle of Duchenne muscular dystrophy patients by systemic administration of both phosphorodiamidate morpholino oligomers (PMO) and 2'-O-methyl phosphorothioate. Peptide-conjugated phosphorodiamidate morpholino offers significantly higher efficiency than phosphorodiamidate morpholino, with the ability to induce near-normal levels of dystrophin, and restores function in both skeletal and cardiac muscle. We examined 1-year systemic efficacy of peptide-conjugated phosphorodiamidate morpholino targeting exon 23 in dystrophic mdx mice. The LD(50) of peptide-conjugated phosphorodiamidate morpholino was determined to be approximately 85 mg/kg. The half-life of dystrophin expression was approximately 2 months in skeletal muscle, but shorter in cardiac muscle. Biweekly injection of 6 mg/kg peptide-conjugated phosphorodiamidate morpholino produced >20% dystrophin expression in all skeletal muscles and ≤5% in cardiac muscle, with improvement in muscle function and pathology and reduction in levels of serum creatine kinase. Monthly injections of 30 mg/kg peptide-conjugated phosphorodiamidate morpholino restored dystrophin to >50% normal levels in skeletal muscle, and 15% in cardiac muscle. This was associated with greatly reduced serum creatine kinase levels, near-normal histology, and functional improvement of skeletal muscle. Our results demonstrate for the first time that regular 1-year administration of peptide-conjugated phosphorodiamidate morpholino can be safely applied to achieve significant therapeutic effects in an animal model. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Cost-Effectiveness of a Long-Term Internet-Delivered Worksite Health Promotion Programme on Physical Activity and Nutrition: A Cluster Randomized Controlled Trial

    Science.gov (United States)

    Robroek, Suzan J. W.; Polinder, Suzanne; Bredt, Folef J.; Burdorf, Alex

    2012-01-01

    This study aims to evaluate the cost-effectiveness of a long-term workplace health promotion programme on physical activity (PA) and nutrition. In total, 924 participants enrolled in a 2-year cluster randomized controlled trial, with departments (n = 74) within companies (n = 6) as the unit of randomization. The intervention was compared with a…

  2. Effect of whey protein supplementation on long and short term appetite: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mollahosseini, Mehdi; Shab-Bidar, Sakineh; Rahimi, Mohammad Hossein; Djafarian, Kurosh

    2017-08-01

    Specific components of dairy, such as whey proteins may have beneficial effects on body composition by suppressing appetite, although the findings of existing studies have been inconsistent. Therefore, a meta-analysis of randomized controlled trials was performed to investigate effect of whey protein supplementation on long and short term appetite. A systematic search was conducted to identify eligible publications. Means and SDs for hunger, fullness, satiety, desire to eat and prospective consumption of food, before and after intervention, were extracted and then composite appetite score (CAS) calculated. To pool data, either a fixed-effects model or a random-effects model and for assessing heterogeneity, Cochran's Q and I 2 tests were used. Eight publications met inclusion criteria that 5 records were on short term and 3 records on long term appetite. The meta-analysis showed a significant reduction in long term appetite by 4.13 mm in combined appetite score (CAS) (95% Confidence interval (CI): -6.57, -1.96; p = 0.001). No significant reduction in short term appetite was also seen (Mean difference (MD) = -0.39 95% CI = -2.07, 1.30; p = 0.653). Subgroup analyses by time showed that compared with carbohydrate, the reduction in appetite following consumption of whey consumption was not significant (MD = -0.39, 95% CI = -2.07, 1.3, p = 0.65, I 2  = 0.0%.)A significant reduction in prospective food consumption was seen (MD = -2.17, 95% CI = -3.86, -0.48). The results of our meta-analysis showed that whey protein may reduce the long and short term appetite, but our finding did not show any significant difference in appetite reduction between whey protein and carbohydrate in short duration. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  3. Pressure ulcer multidisciplinary teams via telemedicine: a pragmatic cluster randomized stepped wedge trial in long term care.

    Science.gov (United States)

    Stern, Anita; Mitsakakis, Nicholas; Paulden, Mike; Alibhai, Shabbir; Wong, Josephine; Tomlinson, George; Brooker, Ann-Sylvia; Krahn, Murray; Zwarenstein, Merrick

    2014-02-24

    The study was conducted to determine the clinical and cost effectiveness of enhanced multi-disciplinary teams (EMDTs) vs. 'usual care' for the treatment of pressure ulcers in long term care (LTC) facilities in Ontario, Canada We conducted a multi-method study: a pragmatic cluster randomized stepped-wedge trial, ethnographic observation and in-depth interviews, and an economic evaluation. Long term care facilities (clusters) were randomly allocated to start dates of the intervention. An advance practice nurse (APN) with expertise in skin and wound care visited intervention facilities to educate staff on pressure ulcer prevention and treatment, supported by an off-site hospital based expert multi-disciplinary wound care team via email, telephone, or video link as needed. The primary outcome was rate of reduction in pressure ulcer surface area (cm2/day) measured on before and after standard photographs by an assessor blinded to facility allocation. Secondary outcomes were time to healing, probability of healing, pressure ulcer incidence, pressure ulcer prevalence, wound pain, hospitalization, emergency department visits, utility, and cost. 12 of 15 eligible LTC facilities were randomly selected to participate and randomized to start date of the intervention following the stepped wedge design. 137 residents with a total of 259 pressure ulcers (stage 2 or greater) were recruited over the 17 month study period. No statistically significant differences were found between control and intervention periods on any of the primary or secondary outcomes. The economic evaluation demonstrated a mean reduction in direct care costs of $650 per resident compared to 'usual care'. The qualitative study suggested that onsite support by APN wound specialists was welcomed, and is responsible for reduced costs through discontinuation of expensive non evidence based treatments. Insufficient allocation of nursing home staff time to wound care may explain the lack of impact on healing

  4. Peptides: Production, bioactivity, functionality, and applications

    DEFF Research Database (Denmark)

    Hajfathalian, Mona; Ghelichi, Sakhi; García Moreno, Pedro Jesús

    2017-01-01

    Production of peptides with various effects from proteins of different sources continues to receive academic attention. Researchers of different disciplines are putting increasing efforts to produce bioactive and functional peptides from different sources such as plants, animals, and food industry...... by-products. The aim of this review is to introduce production methods of hydrolysates and peptides and provide a comprehensive overview of their bioactivity in terms of their effects on immune, cardiovascular, nervous, and gastrointestinal systems. Moreover, functional and antioxidant properties...... of hydrolysates and isolated peptides are reviewed. Finally, industrial and commercial applications of bioactive peptides including their use in nutrition and production of pharmaceuticals and nutraceuticals are discussed....

  5. Short-term administration of glucagon-like peptide-2. Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon

    DEFF Research Database (Denmark)

    Haderslev, K V; Jeppesen, P B; Hartmann, B

    2002-01-01

    Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of short-bowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition ...

  6. Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg

    2015-01-01

    Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether......-mediated glucose uptake in skeletal muscle by 90% (Prights...

  7. Peri-apatite coating decreases uncemented tibial component migration: long-term RSA results of a randomized controlled trial and limitations of short-term results.

    Science.gov (United States)

    Van Hamersveld, Koen T; Marang-Van De Mheen, Perla J; Nelissen, Rob G H H; Toksvig-Larsen, Sören

    2018-05-09

    Background and purpose - Biological fixation of uncemented knee prostheses can be improved by applying hydroxyapatite coating around the porous surface via a solution deposition technique called Peri-Apatite (PA). The 2-year results of a randomized controlled trial, evaluating the effect of PA, revealed several components with continuous migration in the second postoperative year, particularly in the uncoated group. To evaluate whether absence of early stabilization is diagnostic of loosening, we now present long-term follow-up results. Patients and methods - 60 patients were randomized to PA-coated or uncoated (porous only) total knee arthroplasty of which 58 were evaluated with radiostereometric analysis (RSA) performed at baseline, at 3 months postoperatively and at 1, 2, 5, 7, and 10 years. A linear mixed-effects model was used to analyze the repeated measurements. Results - PA-coated components had a statistically significantly lower mean migration at 10 years of 0.94 mm (95% CI 0.72-1.2) compared with the uncoated group showing a mean migration of 1.72 mm (95% CI 1.4-2.1). Continuous migration in the second postoperative year was seen in 7 uncoated components and in 1 PA-coated component. All of these implants stabilized after 2 years except for 2 uncoated components. Interpretation - Peri-apatite enhances stabilization of uncemented components. The number of components that stabilized after 2 years emphasizes the importance of longer follow-up to determine full stabilization and risk of loosening in uncemented components with biphasic migration profiles.

  8. Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial.

    Science.gov (United States)

    Cusi, Kenneth; Orsak, Beverly; Bril, Fernando; Lomonaco, Romina; Hecht, Joan; Ortiz-Lopez, Carolina; Tio, Fermin; Hardies, Jean; Darland, Celia; Musi, Nicolas; Webb, Amy; Portillo-Sanchez, Paola

    2016-09-06

    The metabolic defects of nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes mellitus (T2DM) seem to be specifically targeted by pioglitazone. However, information about its long-term use in this population is limited. To determine the efficacy and safety of long-term pioglitazone treatment in patients with NASH and prediabetes or T2DM. Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT00994682). University hospital. Patients (n = 101) with prediabetes or T2DM and biopsy-proven NASH were recruited from the general population and outpatient clinics. All patients were prescribed a hypocaloric diet (500-kcal/d deficit from weight-maintaining caloric intake) and then randomly assigned to pioglitazone, 45 mg/d, or placebo for 18 months, followed by an 18-month open-label phase with pioglitazone treatment. The primary outcome was a reduction of at least 2 points in the nonalcoholic fatty liver disease activity score in 2 histologic categories without worsening of fibrosis. Secondary outcomes included other histologic outcomes, hepatic triglyceride content measured by magnetic resonance and proton spectroscopy, and metabolic parameters. Among patients randomly assigned to pioglitazone, 58% achieved the primary outcome (treatment difference, 41 percentage points [95% CI, 23 to 59 percentage points]) and 51% had resolution of NASH (treatment difference, 32 percentage points [CI, 13 to 51 percentage points]) (P < 0.001 for each). Pioglitazone treatment also was associated with improvement in individual histologic scores, including the fibrosis score (treatment difference, -0.5 [CI, -0.9 to 0.0]; P = 0.039); reduced hepatic triglyceride content from 19% to 7% (treatment difference, -7 percentage points [CI, -10 to -4 percentage points]; P < 0.001); and improved adipose tissue, hepatic, and muscle insulin sensitivity (P < 0.001 vs. placebo for all). All 18-month metabolic and histologic improvements persisted over 36 months of

  9. Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Jia, Lei; Liu, Xuan; Bai, Yong Yi; Li, Shao Hua; Sun, Kai; He, Chen; Hui, Rutai

    2010-07-01

    The effect of cocoa products on lipid changes is controversial. We aimed to identify and quantify the effect of cocoa on total cholesterol, LDL cholesterol, and HDL cholesterol. A comprehensive literature search was conducted for relevant trials of cocoa on lipid profile. Weighted mean differences were calculated for net changes in lipid concentrations by using fixed-effects or random-effects models. Previously defined subgroup analyses were performed to identify the source of heterogeneity. Eight trials (involving 215 participants) were included and evaluated. Because there was only one relatively longer-term study, we focused on the short-term data to evaluate the effects of cocoa on plasma lipid. Cocoa consumption significantly lowered LDL cholesterol by 5.87 mg/dL (95% CI: -11.13, -0.61; P consumption significantly reduced blood cholesterol, but the changes were dependent on the dose of cocoa consumption and the healthy status of participants. There was no dose response and no effect in healthy participants. Future high-quality studies are needed to determine the efficiency of moderate cocoa consumption on lipid profile in long-term intervention and in subjects with other cardiometabolic risk factors.

  10. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering.

    Science.gov (United States)

    Gao, Xiang; Zhang, Xiaohong; Song, Jinlin; Xu, Xiao; Xu, Anxiu; Wang, Mengke; Xie, Bingwu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2015-01-01

    The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.

  11. Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials.

    Science.gov (United States)

    Coca, Steven G; Zabetian, Azadeh; Ferket, Bart S; Zhou, Jing; Testani, Jeffrey M; Garg, Amit X; Parikh, Chirag R

    2016-08-01

    Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short-term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between-group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo-controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials. Copyright © 2016 by the American Society of Nephrology.

  12. Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial.

    Science.gov (United States)

    Hurtado, R; Celani, M; Geber, S

    2016-10-01

    To evaluate the effect of short-term hormone replacement therapy with 0.625 mg conjugated estrogens daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. We performed a double-blinded, randomized, controlled trial over 3 years. Randomization was performed using computer-generated sorting. All participants were blinded to the use of conjugated equine estrogens (CEE) or placebo and FMD was assessed by a blinded examiner, before and after 28 days of medication. A total of 64 healthy postmenopausal women were selected and randomly assigned into two groups of treatment: 0.625 mg of CEE or placebo. FMD values were statistically different between the groups (p = 0.025): the group receiving CEE showed a FMD value of 0.011 compared to the placebo group (FMD = -0.082). The two groups were additionally evaluated for homogeneity through the Shapiro-Wilk test in respect to variables that could interfere with endothelial function such as age (p = 0.729), body mass index (p = 0.891), and time since menopause (p = 0.724). Other variables were excluded during selection of the participants such as chronic vascular conditions, smoking, and sedentary lifestyle. Our results demonstrate that the administration of 0.625 mg CEE for 28 days is effective in improving vascular nitric oxide-dependent dilation assessed by FMD of the brachial artery in postmenopausal women. NCT01482416.

  13. Non-inferiority of short-term urethral catheterization following fistula repair surgery: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Barone Mark A

    2012-03-01

    Full Text Available Abstract Background A vaginal fistula is a devastating condition, affecting an estimated 2 million girls and women across Africa and Asia. There are numerous challenges associated with providing fistula repair services in developing countries, including limited availability of operating rooms, equipment, surgeons with specialized skills, and funding from local or international donors to support surgeries and subsequent post-operative care. Finding ways of providing services in a more efficient and cost-effective manner, without compromising surgical outcomes and the overall health of the patient, is paramount. Shortening the duration of urethral catheterization following fistula repair surgery would increase treatment capacity, lower costs of services, and potentially lower risk of healthcare-associated infections among fistula patients. There is a lack of empirical evidence supporting any particular length of time for urethral catheterization following fistula repair surgery. This study will examine whether short-term (7 day urethral catheterization is not worse by more than a minimal relevant difference to longer-term (14 day urethral catheterization in terms of incidence of fistula repair breakdown among women with simple fistula presenting at study sites for fistula repair service. Methods/Design This study is a facility-based, multicenter, non-inferiority randomized controlled trial (RCT comparing the new proposed short-term (7 day urethral catheterization to longer-term (14 day urethral catheterization in terms of predicting fistula repair breakdown. The primary outcome is fistula repair breakdown up to three months following fistula repair surgery as assessed by a urinary dye test. Secondary outcomes will include repair breakdown one week following catheter removal, intermittent catheterization due to urinary retention and the occurrence of septic or febrile episodes, prolonged hospitalization for medical reasons, catheter blockage, and

  14. FIVE-YEAR OUTCOMES AFTER LONG-TERM OXANDROLONE ADMINISTRATION IN SEVERELY BURNED CHILDREN: A RANDOMIZED CLINICAL TRIAL.

    Science.gov (United States)

    Reeves, Patrick T; Herndon, David N; Tanksley, Jessica D; Jennings, Kristofer; Klein, Gordon L; Mlcak, Ronald P; Clayton, Robert P; Crites, Nancy N; Hays, Joshua P; Andersen, Clark; Lee, Jong O; Meyer, Walter; Suman, Oscar E; Finnerty, Celeste C

    2016-04-01

    Administration of oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ≥30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term oxandrolone administration (p patients receiving oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with oxandrolone administration. Long-term oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p patients receiving long-term oxandrolone to previously described patients receiving 12 months of oxandrolone revealed that long-term oxandrolone administration imparted significantly greater increases in WB-BMC, WB-BMD, and LS-BMD (p burned pediatric patients significantly improves WB BMC, LS BMC, LS BMD, and height velocity. The administration of long-term oxandrolone was more efficacious than

  15. Towards the characterization of short-term memory of zebrafish: effect of fixed versus random reward location.

    Science.gov (United States)

    Fernandes, Yohaan; Talpos, Andrea; Gerlai, Robert

    2015-01-02

    The zebrafish has been proposed as an efficient tool for the analysis of behavioral and neurobiological mechanisms of learning and memory. However, compared to traditional laboratory rodents, it is a relatively newcomer. In fact, only limited information on its mnemonic and cognitive abilities has been obtained, and only a small number of learning and memory paradigms have been available for its testing. Previously, we have shown that zebrafish are capable of learning the systematic alternating sequence of reward location in a shuttle box task in which we evaluated behavioral responses manually. Here, we employ a computerized, automated version of this task. We study whether zebrafish can remember the prior location of a reward (the sight of conspecifics) when the location is fixed (constant), or when the sequence of the location of presentation randomly changes between the left and the right side of the experimental tank. We also analyze performance features including the swim speed of experimental fish as well as the temporal changes of the position of fish when the reward (stimulus) is not presented. Our results show that under both the fixed and randomly changing reward location conditions zebrafish exhibit a significant preference for the prior location of reward, albeit the preference is stronger under the fixed location condition. We conclude that adult zebrafish have short-term associative memory that can be induced and quantified in an automated manner. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Short-Term Effect of Laser Acupuncture on Lower Back Pain: A Randomized, Placebo-Controlled, Double-Blind Trial

    Directory of Open Access Journals (Sweden)

    Jae-Young Shin

    2015-01-01

    Full Text Available Purpose. This trial was performed to investigate the efficacy of laser acupuncture for the alleviation of lower back pain. Methods. This was a randomized, placebo-controlled, double-blind trial. Fifty-six participants were randomly assigned to either the laser acupuncture group (n=28 or the sham laser acupuncture group (n=28. Participants in both groups received three treatment sessions over the course of one week. Thirteen acupuncture points were selected. The visual analogue scale for pain, pressure pain threshold, Patient Global Impression of Change, and Euro-Quality-of-Life Five Dimensions questionnaire (Korean version were used to evaluate the effect of laser acupuncture treatment on lower back pain. Results. There were no significant differences in any outcome between the two groups, although the participants in both groups showed a significant improvement in each assessed parameter relative to the baseline values. Conclusion. Although there was no significant difference in outcomes between the two groups, the results suggest that laser acupuncture can provide effective pain alleviation and can be considered an option for relief from lower back pain. Further studies using long-term intervention, a larger sample size, and rigorous methodology are required to clarify the effect of laser acupuncture on lower back pain.

  17. Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

    Science.gov (United States)

    Ishibashi, Keiichiro; Ishida, Hideyuki; Kuwabara, Kouki; Ohsawa, Tomonori; Okada, Norimichi; Yokoyama, Masaru; Kumamoto, Kensuke

    2014-04-01

    To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

  18. Active intervention in patients with whiplash-associated disorders improves long-term prognosis: a randomized controlled clinical trial.

    Science.gov (United States)

    Rosenfeld, Mark; Seferiadis, Aris; Carlsson, Jane; Gunnarsson, Ronny

    2003-11-15

    Three-year follow-up of a prospective randomized trial in 97 patients exposed to whiplash trauma in motor vehicle collisions. To compare the long-term efficacy of active intervention with that of standard intervention and the effect of early versus delayed initiation of intervention. There is no strong evidence for many treatments for whiplash-associated disorders. Some studies provide weak evidence supporting active intervention. Patients were randomized to an intervention using frequent active cervical rotation complemented by assessment and treatment according to McKenzie's principles or to a standard intervention of initial rest, recommended soft collar, and gradual self-mobilization. To test the time factor, interventions were either made within 96 hours or delayed 14 days from collision. The effects of the two interventions and the time factor on pain intensity, cervical range of motion, and sick leave were analyzed at 6 months and 3 years. Cervical range of motion at 3 years was also compared with that in matched, unexposed individuals. Pain intensity and sick leave were significantly (P whiplash-associated disorders, active intervention is more effective in reducing pain intensity and sick leave, and in retaining/regaining total range of motion than a standard intervention. Active intervention can be carried out as home exercises initiated and supported by appropriately trained health professionals.

  19. Short-term tibolone does not interfere with endothelial function: a double-blinded, randomized, controlled trial.

    Science.gov (United States)

    Celani, M F S; Hurtado, R; Brandão, A H F; Maciel da Fonseca, A M R; Geber, S

    2016-06-01

    Objective To evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. Methods We performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo. Results A total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo, p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar. Conclusion Our results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery.

  20. Impact of Vitamin D Supplementation on Gross Motor Development of Healthy Term Infants: A Randomized Dose-Response Trial.

    Science.gov (United States)

    Wicklow, Brandy; Gallo, Sina; Majnemer, Annette; Vanstone, Catherine; Comeau, Kathryn; Jones, Glenville; L'Abbe, Mary; Khamessan, Ali; Sharma, Atul; Weiler, Hope; Rodd, Celia

    2016-08-01

    In addition to benefits for bone health, vitamin D is implicated in muscle function in children and adults. To determine if vitamin D dosage positively correlated with gross motor development at 3 and 6 months of age. We hypothesized that higher doses would be associated with higher scores for gross motor skills. A consecutive sample of 55 healthy, term, and breastfed infants from Montreal, Canada were recruited from a randomized trial of vitamin D supplementation between 2009 and 2012. Infants were randomized to 400 International Units (IU) (n = 19), 800 IU (n = 18) or 1,200 IU (n = 18) vitamin D3/day. Motor performance at 3 and 6 months was quantified by the Alberta Infant Motor Scale (AIMS). Plasma vitamin D3 metabolites were measured by tandem mass spectrometry. AIMS scores did not differ at 3 months. However, total AIMS scores and sitting subscores were significantly higher at 6 months in infants receiving 400 IU/day compared to 800 IU/day and 1,200 IU/day groups (p gross motor achievements were significantly higher in infants receiving 400 IU/day vitamin D. Our findings also support longer infants being slightly delayed.

  1. Randomized cross-over trial of short-term water-only fasting: metabolic and cardiovascular consequences.

    Science.gov (United States)

    Horne, B D; Muhlestein, J B; Lappé, D L; May, H T; Carlquist, J F; Galenko, O; Brunisholz, K D; Anderson, J L

    2013-11-01

    Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p fasting intervention acutely increased human growth hormone (p = 1.1 × 10⁻⁴), hemoglobin (p = 4.8 × 10⁻⁷), red blood cell count (p = 2.5 × 10⁻⁶), hematocrit (p = 3.0 × 10⁻⁶), total cholesterol (p = 5.8 × 10⁻⁵), and high-density lipoprotein cholesterol (p = 0.0015), and decreased triglycerides (p = 1.3 × 10⁻⁴), bicarbonate (p = 3.9 × 10⁻⁴), and weight (p = 1.0 × 10⁻⁷), compared to a day of usual eating. For those randomized to fast the first day (n = 16), most factors including human growth hormone and cholesterol returned to baseline after the full 48 h, with the exception of weight (p = 2.5 × 10⁻⁴) and (suggestively significant) triglycerides (p = 0.028). Fasting induced acute changes in biomarkers of metabolic, cardiovascular, and general health. The long-term consequences of these short-term changes are unknown but repeated episodes of periodic short-term fasting should be evaluated as a preventive treatment with the potential to reduce metabolic disease risk. Clinical trial registration (ClinicalTrials.gov): NCT01059760 (Expression of Longevity Genes in Response to Extended Fasting [The Fasting and Expression of Longevity Genes during Food abstinence {FEELGOOD} Trial]). Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Randomized controlled trial of laparoscopic Heller myotomy plus Dor fundoplication versus Nissen fundoplication for achalasia: long-term results.

    Science.gov (United States)

    Rebecchi, Fabrizio; Giaccone, Claudio; Farinella, Eleonora; Campaci, Roberto; Morino, Mario

    2008-12-01

    To compare in a prospective, randomized trial the long-term results of laparoscopic Heller myotomy plus Dor fundoplication versus laparoscopic Heller myotomy plus floppy-Nissen for achalasia. Anterior fundoplication is usually performed after Heller myotomy to control GER; however, the incidence of postoperative GER ranges between 10% and 30%. Total fundoplication may aid in reducing GER rates. From December 1993 to September 2002, 153 patients with achalasia underwent Heller laparoscopic myotomy plus antireflux fundoplication. Of these, 9 were excluded from the study. The remaining 144 patients were randomly assigned to 2 treatment groups: Heller laparoscopic myotomy plus anterior fundoplication (Dor procedure) or Heller laparoscopic myotomy plus total fundoplication (floppy-Nissen procedure). The primary end point was incidence of clinical and instrumental GER after a minimum of 60 months follow-up. The secondary end point was recurrence of dysphagia. Follow-up clinical assessments were performed at 1, 3, 12, and 60 months using a modified DeMeester Symptom Scoring System (MDSS). Esophageal manometry and 24-hour pH monitoring were performed at 3, 12, and 60 months postoperative. Of the 144 patients originally included in the study, 138 were available for long-term analysis: 71 (51%) underwent antireflux fundoplication plus a Dor procedure (H + D group) and 67 (49%) antireflux fundoplication plus a Nissen procedure (H + N group). No mortality was observed. The mean follow-up period was 125 months. No statistically significant differences in clinical (5.6% vs. 0%) or instrumental GER (2.8% vs. 0%) were found between the 2 groups; however, a statistically significant difference in dysphagia rates was noted (2.8% vs. 15%; P Heller myotomy.

  3. Short- and long-term effects of mud-bath treatment on hand osteoarthritis: a randomized clinical trial

    Science.gov (United States)

    Fioravanti, Antonella; Tenti, Sara; Giannitti, Chiara; Fortunati, Nicola Angelo; Galeazzi, Mauro

    2014-01-01

    The aim of this study was to evaluate both the short-term and the long-term effectiveness of spa therapy in patients with primary hand osteoarthritis (OA). This was a prospective randomized, single blind controlled trial. Sixty outpatients with primary bilateral hand OA were included in the study and randomized to one of two groups. One group ( n = 30) was treated with 12 daily local mud packs and generalized thermal baths with a sulfate-calcium-magnesium-fluorides mineral water added to usual treatment. The control group ( n = 30) continued regular outpatient care routine (exercise, NSAIDs and/or analgesics). Each patient was examined at baseline, after 2 weeks, and after 3, 6, 9 and 12 months. Primary outcome measures were global spontaneous hand pain on a visual analogue scale (VAS) and the functional index for hand osteoarthritis (FIHOA) score; secondary outcomes were health assessment questionnaire (HAQ), duration of morning stiffness, medical outcomes study 36-item short form (SF-36) and symptomatic drugs consumption. Our results demonstrated that the efficacy of spa therapy was significant in all the assessed parameters, both at the end of therapy and after 3 months; the values of FIHOA, HAQ and drugs consumption continued to be significantly better after 6 months in comparison with baseline. There were no significant modifications of the parameters throughout the follow-up in the control group. Differences between the two groups were significant for all parameters at the 15th day and at 3 months follow-up; regarding FIHOA, HAQ, and symptomatic drugs consumption, the difference between the two groups persisted and was significant at 6month follow-up. Tolerability of spa therapy seemed to be good. In conclusion, our results confirm that the beneficial effects of spa therapy in patients with hand OA last over time.

  4. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

    Science.gov (United States)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

  5. Antimicrobial Peptides: An Introduction.

    Science.gov (United States)

    Haney, Evan F; Mansour, Sarah C; Hancock, Robert E W

    2017-01-01

    The "golden era" of antibiotic discovery has long passed, but the need for new antibiotics has never been greater due to the emerging threat of antibiotic resistance. This urgency to develop new antibiotics has motivated researchers to find new methods to combat pathogenic microorganisms resulting in a surge of research focused around antimicrobial peptides (AMPs; also termed host defense peptides) and their potential as therapeutics. During the past few decades, more than 2000 AMPs have been identified from a diverse range of organisms (animals, fungi, plants, and bacteria). While these AMPs share a number of common features and a limited number of structural motifs; their sequences, activities, and targets differ considerably. In addition to their antimicrobial effects, AMPs can also exhibit immunomodulatory, anti-biofilm, and anticancer activities. These diverse functions have spurred tremendous interest in research aimed at understanding the activity of AMPs, and various protocols have been described to assess different aspects of AMP function including screening and evaluating the activities of natural and synthetic AMPs, measuring interactions with membranes, optimizing peptide function, and scaling up peptide production. Here, we provide a general overview of AMPs and introduce some of the methodologies that have been used to advance AMP research.

  6. Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins

    NARCIS (Netherlands)

    Nahuis, M. J.; Kose, N.; Bayram, N.; van Dessel, H. J. H. M.; Braat, D. D. M.; Hamilton, C. J. C. M.; Hompes, P. G. A.; Bossuyt, P. M.; Mol, B. W. J.; van der Veen, F.; van Wely, M.

    2011-01-01

    Long-term effects of laparoscopic electrocautery of the ovaries are unknown. To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins, we followed women with clomiphene-resistant polycystic ovary syndrome (PCOS) randomly allocated to one of these treatments

  7. Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins

    NARCIS (Netherlands)

    Nahuis, M.J.; Kose, N.; Bayram, N.; Dessel, H.J. van; Braat, D.D.M.; Hamilton, C.J.C.M.; Hompes, P.G.; Bossuyt, P.M.; Mol, B.W.; Veen, F. van der; Wely, M.H. van

    2011-01-01

    BACKGROUND: Long-term effects of laparoscopic electrocautery of the ovaries are unknown. To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins, we followed women with clomiphene-resistant polycystic ovary syndrome (PCOS) randomly allocated to one of these

  8. Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

    Science.gov (United States)

    Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

    2018-06-01

    The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Personality disorder moderates outcome in short- and long-term group analytic psychotherapy: A randomized clinical trial.

    Science.gov (United States)

    Lorentzen, Steinar; Ruud, Torleif; Fjeldstad, Anette; Høglend, Per A

    2015-06-01

    In a randomized clinical trial, short- and long-term psychodynamic group psychotherapy (STG and LTG, respectively) schedules were equally effective for the 'typical' patient during a 3-year study period. Although several studies have reported good effects for patients with personality disorders (PD) in diverse forms of psychotherapy, the significance of treatment duration is unclear. Therefore, we tested the hypothesis that PD patients would improve more during and after LTG than STG. A randomized, longitudinal, prospective study contrasting the outcomes during and after short- and long-term dynamic group psychotherapies. One hundred and sixty-seven outpatients with mood disorders, anxiety disorders, or PD were randomized to STG or LTG (respectively, 20 or 80 weekly sessions of 90 min each). Outcome measures are as follows: symptoms (SCL-90-R), interpersonal problems (IIP-C), and psychosocial functioning (GAF split version: GAF-Symptom and GAF-Function). PD pathology (number of PD criteria items) was selected a priori as a putative moderator of treatment effects. Change during the 3-year study period was assessed using linear mixed models. The study was registered at ClinicalTrials.gov as NCT 00021417. Our hypothesis was supported, as patients with PD improved significantly more regarding all outcome variables in LTG than STG. For patients without PD, the rate of change was similar across 3 years; however, the rate of change in symptoms and interpersonal problems was higher in STG during the first 6 months. The effectiveness of LTG is higher for patients with co-morbid PD. Patients without PD do not appear to experience additional gain from LTG. Clinical implications: LTG demonstrates better effectiveness than STG for patients with personality disorder co-morbidity (PD). Patients without PD do not appear to experience additional gain from attending LTG. Correct initial allocation to treatment duration may prevent disruptive breaks in relationships and lead to both

  10. Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

    International Nuclear Information System (INIS)

    Kruisbrink, J.; Boer, G.J.

    1984-01-01

    Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero

  11. Randomized Comparison of Isosorbide Mononitrate and PGE2 Gel for Cervical Ripening at Term including High Risk Pregnancy

    Directory of Open Access Journals (Sweden)

    Kavita Agarwal

    2014-01-01

    Full Text Available Aims. Prostaglandin E2 is the most commonly used drug for cervical ripening prior to labour induction. However, there are concerns regarding uterine tachysystole and nonreassuring fetal heart (N-RFH. Isosorbide mononitrate (IMN has been used successfully for cervical ripening. The present study was conducted to compare the two drugs for cervical ripening at term in hospital. Methods. Two hundred women with term pregnancies referred for induction of labour with Bishop score less than 6 were randomly allocated to receive either 40 mg IMN tablet vaginally (n=100 or 0.5 mg PGE2 gel intracervically (n=100. Adverse effects, progress, and outcomes of labour were assessed. Results. PGE2 group had significantly higher postripening mean Bishop score, shorter time from start of medication to vaginal delivery (13.37 ± 10.67 hours versus 30.78 ± 17.29 hours, and shorter labour-delivery interval compared to IMN group (4.53 ± 3.97 hours versus 7.34 ± 5.51 hours. However, PGE2 group also had significantly higher incidence of uterine tachysystole (15% and N-RFH (11% compared to none in IMN group, as well as higher caesarean section rate (27% versus 17%. Conclusions. Cervical ripening with IMN was less effective than PGE2 but resulted in fewer adverse effects and was safer especially in high risk pregnancies.

  12. Effectiveness of zinc supplementation to full term normal infants: a community based double blind, randomized, controlled, clinical trial.

    Directory of Open Access Journals (Sweden)

    K V Radhakrishna

    Full Text Available The study was aimed to test whether zinc supplementation, if initiated early, can prevent stunting and promote optimum body composition in full term infants. For this, full term pregnant women from low income urban community were enrolled and were followed-up for 24 months postpartum. Body mass index (BMI was calculated from maternal weight and height that were collected one month after delivery. Infants' weight, and length, head, chest and mid upper arm circumferences and skin fold thicknesses at triceps, biceps and subscapular area were collected at baseline (before randomization and once in three months up till 24 months. Three hundred and twenty four infants were randomized and allocated to zinc (163 or placebo (161 groups respectively. Supplementation of zinc was initiated from 4 months of age and continued till children attained 18 months. The control (placebo group of children received riboflavin 0.5 mg/day, whereas the intervention (zinc group received 5 mg zinc plus riboflavin 0.5 mg/day. When infants were 18 months old, dietary intakes (in 78 children were calculated by 24 hour diet recall method and hemoglobin, zinc, copper and vitamin A were quantified in blood samples collected from 70 children. The results showed prevalence of undernutrition (body mass index <18.5 in 37% of the mothers. Mean±SD calorie consumption and zinc intakes from diets in infants were 590±282.8 Kcal/day and 0.97±0.608 mg/day respectively. Multiple linear regression models demonstrated maternal weight as a strong predictor of infants' weight and length at 18 months of age. As expected, diarrhea duration impacted infants' linear growth and weight gain adversely. Zinc supplementation for a mean period of 190 days, starting from 4 months up to 18 months of age, in full term normal infants, consuming an average energy of 590 Kcal/day, had significant effect on the skin fold thicknesses, but not on their linear growth.Clinical Trail Registration India (CTRI CTRI

  13. Nanostructured self-assembling peptides as a defined extracellular matrix for long-term functional maintenance of primary hepatocytes in a bioartificial liver modular device

    Directory of Open Access Journals (Sweden)

    Giri S

    2013-04-01

    Full Text Available Shibashish Giri,1 Ulf-Dietrich Braumann,2,3 Priya Giri,1,3 Ali Acikgöz,1,4 Patrick Scheibe,3,5 Karen Nieber,6 Augustinus Bader1 1Department of Cell Techniques and Applied Stem Cell Biology, Center for Biotechnology and Biomedicine (BBZ, 2Institute for Medical Informatics, Statistics, and Epidemiology (IMISE, University of Leipzig, Leipzig, Germany; 3Interdisciplinary Center for Bioinformatics (IZBI, University of Leipzig, Leipzig, Germany; 4Klinikum St Georg, Leipzig, Germany; 5Translational Center for Regenerative Medicine (TRM Leipzig, 6Department of Pharmacology for Natural Sciences, Institute of Pharmacy, University of Leipzig, Leipzig, Germany Abstract: Much effort has been directed towards the optimization of the capture of in vivo hepatocytes from their microenvironment. Some methods of capture include an ex vivo cellular model in a bioreactor based liver module, a micropatterned module, a microfluidic 3D chip, coated plates, and other innovative approaches for the functional maintenance of primary hepatocytes. However, none of the above methods meet US Food and Drug Administration (FDA guidelines, which recommend and encourage that the duration of a toxicity assay of a drug should be a minimum of 14 days, to a maximum of 90 days for a general toxicity assay. Existing innovative reports have used undefined extracellular matrices like matrigel, rigid collagen, or serum supplementations, which are often problematic, unacceptable in preclinical and clinical applications, and can even interfere with experimental outcomes. We have overcome these challenges by using integrated nanostructured self-assembling peptides and a special combination of growth factors and cytokines to establish a proof of concept to mimic the in vivo hepatocyte microenvironment pattern in vitro for predicting the in vivo drug hepatotoxicity in a scalable bioartificial liver module. Hepatocyte functionality (albumin, urea was measured at days 10, 30, 60, and 90 and we

  14. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans

    1990-01-01

    for antibody binding to the immunizing antigen. Antisera to C-peptide 2, stained islet beta-cells on mouse and rat, but not monkey pancreas sections in immunocytochemical analysis. Preabsorption to the synthetic C-peptide 2, but not the synthetic mouse and rat C-peptide 1 abolished staining. In conclusion we......Mice and rats have two functional non-allelic insulin genes. By using a synthetic peptide representing a common sequence in mouse and rat C-peptide 2 as antigen, we have produced rabbit antisera specific for an epitope which is not present in mouse or rat C-peptide 1. Long-term immunization did...... not seem to increase the end point titre as tested in direct ELISA. The specificity of the antiserum was determined by competitive ELISA and histochemistry on pancreas sections. Only the synthetic C-peptide 2, but not the homologous synthetic C-peptide 1 from mouse and rat competed efficiently in ELISA...

  15. A multicomponent exercise program improves physical function in long-term nursing home residents: A randomized controlled trial.

    Science.gov (United States)

    Arrieta, Haritz; Rezola-Pardo, Chloe; Zarrazquin, Idoia; Echeverria, Iñaki; Yanguas, Jose Javier; Iturburu, Miren; Gil, Susana Maria; Rodriguez-Larrad, Ana; Irazusta, Jon

    2018-03-01

    To investigate the impact of a multicomponent exercise program on anthropometry, physical function, and physical activity on older adults living in long-term nursing homes (LTNH), we conducted a randomized controlled trial involving 112 participants aged 84.9 ± 6.9 years. Participants were randomly assigned to an intervention (IG) or control group (CG). The IG participated in a 3-month multicomponent exercise intervention focused on strength, balance, stretching exercises, and walking recommendations. Subjects in the CG participated in routine activities. Analyses of outcome parameters were performed in the entire sample and in two subgroups, classified according to participants' physical function score at baseline. The group-by-time interaction, favoring the IG, was significant for the entire sample and for the participants in the low physical function subgroup for the following parameters: waist circumference, 30-s chair-stand, arm-curl, 8-ft timed up-and-go, SPPB score, gait speed, and Berg scale (p < .05). In participants with higher physical function at baseline, significant group-by-time interaction was observed in the SPPB score and Berg scale (p < .05). When differences were analyzed within groups, the IG maintained or improved in all assessed parameters, while participants in the CG showed a marked decline. Our study showed that a multicomponent exercise program is effective for older people living in LTNH. This is especially relevant in those with lower physical function scores. The lower efficacy of the program in participants with better function might be due to the insufficient exercise demands of our intervention for more fit residents. Future studies should analyze the effects of programs with higher intensities in older people with intermediate to high physical function. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. A pilot randomized crossover trial assessing the safety and short-term effects of pomegranate supplementation in hemodialysis patients.

    Science.gov (United States)

    Rivara, Matthew B; Mehrotra, Rajnish; Linke, Lori; Ruzinski, John; Ikizler, T Alp; Himmelfarb, Jonathan

    2015-01-01

    Oxidative stress and systemic inflammation are highly prevalent in patients undergoing maintenance hemodialysis (MHD) and are linked to excess cardiovascular risk. This study examined whether short-term supplementation with pomegranate juice and extract is safe and well tolerated by MHD patients. The secondary aim was to assess the effect of pomegranate supplementation on oxidative stress, systemic inflammation, monocyte function, and blood pressure. Prospective, randomized, crossover, pilot clinical trial (NCT01562340). The study was conducted from March to October 2012 in outpatient dialysis facilities in the Seattle metropolitan area. Twenty-four patients undergoing MHD (men, 64%; mean age, 61 ± 14 years) were randomly assigned to receive pomegranate juice or extract during a 4-week intervention period. After a washout period, all patients received the alternative treatment during a second 4-week intervention period. Patients assigned to receive pomegranate juice received 100 mL of juice before each dialysis session. Patients assigned to receive pomegranate extract were given 1,050 mg of extract daily. The main outcome measures were safety and tolerability of pomegranate juice and extract. Additional secondary outcomes assessed included serum lipids, laboratory biomarkers of inflammation (C-reactive protein and interleukin 6) and oxidative stress (plasma F2 isoprostanes and isofurans), monocyte cytokine production, and predialysis blood pressure. Both pomegranate juice and extract were safe and well tolerated by study participants. Over the study period, neither treatment had a significant effect on lipid profiles, plasma C-reactive protein, interleukin 6, F2-isoprostane or isofuran concentrations, predialysis systolic or diastolic blood pressure nor changed the levels of monocyte cytokine production. Both pomegranate juice and extract are safe and well tolerated by patients undergoing MHD but do not influence markers of inflammation or oxidative stress

  17. Long term effect of depression care management on mortality in older adults: follow-up of cluster randomized clinical trial in primary care

    OpenAIRE

    Gallo, Joseph J; Morales, Knashawn H; Bogner, Hillary R; Raue, Patrick J; Zee, Jarcy; Bruce, Martha L; Reynolds, Charles F

    2013-01-01

    Objective To investigate whether an intervention to improve treatment of depression in older adults in primary care modified the increased risk of death associated with depression. Design Long term follow-up of multi-site practice randomized controlled trial (PROSPECT?Prevention of Suicide in Primary Care Elderly: Collaborative Trial). Setting 20 primary care practices in New York City, Philadelphia, and Pittsburgh, USA, randomized to intervention or usual care. Participants 1226 participants...

  18. Lack of effect of the glucagon-like peptide-1 receptor agonist liraglutide on psoriasis in glucose-tolerant patients – a randomized placebo-controlled trial

    DEFF Research Database (Denmark)

    Faurschou, A; Gyldenløve, M; Rohde, U

    2015-01-01

    BACKGROUND: It has been proposed that glucagon-like peptide-1 receptor (GLP-1R) agonists used for the treatment of patients with type 2 diabetes might also improve their psoriasis. OBJECTIVE: To assess the efficacy and safety of the GLP-1R agonist liraglutide in glucose-tolerant patients with pla...... end points were improvement in PASI and dermatology life quality index (DLQI). Secondary end points included changes in weight and high sensitive C-reactive protein (hsCRP) levels, as well as adverse events. RESULTS: After 8 weeks of treatment, no significant change in PASI was found.......2 (liraglutide); P = 0.992). Liraglutide treatment resulted in a bodyweight loss of 4.7 ± 2.5 kg compared with 1.6 ± 2.7 kg in the placebo group (P = 0.014) accompanied by decreased cholesterol levels. No serious adverse events occurred during the 8-week observation period. The most common complaint...... was transient nausea, which occurred in 45% of the liraglutide-treated patients but in none from the placebo group. CONCLUSION: Liraglutide treatment for 8 weeks did not significantly change PASI, DLQI, or hsCRP in a small group of glucose-tolerant obese patients with plaque psoriasis compared with placebo...

  19. Effects of short-term glucocorticoid deprivation on growth hormone (GH) response to GH-releasing peptide-6: Studies in normal men and in patients with adrenal insufficiency

    OpenAIRE

    Pinto, Ana Claudia de Assis Rocha [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Martins, Manoel R. [UNIFESP; Brunner, Elisa [UNIFESP; Lengyel, Ana Maria Judith [UNIFESP

    2000-01-01

    There are no data in the literature about the effects of glucocorticoid deprivation on GH-releasing peptide-g (GHRP-6)-induced GH release. the aims of this study were to evaluate GH responsiveness to GHRP-6 1) after metyrapone administration in normal men, and 2) in patients with chronic hypocortisolism after glucocorticoid withdrawal for 72 h. in normal subjects, metyrapone ingestion did not alter significantly GH responsiveness to GHRP-6 [n = 8; peak, 39.3 +/- 7.1 mu g/L; area under the cur...

  20. Semisolid meal enriched in oat bran decreases plasma glucose and insulin levels, but does not change gastrointestinal peptide responses or short-term appetite in healthy subjects

    DEFF Research Database (Denmark)

    Juvonen, Kristiina R.; Salmenkallio-Marttila, Marjatta; Lyly, Marika

    2011-01-01

    types and amounts of DF exert are still poorly understood. METHODS AND RESULTS: We investigated the effects of wheat and oat brans alone and as combination in semisolid food matrix on postprandial appetite profile and gastrointestinal (GI) hormonal responses. Twenty healthy, normal-weight subjects (5...... including 5 g wheat bran DF + 5 g oat bran DF. Blood samples were drawn before and 15, 30, 45, 60, 90, 120 and 180 min after the test meals to determine plasma glucose, ghrelin, peptide YY (PYY) and serum insulin concentrations. Subjective profiles of appetite were assessed using visual analogue scales (VAS...

  1. Remifentanil analgesia during external cephalic version for breech presentation in nulliparous women at term: A randomized controlled trial.

    Science.gov (United States)

    Wang, Zhi-Hong; Yang, Yi; Xu, Gui-Ping

    2017-03-01

    The aim of the study was to assess the efficacy and safety of remifentanil for pain relief during external cephalic version (ECV) for breech presentation in nulliparous women at term. A total of 144 nulliparous women with singleton breech presentation were randomly divided into the intervention group and the placebo group, with 72 subjects in each group. The subjects in the intervention group received remifentanil (infused at 0.1 μg kg min with demand boluses of 0.1 μg/kg), whereas those in the placebo group were given saline placebo. This study was conducted from May 2013 to April 2016. The outcomes measures include pain (measured with the visual analog scale, VAS), success rate of ECV, maternal satisfaction for ECV, and adverse events. A total of 137 participants completed the study. The intervention with remifentanil showed greater efficacy than did placebo in decreasing the VAS score immediately after ECV (intervention group 4.3 ± 2.2 vs placebo group 6.4 ± 2.5, P < 0.01). A significant difference in the ECV success rate was also found between the 2 groups (intervention group 56.9% vs placebo group 38.9%, P = 0.03). In addition, a significant difference in the satisfaction score was also detected (intervention group 9.3 ± 0.9 vs placebo group 6.7 ± 1.2, P < 0.01). The observed adverse events were similar between the 2 groups. This study shows that remifentanil could decrease pain, improve the ECV success rate, and improve satisfaction in nulliparous women at term during the period of ECV. Furthermore, it is also well tolerated with few adverse events.

  2. Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: A randomized, controlled trial.

    Science.gov (United States)

    Klek, Stanislaw; Scislo, Lucyna; Walewska, Elzbieta; Choruz, Ryszard; Galas, Aleksander

    2017-04-01

    The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN). In all patients, short- and long-term (5 y) survival was analyzed. Analysis of the overall survival time did not reveal differences between groups (P = 0.663). Until the end of the third month, however, there were nine deaths in the standard enteral nutrition group and no deaths in the EEN group (16.7% versus 0.0%, P = 0.004). The univariate analyses suggested that the EEN group may have lower risk, especially during the first year after intervention. A significant reduction in the risk of death was seen during the early period after surgery (first 6 mo) in the EEN group in stage IV patients (hazard ratio = 0.25, P = 0.049). The use of enriched enteral diet did not influence, however, the risk of dying when patients were analyzed together. The study does not support the beneficial effect of enriched enteral nutrition in long-term survival; however, the positive impact on the stage IV patients suggests the need for further, more detailed studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. A randomized controlled trial of a supported employment program for persons with long-term mental illness in Hong Kong.

    Science.gov (United States)

    Kin Wong, Kenny; Chiu, Rose; Tang, Betty; Mak, Donald; Liu, Joanne; Chiu, Siu Ning

    2008-01-01

    Supported employment is an evidence-based practice that has proved to be consistently more effective than conventional vocational rehabilitation in helping people with severe mental illness find and sustain competitive employment. Most research on the effectiveness of supported employment comes from the United States. This study examined the effectiveness and applicability of a supported employment program based on the individual placement and support model in a Hong Kong setting. Ninety-two unemployed individuals with long-term mental illness who desired competitive employment were randomly assigned to either a supported employment program or a conventional vocational rehabilitation program and followed up for 18 months. Both vocational and nonvocational outcomes were measured. Over the 18-month study period, compared with participants in the conventional vocational rehabilitation program, those in the supported employment group were more likely to work competitively (70% versus 29%; odds ratio=5.63, 95% confidence interval=2.28-13.84), held a greater number of competitive jobs, earned more income, worked more days, and sustained longer job tenures. Repeated-measures analysis of variance found no substantive differences between participants in the two groups and no significant change from baseline over time for psychiatric symptoms and self-perceived quality of life. Consistent with previous research findings in the United States, the supported employment program was more effective than the conventional vocational rehabilitation program in helping individuals with long-term mental illness find and sustain competitive employment in a Hong Kong setting. The supported employment program based on the individual placement and support model can thus be recommended for wider use in local mental health practice.

  4. Effects of a short-term parental education program on childhood atopic dermatitis: a randomized controlled trial.

    Science.gov (United States)

    Futamura, Masaki; Masuko, Ikuyo; Hayashi, Keiichi; Ohya, Yukihiro; Ito, Komei

    2013-01-01

    Parental education is important in managing childhood atopic dermatitis (AD). We evaluated the long-term effects of a 2-day parental education program (PEP) on childhood AD. In an investigator-blinded, randomized controlled trial, 59 children age 6 months to 6 years with moderate to severe AD and their mothers were recruited in Japan. Participants were given a booklet about AD and received conventional treatment alone or in combination with a 2-day PEP comprising three lectures, three practical sessions, and a group discussion. The primary outcome was evaluation of eczema severity using SCORing Atopic Dermatitis (SCORAD) at 6 months. Secondary outcomes included changes in symptom scores, amount of corticosteroid used, parental quality of life as determined according to the Dermatitis Family Impact questionnaire, and change in parental anxiety regarding the use of corticosteroids in their children. Participants in the PEP group had a significantly lower SCORAD score than those in the control group at 6 months (mean difference 10.0, 95% confidence interval [CI] = 2.3-17.7, p = 0.01) and objective SCORAD score (mean difference 7.1, 95% CI = 0.8-13.5, p = 0.03). The sleeplessness symptom score (mean difference 1.6, 95% CI = 0.0-3.1, p = 0.048) and corticosteroid anxiety score (p = 0.02) in the PEP group were significantly better than in the control group at 6 months. There was no significant difference between groups in the amount of corticosteroid used or quality of life. The PEP had positive long-term effects on eczema severity and parental anxiety about corticosteroid usage. © 2013 Wiley Periodicals, Inc.

  5. The Impact of Short-Term Video Games on Performance among Children with Developmental Delays: A Randomized Controlled Trial

    Science.gov (United States)

    Hsieh, Ru-Lan; Lee, Wen-Chung; Lin, Jui-Hsiang

    2016-01-01

    This prospective, randomized controlled study investigated the effects of short-term interactive video game playing among children with developmental delays participating in traditional rehabilitation treatment at a rehabilitation clinic. One hundred and one boys and 46 girls with a mean age of 5.8 years (range: 3 to 12 years) were enrolled in this study. All patients were confirmed to suffer from developmental delays, and were participating in traditional rehabilitation treatment. Children participated in two periods of 4 weeks each, group A being offered intervention of eight 30-minute sessions of interactive video games in the first period, and group B in the second, in addition to the traditional rehabilitation treatment. The physical, psychosocial, and total health of the children was periodically assessed using the parent-reported Pediatric Quality of Life Inventory-Generic Core Scales (PedsQL); and the children’s upper extremity and physical function, transfer and basic mobility, sports and physical functioning, and global functioning were assessed using the Pediatric Outcomes Data Collection Instrument. Parental impact was evaluated using the PedsQL-Family Impact Module for family function, PedsQL-Health Satisfaction questionnaire for parents’ satisfaction with their children’s care and World Health Organization-Quality of Life-Brief Version for quality of life. Compared with the baseline, significant improvements of physical function were observed in both groups (5.6 ± 19.5, p = 0.013; 4.7 ± 13.8, p = 0.009) during the intervention periods. No significant improvement of psychosocial health, functional performance, or family impact was observed in children with developmental delays. Short-term interactive video game play in conjunction with traditional rehabilitation treatment improved the physical health of children with developmental delays. Trial Registration: ClinicalTrials.gov NCT02184715 PMID:26983099

  6. The Impact of Short-Term Video Games on Performance among Children with Developmental Delays: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Ru-Lan Hsieh

    Full Text Available This prospective, randomized controlled study investigated the effects of short-term interactive video game playing among children with developmental delays participating in traditional rehabilitation treatment at a rehabilitation clinic. One hundred and one boys and 46 girls with a mean age of 5.8 years (range: 3 to 12 years were enrolled in this study. All patients were confirmed to suffer from developmental delays, and were participating in traditional rehabilitation treatment. Children participated in two periods of 4 weeks each, group A being offered intervention of eight 30-minute sessions of interactive video games in the first period, and group B in the second, in addition to the traditional rehabilitation treatment. The physical, psychosocial, and total health of the children was periodically assessed using the parent-reported Pediatric Quality of Life Inventory-Generic Core Scales (PedsQL; and the children's upper extremity and physical function, transfer and basic mobility, sports and physical functioning, and global functioning were assessed using the Pediatric Outcomes Data Collection Instrument. Parental impact was evaluated using the PedsQL-Family Impact Module for family function, PedsQL-Health Satisfaction questionnaire for parents' satisfaction with their children's care and World Health Organization-Quality of Life-Brief Version for quality of life. Compared with the baseline, significant improvements of physical function were observed in both groups (5.6 ± 19.5, p = 0.013; 4.7 ± 13.8, p = 0.009 during the intervention periods. No significant improvement of psychosocial health, functional performance, or family impact was observed in children with developmental delays. Short-term interactive video game play in conjunction with traditional rehabilitation treatment improved the physical health of children with developmental delays.ClinicalTrials.gov NCT02184715.

  7. The Impact of Short-Term Video Games on Performance among Children with Developmental Delays: A Randomized Controlled Trial.

    Science.gov (United States)

    Hsieh, Ru-Lan; Lee, Wen-Chung; Lin, Jui-Hsiang

    2016-01-01

    This prospective, randomized controlled study investigated the effects of short-term interactive video game playing among children with developmental delays participating in traditional rehabilitation treatment at a rehabilitation clinic. One hundred and one boys and 46 girls with a mean age of 5.8 years (range: 3 to 12 years) were enrolled in this study. All patients were confirmed to suffer from developmental delays, and were participating in traditional rehabilitation treatment. Children participated in two periods of 4 weeks each, group A being offered intervention of eight 30-minute sessions of interactive video games in the first period, and group B in the second, in addition to the traditional rehabilitation treatment. The physical, psychosocial, and total health of the children was periodically assessed using the parent-reported Pediatric Quality of Life Inventory-Generic Core Scales (PedsQL); and the children's upper extremity and physical function, transfer and basic mobility, sports and physical functioning, and global functioning were assessed using the Pediatric Outcomes Data Collection Instrument. Parental impact was evaluated using the PedsQL-Family Impact Module for family function, PedsQL-Health Satisfaction questionnaire for parents' satisfaction with their children's care and World Health Organization-Quality of Life-Brief Version for quality of life. Compared with the baseline, significant improvements of physical function were observed in both groups (5.6 ± 19.5, p = 0.013; 4.7 ± 13.8, p = 0.009) during the intervention periods. No significant improvement of psychosocial health, functional performance, or family impact was observed in children with developmental delays. Short-term interactive video game play in conjunction with traditional rehabilitation treatment improved the physical health of children with developmental delays. ClinicalTrials.gov NCT02184715.

  8. β-Glucan and Dark Chocolate: A Randomized Crossover Study on Short-Term Satiety and Energy Intake

    Directory of Open Access Journals (Sweden)

    Asli Akyol

    2014-09-01

    Full Text Available Aim: The aims of this study were to adapt a traditional recipe into a healthier form by adding 3 g of oat β-glucan, substituting milk chocolate to dark chocolate with 70% cocoa, and to examine the effect of these alterations on short-term satiety and energy intake. Materials and Methods: Study subjects (n = 25 were tested in a randomized, crossover design with four products closely matched for energy content. Four different versions of a traditional recipe including milk chocolate-control (CON, oat β-glucan (B-GLU, dark chocolate (DARK or oat β-glucan and dark chocolate (B-GLU + DARK were given to subjects on different test days. After subjects were asked to report visual analog scale (VAS scores on sensory outcomes and related satiety for four hours ad libitum, lunch was served and energy intake of individuals was measured. Results: VAS scores indicated that none of the test foods exerted an improved effect on satiety feelings. However, energy intake of individuals during ad libitum lunch was significantly lower in dark chocolate groups (CON: 849.46 ± 47.45 kcal versus DARK: 677.69 ± 48.45 kcal and B-GLU + DARK: 691.08 ± 47.45 kcal, p = 0.014. Conclusion: The study demonstrated that substituting dark chocolate for milk chocolate is more effective in inducing satiety during subsequent food intake in healthy subjects.

  9. Bidirectional Long Short-Term Memory Network with a Conditional Random Field Layer for Uyghur Part-Of-Speech Tagging

    Directory of Open Access Journals (Sweden)

    Maihemuti Maimaiti

    2017-11-01

    Full Text Available Uyghur is an agglutinative and a morphologically rich language; natural language processing tasks in Uyghur can be a challenge. Word morphology is important in Uyghur part-of-speech (POS tagging. However, POS tagging performance suffers from error propagation of morphological analyzers. To address this problem, we propose a few models for POS tagging: conditional random fields (CRF, long short-term memory (LSTM, bidirectional LSTM networks (BI-LSTM, LSTM networks with a CRF layer, and BI-LSTM networks with a CRF layer. These models do not depend on stemming and word disambiguation for Uyghur and combine hand-crafted features with neural network models. State-of-the-art performance on Uyghur POS tagging is achieved on test data sets using the proposed approach: 98.41% accuracy on 15 labels and 95.74% accuracy on 64 labels, which are 2.71% and 4% improvements, respectively, over the CRF model results. Using engineered features, our model achieves further improvements of 0.2% (15 labels and 0.48% (64 labels. The results indicate that the proposed method could be an effective approach for POS tagging in other morphologically rich languages.

  10. A Permutation Importance-Based Feature Selection Method for Short-Term Electricity Load Forecasting Using Random Forest

    Directory of Open Access Journals (Sweden)

    Nantian Huang

    2016-09-01

    Full Text Available The prediction accuracy of short-term load forecast (STLF depends on prediction model choice and feature selection result. In this paper, a novel random forest (RF-based feature selection method for STLF is proposed. First, 243 related features were extracted from historical load data and the time information of prediction points to form the original feature set. Subsequently, the original feature set was used to train an RF as the original model. After the training process, the prediction error of the original model on the test set was recorded and the permutation importance (PI value of each feature was obtained. Then, an improved sequential backward search method was used to select the optimal forecasting feature subset based on the PI value of each feature. Finally, the optimal forecasting feature subset was used to train a new RF model as the final prediction model. Experiments showed that the prediction accuracy of RF trained by the optimal forecasting feature subset was higher than that of the original model and comparative models based on support vector regression and artificial neural network.

  11. Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

    Science.gov (United States)

    Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

    2015-09-01

    To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Long-term effects of the Mediterranean lifestyle program: a randomized clinical trial for postmenopausal women with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ritzwoller Debra P

    2007-01-01

    Full Text Available Abstract Background Multiple-risk-factor interventions offer a promising means for addressing the complex interactions between lifestyle behaviors, psychosocial factors, and the social environment. This report examines the long-term effects of a multiple-risk-factor intervention. Methods Postmenopausal women (N = 279 with type 2 diabetes participated in the Mediterranean Lifestyle Program (MLP, a randomized, comprehensive lifestyle intervention study. The intervention targeted healthful eating, physical activity, stress management, smoking cessation, and social support. Outcomes included lifestyle behaviors (i.e., dietary intake, physical activity, stress management, smoking cessation, psychosocial variables (e.g., social support, problem solving, self-efficacy, depression, quality of life, and cost analyses at baseline, and 6, 12, and 24 months. Results MLP participants showed significant 12- and 24-month improvements in all targeted lifestyle behaviors with one exception (there were too few smokers to analyze tobacco use effects, and in psychosocial measures of use of supportive resources, problem solving, self-efficacy, and quality of life. Conclusion The MLP was more effective than usual care over 24 months in producing improvements on behavioral and psychosocial outcomes. Directions for future research include replication with other populations.

  13. β-Glucan and dark chocolate: a randomized crossover study on short-term satiety and energy intake.

    Science.gov (United States)

    Akyol, Asli; Dasgin, Halil; Ayaz, Aylin; Buyuktuncer, Zehra; Besler, H Tanju

    2014-09-23

    The aims of this study were to adapt a traditional recipe into a healthier form by adding 3 g of oat β-glucan, substituting milk chocolate to dark chocolate with 70% cocoa, and to examine the effect of these alterations on short-term satiety and energy intake. Study subjects (n = 25) were tested in a randomized, crossover design with four products closely matched for energy content. Four different versions of a traditional recipe including milk chocolate-control (CON), oat β-glucan (B-GLU), dark chocolate (DARK) or oat β-glucan and dark chocolate (B-GLU + DARK) were given to subjects on different test days. After subjects were asked to report visual analog scale (VAS) scores on sensory outcomes and related satiety for four hours ad libitum, lunch was served and energy intake of individuals was measured. VAS scores indicated that none of the test foods exerted an improved effect on satiety feelings. However, energy intake of individuals during ad libitum lunch was significantly lower in dark chocolate groups (CON: 849.46 ± 47.45 kcal versus DARK: 677.69 ± 48.45 kcal and B-GLU + DARK: 691.08 ± 47.45 kcal, p = 0.014). The study demonstrated that substituting dark chocolate for milk chocolate is more effective in inducing satiety during subsequent food intake in healthy subjects.

  14. Acute and Short-Term Toxicities of Conventionally Fractionated Versus Hypofractionated Whole Breast Irradiation in a Prospective, Randomized Trial

    Science.gov (United States)

    Shaitelman, Simona F.; Schlembach, Pamela J.; Arzu, Isidora; Ballo, Matthew; Bloom, Elizabeth S.; Buchholz, Daniel; Chronowski, Gregory M.; Dvorak, Tomas; Grade, Emily; Hoffman, Karen E.; Kelly, Patrick; Ludwig, Michelle; Perkins, George H.; Reed, Valerie; Shah, Shalin; Stauder, Michael C.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy A.; Ensor, Joe; Baumann, Donald; Thompson, Alastair M.; Amaya, Diana; Davis, Tanisha; Guerra, William; Hamblin, Lois; Hortobagyi, Gabriel; Hunt, Kelly K.; Buchholz, Thomas A.; Smith, Benjamin D.

    2015-01-01

    IMPORTANCE The most appropriate dose-fractionation for whole breast irradiation (WBI) remains uncertain. OBJECTIVE To assess acute and six-month toxicity and quality of life (QoL) with conventionally fractionated WBI (CF-WBI) versus hypofractionated WBI (HF-WBI). DESIGN Unblinded randomized trial of CF-WBI (n=149; 50 Gy/25 fractions + boost [10–14 Gy/5–7 fractions]) versus HF-WBI (n=138; 42.56 Gy/16 fractions + boost [10–12.5 Gy/4–5 fractions]). SETTING Community-based and academic cancer centers. PARTICIPANTS 287 women age ≥ 40 years with stage 0–II breast cancer treated with breast-conserving surgery for whom whole breast irradiation without addition of a third field was recommended. 76% (n=217) were overweight or obese. Patients were enrolled from February 2011 through February 2014. INTERVENTION(S) FOR CLINICAL TRIALS CF-WBI versus HF-WBI. MAIN OUTCOME MEASURES Physician-reported acute and six-month toxicities using NCICTCv4.0 and patient-reported QoL using the FACT-B version 4. All analyses were intention-to-treat, with outcomes compared using chi-square, Cochran-Armitage test, and ordinal logistic regression. Patients were followed for a minimum of 6 months. RESULTS Treatment arms were well-matched for baseline characteristics including FACT-B total score (P=0.46) and individual QoL items such as lack of energy (P=0.86) and trouble meeting family needs (P=0.54). Maximal physician-reported acute dermatitis (P<0.001), pruritus (P<0.001), breast pain (P=0.001), hyperpigmentation (P=0.002), and fatigue (P=0.02) during radiation were lower in patients randomized to HF-WBI. Overall grade ≥2 acute toxicity was less with HF-WBI vs. CF-WBI (47% vs. 78%; P<0.001). Six months after radiation, physicians reported less fatigue in patients randomized to HF-WBI (P=0.01), and patients randomized to HF-WBI reported less lack of energy (P<0.001) and less trouble meeting family needs (P=0.01). Multivariable regression confirmed the superiority of HF-WBI in terms

  15. Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

    Directory of Open Access Journals (Sweden)

    Rahu Mati

    2008-08-01

    Full Text Available Abstract Background Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. Methods The Estonian Postmenopausal Hormone Therapy trial (EPHT, originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT on health services utilization. Results After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. Conclusion Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old drug for a new preventive indication? In preventive drug trials companies may

  16. Primary structure and conformational analysis of peptide methionine-tyrosine, a peptide related to neuropeptide Y and peptide YY isolated from lamprey intestine

    DEFF Research Database (Denmark)

    Conlon, J M; Bjørnholm, B; Jørgensen, Flemming Steen

    1991-01-01

    A peptide belonging to the pancreatic-polypeptide-fold family of regulatory peptides has been isolated from the intestine of an Agnathan, the sea lamprey (Petromyzon marinus). The primary structure of the peptide (termed peptide methionine-tyrosine) was established as Met-Pro-Pro-Lys-Pro-Asp-Asn-...... in a preferred structure in which the conformation of the beta-turn between the two helical domains (residues 9-14) is appreciably different....

  17. Adherence and success in long-term weight loss diets: the dietary intervention randomized controlled trial (DIRECT).

    Science.gov (United States)

    Greenberg, Ilana; Stampfer, Meir J; Schwarzfuchs, Dan; Shai, Iris

    2009-04-01

    Data are limited as to whether participants in diet trials truly adhere to their assigned diet and the factors that affect their adherence. We evaluated success and adherence in a two-year dietary intervention randomized controlled trial (DIRECT) in which 322 moderately obese participants (mean age 52 yrs, mean body-mass-index (BMI) 31 kg/m(2), 86% men) were randomized to one of three groups: low-fat, Mediterranean, or low-carbohydrate diets. Overall compliance at month-24 was 85%, with 90% in low-fat, 85% in Mediterranean, and 78% in low-carbohydrate diet (p = .042 between groups). Attrition was higher in women (29% vs. 14% men, p = .001) and current smokers (25% vs. 14% among maintainers, p = 0.04). In a multivariate model, independent predictors of dropping-out were: higher baseline BMI (OR = 1.11; CI: 1.03-1.21) and less weight loss at month-6 (OR = 1.20; CI: 1.1-1.3). In a multivariate model, greater weight loss achieved at month-6 was the main predictor associated with success in weight loss (> 5%) over 2 years (OR = 1.5; CI: 1.35-1.67). Self-reported complete adherence score to diet was greater on low-carbohydrate diet (p low-fat) until month-6, but dropped overall from 81% at month-1 to 57% at month-24. Holidays were a trigger to a significant decrease in adherence followed by a partial rebound. Changes in diet composition from month-1 to month-12 were more pronounced in the multi-stage low-carbohydrate diet-group (p < .05). Generally, the most irresistible restricted food items were cookies (45% of dieters) and fruits (30%). Among the physically active (n = 107), 44% reported a tendency to eat less after exercising compared to 10% who tended to eat more. Initial 6-month reduction in weight is the main predictor of both long-term retention and success in weight loss. Special attention is needed for women, current smokers, and during holidays. Physical activity is associated with subsequent reduction in energy intake.

  18. Designing anticancer peptides by constructive machine learning.

    Science.gov (United States)

    Grisoni, Francesca; Neuhaus, Claudia; Gabernet, Gisela; Müller, Alex; Hiss, Jan; Schneider, Gisbert

    2018-04-21

    Constructive machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a generative model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short-term memory cells was trained on alpha-helical cationic amphipathic peptide sequences and then fine-tuned with 26 known ACPs. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a long-term antibacterial activity in vitro against clinical isolates of Staphylococcus epidermidis

    Directory of Open Access Journals (Sweden)

    Anna Maria Piras

    2015-04-01

    Full Text Available Nowadays, the alarming rise in multidrug-resistant microorganisms urgently demands for suitable alternatives to current antibiotics. In this regard, antimicrobial peptides (AMPs have received growing interest due to their broad spectrum of activities, potent antimicrobial properties, unique mechanisms of action and low tendency to induce resistance. However, their pharmaceutical development is hampered by potential toxicity, relatively low stability and manufacturing costs. In the present study, we tested the hypothesis that the encapsulation of the frog-skin derived AMP temporin B (TB into chitosan nanoparticles (CS-NPs could increase peptide’s antibacterial activity, while reducing its toxic potential. TB-loaded CS-NPs with good dimensional features were prepared, based on the ionotropic gelation between CS and sodium tripolyphosphate. The encapsulation efficiency of TB in the formulation was up to 75%. Release kinetic studies highlighted a linear release of the peptide from the nanocarrier, in the adopted experimental conditions. Interestingly, the encapsulation of TB in CS-NPs demonstrated to reduce significantly the peptide’s cytotoxicity against mammalian cells. Additionally, the nanocarrier evidenced a sustained antibacterial action against various strains of Staphylococcus epidermidis for at least 4 days, with up to 4-log reduction in the number of viable bacteria compared to plain CS-NPs at the end of the observational period. Of note, the antimicrobial evaluation tests demonstrated that while the intrinsic antimicrobial activity of CS ensured a burst effect, the gradual release of TB further reduced the viable bacterial count, preventing the regrowth of the residual cells and ensuring a long-lasting antibacterial effect. The developed nanocarrier is eligible for the administration of several AMPs of therapeutic interest with physical-chemical characteristics analogue to those of TB.

  20. Effects of delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in term infants: a randomized controlled trial.

    Science.gov (United States)

    Mercer, J S; Erickson-Owens, D A; Collins, J; Barcelos, M O; Parker, A B; Padbury, J F

    2017-03-01

    The objective of the study was to measure the effects of a 5-min delay (DCC) versus immediate cord clamping (ICC) on residual placental blood volume (RPBV) at birth, and hemoglobin and serum bilirubin at 24 to 48 h of age. In this prospective randomized controlled trial, 73 women with term (37 to 41 weeks) singleton fetuses were randomized to DCC (⩾5 min; n=37) or ICC (protocol violations. Cord milking was the proxy for DCC (n=11) when the provider could not wait. Infants randomized to DCC compared with ICC had significantly less RPBV (20.0 versus 30.8 ml kg -1 , Phemoglobin levels (19.4 versus 17.8 g dl -1 , P=0.002) at 24 to 48 h, with no difference in bilirubin levels. Term infants had early hematological advantage of DCC without increases in hyperbilirubinemia or symptomatic polycythemia.

  1. Cost-effectiveness of a long-term Internet-delivered worksite health promotion programme on physical activity and nutrition: A cluster randomized controlled trial

    NARCIS (Netherlands)

    S.J.W. Robroek (Suzan); S. Polinder (Suzanne); F.J. Bredt (Folef); A. Burdorf (Alex)

    2012-01-01

    textabstractThis study aims to evaluate the cost-effectiveness of a long-term workplace health promotion programme on physical activity (PA) and nutrition. In total, 924 participants enrolled in a 2-year cluster randomized controlled trial, with departments (n = 74) within companies (n = 6) as the

  2. The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

    Science.gov (United States)

    Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

    2016-01-01

    Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

  3. The coping with depression course: Short term outcomes and mediating effects of a randomized controlled trial in the treatment of subclinical depression

    NARCIS (Netherlands)

    Allart-van Dam, E.; Hosman, C.M.H.; Hoogduin, C.A.L.; Schaap, C.P.D.R.

    2003-01-01

    This article reports on a randomized controlled trial investigating the short-term effectiveness of the Coping With Depression course in a sample of adults seriously at risk of developing major depression. In addition, possible mediating properties of several proximal outcome variables were

  4. The Coping with Depression course : Short-term outcomes and mediating effects of a randomized controlled trial in the treatment of subclinical depression

    NARCIS (Netherlands)

    Allart-van Dam, E; Hosman, CMH; Hoogduin, CAL; Schaap, CPDR

    2003-01-01

    This article reports on a randomized controlled trial investigating the short-term effectiveness of the Coping With Depression course in a sample of adults seriously at risk of developing major depression. In addition, possible mediating properties of several proximal outcome variables were

  5. Is a long-term high-intensity exercise program effective and safe in patients with rheumatoid arthritis? Results of a randomized controlled trial

    NARCIS (Netherlands)

    de Jong, Zuzana; Munneke, Marten; Zwinderman, Aeilko H.; Kroon, Herman M.; Jansen, Annemarie; Ronday, Karel H.; van Schaardenburg, Dirkjan; Dijkmans, Ben A. C.; van den Ende, Cornelia H. M.; Breedveld, Ferdinand C.; Vliet Vlieland, Theodora P. M.; Hazes, Johanna M. W.

    2003-01-01

    OBJECTIVE: There are insufficient data on the effects of long-term intensive exercise in patients with rheumatoid arthritis (RA). We undertook this randomized, controlled, multicenter trial to compare the effectiveness and safety of a 2-year intensive exercise program (Rheumatoid Arthritis Patients

  6. Is a long-term high-intensity exercise program effective and safe in patients with rheumatoid arthritis? Results of a randomized controlled trial.

    NARCIS (Netherlands)

    Jong, Z. de; Munneke, M.; Zwinderman, A.H.; Kroon, H.M.; Jansen, A.; Ronday, K.H.; Schaardenburg, D. van; Dijkmans, B.A.C.; Ende, C.H.M. van den; Breedveld, F.C.; Vliet Vlieland, T.P.M.; Hazes, J.M.W.

    2003-01-01

    OBJECTIVE: There are insufficient data on the effects of long-term intensive exercise in patients with rheumatoid arthritis (RA). We undertook this randomized, controlled, multicenter trial to compare the effectiveness and safety of a 2-year intensive exercise program (Rheumatoid Arthritis Patients

  7. The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study

    Directory of Open Access Journals (Sweden)

    De Backer L

    2011-11-01

    Full Text Available L De Backer¹, W Vos², B Dieriks¹, D Daems¹, S Verhulst¹, S Vinchurkar², K Ides¹, J De Backer², P Germonpre¹, W De Backer¹1Antwerp University Hospital, Department of Respiratory Medicine, 2FluidDa, Antwerp, BelgiumIntroduction: Noninvasive ventilation (NIV is a well-established treatment for acute-on-chronic respiratory failure in hypercapnic COPD patients. Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention.Methods: In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV1 30.5 [±5.1] %pred, PaO2 65 [±6] mmHg, PaCO2 52.4 [±6.0] mmHg or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA] (n = 10, age 65 [±7] years, FEV1 29.5 [±9.0] %pred, PaO2 59 [±13] mmHg, PaCO2 55.4 [±7.7] mmHg for 6 months. We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw and post-processing with computer methods (providing airway resistance, iRaw giving overall a functional image of the separate airways and lobes.Results: In both groups there was a nonsignificant change in FEV1 (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg. PaCO2 dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS. Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients. Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was

  8. The effects of short-term alpha-ketoisocaproic acid supplementation on exercise performance: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Yarrow Joshua F

    2007-07-01

    Full Text Available Abstract Background This study examined the efficacy of short-term alpha-ketoisocaproic acid (KIC monotherapy supplementation immediately prior to moderate- and high-intensity single bout exercise performance. Methods Thirteen resistance trained men (22.8 ± 2.5 years; 81.6 ± 12.6 kg participated in a prospective, randomized, double blind, placebo controlled crossover experiment. Each subject completed one familiarization and four experimental trials with either 1.5 g or 9.0 g of either KIC or isocaloric placebo control (CONT, following an overnight fast. During the experimental trials, subjects consumed the supplement regimen and then completed leg and chest press repetitions to failure and 30 s of repeated maximal vertical jumping (VJ on a force plate. Results In this treatment regimen, no significant differences (p > 0.05 were observed between dosages or conditions for leg press (low CONT = 19.8 ± 0.4 SEM, low KIC = 21.0 ± 0.5, high CONT = 20.1 ± 0.3, high KIC = 22.4 ± 0.6 or chest press (low CONT = 18.1 ± 0.2, low KIC = 18.5 ± 0.3, high CONT = 17.8 ± 0.3, high KIC = 18.0 ± 0.3 repetitions to failure. Additionally, no significant differences were observed for peak or mean VJ performance (low CONT = 34.6 ± 2.2 cm and 28.6 ± 1.8 cm; low KIC = 35.6 ± 2.0 cm and 29.4 ± 1.6 cm; high CONT = 35.7 ± 2.1 cm and 29.4 ± 1.7 cm; high KIC = 34.8 ± 2.3 cm and 28.3 ± 1.7 cm, respectively. Conclusion Based on our results, we conclude that acute KIC ingestion by itself with no other ergogenic supplement, immediately prior to exercise, did not alter moderate- nor high-intensity single-bout exercise performance in young resistance-trained males. This study addressed single-dose single-bout performance events; the efficacy of KIC monotherapy supplementation on repeated high-intensity exercise bouts and long-term exercise training remains unknown.

  9. Short Term Analgesic Effects of 5% Dextrose Epidural Injections for Chronic Low Back Pain: A Randomized Controlled Trial.

    Science.gov (United States)

    Maniquis-Smigel, Liza; Dean Reeves, Kenneth; Jeffrey Rosen, Howard; Lyftogt, John; Graham-Coleman, Cassie; Cheng, An-Lin; Rabago, David

    2017-02-01

    Hypertonic dextrose injection (prolotherapy) is reported to reduce pain including non-surgical chronic low back pain (CLBP), and subcutaneous injection of 5% dextrose is reported to reduce neurogenic pain, hyperalgesia and allodynia. The mechanism in both cases is unclear, though a direct effect of dextrose on neurogenic pain has been proposed. This study assessed the short-term analgesic effects of epidural 5% dextrose injection compared with saline for non-surgical CLBP. Randomized double-blind (injector, participant) controlled trial. Adults with moderate-to-severe non-surgical low back pain with radiation to gluteal or leg areas for at least 6 months received a single epidurogram-confirmed epidural injection of 10 mL of 5% dextrose or 0.9% saline using a published vertical caudal injection technique. The primary outcome was change in a numerical rating scale (NRS, 0 - 10 points) pain score between baseline and 15 minutes; and 2, 4, and 48 hours and 2 weeks post-injection. The secondary outcome was percentage of participants achieving 50% or more pain improvement at 4 hours. No baseline differences existed between groups; 35 participants (54 ± 10.7 years old; 11 female) with moderate-to-severe CLBP (6.7 ± 1.3 points) for 10.6 ± 10.5 years. Dextrose participants reported greater NRS pain score change at 15 minutes (4.4 ± 1.7 vs 2.4 ± 2.8 points; P = 0.015), 2 hours (4.6 ± 1.9 vs 1.8 ± 2.8 points; P = 0.001), 4 hours (4.6 ± 2.0 vs 1.4 ± 2.3 points; P dextrose recipients and 19% (3/16) of saline recipients reported ≥ 50% pain reduction at 4 hours (P dextrose on pain at the dorsal root level; waning pain control at 2 weeks suggests the need to assess the effect of serial dextrose epidural injections in a long-term study with robust outcome assessment.

  10. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial.

    Science.gov (United States)

    Woody, George E; Poole, Sabrina A; Subramaniam, Geetha; Dugosh, Karen; Bogenschutz, Michael; Abbott, Patrick; Patkar, Ashwin; Publicker, Mark; McCain, Karen; Potter, Jennifer Sharpe; Forman, Robert; Vetter, Victoria; McNicholas, Laura; Blaine, Jack; Lynch, Kevin G; Fudala, Paul

    2008-11-05

    The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Opioid-positive urine test result at weeks 4, 8, and 12. The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; chi(2)(1) = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use (chi(2)(1) = 18.45, P < .001), less injecting (chi(2)(1) = 6.00, P = .01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested

  11. Medium-term effectiveness of online behavioral training in migraine self-management: A randomized trial controlled over 10 months.

    Science.gov (United States)

    Sorbi, M J; Kleiboer, A M; van Silfhout, H G; Vink, G; Passchier, J

    2015-06-01

    This randomized, controlled trial examined the medium-term effectiveness of online behavioral training in migraine self-management (oBT; N = 195) versus waitlist control (WLC; N = 173) on attack frequency, indicators of self-management (primary outcomes), headache top intensity, use of rescue medications, quality of life and disability (secondary outcomes). An online headache diary following the ICHD-II and questionnaires were completed at baseline (T0), post-training (T1) and six months later (T2). Missing data (T1: 24%; T2: 37%) were handled by multiple imputation. We established effect sizes (ES) and tested between-group differences over time with linear mixed modelling techniques based on the intention-to-treat principle. At T2, attack frequency had improved significantly in oBT (-23%, ES = 0.66) but also in WLC (-19%; ES = 0.52). Self-efficacy, internal and external control in migraine management--and triptan use--improved only in oBT, however. This indicates different processes in both groups and could signify (the start of) active self-management in oBT. Also, only oBT improved migraine-specific quality of life to a sizable extent. oBT produced self-management gains but could not account for improved attack frequency, because WLC improved as well. The perspective that BT effects develop gradually, and that online delivery will boost BT outreach, justifies further research. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. [Alcohol versus bath and natural drying for term newborns' umbilical cord care: a prospective randomized clinical trial].

    Science.gov (United States)

    Covas, María del Carmen; Alda, Ernesto; Medina, María Sol; Ventura, Silvia; Pezutti, Ornella; Paris de Baeza, Ana; Sillero, Josefna; Esandi, María Eugenia

    2011-08-01

    Umbilical cord (UC) care is a cause of concern for parents right from birth until its separation. Standard practice in Argentina includes frequent cleansing of the UC with alcohol and body bath only two days after its separation. The effect of different methods of UC care on its separation time and on colonization with microorganisms has been insufficiently explored. Main: To compare the effect on time of UC separation when using body bath with neutral soap followed by natural drying of the UC vs. standard care. Secondary: a) colonization rates during hospitalization; b) incidence of skin infection and conjunctivitis and c) parental comfort with both types of care. Normal term newborns (≥37 weeks), born at the HPS, and whose parents provided informed consent. Open prospective controlled clinical trial, with random allocation to two groups: study group -natural drying of the UC and body bath with neutral soap- and control group -UC hygiene with alcohol 70% at each diaper change until its separation and bath two days later-. UC separation time; UC colonization during hospital stay and skin and conjunctive infections in the first 30 days of life were monitored. Analysis was by intention-to-treat. 362 newborns were included, 181 in each group. The groups were well balanced in baseline characteristics. Being in the study group was associated with a shorter time to UC separation (median [interquartile range]= 6.00 [3] vs. 7.00 [4] days; p natural drying of the UC reduced the time to cord separation. This practice increased the colonization rate, but the risk of skin and conjunctive infections was apparently not modified by it. However, the study has insufficient power for secondary outcomes. Health care providers should continue to develop evidence to support or eliminate historical practices.

  13. Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Jie-Li Li

    2018-04-01

    Full Text Available We aimed to quantitatively synthesize data from randomized controlled trials (RCTs concerning maintenance for multiple myeloma (MM. We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA to determine adequacy of sample size for overall and subgroup meta-analyses. We performed network meta-analysis (NMA to compare and rank included regimens. A total of 22 RCTs involving 9,968 MM patients and 15 regimens were included, the overall quality of which was adequate. Significant heterogeneity was detected for progression-free survival (PFS but not overall survival (OS. Meta-analyses showed that maintenance containing new agents significantly improved PFS but not OS [PFS: Hazard Ratio (HR = 0.59, 95% Confidence Interval (CI = 0.54 to 0.64; OS: HR = 0.93, 95% CI = 0.87 to 1.00], compared with controls. Subgroup analyses revealed lenalidomide (Len-based therapies better than thalidomide-based ones (HR = 0.50 and 0.66, respectively; P = 0.001. NMA revealed that most of the maintenance regimens containing new agents were significantly better than simple observation in terms of PFS but not OS. Len single agent was the most effective, considering PFS and OS both. We concluded that conventional maintenance has very limited effect. Maintenance containing new agents is highly effective in improving PFS, but has very limited effect on OS. Maintenance with Len may have the largest survival benefits. Emerging strategies may further change the landscape of maintenance of MM.

  14. The effect of perioperative probiotics treatment for colorectal cancer: short-term outcomes of a randomized controlled trial.

    Science.gov (United States)

    Yang, Yongzhi; Xia, Yang; Chen, Hongqi; Hong, Leiming; Feng, Junlan; Yang, Jun; Yang, Zhe; Shi, Chenzhang; Wu, Wen; Gao, Renyuan; Wei, Qing; Qin, Huanlong; Ma, Yanlei

    2016-02-16

    This study was designed to mainly evaluate the anti-infective effects of perioperative probiotic treatment in patients receiving confined colorectal cancer (CRC) respective surgery. From November 2011 to September 2012, a total of 60 patients diagnosed with CRC were randomly assigned to receive probiotic (n = 30) or placebo (n = 30) treatment. The operative and post-operative clinical results including intestinal cleanliness, days to first - flatus, defecation, fluid diet, solid diet, duration of pyrexia, average heart rate, length of intraperitoneal drainage, length of antibiotic therapy, blood index changes, rate of infectious and non-infectious complications, postoperative hospital stay, and mortality were investigated. The patient demographics were not significantly different (p > 0.05) between the probiotic treated and the placebo groups. The days to first flatus (3.63 versus 3.27, p = 0.0274) and the days to first defecation (4.53 versus 3.87, p = 0.0268) were significantly improved in the probiotic treated patients. The incidence of diarrhea was significantly lower (p = 0.0352) in probiotics group (26.67%, 8/30) compared to the placebo group (53.33%, 16/30). There were no statistical differences (p > 0.05) in other infectious and non-infectious complication rates including wound infection, pneumonia, urinary tract infection, anastomotic leakage, and abdominal distension. In conclusion, for those patients undergoing confined CRC resection, perioperative probiotic administration significantly influenced the recovery of bowel function, and such improvement may be of important clinical significance in reducing the short-term infectious complications such as bacteremia.

  15. Effect of Talbinah food consumption on depressive symptoms among elderly individuals in long term care facilities, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Badrasawi MM

    2013-03-01

    Full Text Available Manal M Badrasawi, Suzana Shahar, Zahara Abd Manaf, Hasnah HaronDietetics program, School of Health Care Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaAbstract: Talbinah is a barley syrup cooked with milk and sweetened by honey. In his famous Hadith on Talbinah, the Prophet Mohammad (SAW recommended it when sad events happen for its effect on soothing hearts and relieving sadness. This 3-week crossover designed, randomized clinical trial was conducted to determine the effect of Talbinah on mood and depression among institutionalized elderly people in Seremban. A sample of 30 depressed elderly subjects (21 men and 9 women was selected from the long term care facility. Three different interview-based validated scales (Geriatric Depression Scale, Depression Anxiety Stress Scales, and Profile of Mood States were used to determine mood, depression, stress, and anxiety at week 0, 3, 4, and 7. The nutritional value of Talbinah was examined using proximate food analysis, minerals content analysis, and differential amino acid analysis. The results indicated that Talbinah is a high carbohydrate food (86.4% and has a high tryptophan: branch chain amino acids ratio (1:2. A Wilcoxon nonparametric test showed that there was a statistically significant decrease on depression, stress, and mood disturbances scores among the intervention group (P < 0.05 for all parameters. In conclusion, Talbinah has the potential to reduce depression and enhance mood among the subjects. Ingestion of functional foods such as Talbinah may provide a mental health benefit to elderly people.Keywords: Talbinah, food and depression, cross over study, elderly

  16. Short-term effects of customized arch support insoles on symptomatic flexible flatfoot in children: A randomized controlled trial.

    Science.gov (United States)

    Hsieh, Ru-Lan; Peng, Hui-Ling; Lee, Wen-Chung

    2018-05-01

    Limited evidence is available regarding the effects of insoles on pediatric flexible flatfoot because of the heterogeneity and low methodological quality of previous studies. The purpose of this prospective trial is to examine the short-term effects of customized arch support insoles on symptomatic flexible flatfoot in children by using the International Classification of Functioning, randomized controlled Disability, and Health (ICF) framework. This study was conducted in a rehabilitation outpatient clinic of a teaching hospital. Fifty-two children with symptomatic flexible flatfoot were included. The children in the treatment group wore customized arch support insoles for 12 weeks, whereas those in the control group did not wear the insoles. Both clinical and radiographic measurements, including the navicular drop, foot posture index, Beighton hypermobility score, talonavicular coverage angle, calcaneal inclination angle, and calcaneal-first metatarsal angle, were used for diagnosing flexible flatfoot. Physical activity (10-m normal and fast walking, stair ascent, stair descent, and chair rising), physical function, and psychometric properties (Pediatric Outcome Data Collection Instrument and Pediatric Quality of Life Inventory) were evaluated at the baseline and 12 weeks after the intervention. Compared with the control group, the treatment group exhibited significant improvement in pain/comfort (P = .048), physical health (P = .035), stair ascent time (P = .015), upper extremity and physical function (P = .016), and transfer and basic mobility (P = .042) during the intervention period. Children with flexible flatfoot who wore customized arch support insoles for 12 weeks exhibited significantly improved pain/comfort, physical health, stair ascent time, upper extremity and physical function, and transfer and basic mobility. These variables belong to the domains of body functions and structures and activity and participation in the ICF

  17. Long-term Follow-up of a Randomized Controlled Trial Comparing Scarf to Chevron Osteotomy in Hallux Valgus Correction.

    Science.gov (United States)

    Jeuken, Ralph M; Schotanus, Martijn G M; Kort, Nanne P; Deenik, Axel; Jong, Bob; Hendrickx, Roel P M

    2016-07-01

    Hallux valgus is one of the most common foot deformities. This long-term follow-up study compared the results of 2 widely used operative treatments for hallux valgus: the scarf and chevron osteotomy. Conventional weight bearing anteroposterior (AP) radiographs of the foot were made for evaluating the intermetatarsal angle and hallux valgus angle. For clinical evaluation, the American Orthopaedic Foot & Ankle Society (AOFAS) rating system for the hallux metatarsophalangeal-interphalangeal scale was used together with physical examination of the foot. These data were compared with the results from the original study. The Short Form 36 questionnaire, the Manchester-Oxford Foot Questionnaire (MOXFQ), and a general questionnaire including a visual analog scale (VAS) pain score were used for subjective evaluation. The primary outcome measures were the radiologic recurrence of hallux valgus and reoperation rate of the same toe. Secondary outcome measures were the results from the radiographs and subjective and clinical evaluation. The response rate was 76% at the follow-up of 14 years; in the chevron group, 37 feet were included compared with 36 feet in the scarf group. Twenty-eight feet in the chevron group and 27 in the scarf group developed recurrence of hallux valgus (P = .483). One patient in the scarf group had a reoperation of the same toe compared with none in the chevron group (P = .314). Current VAS pain scores and results from the SF-36, MOXFQ, and AOFAS did not significantly differ between groups. Both techniques showed similar results after 2 years of follow-up. At 14 years of follow-up, neither technique was superior in preventing recurrence. Level II, randomized controlled trial. © The Author(s) 2016.

  18. Patient preference compared with random allocation in short-term psychodynamic supportive psychotherapy with indicated addition of pharmacotherapy for depression.

    NARCIS (Netherlands)

    Van, H.L.; Dekker, J.J.M.; Koelen, J.; Kool, S.; van Aalst, G.; Hendriksen, I.J.M.; Peen, J.; Schoevers, R.A.

    2009-01-01

    Depressed patients randomized to psychotherapy were compared with those who had been chosen for psychotherapy in a treatment algorithm, including addition of an antidepressant in case of early nonresponse. There were no differences between randomized and by-preference patients at baseline in

  19. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  20. Amide I SFG Spectral Line Width Probes the Lipid-Peptide and Peptide-Peptide Interactions at Cell Membrane In Situ and in Real Time.

    Science.gov (United States)

    Zhang, Baixiong; Tan, Junjun; Li, Chuanzhao; Zhang, Jiahui; Ye, Shuji

    2018-06-13

    The balance of lipid-peptide and peptide-peptide interactions at cell membrane is essential to a large variety of cellular processes. In this study, we have experimentally demonstrated for the first time that sum frequency generation vibrational spectroscopy can be used to probe the peptide-peptide and lipid-peptide interactions in cell membrane in situ and in real time by determination of the line width of amide I band of protein backbone. Using a "benchmark" model of α-helical WALP23, it is found that the dominated lipid-peptide interaction causes a narrow line width of the amide I band, whereas the peptide-peptide interaction can markedly broaden the line width. When WALP23 molecules insert into the lipid bilayer, a quite narrow line width of the amide I band is observed because of the lipid-peptide interaction. In contrast, when the peptide lies down on the bilayer surface, the line width of amide I band becomes very broad owing to the peptide-peptide interaction. In terms of the real-time change in the line width, the transition from peptide-peptide interaction to lipid-peptide interaction is monitored during the insertion of WALP23 into 1,2-dipalmitoyl- sn-glycero-3-phospho-(1'- rac-glycerol) (DPPG) lipid bilayer. The dephasing time of a pure α-helical WALP23 in 1-palmitoyl-2-oleoyl- sn-glycero-3-phospho-(1'- rac-glycerol) and DPPG bilayer is determined to be 2.2 and 0.64 ps, respectively. The peptide-peptide interaction can largely accelerate the dephasing time.

  1. Flanking signal and mature peptide residues influence signal peptide cleavage

    Directory of Open Access Journals (Sweden)

    Ranganathan Shoba

    2008-12-01

    Full Text Available Abstract Background Signal peptides (SPs mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I, and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i eukaryotes (Euk (ii Gram-positive (Gram+ bacteria, and (iii Gram-negative (Gram- bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs.

  2. The glucagon-like peptide-1 receptor in the ventromedial hypothalamus reduces short-term food intake in male mice by regulating nutrient sensor activity.

    Science.gov (United States)

    Burmeister, Melissa A; Brown, Jacob D; Ayala, Jennifer E; Stoffers, Doris A; Sandoval, Darleen A; Seeley, Randy J; Ayala, Julio E

    2017-12-01

    Pharmacological activation of the glucagon-like peptide-1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent on AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR). We found that pharmacological inhibition of glycolysis, and thus activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect. Furthermore, we found that Ex4-mediated anorexia in the VMH involved mTOR but not acetyl-CoA carboxylase, two downstream targets of AMPK. We support this by showing that Ex4 activates mTOR signaling in the VMH and Chinese hamster ovary (CHO)-K1 cells. In contrast to the clear acute pharmacological impact of the these receptors on food intake, knockdown of the VMH Glp1r conferred no changes in energy balance in either chow- or high-fat-diet-fed mice, and the acute anorectic and glucose tolerance effects of peripherally dosed GLP-1RA were preserved. These results show that the VMH GLP-1R regulates food intake by engaging key nutrient sensors but is dispensable for the effects of GLP-1RA on nutrient homeostasis. Copyright © 2017 the American Physiological Society.

  3. Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, X.Q. [Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China); Hong, H.S. [Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Lin, X.H. [Department of Emergency Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Chen, L.L. [Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Li, Y.H. [Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China)

    2014-07-11

    The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

  4. Circumferential fusion is dominant over posterolateral fusion in a long-term perspective: cost-utility evaluation of a randomized controlled trial in severe, chronic low back pain

    DEFF Research Database (Denmark)

    Soegaard, Rikke; Bünger, Cody E; Christiansen, Terkel

    2007-01-01

    STUDY DESIGN: Cost-utility evaluation of a randomized, controlled trial with a 4- to 8-year follow-up. OBJECTIVE: To investigate the incremental cost per quality-adjusted-life-year (QALY) when comparing circumferential fusion to posterolateral fusion in a long-term, societal perspective. SUMMARY...... OF BACKGROUND DATA: The cost-effectiveness of circumferential fusion in a long-term perspective is uncertain but nonetheless highly relevant as the ISSLS prize winner 2006 in clinical studies reported the effect of circumferential fusion superior to the effect of posterolateral fusion. A recent trial found...... no significant difference between posterolateral and circumferential fusion reporting cost-effectiveness from a 2-year viewpoint. METHODS: A total of 146 patients were randomized to posterolateral or circumferential fusion and followed 4 to 8 years after surgery. The mean age of the cohort was 46 years (range...

  5. InfAcrOnt: calculating cross-ontology term similarities using information flow by a random walk

    OpenAIRE

    Cheng, Liang; Jiang, Yue; Ju, Hong; Sun, Jie; Peng, Jiajie; Zhou, Meng; Hu, Yang

    2018-01-01

    Background Since the establishment of the first biomedical ontology Gene Ontology (GO), the number of biomedical ontology has increased dramatically. Nowadays over 300 ontologies have been built including extensively used Disease Ontology (DO) and Human Phenotype Ontology (HPO). Because of the advantage of identifying novel relationships between terms, calculating similarity between ontology terms is one of the major tasks in this research area. Though similarities between terms within each o...

  6. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  7. Dissonance and Healthy Weight Eating Disorder Prevention Programs: Long-Term Effects from a Randomized Efficacy Trial

    Science.gov (United States)

    Stice, Eric; Marti, C. Nathan; Spoor, Sonja; Presnell, Katherine; Shaw, Heather

    2008-01-01

    Adolescent girls with body dissatisfaction (N = 481, SD = 1.4) were randomized to a dissonance-based thin-ideal internalization reduction program, healthy weight control program, expressive writing control condition, or assessment-only control condition. Dissonance participants showed significantly greater decreases in thin-ideal internalization,…

  8. Remediating Organizational Functioning in Children with ADHD: Immediate and Long-Term Effects from a Randomized Controlled Trial

    Science.gov (United States)

    Abikoff, Howard; Gallagher, Richard; Wells, Karen C.; Murray, Desiree W.; Huang, Lei; Lu, Feihan; Petkova, Eva

    2013-01-01

    Objective: The study compared the efficacy of 2 behavioral interventions to ameliorate organization, time management, and planning (OTMP) difficulties in 3rd- to 5th-grade children with attention-deficit/hyperactivity disorder (ADHD). Method: In a dual-site randomized controlled trial, 158 children were assigned to organizational skills training…

  9. Home Computers and Child Outcomes: Short-Term Impacts from a Randomized Experiment in Peru. NBER Working Paper No. 18818

    Science.gov (United States)

    Beuermann, Diether W.; Cristia, Julian P.; Cruz-Aguayo, Yyannu; Cueto, Santiago; Malamud, Ofer

    2013-01-01

    This paper presents results from a randomized control trial in which approximately 1,000 OLPC XO laptops were provided for home use to children attending primary schools in Lima, Peru. The intervention increased access and use of home computers, with some substitution away from computer use outside the home. Beneficiaries were more likely to…

  10. Coffee, hunger, and peptide YY.

    Science.gov (United States)

    Greenberg, James A; Geliebter, Allan

    2012-06-01

    There is evidence from several empirical studies suggesting that coffee may help people control body weight. Our objective was to assess the effects of caffeine, caffeinated coffee, and decaffeinated coffee, both alone and in combination with 75 g of glucose, on perceived hunger and satiety and related peptides. We conducted a placebo-controlled single-blinded randomized 4-way crossover trial. Eleven healthy male volunteers (mean age, 23.5 ± 5.7 years; mean BMI, 23.6 ± 4.2 kg/m(2)) ingested 1 of 3 test beverages (caffeine in water, caffeinated coffee, or decaffeinated coffee) or placebo (water), and 60 minutes later they ingested the glucose. Eight times during each laboratory visit, hunger and satiety were assessed by visual analog scales, and blood samples were drawn to measure 3 endogenous peptides associated with hunger and satiety: ghrelin, peptide YY (PYY), and leptin. Compared to placebo, decaffeinated coffee yielded significantly lower hunger during the whole 180-minute study period and higher plasma PYY for the first 90 minutes (p hunger or PYY. Caffeinated coffee showed a pattern between that of decaffeinated coffee and caffeine in water. These findings suggest that one or more noncaffeine ingredients in coffee may have the potential to decrease body weight. Glucose ingestion did not change the effects of the beverages. Our randomized human trial showed that decaffeinated coffee can acutely decrease hunger and increase the satiety hormone PYY.

  11. A randomized lifestyle intervention with 5-year follow-up in subjects with impaired glucose tolerance: pronounced short-term impact but long-term adherence problems

    DEFF Research Database (Denmark)

    Lindahl, Bernt; Nilssön, Torbjörn K; Borch-Johnsen, Knut

    2009-01-01

    AIMS: To compare data on cardiovascular risk factor changes in lipids, insulin, proinsulin, fibrinolysis, leptin and C-reactive protein, and on diabetes incidence, in relation to changes in lifestyle. METHODS: The study was a randomized lifestyle intervention trial conducted in northern Sweden......, and reduced the risk for type 2 diabetes, but the effects persisted only as long as the new lifestyle was maintained. Increased physical activity seemed to be the behaviour that was most easy to preserve....... between 1995 and 2000, in 168 individuals with impaired glucose tolerance (IGT) and body mass index above 27 at start. The intensive intervention group (n = 83) was subjected to a 1-month residential lifestyle programme. The usual care group (n = 85) participated in a health examination ending...

  12. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1 Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Henrik H Hansen

    Full Text Available One of the major histopathological hallmarks of Alzheimer's disease (AD is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1 receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP and presenilin-1 (PS1 are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9 of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c., or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.. In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.

  13. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  14. Long-term benefit and cost-effectiveness analysis of screening for abdominal aortic aneurysms from a randomized controlled trial

    DEFF Research Database (Denmark)

    Lindholt, J S; Sørensen, J; Søgaard, Rikke

    2010-01-01

    The aim was to estimate long-term mortality benefits and cost-effectiveness of screening for abdominal aortic aneurysm (AAA) in men aged 64-73 years.......The aim was to estimate long-term mortality benefits and cost-effectiveness of screening for abdominal aortic aneurysm (AAA) in men aged 64-73 years....

  15. Predictors of Short- and Long-Term Attrition From the Parents as Agents of Change Randomized Controlled Trial for Managing Pediatric Obesity.

    Science.gov (United States)

    Spence, Nicholas D; Newton, Amanda S; Keaschuk, Rachel A; Ambler, Kathryn A; Jetha, Mary M; Holt, Nicholas L; Rosychuk, Rhonda J; Spence, John C; Sharma, Arya M; Ball, Geoff D C

    Attrition in pediatric weight management is a substantial problem. This study examined factors associated with short- and long-term attrition from a lifestyle and behavioral intervention for parents of children with overweight or obesity. Fifty-two families with children ages 6 to 12 years old and body mass index at or above the 85th percentile participated in a randomized controlled trial focused on parents, comparing parent-based cognitive behavioral therapy with parent-based psychoeducation for pediatric weight management. We examined program attrition using two clinical phases of the intervention: short-term and long-term attrition, modeled using the general linear model. Predictors included intervention type, child/parent weight status, sociodemographic factors, and health of the family system. Higher self-assessed health of the family system was associated with lower short-term attrition; higher percentage of intervention sessions attended by parents was associated with lower long-term attrition. Different variables were significant in our short- and long-term models. Attrition might best be conceptualized based on short- and long-term phases of clinical, parent-based interventions for pediatric weight management. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  16. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  17. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  18. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  19. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  20. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  1. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  2. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  3. Long-term effect of physical activity counseling on mobility limitation among older people: a randomized controlled study

    DEFF Research Database (Denmark)

    Mänty, Minna Regina; Heinonen, Ari; Leinonen, Raija

    2009-01-01

    counseling-induced benefits persist after cessation of the intervention. METHODS: In a 2-year, single-blinded, randomized controlled study, 632 sedentary participants aged 75-81 years were randomly assigned into the intervention (n = 318) or control (n = 314) group. The intervention group received a single......BACKGROUND: Physical activity counseling increases physical activity among older people, but its effectiveness on mobility, that is, maintaining the ability to move independently, is unknown. We studied the effect of physical activity counseling on mobility among older people and evaluated whether...... individualized physical activity counseling session with a supportive telephone contact every 4 months for 2 years. The outcome measures-perceived difficulty in advanced (walking 2 km) and basic (walking 0.5 km) mobility-were gathered semiannually during the intervention and the 1.5-year postintervention follow...

  4. Long-term results of a randomized trial in locally advanced rectal cancer: no benefit from adding a brachytherapy boost

    DEFF Research Database (Denmark)

    Appelt, Ane L; Vogelius, Ivan R; Pløen, John

    2014-01-01

    PURPOSE/OBJECTIVE(S): Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS: Between March 2005 and November 2008, 248...... patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic...... on stratification for tumor regression grade and resection margin status indicated the presence of response migration. CONCLUSIONS: Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical...

  5. A cardioactive peptide from the southern armyworm, Spodoptera eridania.

    Science.gov (United States)

    Furuya, K; Hackett, M; Cirelli, M A; Schegg, K M; Wang, H; Shabanowitz, J; Hunt, D F; Schooley, D A

    1999-01-01

    A cardioactive peptide was isolated from extracts of whole heads of the southern armyworm, Spodoptera eridania. This peptide has the sequence ENFAVGCTPGYQRTADGRCKPTF (Mr = 2516.8), determined from both Edman sequencing and tandem mass spectrometry in combination with off-line micropreparative capillary liquid chromatography. This peptide, termed Spoer-CAP23, has excitatory effects on a semi-isolated heart from larval Manduca sexta, causing an inotropic effect at low concentrations of peptide and chronotropic and inotropic effects at high doses. The threshold concentration for stimulatory effects of the synthetic peptide on the semi-isolated heart was about 1 nM, suggesting a physiological role as a neuropeptide.

  6. The preparation and identification of peptide imaging agent of lung cancer

    International Nuclear Information System (INIS)

    Chu Liping; Wang Yan; Wang Yueying; Liu Jinjian; Wu Hongying; Liu Jianfeng

    2010-01-01

    Objective: To screen in vivo lung cancer specific binding 7-peptide from T7 phage display random peptide library and prepare peptide imaging agent in early in early diagnosis of lung cancer. Methods: Used phage display in vivo technology to get the 7-peptide phage that can bind the lung cancer specifically, then sequenced and synthesized 7-peptide. After being labeled by 125 I, this 7-peptide was injected into mice via vein and the distribution in the mice tumor mold was observed. Results: One 7-peptide was obtained after four rounds of screening, and the peptide could bind lung cancer tissue specifically. Metabolism of this peptide in mice was fast and imaging of lung cancer was best two hours later after injection. The distribution in vivo decreased and almost disappeared after six hours. Conclusion: This 7-peptide could be used to image and diagnose of lung cancer effectively. (authors)

  7. Short-term and long-term effects of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with renal impairment: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Li, Ruifei; Wang, Rui; Li, Haixia; Sun, Sihao; Zou, Meijuan; Cheng, Gang

    2016-09-01

    To assess the short-term and long-term effects of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus patients with renal impairment, a meta-analysis of randomized clinical trials of DPP-4 inhibitor interventions in type 2 diabetes mellitus patients with renal impairment was performed. PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched through the end of March 2015. Randomized clinical trials were selected if (1) DPP-4 inhibitors were compared with a placebo or other active-comparators, (2) the treatment duration was ≥12 weeks and (3) data regarding changes in haemoglobin A1c (HbA1c ), changes in fasting plasma glucose or hypoglycaemia and other adverse events were reported. Of 790 studies, ten studies on eight randomized clinical trials were included. Compared with the control group, DPP-4 inhibitors were associated with a greater HbA1c reduction in both the short-term [mean differences (MD) = -0.45, 95% confidence intervals (-0.57, -0.33), p 1] and long-term [MD = -0.33, 95% confidence intervals (-0.63, -0.03), p = 0.03] treatments. However, the long-term greater reduction in HbA1c with DPP-4 inhibitor treatment was only significant when the control treatment comprised placebo plus stable background treatment, but not glipizide plus stable background treatment. DPP-4 inhibitors were associated with a greater fasting plasma glucose reduction [MD = -12.59, 95% confidence intervals (-22.01, -3.17), p = 0.009] over the short-term; however, this effect was not present over the long-term. Regarding the hypoglycaemia adverse events assessment, the long-term treatment data indicated there was no increased risk of hypoglycaemia compared with placebo or active-controlled anti-diabetic drugs. The present meta-analysis confirms that DPP-4 inhibitors are effective and equivalent to other agents in type 2 diabetes mellitus patients with renal impairment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015

  8. Short-term and long-term effect of diaphragm biofeedback training in gastroesophageal reflux disease: an open-label, pilot, randomized trial.

    Science.gov (United States)

    Sun, X; Shang, W; Wang, Z; Liu, X; Fang, X; Ke, M

    2016-10-01

    This study investigated the effectiveness of diaphragm biofeedback training (DBT) for patients with gastroesophageal reflux disease (GERD). A total of 40 patients with GERD treated at the Peking Union Medical College Hospital between September 2004 and July 2006 were randomized to receive DBT and rabeprazole proton pump inhibitor (PPI) or rabeprazole alone. The DBT + rabeprazole group received DBT during the 8-week initial treatment; the rabeprazole group did not. During the 6-month follow up, all patients took acid suppression according to their reflux symptoms, and the patients in the DBT + rabeprazole group were required to continue DBT. The primary outcome (used for power analysis) was the amount of acid suppression used at 6 months. Secondary outcomes were reflux symptoms, health-related quality of life (HRQL), and esophageal motility differences after the 8-week treatment compared with baseline. Acid suppression usage significantly decreased in the DBT + rabeprazole group compared with the rabeprazole group at 6 months (P reflux symptoms and GERD-HRQL were significantly improved in both groups (P gastroesophageal junction pressure (GEJP) significantly increased in the DBT + rabeprazole group (P reflux barrier, providing a non-pharmacological maintenance therapy and reducing medical costs for patients with GERD. © 2015 International Society for Diseases of the Esophagus.

  9. Cost-effectiveness of a mild compared with a standard strategy for IVF: a randomized comparison using cumulative term live birth as the primary endpoint.

    Science.gov (United States)

    Polinder, S; Heijnen, E M E W; Macklon, N S; Habbema, J D F; Fauser, B J C M; Eijkemans, M J C

    2008-02-01

    BACKGROUND Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P costs over a 12-month period (8333 versus euro10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were euro19 156 in the mild strategy and euro24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was euro185 000 per extra pregnancy leading to term live birth. CONCLUSIONS Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.

  10. Neoglycolipids for Prolonging the Effects of Peptides

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok; Mannerstedt, Karin Margareta Sophia; Wismann, Pernille

    2017-01-01

    Novel principles for optimizing the properties of peptide-based drugs are needed in order to leverage their full pharmacological potential. We present the design, synthesis, and evaluation of a library of neoglycolipidated glucagon-like peptide 1 (GLP-1) analogues, which are valuable drug...... was maintained or even improved compared to native GLP-1. This translated into pronounced in vivo efficacy in terms of both decreased acute food intake and improved glucose homeostasis in mice. Thus, we propose neoglycolipidation as a novel, general method for modulating the properties of therapeutic peptides...

  11. Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

    Science.gov (United States)

    Wali, Ramesh K; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J; Rodriguez, L M; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K

    2018-01-01

    Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. ClinicalTrials.gov NCT00828984.

  12. Randomized controlled clinical trial of long-term chemo-mechanical caries removal using PapacarieTM gel

    Directory of Open Access Journals (Sweden)

    Lara Jansiski MOTTA

    2014-07-01

    Full Text Available Objectives: Compare the effectiveness of PapacarieTM gel for the chemo-mechanical removal of carious lesions on primary teeth to conventional caries removal with a low-speed bur with regard to execution time, clinical aspects and radiographic findings. Material and Methods: A randomized controlled clinical trial with a split-mouth design was carried out. The sample was composed of 20 children aged four to seven years, in whom 40 deciduous teeth were randomly divided into two groups: chemo-mechanical caries removal with PapacarieTM and removal of carious dentin with a low-speed bur. Each child underwent both procedures and served as his/her own control. Restorations were performed with glass ionomer cement. The time required to perform the procedure was also analyzed. The patients underwent longitudinal clinical and radiographic follow-up of the restorations. Results: No statistically significant difference between groups was found regarding the time required to perform the procedures and the radiographic follow up. Statistically significant differences between groups were found in the clinical evaluation at 6 and 18 months after treatment. Conclusion: PapacarieTM is as effective as the traditional method for the removal of carious dentin on deciduous teeth, but offers the advantages of the preservation of sound dental tissue as well as the avoidance of sharp rotary instruments and local anesthesia.

  13. Long-term effects of weight reduction on the severity of psoriasis in a cohort derived from a randomized trial

    DEFF Research Database (Denmark)

    Jensen, Peter; Christensen, Robin; Zachariae, Claus

    2016-01-01

    randomized phase with an LED for 8 wk and 8 wk of normal food intake combined with 2 LED products/d, followed by a 48-wk period of weight maintenance with the latter diet. After the randomization phase, the control group received the same 8 + 8-wk LED intervention, and all patients were then followed for 48...... who were allocated to a control group or a low-energy diet (LED) group. Here we followed the participants for an additional 48-wk period. In total, 56 patients with psoriasis [mean ± SD body mass index (in kg/m(2)): 34.4 ± 5.3] underwent a 64-wk weight-loss program consisting of an initial 16-wk...... wk while on the weight-loss maintenance diet. The main outcome was the Psoriasis Area and Severity Index (PASI), and secondary outcome was the Dermatology Life Quality Index (DLQI). RESULTS: For the present study, 56 patients were eligible, 38 agreed to participate, and 32 completed. After the 16-wk...

  14. [Work-Related Medical Rehabilitation in Cancer Rehabilitation - Short-Term Results from a Cluster-Randomized Multicenter-Trial].

    Science.gov (United States)

    Wienert, Julian; Bethge, Matthias

    2018-05-25

    Rehabilitation programs that support return to work become increasingly relevant for cancer survivors. In Germany, such programs were established as work-related medical rehabilitation (WMR). The study investigated whether WMR leads to better results compared to medical rehabilitation (MR). We report effects on secondary outcomes when the rehabilitation program was completed. Clusters of participants were randomly assigned to WMR or MR. Patients of working age and an elevated risk of not returning to work were included. The grade of implementation was assessed by dose delivered and dose received. Study outcomes were assessed using scales measuring functioning and symptoms, coping with illness as well as self-reported work ability. Treatment effects were estimated using mixed linear models. From 232 planned randomized intervention groups, 165 (71%) were realized. In total, 476 patients were included. Mean age of participants was 50.7 years (SD=7.3). Most frequent primary diagnoses were malignant neoplasms of the breast. Participants in the WMR program reported significantly better outcomes regarding quality of life (SMD=0.17-0.25), fatigue (SMD=0.18-0.27), coping with illness (SMD=0.17-0.22), and self-reported work-ability (SMD=0.16) compared to participants in MR program (all p<0.05). The results indicate a positive effect in favor of WMR for cancer patients with an elevated risk of not returning to work at the end of their treatment. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Effects of modafinil on attention performance, short-term memory and executive function in university students: a randomized trial.

    Science.gov (United States)

    Fernández, Alejandro; Mascayano, Franco; Lips, Walter; Painel, Andrés; Norambuena, Jonathan; Madrid, Eva

    2015-06-30

    Modafinil is a drug developed and used for the treatment of excessive lethargy. Even though very effective for sleep disorders, it is still controversial whether modafinil can improve performance in high-order cognitive processes such as memory and executive function. This randomized, double-blind, placebo-controlled, crossover trial was designed to evaluate the effect of modafinil (compared to placebo) on the cognitive functions of healthy students. 160 volunteers were recruited and allocated randomly to modafinil or placebo group, and were assessed using the Stroop Test, BCET test and Digit span test. We found a significant difference in favor of modafinil compared to placebo in the proportion of correct answers of Stroop Test in congruent situation. A significant shorter latency of modafinil group in the incongruent situation of Stroop test was also found. No differences were found in Digit Span, or BCET tests. The study demonstrated that modafinil does not enhance the global cognitive performance of healthy non-sleep deprived students, except regarding non-demanding tasks. In particular, this drug does not seem to have positive effects on mental processes that sustain studying tasks in the college population under normal conditions. We expect these findings to demystify the use of this drug and help decision making concerning pharmacological public policies.

  16. Long-term effect of exercise therapy in patients with osteoarthritis: a randomized controlled trial comparing two different physiotherapy interventions.

    NARCIS (Netherlands)

    Pisters, M.; Veenhof, C.; Schellevis, F.; Bakker, D. de; Dekker, J.

    2011-01-01

    Purpose: To determine if behavioural graded activity (BGA) results in better long-term effectiveness (5 years after inclusion) than usual exercise therapy (UC; usual care) in patients with OA of the hip or knee. Relevance: The positive effects of exercise therapy in patients with osteoarthritis seem

  17. Dutch iliac stent trial : Long-term results in patients randomized for primary or selective stent placement

    NARCIS (Netherlands)

    Klein, W.M.; van der Graaf, Y.; Seegers, J.; Spithoven, J.H.; Buskens, E.; van Baal, J.G.; Buth, J.; Moll, F.L.; Overtoom, T.T.C.; van Sambeek, M.R.H.M.; Mali, W.P.T.M.

    Purpose: To determine long-term results of the prospective Dutch Iliac Stent Trial. Materials and Methods: The study protocol was approved by local institutional review boards. All patients gave written informed consent. Two hundred seventy-nine patients (201 men, 78 women; mean age, 58 years) with

  18. Depression treatment after myocardial infarction and long-term risk of subsequent cardiovascular events and mortality: A randomized controlled trial

    NARCIS (Netherlands)

    Zuidersma, M.; Conradi, H.J.; van Melle, J.P.; Ormel, J.; de Jonge, P.

    2013-01-01

    Objective: Evaluating the effects of implementing an antidepressant treatment strategy in depressed myocardial infarction (MI)-patients on long-term cardiovascular outcomes and all-cause mortality. Methods: MI-patients were evaluated for the presence of a diagnosis of post-MI depression at 3, 6, 9

  19. Depression treatment after myocardial infarction and long-term risk of subsequent cardiovascular events and mortality : A randomized controlled trial

    NARCIS (Netherlands)

    Zuidersma, Marij; Conradi, Henk Jan; van Melle, Joost P.; Ormel, Johan; de Jonge, Peter

    Objective: Evaluating the effects of implementing an antidepressant treatment strategy in depressed myocardial infarction (MI)-patients on long-term cardiovascular outcomes and all-cause mortality. Methods: MI-patients were evaluated for the presence of a diagnosis of post-MI depression at 3, 6, 9

  20. Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study

    Science.gov (United States)

    Ota, Tsuguhito; Kato, Ken-ichiro; Takeshita, Yumie; Misu, Hirofumi; Kaneko, Shuichi

    2018-01-01

    Objective We evaluated the effects of ursodeoxycholic acid (UDCA) on glucagon-like peptide-1 (GLP-1) secretion and glucose tolerance in patients with type 2 diabetes with chronic liver disease. Research design and methods Japanese patients with type 2 diabetes (glycated hemoglobin (HbA1c) levels ≥7.0%) and chronic liver disease were included in this study. Sixteen patients (HbA1c level, 7.2%±0.6%(55.2 mmol/mol)) were randomized to receive 900 mg UDCA for 12 weeks followed by 50 mg sitagliptin add-on therapy for 12 weeks (UDCA-first group; n=8) or 50 mg sitagliptin for 12 weeks followed by 900 mg UDCA add-on therapy for 12 weeks (sitagliptin-first group; n=8). All patients underwent a liquid high-fat meal test before and after 12 or 24 weeks of treatment. Results The baseline characteristics were similar between the UDCA-first and sitagliptin-first groups. There was a decrease in body weight (72.5±8.4 to 70.6±8.6 kg; P=0.04) and the HbA1c level (7.0%±0.3% to 6.4%±0.5%(53.0 to 46.4 mmol/mol); P=0.01) in the UDCA-first group. The HbA1c level decreased further after sitagliptin administration (6.4%±0.5% to 6.0%±0.4%(46.4 to 42.1 mmol/mol); P<0.01). Although there were no initial changes in the weight and HbA1c level in the sitagliptin-first group, the HbA1c level decreased after UDCA addition (7.1%±1.1% to 6.6%±0.9%(54.1 to 48.6 mmol/mol); P=0.04). UDCA alone increased the area under the curve0–30 for GLP-1 response (115.4±47.2 to 221.9±48.9 pmol·min/L; P<0.01), but not the glucose-dependent insulinotropic polypeptide response, in the UDCA-first group. Conclusions UDCA treatment resulted in a greater reduction in HbA1c levels, and an increased early phase GLP-1 secretion. Trial registration number NCT01337440. PMID:29607050

  1. [Plant signaling peptides. Cysteine-rich peptides].

    Science.gov (United States)

    Ostrowski, Maciej; Kowalczyk, Stanisław

    2015-01-01

    Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation.

  2. Regulatory competence and social communication in term and preterm infants at 12 months corrected age. Results from a randomized controlled trial.

    Science.gov (United States)

    Olafsen, Kåre S; Rønning, John A; Handegård, Bjørn Helge; Ulvund, Stein Erik; Dahl, Lauritz Bredrup; Kaaresen, Per Ivar

    2012-02-01

    Temperamental regulatory competence and social communication in term and preterm infants at 12 months corrected age was studied in a randomized controlled intervention trial aimed at enhancing maternal sensitive responsiveness. Surviving infants communication with the Early Social Communication Scales. Preterm intervention infants with low regulatory competence had higher responding to joint attention than preterm control infants. A sensitizing intervention may moderate the association between temperament and social communication, and thus allow an alternative functional outlet for preterm infants low in regulatory competence. The finding may have implications for conceptualizations of the role of early sensitizing interventions in promoting important developmental outcomes for premature infants. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Long-term effects of 1-year maintenance training on physical functioning and health status in patients with COPD: A randomized controlled study

    DEFF Research Database (Denmark)

    Ringbaek, Thomas; Brondum, Eva; Martinez, Gerd

    2010-01-01

    PURPOSE: To examine whether maintenance training (MT) for 1 year improved the long-term effects of a 7-week chronic obstructive pulmonary disease (COPD) rehabilitation program. METHODS: After a 7-week outpatient rehabilitation program, 96 patients with COPD were randomized to either an MT group (n...... study period. Primary effect parameters were Endurance Shuttle Walk Test (ESWT) time and health status (St. George's Respiratory Questionnaire, SGRQ). Secondary effect parameters were adherence to supervised training, dropout rates, and hospitalization. RESULTS: Compared with the control group, the MT...... or hospital admissions, compared with unsupervised daily training at home. The effect of the MT was closely related to adherence to the program....

  4. [Correlation analysis of the pre-pregnant body mass index, the gestational weight gain and umbilical cord blood C peptide].

    Science.gov (United States)

    Chen, X L; Han, Y; Zhao, X M; Liu, Y; Lü, J J

    2017-01-03

    Objective: To explore the correlation among the pre-pregnant body mass index (BMI), gestational weight gain (GWG) and umbilical cord blood C peptide, and to investigate the influence of maternal weight management on the incidence of baby long-term metabolic syndrome. Methods: During May to Aug.2015, 485 pregnant women in Zhejiang Taizhou first people's hospital and Taizhou Huangyan maternal &child care service centre were selected in random and divided into four groups according to pre-pregnant BMI: low body mass, normal body mass, over body mass and obese group, and also divided into two groups for getting gestational diabetes mellitus (GDM) or not. According to the gestational weight gain (GWG), all the cases were divided into two groups: above the Institute Of Medicine (IMO) 2009 recommendations or not. According to the outcome, the GDM group which had received weight control treatment, was divided into successful treat group or not. At last, we tested the umbilical cord blood C peptide and birth weight of each newborn and compared the difference in all subgroups. The correlation between the umbilical cord blood C peptide and birth weight were analysed. Results: (1) In the pre-pregnant BMI groups, there were significant differences of incidence of GDM ( P 0.05). (2) Newborn birth weight and the umbilical cord blood C peptide were positively correlated ( r =0.673, P newborn birth weight in all subgroups. (4) All groups showed correlations with neonatal umbilical cord blood C peptide, the GDM mostly (β=0.58), pre-pregnant BMI secondly (β: 0.36, 0.38) , and GWG weakly (β=0.17). (5) By stratification analysis, in GDM group, low body mass was negatively correlated with umbilical cord blood C peptide ( P gestational weight gain and umbilical cord blood C peptide. Suitable maternal weight control especially pre-pregnant body mass index control will lower the baby long-term metabolic syndrome incidence.

  5. Cationic antimicrobial peptides inactivate Shiga toxin-encoding bacteriophages

    Science.gov (United States)

    Del Cogliano, Manuel E.; Hollmann, Axel; Martinez, Melina; Semorile, Liliana; Ghiringhelli, Pablo D.; Maffía, Paulo C.; Bentancor, Leticia V.

    2017-12-01

    Shiga toxin (Stx) is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC) infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs) are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: 1) direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, 2) cationic properties are necessary but not sufficient for bacteriophage inactivation, and 3) inactivation by cationic peptides could be sequence (or structure) specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

  6. Cationic Antimicrobial Peptides Inactivate Shiga Toxin-Encoding Bacteriophages

    Directory of Open Access Journals (Sweden)

    Manuel E. Del Cogliano

    2017-12-01

    Full Text Available Shiga toxin (Stx is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non-alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: (1 direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, (2 cationic properties are necessary but not sufficient for bacteriophage inactivation, and (3 inactivation by cationic peptides could be sequence (or structure specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

  7. The non-random walk of stock prices: the long-term correlation between signs and sizes

    Science.gov (United States)

    La Spada, G.; Farmer, J. D.; Lillo, F.

    2008-08-01

    We investigate the random walk of prices by developing a simple model relating the properties of the signs and absolute values of individual price changes to the diffusion rate (volatility) of prices at longer time scales. We show that this benchmark model is unable to reproduce the diffusion properties of real prices. Specifically, we find that for one hour intervals this model consistently over-predicts the volatility of real price series by about 70%, and that this effect becomes stronger as the length of the intervals increases. By selectively shuffling some components of the data while preserving others we are able to show that this discrepancy is caused by a subtle but long-range non-contemporaneous correlation between the signs and sizes of individual returns. We conjecture that this is related to the long-memory of transaction signs and the need to enforce market efficiency.

  8. Guideline for Adopting the Local Reaction Assumption for Porous Absorbers in Terms of Random Incidence Absorption Coefficients

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho

    2011-01-01

    resistivity and the absorber thickness on the difference between the two surface reaction models are examined and discussed. For a porous absorber backed by a rigid surface, the assumption of local reaction always underestimates the random incidence absorption coefficient and the local reaction models give...... incidence acoustical characteristics of typical building elements made of porous materials assuming extended and local reaction. For each surface reaction, five well-established wave propagation models, the Delany-Bazley, Miki, Beranek, Allard-Champoux, and Biot model, are employed. Effects of the flow...... errors of less than 10% if the thickness exceeds 120 mm for a flow resistivity of 5000 Nm-4s. As the flow resistivity doubles, a decrease in the required thickness by 25 mm is observed to achieve the same amount of error. For an absorber backed by an air gap, the thickness ratio between the material...

  9. Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial.

    Science.gov (United States)

    Bonelli, Luigina; Puntoni, Matteo; Gatteschi, Beatrice; Massa, Paolo; Missale, Guido; Munizzi, Francesco; Turbino, Laura; Villanacci, Vincenzo; De Censi, Andrea; Bruzzi, Paolo

    2013-06-01

    Patients who undergo polypectomy are at increased risk of adenoma recurrence. The preventive potential of vitamins (A, C and E) and selenium supplementation represent an interesting opportunity for colorectal cancer prevention. To assess the efficacy of a combination of these micronutrients in reducing the incidence of recurrent adenomas in subjects on post-polypectomy endoscopic follow-up, a double-blind placebo-controlled randomized trial was started in Italy in 1988. A total of 411 patients were randomized to receive either an active compound (200 μg selenium, 30 mg zinc, 2 mg vitamin A, 180 mg vitamin C, 30 mg vitamin E) or a placebo daily for 5 years. Of them, 330 had follow-up colonoscopy (164 in the intervention and 166 in the placebo group). After a median follow-up of 4 years (range 1-15 years), 100 patients had recurrence: 38 in the intervention and 62 in the placebo arm. The 15-year cumulative incidence of recurrence was 48.3% in the intervention and 64.5% in the placebo arm (HR = 0.59; log-rank P = 0.009). A 39% reduction of the risk of recurrence was observed in the intervention compared to the placebo group (adjusted HR = 0.61; 95% CI 0.41-0.92): the risk reduction was similar for small tubular (adjusted HR = 0.61; 95% CI 0.37-0.99) and advanced adenomas (adjusted HR = 0.50; 95% CI 0.24-1.01). Our study showed a statistically significant effect of antioxidant supplementation on adenoma recurrence. Further clinical trials are needed to address the role of antioxidants in subgroups of subjects at increased risk for colorectal cancer.

  10. Artificial neural network study on organ-targeting peptides

    Science.gov (United States)

    Jung, Eunkyoung; Kim, Junhyoung; Choi, Seung-Hoon; Kim, Minkyoung; Rhee, Hokyoung; Shin, Jae-Min; Choi, Kihang; Kang, Sang-Kee; Lee, Nam Kyung; Choi, Yun-Jaie; Jung, Dong Hyun

    2010-01-01

    We report a new approach to studying organ targeting of peptides on the basis of peptide sequence information. The positive control data sets consist of organ-targeting peptide sequences identified by the peroral phage-display technique for four organs, and the negative control data are prepared from random sequences. The capacity of our models to make appropriate predictions is validated by statistical indicators including sensitivity, specificity, enrichment curve, and the area under the receiver operating characteristic (ROC) curve (the ROC score). VHSE descriptor produces statistically significant training models and the models with simple neural network architectures show slightly greater predictive power than those with complex ones. The training and test set statistics indicate that our models could discriminate between organ-targeting and random sequences. We anticipate that our models will be applicable to the selection of organ-targeting peptides for generating peptide drugs or peptidomimetics.

  11. FIVE-YEAR OUTCOMES AFTER LONG-TERM OXANDROLONE ADMINISTRATION IN SEVERELY BURNED CHILDREN: A RANDOMIZED CLINICAL TRIAL

    OpenAIRE

    Reeves, Patrick T; Herndon, David N; Tanksley, Jessica D; Jennings, Kristofer; Klein, Gordon L; Mlcak, Ronald P; Clayton, Robert P; Crites, Nancy N; Hays, Joshua P; Andersen, Clark; Lee, Jong O; Meyer, Walter; Suman, Oscar E; Finnerty, Celeste C

    2016-01-01

    Administration of oxandrolone, a non-aromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD...

  12. Effect of Sucrose Analgesia, for Repeated Painful Procedures, on Short-term Neurobehavioral Outcome of Preterm Neonates: A Randomized Controlled Trial.

    Science.gov (United States)

    Banga, Shreshtha; Datta, Vikram; Rehan, Harmeet Singh; Bhakhri, Bhanu Kiran

    2016-04-01

    Safety of oral sucrose, commonly used procedural analgesic in neonates, is questioned. To evaluate the effect of sucrose analgesia, for repeated painful procedures, on short-term neurobehavioral outcome of preterm neonates. Stable preterm neonates were randomized to receive either sucrose or distilled water orally, for every potentially painful procedure during the first 7 days after enrollment. Neurodevelopmental status at 40 weeks postconceptional age (PCA) measured using the domains of Neurobehavioral Assessment of Preterm Infants scale. A total of 93 newborns were analyzed. The baseline characteristics of the groups were comparable. No statistically significant difference was observed in the assessment at 40 weeks PCA, among the groups. Use of sucrose analgesia, for repeated painful procedures on newborns, does not lead to any significant difference in the short-term neurobehavioral outcome. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Efficacy of psychodynamic short-term psychotherapy for depressed breast cancer patients: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Zwerenz Rüdiger

    2012-12-01

    Full Text Available Abstract Background There is a lack of psychotherapeutic trials of treatments of comorbid depression in cancer patients. Our study determines the efficacy of a manualized short-term psychodynamic psychotherapy and predictors of outcome by personality and quality of the therapeutic relationship. Methods/design Eligible breast cancer patients with comorbid depression are assigned to short-term psychodynamic psychotherapy (up to 20 + 5 sessions or to treatment as usual (augmented by recommendation for counseling center and physician information. We plan to recruit a total of 180 patients (90 per arm in two centers. Assessments are conducted pretreatment, after 6 (treatment termination and 12 months (follow-up. The primary outcome measures are reduction of the depression score in the Hospital Anxiety and Depression Scale and remission of depression as assessed by means of the Structured Clinical Interview for DSM IV Disorders by independent, blinded assessors at treatment termination. Secondary outcomes refer to quality of life. Discussion We investigate the efficacy of short-term psychodynamic psychotherapy in acute care and we aim to identify predictors for acceptance and success of treatment. Trial registration ISRCTN96793588

  14. In-hospital and long-term outcomes of congestive heart failure: Predictive value of B-type and amino-terminal pro-B-type natriuretic peptides and their ratio.

    Science.gov (United States)

    Dai, Yuxiang; Yang, Jun; Takagi, Atsutoshi; Konishi, Hakuoh; Miyazaki, Tetsuro; Masuda, Hiroshi; Shimada, Kazunori; Miyauchi, Katsumi; Daida, Hiroyuki

    2017-08-01

    Relative changes in B-type natriuretic peptide (BNP) and amino terminal pro-BNP (NT-proBNP) levels may help to assess the risk of congestive heart failure (CHF). However, whether these levels at the time of admission enable the prediction of outcomes with acute exacerbation remains unknown. The current study determined the abilities of BNP, NT-proBNP and their ratio to predict in-hospital and long-term outcomes of patients with CHF. Patients who were admitted to the cardiac care unit of Juntendo University Hospital (Tokyo, Japan) with acute CHF onset were consecutively enrolled into the present observational study. Serum levels of BNP and NT-proBNP were immediately measured on admission, and other biomarkers and clinical data were also investigated. Of 195 enrolled patients, 16 (8.2%) succumbed to CHF in hospital and 124 (69.3%) reached the endpoint of mortality or readmission following a median follow-up of 14 months. Multiple linear regression analysis revealed body mass index, low density lipoprotein cholesterol, hemoglobin, estimated glomerular filtration rate and C-reactive protein as independent predictors of the NT-proBNP/BNP ratio. BNP, NT-proBNP and their ratio were significantly higher among those who succumbed to CHF than in those who remained alive in hospital (P<0.05). Logistic regression analysis indicated that the ratio was an independent predictor for in-hospital mortality and long-term outcomes. In conclusion, the ratio of NT-proBNP to BNP more effectively predicts in-hospital outcomes than either factor alone and it may also help to predict outcomes among patients with acute exacerbation of HF.

  15. Health-related quality of life of young adults with Turner syndrome following a long-term randomized controlled trial of recombinant human growth hormone

    Directory of Open Access Journals (Sweden)

    Van Vliet Guy

    2011-05-01

    Full Text Available Abstract Background There are limited long-term randomized controlled trials of growth hormone (GH supplementation to adult height and few published reports of the health-related quality of life (HRQOL following treatment. The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome (TS yielded data to examine whether GH supplementation resulted in a higher HRQOL (either due to taller stature or from the knowledge that active treatment and not placebo had been received or alternatively a lower HRQOL (due to medicalization from years of injections. Methods The original trial randomized 154 Canadian girls with TS aged 7-13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections; estrogen prescription for induction of puberty was standardized. Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up. The instrument used to study HRQOL was the SF-36, summarized into physical and mental component scales (PCS and MCS; higher scores indicate better HRQOL. Results Thirty-four of the 48 eligible participants (71% consented to participate; data were missing for one patient. Both groups (GH and no treatment had normal HRQOL at this post-treatment assessment. The GH group had a (mean ± SD PCS score of 56 ± 5; the untreated group 58 ± 4; mean score for 16-24 year old females in the general population 53.5 ± 6.9. The GH group had a mean MCS score of 52 ± 6; the untreated group 49 ± 13; mean score for 16-24 year old females in the general population 49.6 ± 9.8. Secondary analyses showed no relationship between HRQOL and height. Conclusions We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term randomized controlled trial, confirming larger observational studies. We suggest that it remains

  16. Long-term outcomes and recurrence patterns of standard versus extended pancreatectomy for pancreatic head cancer: a multicenter prospective randomized controlled study.

    Science.gov (United States)

    Jang, Jin-Young; Kang, Jae Seung; Han, Youngmin; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook; Park, Sang Jae; Han, Sung-Sik; Yoon, Dong Sup; Park, Joon Seong; Yu, Hee Chul; Kang, Koo Jeong; Kim, Sang Geol; Lee, Hongeun; Kwon, Wooil; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Sun-Whe

    2017-07-01

    Our previous randomized controlled trial revealed no difference in 2-year overall survival (OS) between extended and standard resection for pancreatic adenocarcinoma. The present study evaluated the 5-year OS and recurrence patterns according to the extent of pancreatectomy. Between 2006 and 2009, 169 consecutive patients were prospectively enrolled and randomized to standard (n = 83) or extended resection (n = 86) groups to compare 5-year OS rate, long-term recurrence patterns and factors associated with long-term survival. The surgical R0 rate was similar between the standard and extended groups (85.5 vs. 90.7%, P = 0.300). Five-year OS (18.4 vs. 14.4%, P = 0.388), 5-year disease-free survival (14.8 vs. 14.0%, P = 0.531), and overall recurrence rates (74.7 vs. 69.9%, P = 0.497) were not significantly different between the two groups, although the incidence of peritoneal seeding was higher in the extended group (25 vs. 8.1%, P = 0.014). Extended pancreatectomy does not have better short-term and long-term survival outcomes, and shows similar R0 rates and overall recurrence rates compared with standard pancreatectomy. Extended pancreatectomy does not have to be performed routinely for all cases of resectable pancreatic adenocarcinoma, especially considering its associated increased morbidity shown in our previous study. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  17. Snoezelen, structured reminiscence therapy and 10-minutes activation in long term care residents with dementia (WISDE: study protocol of a cluster randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Becker Christiane

    2010-01-01

    Full Text Available Abstract Background People with dementia are often inapproachable due to symptoms of their illness. Therefore nurses should establish relationships with dementia patients via their remaining resources and facilitate communication. In order to achieve this, different targeted non-pharmacological interventions are recommended and practiced. However there is no sufficient evidence about the efficacy of most of these interventions. A number of publications highlight the urgent need for methodological sound studies so that more robust conclusions may be drawn. Methods/Design The trial is designed as a cluster randomized controlled trial with 20 nursing homes in Saxony and Saxony-Anhalt (Germany as the units of randomization. Nursing homes will be randomly allocated into 4 study groups consisting of 5 clusters and 90 residents: snoezelen, structured reminiscence therapy, 10-minutes activation or unstructured verbal communication (control group. The purpose is to determine whether the interventions are effective to reduce apathy in long-term care residents with dementia (N = 360 as the main outcome measure. Assessments will be done at baseline, 3, 6 and 12 months after beginning of the interventions. Discussion This trial will particularly contribute to the evidence on efficacy of non-pharmacological interventions in dementia care. Trial Registration ClinicalTrials.gov NCT00653731

  18. Short-term effectiveness of web-based guided self-help for phobic outpatients: randomized controlled trial.

    Science.gov (United States)

    Kok, Robin N; van Straten, Annemieke; Beekman, Aartjan T F; Cuijpers, Pim

    2014-09-29

    Internet-based guided self-help has been successfully used in the general population, but it is unknown whether this method can be effectively used in outpatient clinics for patients waiting for face-to-face psychotherapy for phobias. The aim was to assess the clinical effectiveness of Phobias Under Control, an Internet-based intervention based on exposure therapy with weekly guidance. We conducted a randomized controlled trial, recruiting 212 outpatients scheduled to receive face-to-face psychotherapy for any type of phobia at an outpatient clinic. Participants suffering from at least 1 DSM-IV or ICD-10 classified phobia (social phobia, agoraphobia with or without panic disorder, and/or specific phobia as ascertained by a telephone interview at baseline) were randomly allocated to either a 5-week Internet-based guided self-help program based on exposure therapy with weekly student support followed by face-to-face psychotherapy (n=105) or a wait-list control group followed by face-to-face psychotherapy (n=107). Primary outcome was the Fear Questionnaire (FQ). Secondary outcomes were the Beck Anxiety Inventory (BAI) and Center of Epidemiological Studies-Depression scale (CES-D). Assessments took place by telephone at baseline (T0) and on the Internet at posttest (T1, self-assessment at 5 weeks after baseline). Missing data at T1 were imputed. At posttest, analysis of covariance on the intention-to-treat sample showed significant but small effect sizes between intervention and control groups on the FQ (d=0.35, P=.02), CES-D (d=0.34, P=.03), and a nonsignificant effect size on the BAI (d=0.28. P=.05). Although initial acceptance was good, high nonresponse was observed, with 86 of 212 participants (40.5%) lost to follow-up at T1 and only 14 of 105 (13.3%) intervention participants finishing all 5 weeks. Phobias Under Control is modestly effective in lowering phobic and depressive symptoms in a relatively short period and may be clinically beneficial when implemented in

  19. Long-Term Results of a Randomized Trial in Locally Advanced Rectal Cancer: No Benefit From Adding a Brachytherapy Boost

    International Nuclear Information System (INIS)

    Appelt, Ane L.; Vogelius, Ivan R.; Pløen, John; Rafaelsen, Søren R.; Lindebjerg, Jan; Havelund, Birgitte M.; Bentzen, Søren M.; Jakobsen, Anders

    2014-01-01

    Purpose/Objective(s): Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. Methods and Materials: Between March 2005 and November 2008, 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic complete response (pCR) at the time of surgery; secondary endpoints included overall survival (OS), progression-free survival (PFS), and freedom from locoregional failure. Results: Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. In all, 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up time of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, hazard ratio [HR] = 1.24, P=.34) and PFS (63.9% vs 52.0%, HR=1.22, P=.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, P=.06) in the standard and in the brachytherapy arms, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration. Conclusions: Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery

  20. On the short-term predictability of fully digital chaotic oscillators for pseudo-random number generation

    KAUST Repository

    Radwan, Ahmed Gomaa

    2014-06-18

    This paper presents a digital implementation of a 3rd order chaotic system using the Euler approximation. Short-term predictability is studied in relation to system precision, Euler step size and attractor size and optimal parameters for maximum performance are derived. Defective bits from the native chaotic output are neglected and the remaining pass the NIST SP. 800-22 tests without post-processing. The resulting optimized pseudorandom number generator has throughput up to 17.60 Gbits/s for a 64-bit design experimentally verified on a Xilinx Virtex 4 FPGA with logic utilization less than 1.85%.

  1. On the short-term predictability of fully digital chaotic oscillators for pseudo-random number generation

    KAUST Repository

    Radwan, Ahmed Gomaa; Mansingka, Abhinav S.; Salama, Khaled N.; Zidan, Mohammed A.

    2014-01-01

    This paper presents a digital implementation of a 3rd order chaotic system using the Euler approximation. Short-term predictability is studied in relation to system precision, Euler step size and attractor size and optimal parameters for maximum performance are derived. Defective bits from the native chaotic output are neglected and the remaining pass the NIST SP. 800-22 tests without post-processing. The resulting optimized pseudorandom number generator has throughput up to 17.60 Gbits/s for a 64-bit design experimentally verified on a Xilinx Virtex 4 FPGA with logic utilization less than 1.85%.

  2. Empowering Parents of Obese Children (EPOC): A randomized controlled trial on additional long-term weight effects of parent training.

    Science.gov (United States)

    Warschburger, Petra; Kroeller, Katja; Haerting, Johannes; Unverzagt, Susanne; van Egmond-Fröhlich, Andreas

    2016-08-01

    Although inpatient lifestyle treatment for obese children and adolescents can be highly effective in the short term, long-term results are unconvincing. One possible explanation might be that the treatment takes place far from parents' homes, limiting the possibility to incorporate the parents, who play a major role in establishing and maintaining a healthy lifestyle in childhood and adolescence. The main goal was to develop a brief behaviorally oriented parent training program that enhances 'obesity-specific' parenting skills in order to prevent relapse. We hypothesized that the inclusion of additional parent training would lead to an improved long-term weight course of obese children. Parents of obese children (n = 686; 7-13 years old) either participated in complementary cognitive-behavioral group sessions (n = 336) or received written information only (n = 350) during the inpatient stay. Children of both groups attended multidisciplinary inpatient rehabilitation. BMI-SDS as a primary outcome was evaluated at baseline, post-intervention and at 6- and 12-month follow-up. Intention-to-treat (ITT) as well as per-protocol analyses (PPA) were performed. A significant within-group decrease of 0.24 (95% CI 0.18 to 0.30) BMI-SDS points from the beginning of the inpatient stay through the first year was found, but no group difference at the one-year follow-up (mean difference 0.02; 95% CI -0.04 to 0.07). We also observed an increase in quality of life scores, intake of healthy food and exercise for both groups, without differences between groups (ITT and PPA). Thus, while the inpatient treatment proved highly effective, additional parent training did not lead to better results in long-term weight maintenance or to better psychosocial well-being compared to written psycho-educational material. Further research should focus on subgroups to answer the question of differential treatment effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Stress-relieving effects of short-term balneotherapy - a randomized controlled pilot study in healthy adults.

    Science.gov (United States)

    Matzer, Franziska; Nagele, Eva; Bahadori, Babak; Dam, Karl; Fazekas, Christian

    2014-01-01

    Stress-relieving effects of balneotherapy compared to progressive muscle relaxation (PMR) and to resting were investigated by measuring subjective relaxation and salivary cortisol. It was also examined whether participants with a high versus low stress level would have a different relaxation response. A sample of healthy volunteers was randomized to balneotherapy, PMR, or a resting control group, each intervention lasting for 25 min. Pre- and post-intervention salivary cortisol samples were collected, and participants rated their status of relaxation on a quantitative scale. In addition, 3 questionnaires were applied to detect participants' stress level and bodily complaints. 49 healthy participants were recruited (65.3% female). In a pre-post comparison, salivary cortisol decreased (F = 23.53, p balneotherapy group rated themselves as more relaxed after the intervention as compared to the other groups (F = 5.22, p balneotherapy seems to be more beneficial with regard to subjective relaxation effects and similarly beneficial with regard to a decrease in salivary cortisol. © 2014 S. Karger GmbH, Freiburg.

  4. Long-Term Effects of Goshajinkigan in Prevention of Diabetic Complications: A Randomized Open-Labeled Clinical Trial

    Directory of Open Access Journals (Sweden)

    K. Watanabe

    2014-01-01

    Full Text Available Objective. This clinical trial was designed to investigate whether goshajinkigan reduces the onset of diabetic complications or not. Materials and Methods. A total of 332 type 2 diabetic mellitus patients were registered from 9 clinical centers from March 2000 to August 2007. Patients were randomly assigned to take goshajinkigan extract powder, 2.5 grams for 3 times a day or no kampo therapy, additionally to the regular treatment. The primary endpoints were the onset of macrovascular diseases or progression of nephropathy or retinopathy. Statistical analysis was performed by the intention-to-treat method. Results. After 5 years of observation, 116 patients were submitted to analysis. Among them, no macrovascular events were observed in both groups. Although 43 participants had upstaging of retinopathy or nephropathy in total, there was no significant difference between goshajinkigan group and control group. Deterioration of ankle reflex was suppressed in goshajinkigan group. Also glycated hemoglobin, and fasting plasma glucose were decreased in the goshajinkigan group. Conclusion. Although the power of analysis was too low to demonstrate any effects of goshajinkigan on the progression of macrovascular diseases, retinopathy or nephropathy, goshajinkigan may be beneficial for diabetic neuropathy and glycemic control.

  5. The efficacy of short-term psycho-oncological interventions for women with gynaecological cancer: a randomized study.

    Science.gov (United States)

    Goerling, Ute; Jaeger, Carolin; Walz, Annette; Stickel, Anna; Mangler, Mandy; van der Meer, Elke

    2014-01-01

    We aimed to examine the efficacy of two psycho-oncological interventions in anxiety, depression, and self-perceived as well as physiological stress in inpatients with gynaecological cancer. Forty-five women were included in the trial. Thirty-five were categorized as being at high risk of anxiety and depression, and were randomized to either a single psycho-oncological therapy session or a single-session relaxation intervention. A significant decrease in anxiety [mean (t0) = 12, mean (t1) = 7.47, p = 0.001] and depression [mean (t0) = 9.71, mean (t1) = 6.35, p psycho-oncological intervention group. In the relaxation group, anxiety also significantly decreased [mean (t0) = 11.67, mean (t1) = 8.22, p = 0.003], whereas depression did not. A comparative analysis of both interventions showed a trend in favour of psycho-oncological therapy for the treatment of depression (F = 3.3, p = 0.078). However, self-reported stress (p = 0.031) and different objective stress parameters only significantly decreased in the relaxation group. Psycho-oncological interventions should represent an essential part of interdisciplinary care for gynaecological cancer patients. Both types of intervention may reduce anxiety. However, the single psycho-oncological therapy session might be slightly more effective in treating depression, whereas the single-session relaxation intervention seems to have a stronger effect on physiological stress parameters. © 2014 S. Karger AG, Basel.

  6. Hysteroscopic Endometrial Resection Versus Laparoscopic Supracervical Hysterectomy for Abnormal Uterine Bleeding: Long-term Follow-up of a Randomized Trial.

    Science.gov (United States)

    Zupi, Errico; Centini, Gabriele; Lazzeri, Lucia; Finco, Andrea; Exacoustos, Caterina; Afors, Karolina; Zullo, Fulvio; Petraglia, Felice

    2015-01-01

    To compare long-term efficacy of laparoscopic supracervical hysterectomy (LSH) and hysteroscopic endometrial ablation (HEA) in treating persistent abnormal uterine bleeding. Canadian Task Force II-2. University hospital. One hundred fifty-three women treated for abnormal uterine bleeding by LSH or HEA. Long-term follow-up assessment of reintervention rate and quality of life (QoL) using the Quality Metric's Health Survey Short Form 12. This study is the long-term follow-up of a randomized control trial conducted in 2003 comparing LSH and HEA in terms of reoperation rate and QoL. Starting from November 2010 all patients included in the first trial were invited to participate in this study and clinically evaluated through vaginal examination and transvaginal ultrasound. After a mean follow-up of 14.4 years, 29% of patients (20/71) treated with HEA underwent further surgery, whereas no patients after LSH had symptom recurrence. The reintervention rate was significantly higher in the HEA group (p abnormal uterine bleeding when compared with HEA. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  7. Effects of a dietary intervention on gastrointestinal symptoms after prostate cancer radiotherapy: Long-term results from a randomized controlled trial

    International Nuclear Information System (INIS)

    Pettersson, Anna; Nygren, Peter; Persson, Christina; Berglund, Anders; Turesson, Ingela; Johansson, Birgitta

    2014-01-01

    Background and purpose: To evaluate the long-term effects of dietary intervention on gastrointestinal symptoms after highly dose-escalated radiotherapy for localized prostate cancer, using boost with protons or high-dose-rate brachytherapy. Materials and methods: Patients were randomized to an intervention group (n = 64) advised to reduce insoluble dietary fiber and lactose intake, or to a standard care group (n = 66) advised to continue their usual diet. Gastrointestinal symptoms, other domains of health-related quality of life (HRQOL), and dietary intake were evaluated for ⩽24 months post-radiotherapy with the European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-C30 and QLQ-PR25, Gastrointestinal Side Effects Questionnaire, and Food Frequency Questionnaire. The effect of the intervention on gastrointestinal symptoms was evaluated using generalized estimating equations. Results: Dietary intervention had no obvious effect on long-term gastrointestinal symptoms or HRQOL. The intervention group markedly reduced their dietary fiber and lactose intake during radiotherapy, but adherence tended to decline over time. The vast majority of long-term gastrointestinal symptoms were reported as ‘a little’, with a noticeable difference from pre-treatment only for unintentional stool leakage, limitations on daily activities, and mucus discharge. Conclusion: Long-term gastrointestinal symptoms were predominantly mild, and dietary intervention was not superior to a usual diet in preventing these symptoms

  8. Long-term follow-up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple procedure for chronic pancreatitis.

    Science.gov (United States)

    Müller, M W; Friess, H; Martin, D J; Hinz, U; Dahmen, R; Büchler, M W

    2008-03-01

    Duodenum-preserving pancreatic head resection according to Beger and the pylorus-preserving Whipple (ppWhipple) procedure were compared in patients with chronic pancreatitis (CP) in a randomized clinical trial. Perioperative data and short-term outcome have been reported previously. The present study evaluated long-term follow-up. Forty patients were enrolled originally, 20 in each group. Long-term follow-up included mortality, morbidity, pain status, occupational rehabilitation, quality of life (QoL), and endocrine and exocrine function at median follow-up of 7 and 14 years. One patient who had a ppWhipple procedure was lost to follow-up. There were five late deaths in each group. No differences were noted in pain status and exocrine pancreatic function. Loss of appetite was significantly worse in the ppWhipple group at 14 years' follow-up, but there were no other differences in QoL parameters examined. After 14 years, diabetes mellitus was present in seven of 15 patients who had the Beger procedure and 11 of 14 patients after ppWhipple resection (P = 0.128). After long-term follow-up of up to 14 years early advantages of the Beger procedure were no longer present. 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  9. Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach.

    Science.gov (United States)

    Lammers, Laureen A; Achterbergh, Roos; van Schaik, Ron H N; Romijn, Johannes A; Mathôt, Ron A A

    2017-10-01

    Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting. Pharmacokinetic parameters of the probe drugs were analyzed using the nonlinear mixed-effects modeling software NONMEM. Short-term fasting increased systemic caffeine clearance by 17% (p = 0.04) and metoprolol clearance by 13% (p < 0.01), whereas S-warfarin clearance decreased by 19% (p < 0.01). Fasting did not affect bioavailability. The study demonstrates that short-term fasting alters CYP-mediated drug metabolism in a non-uniform pattern without affecting oral bioavailability.

  10. Radiation Therapy Did Not Induce Long-Term Changes in Rectal Mucosa: Results From the Randomized Scandinavian Prostate Cancer Group 7 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Slagsvold, Jens Erik, E-mail: Jens.Erik.Slagsvold@stolav.no [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Viset, Trond [Department of Pathology, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Wibe, Arne [Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim (Norway); Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Kaasa, Stein [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); European Palliative Care Research Center, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim (Norway); Widmark, Anders [Department of Radiation Sciences, Cancercentrum, Umeå (Sweden); Lund, Jo-Åsmund [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); European Palliative Care Research Center, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim (Norway)

    2016-07-15

    Purpose: To investigate long-term changes in the rectal mucosa after curative external beam radiation therapy in the treatment of prostate cancer. Methods and Materials: In the Scandinavian Prostate Cancer Group 7 trial, 880 men with locally advanced prostate cancer were randomized to hormonal therapy alone versus hormonal therapy plus radiation therapy to 70 Gy. A subcohort from this trial being randomized at our center (n=178) was invited to a study on late anorectal side effects during 2003-2005, approximately 5 years after treatment, including measuring health-reported quality of life and physician-assessed toxicity score by the Late Effects Normal Tissue Task Force/Subjective, Objective, Management, Analytic (LENT/SOMA) and European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group score. Sixty-seven patients had a rectal mucosa biopsy. Sixty-four biopsies were included in the final analysis, of which 33 patients were randomized to hormonal treatment and 31 to hormonal treatment plus radiation therapy. The presence of fibrosis, number of capillaries, and lymphocyte infiltration was then evaluated by light microscopy. Results: The group receiving radiation therapy had significantly higher LENT/SOMA and function/bother scale scores than the group that only received hormonal treatment, but there was no significant difference in the presence of fibrosis, ectasia, number of capillaries in the lamina propria, or lymphocyte infiltration between the groups. Conclusion: Radiation therapy to 70 Gy to the prostate does not induce long-term microscopic mucosal changes in the rectum 5 years after treatment. This is in contrast to the general assumption that structural changes, including fibrosis, seen after radiation therapy include the mucosa. We speculate that the main late effects of radiation therapy on the structure of the rectum are located in the deeper layers of the rectal wall than the mucosa.

  11. Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial.

    Science.gov (United States)

    Belgaid, Djouhar Roufeida; Khan, Zara; Zaidi, Mariam; Hobbs, Adrian

    2016-09-15

    Assessing the safety and effectiveness of left atrial appendage (LAA) (pouch found in the upper chambers of the heart) occlusion, using the Watchman device compared to long term warfarin therapy (drug that reduces clot formation), in preventing the risk of stroke in patients with atrial fibrillation (most common type of irregular heart beat). 90% of strokes in atrial fibrillation arise from clots forming in this pouch. By mechanically blocking it using the device less clots are suggested to be formed. This is an alternative to taking warfarin especially in patients who cannot take it. 50 sites in the United States enrolled 407 participants. After being randomly allocated, the device group had 269 participants and warfarin group (comparator)had 138 participants. Patients with atrial fibrillation and at high risk of stroke were randomly allocated a group after they were deemed eligible. Patients in the device group had to take warfarin and aspirin for 45days till the complete closure of the LAA. The oral anticoagulant was followed by dual antiplatelet therapy until 6months and then ASA. Patients in the warfarin group have to take it for life and were continually monitored. The study ran for 26months. The trial assessed the rate of adverse events using three endpoints: The PREVAIL trial was not designed to show superiority, but non-inferiority. It met the safety endpoint and one efficacy endpoint for the watchman device compared to long term warfarin for overall efficacy of the device. The results established that LAA occlusion is not worse than warfarin intake for the prevention of stroke more than 1week after randomization. Compared to previous trials, the safety of the device has also improved. LAA occlusion is a reasonable alternative to chronic warfarin therapy in stroke prevention for patients with atrial fibrillation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

    Science.gov (United States)

    Sánchez, Mikel; Fiz, Nicolás; Azofra, Juan; Usabiaga, Jaime; Aduriz Recalde, Enmanuel; Garcia Gutierrez, Antonio; Albillos, Javier; Gárate, Ramón; Aguirre, Jose Javier; Padilla, Sabino; Orive, Gorka; Anitua, Eduardo

    2012-08-01

    This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. Level I, randomized controlled multicenter trial. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  13. Computationally assisted screening and design of cell-interactive peptides by a cell-based assay using peptide arrays and a fuzzy neural network algorithm.

    Science.gov (United States)

    Kaga, Chiaki; Okochi, Mina; Tomita, Yasuyuki; Kato, Ryuji; Honda, Hiroyuki

    2008-03-01

    We developed a method of effective peptide screening that combines experiments and computational analysis. The method is based on the concept that screening efficiency can be enhanced from even limited data by use of a model derived from computational analysis that serves as a guide to screening and combining the model with subsequent repeated experiments. Here we focus on cell-adhesion peptides as a model application of this peptide-screening strategy. Cell-adhesion peptides were screened by use of a cell-based assay of a peptide array. Starting with the screening data obtained from a limited, random 5-mer library (643 sequences), a rule regarding structural characteristics of cell-adhesion peptides was extracted by fuzzy neural network (FNN) analysis. According to this rule, peptides with unfavored residues in certain positions that led to inefficient binding were eliminated from the random sequences. In the restricted, second random library (273 sequences), the yield of cell-adhesion peptides having an adhesion rate more than 1.5-fold to that of the basal array support was significantly high (31%) compared with the unrestricted random library (20%). In the restricted third library (50 sequences), the yield of cell-adhesion peptides increased to 84%. We conclude that a repeated cycle of experiments screening limited numbers of peptides can be assisted by the rule-extracting feature of FNN.

  14. No difference in terms of radiostereometric analysis between fixed- and mobile-bearing total knee arthroplasty: a randomized, single-blind, controlled trial.

    Science.gov (United States)

    Schotanus, M G M; Pilot, P; Kaptein, B L; Draijer, W F; Tilman, P B J; Vos, R; Kort, N P

    2017-09-01

    A concern that arises with any new prosthesis is whether it will achieve satisfactory long-term implant stability. The gold standard of assessing the quality of fixation in a new or relatively new implant is to undertake a randomized controlled trial using radiostereometric analysis. It was hypothesized that both mobile-bearing total knee arthroplasty and fixed-bearing total knee arthroplasty have comparable migration patterns at 2-year follow-up. This study investigated two types of cemented total knee arthroplasty, the mobile- or fixed-bearing variant from the same family with use of radiostereometric analysis. This prospective, patient-blinded, randomized, controlled trial was designed to investigate early migration of the tibia component after two years of follow-up with use of radiostereometric analysis. A total of 50 patients were randomized to receive a mobile- or fixed-bearing TKA from the same family. Patients were evaluated during 2-year follow-up, including radiostereometric analysis, physical and clinical examination and patient reported outcome measures (PROMs). At two-year follow-up, the mean (±SD) maximum total point motion (MTPM) in the fixed-bearing group was 0.82 (±1.16) versus 0.92 mm (±0.64) in the mobile-bearing group (p = n.s) with the largest migration seen during the first 6 weeks (0.45 ± 0.32 vs. 0.54 ± 0.30). The clinical outcome and PROMs significantly improved within each group, not between both groups. Measuring early micromotion is useful for predicting clinical loosening that can lead to revision. The results of this study demonstrate that early migration of the mobile-bearing is similar to that of the fixed-bearing component at two years and was mainly seen in the first weeks after implantation. Randomized, single-blind, controlled trial, Level I.

  15. Peptides in melanoma therapy.

    Science.gov (United States)

    Mocellin, Simone

    2012-01-01

    Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.

  16. Antimicrobial Peptides in Reptiles

    Science.gov (United States)

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  17. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

    NARCIS (Netherlands)

    Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

    2003-01-01

    textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

  18. Effect of a participatory organizational-level occupational health intervention on short-term sickness absence: a cluster randomized controlled trial.

    Science.gov (United States)

    Framke, Elisabeth; Sørensen, Ole Henning; Pedersen, Jacob; Rugulies, Reiner

    2016-05-01

    The aim of this study was to examine whether employees in pre-schools that implemented a participatory organizational-level intervention focusing on the core task at work had a lower incidence of short-term sickness absence compared to employees in the control group. The cluster randomized controlled trial (RCT) comprised 78 pre-schools that were allocated to the intervention (44 pre-schools with 1760 employees) or control (34 pre-schools with 1279 employees) group. The intervention lasted 25 months and followed a stepwise and structured approach, consisting of seminars, workshops, and workplace-directed intervention activities focusing on the core task at work. Using Poisson regression, we tested differences in incidence rates in short-term sickness absence between the intervention and control groups during a 29-months follow-up. Estimated short-term sickness absence days per person-year during follow-up were 8.68 and 9.17 in the intervention and control groups, respectively. The rate ratio (RR) for comparing incident sickness absence in the intervention to control groups during follow-up was 0.93 [95% confidence interval (95% CI) 0.86-1.00] in the crude analysis and 0.89 (95% CI 0.83-0.96) when adjusting for age, sex, job group, type and size of workplace, and workplace average level of previous short-term sickness absence. A supplementary analysis showed that the intervention also was associated with a reduced risk of long-term sickness absence with a crude RR of 0.83 (95% CI 0.69-0.99) and an adjusted RR of 0.84 (95% CI 0.69-1.01). Pre-school employees participating in an organizational-level occupational health intervention focusing on the core task at work had a lower incidence of short-term sickness absence during a 29-month follow-up compared with control group employees.

  19. Progressive Resistance and Balance Training for Falls Prevention in Long-Term Residential Aged Care: A Cluster Randomized Trial of the Sunbeam Program.

    Science.gov (United States)

    Hewitt, Jennifer; Goodall, Stephen; Clemson, Lindy; Henwood, Timothy; Refshauge, Kathryn

    2018-04-01

    Falls prevention is an international priority, and residents of long-term aged care fall approximately 3 times more often than community dwellers. There is a relative scarcity of published trials in this setting. Our objective was to undertake a randomized controlled trial to test the effect of published best practice exercise in long-term residential aged care. The trial was designed to determine if combined high level balance and moderate intensity progressive resistance training (the Sunbeam Program) is effective in reducing the rate of falls in residents of aged care facilities. A cluster randomized controlled trial of 16 residential aged care facilities and 221 participants was conducted. The broad inclusion criterion was permanent residents of aged care. Exclusions were diagnosed terminal illness, no medical clearance, permanent bed- or wheelchair-bound status, advanced Parkinson's disease, or insufficient cognition to participate in group exercise. Assessments were taken at baseline, after intervention, and at 12 months. Randomization was performed by computer-generated sequence to receive either the Sunbeam program or usual care. A cluster refers to an aged care facility. The program consisted of individually prescribed progressive resistance training plus balance exercise performed in a group setting for 50 hours over a 25-week period, followed by a maintenance period for 6 months. The primary outcome measure was the rate of falls (number of falls and days followed up). Secondary outcomes included physical performance (Short Physical Performance Battery), quality of life (36-item Short-Form Health Survey), functional mobility (University of Alabama Life Space Assessment), fear of falling (Falls Efficacy Scale International), and cognition (Addenbrooke's Cognitive Evaluation-revised). The rate of falls was reduced by 55% in the exercise group (incidence rate ratio = 0.45, 95% confidence interval 0.17-0.74); an improvement was also seen in physical

  20. Long-Term Pain Treatment Did Not Improve Sleep in Nursing Home Patients with Comorbid Dementia and Depression: A 13-Week Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Kjersti M. Blytt

    2018-02-01

    Full Text Available Objective: Previous research indicates that pain treatment may improve sleep among nursing home patients. We aimed to investigate the long-term effect of pain treatment on 24-h sleep patterns in patients with comorbid depression and dementia.Design: A 13-week, multicenter, parallel-group, double-blind, placebo-controlled randomized clinical trial conducted between August 2014 and September 2016.Setting: Long-term patients from 47 nursing homes in Norway.Participants: We included 106 patients with comorbid dementia and depression according to the Mini Mental Status Examination (MMSE and the Cornell Scale for Depression in Dementia (CSDD.Intervention: Patients who were not using analgesics were randomized to receive either paracetamol (3 g/day or placebo tablets. Those who already received pain treatment were randomized to buprenorphine transdermal system (maximum 10 μg/h/7 days or placebo transdermal patches.Measurements: Sleep was assessed continuously for 7 days by actigraphy, at baseline and in week 13. Total sleep time (TST, sleep efficiency (SE, sleep onset latency (SOL, wake after sleep onset (WASO, early morning awakening (EMA, and number of wake bouts (NoW were evaluated. In addition, daytime total sleep time (DTS was estimated. Pain was assessed with Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2.Results: The linear mixed model analyses for TST, SE, SOL, WASO, EMA, NoW and DTS showed no statistically significant differences between patients who received active pain treatment and those who received placebo. Post hoc subgroup analyses showed that there were no statistically significant differences between active treatment and placebo from baseline to week 13 in patients who were in pain (MOBID-2 ≥ 3 at baseline, or in patients who had poor sleep (defined as SE < 85% at baseline. Patients who received active buprenorphine showed an increase in TST and SE compared to those who received active paracetamol

  1. Effect of early institutionalization and foster care on long-term white matter development: a randomized clinical trial.

    Science.gov (United States)

    Bick, Johanna; Zhu, Tong; Stamoulis, Catherine; Fox, Nathan A; Zeanah, Charles; Nelson, Charles A

    2015-03-01

    Severe neglect in early life is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in the white matter pathways that underlie emotional and cognitive development are unknown. To examine associations among neglect in early life, early intervention, and the microstructural integrity of white matter pathways in middle childhood. The Bucharest Early Intervention Project is a randomized clinical trial of high-quality foster care as an intervention for institutionally reared children in Bucharest, Romania, from 2000 through the present. During infancy, children were randomly selected to remain in an institution or to be placed in foster care. Those who remained in institutions experienced neglect, including social, emotional, linguistic, and cognitive impoverishment. Developmental trajectories of these children were compared with a group of sociodemographically matched children reared in biological families at baseline and several points throughout development. At approximately 8 years of age, 69 of the original 136 children underwent structural magnetic resonance imaging scans. Four estimates of white matter integrity (fractional anisotropy [FA] and mean [MD], radial [RD], and axial [AD] diffusivity) for 48 white matter tracts throughout the brain were obtained through diffusion tensor imaging. Significant associations emerged between neglect in early life and microstructural integrity of the body of the corpus callosum (FA, β = 0.01 [P = .01]; RD, β = -0.02 [P = .005]; MD, β = -0.01 [P = .02]) and tracts involved in limbic circuitry (fornix crus [AD, β = 0.02 (P = .046)] and cingulum [RD, β = -0.01 (P = .02); MD, β = -0.01 (P = .049)]), frontostriatal circuitry (anterior [AD, β = -0.01 (P = .02)] and superior [AD, β = -0.02 (P = .02); MD, β = -0.01 (P = .03)] corona

  2. Long term effectiveness on prescribing of two multifaceted educational interventions: results of two large scale randomized cluster trials.

    Directory of Open Access Journals (Sweden)

    Nicola Magrini

    Full Text Available INTRODUCTION: Information on benefits and risks of drugs is a key element affecting doctors' prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours. OBJECTIVES: Testing the short and long-term effectiveness on general practitioners' prescribing of small groups meetings led by pharmacists. METHODS: Two cluster open randomised controlled trials (RCTs were carried out in a large scale NHS setting. Ad hoc prepared evidence based material were used considering a therapeutic area approach--TEA, with information materials on osteoporosis or prostatic hyperplasia--and a single drug oriented approach--SIDRO, with information materials on me-too drugs of 2 different classes: barnidipine or prulifloxacin. In each study, all 115 Primary Care Groups in a Northern Italy area (2.2 million inhabitants, 1737 general practitioners were randomised to educational small groups meetings, in which available evidence was provided together with drug utilization data and clinical scenarios. Main outcomes were changes in the six-months prescription of targeted drugs. Longer term results (24 and 48 months were also evaluated. RESULTS: In the TEA trial, one of the four primary outcomes showed a reduction (prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia: prescribing ratio -8.5%, p = 0.03. Another primary outcome (prescription of risedronate showed a reduction at 24 and 48 months (-7.6%, p = 0.02; and -9,8%, p = 0.03, but not at six months (-5.1%, p = 0.36. In the SIDRO trial both primary outcomes showed a statistically significant reduction (prescription of barnidipine -9.8%, p = 0.02; prescription of prulifloxacin -11.1%, p = 0.04, which persisted or increased over time. INTERPRETATION: These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting, and its potentially

  3. Randomized random walk on a random walk

    International Nuclear Information System (INIS)

    Lee, P.A.

    1983-06-01

    This paper discusses generalizations of the model introduced by Kehr and Kunter of the random walk of a particle on a one-dimensional chain which in turn has been constructed by a random walk procedure. The superimposed random walk is randomised in time according to the occurrences of a stochastic point process. The probability of finding the particle in a particular position at a certain instant is obtained explicitly in the transform domain. It is found that the asymptotic behaviour for large time of the mean-square displacement of the particle depends critically on the assumed structure of the basic random walk, giving a diffusion-like term for an asymmetric walk or a square root law if the walk is symmetric. Many results are obtained in closed form for the Poisson process case, and these agree with those given previously by Kehr and Kunter. (author)

  4. Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial

    International Nuclear Information System (INIS)

    Boer, Stephanie M. de; Nout, Remi A.; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Lutgens, Ludy C.H.W.; Steen-Banasik, Elzbieta M. van der; Mens, Jan Willem M.; Slot, Annerie; Stenfert Kroese, Marika C.; Oerlemans, Simone; Putter, Hein; Verhoeven-Adema, Karen W.; Nijman, Hans W.; Creutzberg, Carien L.

    2015-01-01

    Purpose: To evaluate the long-term health-related quality of life (HRQL) after external beam radiation therapy (EBRT) or vaginal brachytherapy (VBT) among PORTEC-2 trial patients, evaluate long-term bowel and bladder symptoms, and assess the impact of cancer on these endometrial cancer (EC) survivors. Patients and Methods: In the PORTEC-2 trial, 427 patients with stage I high–intermediate-risk EC were randomly allocated to EBRT or VBT. The 7- and 10-year HRQL questionnaires consisted of EORTC QLQ-C30; subscales for bowel and bladder symptoms; the Impact of Cancer Questionnaire; and 14 questions on comorbidities, walking aids, and incontinence pads. Analysis was done using linear mixed models for subscales and (ordinal) logistic regression with random effects for single items. A two-sided P value <.01 was considered statistically significant. Results: Longitudinal HRQL analysis showed persisting higher rates of bowel symptoms with EBRT, without significant differences in global health or any of the functioning scales. At 7 years, clinically relevant fecal leakage was reported by 10.6% in the EBRT group, versus 1.8% for VBT (P=.03), diarrhea by 8.4% versus 0.9% (P=.04), limitations due to bowel symptoms by 10.5% versus 1.8% (P=.001), and bowel urgency by 23.3% versus 6.6% (P<.001). Urinary urgency was reported by 39.3% of EBRT patients, 25.5% for VBT, P=.05. No difference in sexual activity was seen between treatment arms. Long-term impact of cancer scores was higher among the patients who had an EC recurrence or second cancer. Conclusions: More than 7 years after treatment, EBRT patients reported more bowel symptoms with impact on daily activities, and a trend for more urinary symptoms, without impact on overall quality of life or difference in cancer survivorship issues.

  5. Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Boer, Stephanie M. de, E-mail: s.m.de_boer.ONCO@lumc.nl [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands); Nout, Remi A. [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands); Jürgenliemk-Schulz, Ina M. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Jobsen, Jan J. [Department of Radiotherapy, Medisch Spectrum Twente, Enschede (Netherlands); Lutgens, Ludy C.H.W. [Department of Radiation Oncology (MAASTRO), University Medical Centre Maastricht (Netherlands); Steen-Banasik, Elzbieta M. van der [Arnhem Radiotherapy Institute (ARTI), Arnhem (Netherlands); Mens, Jan Willem M. [Department of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Slot, Annerie [Radiotherapy Institute Friesland, Leeuwarden (Netherlands); Stenfert Kroese, Marika C. [Department of Radiation Oncology, Radiotherapy Group Deventer, Deventer (Netherlands); Oerlemans, Simone [Research Department, Netherlands Comprehensive Cancer Organization, Eindhoven (Netherlands); Center of Research on Psychology in Somatic Diseases, Tilburg University, Tilburg (Netherlands); Putter, Hein [Department of Medical Statistics, Leiden University Medical Center, Leiden (Netherlands); Verhoeven-Adema, Karen W. [Comprehensive Cancer Center The Netherlands-West, Leiden (Netherlands); Nijman, Hans W. [Department of Gynecologic Oncology, University Medical Center Groningen, Groningen (Netherlands); Creutzberg, Carien L. [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2015-11-15

    Purpose: To evaluate the long-term health-related quality of life (HRQL) after external beam radiation therapy (EBRT) or vaginal brachytherapy (VBT) among PORTEC-2 trial patients, evaluate long-term bowel and bladder symptoms, and assess the impact of cancer on these endometrial cancer (EC) survivors. Patients and Methods: In the PORTEC-2 trial, 427 patients with stage I high–intermediate-risk EC were randomly allocated to EBRT or VBT. The 7- and 10-year HRQL questionnaires consisted of EORTC QLQ-C30; subscales for bowel and bladder symptoms; the Impact of Cancer Questionnaire; and 14 questions on comorbidities, walking aids, and incontinence pads. Analysis was done using linear mixed models for subscales and (ordinal) logistic regression with random effects for single items. A two-sided P value <.01 was considered statistically significant. Results: Longitudinal HRQL analysis showed persisting higher rates of bowel symptoms with EBRT, without significant differences in global health or any of the functioning scales. At 7 years, clinically relevant fecal leakage was reported by 10.6% in the EBRT group, versus 1.8% for VBT (P=.03), diarrhea by 8.4% versus 0.9% (P=.04), limitations due to bowel symptoms by 10.5% versus 1.8% (P=.001), and bowel urgency by 23.3% versus 6.6% (P<.001). Urinary urgency was reported by 39.3% of EBRT patients, 25.5% for VBT, P=.05. No difference in sexual activity was seen between treatment arms. Long-term impact of cancer scores was higher among the patients who had an EC recurrence or second cancer. Conclusions: More than 7 years after treatment, EBRT patients reported more bowel symptoms with impact on daily activities, and a trend for more urinary symptoms, without impact on overall quality of life or difference in cancer survivorship issues.

  6. Effects of selenium on short-term control of hyperthyroidism due to Graves' disease treated with methimazole: results of a randomized clinical trial.

    Science.gov (United States)

    Leo, M; Bartalena, L; Rotondo Dottore, G; Piantanida, E; Premoli, P; Ionni, I; Di Cera, M; Masiello, E; Sassi, L; Tanda, M L; Latrofa, F; Vitti, P; Marcocci, C; Marinò, M

    2017-03-01

    In spite of previous conflicting results, an adjuvant role of selenium in the treatment of Graves' disease (GD) hyperthyroidism has been proposed. To address this issue, a randomized clinical trial was carried out aimed at investigating whether selenium is beneficial on the short-term control of GD hyperthyroidism treated with methimazole (MMI). Thirty newly diagnosed hyperthyroid GD patients were randomly assigned to treatment with: (i) MMI or (ii) MMI plus selenium. Primary outcomes were: control of hyperthyroidism and clinical and biochemical manifestations of hyperthyroidism [heart rate, cholesterol, sex hormone-binding globulin (SHBG), hyperthyroidism symptoms] at 90 days. Baseline features of the two groups did not differ. Serum selenium at baseline was similar in the two groups and within the recommended range to define selenium sufficiency. Selenium increased with treatment in the MMI-selenium group and became significantly higher than in the MMI group. Serum malondialdehyde, a marker of oxidative stress, was similar in the two groups and decreased significantly with treatment, with no difference between groups. Administration of MMI was followed by a reduction of FT 3 and FT 4 , with no difference between groups. Heart rate, SHBG and symptoms of hyperthyroidism decreased, whereas total cholesterol increased in both groups with no difference between groups. Our study, carried out in a selenium-sufficient cohort of GD patients, failed to show an adjuvant role of selenium in the short-term control of hyperthyroidism. However, selenium might be beneficial in patients from selenium-deficient areas, as well as in the long-term outcome of antithyroid treatment.

  7. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

    Science.gov (United States)

    Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

    2016-05-01

    Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. Long-term results of a randomized controlled trial evaluating preoperative chemotherapy in resectable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chen ZW

    2013-06-01

    Full Text Available Zhiwei Chen,* Qingquan Luo,* Hong Jian, Zhen Zhou, Baijun Cheng, Shun Lu, Meilin LiaoShanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equallyObjective: We aimed to evaluate whether preoperative chemotherapy provides benefits in the survival and prognosis of patients with non-small cell lung cancer (NSCLC in resectable stages I to IIIA, except T1N0. Methods: In this randomized, controlled trial, 356 patients with stage I (except for T1N0, II and IIIA NSCLC were assigned to either the preoperative chemotherapy plus surgery arm (179 patients or the primary surgery arm (177 patients. Both treatments were followed by adjuvant chemotherapy. The end point of this study included overall survival (OS, progression-free survival (PFS, and survival rate associated with clinical remission. Results: Statistical survival difference was found between the preoperative chemotherapy plus surgery arm and the surgery-alone arm. However, the median survival time (MST in the preoperative chemotherapy arm was lower than that of surgery-alone arm (MST, 45.42 months vs 57.59 months (P = 0.016. When comparing the effect of preoperative chemotherapy at each stage of NSCLC, a statistical survival difference was found in stage II NSCLC but not in stage I and IIIA (MST 40.86 months vs 80.81 months (P = 0.044. However, no statistically significant difference in PFS was noticed between the two arms, except for stage I NSCLC (hazard radio [HR] = 0.87; 95% CI, 0.561−1.629; P = 0.027. The survival rate was higher for patients who had clinical remission after preoperative chemotherapy, but the differences did not reach statistical significance (MST 42.10 months vs 35.33 months (P = 0.630. Conclusion: Preoperative chemotherapy did not show benefits in OS and PFS for stage I-IIIA NSCLC patients. Keywords: NSCLC, neoadjuvent, mitomycin, cisplatin, vindesine

  9. Ketamine analgesia for inflammatory pain in neonatal rats: a factorial randomized trial examining long-term effects

    Directory of Open Access Journals (Sweden)

    Bhutta Adnan T

    2008-08-01

    Full Text Available Abstract Background Neonatal rats exposed to repetitive inflammatory pain have altered behaviors in young adulthood, partly ameliorated by Ketamine analgesia. We examined the relationships between protein expression, neuronal survival and plasticity in the neonatal rat brain, and correlated these changes with adult cognitive behavior. Methods Using Western immunoblot techniques, homogenates of cortical tissue were analyzed from neonatal rats 18–20 hours following repeated exposure to 4% formalin injections (F, N = 9, Ketamine (K, 2.5 mg/kg × 2, N = 9, Ketamine prior to formalin (KF, N = 9, or undisturbed controls (C, N = 9. Brain tissues from another cohort of rat pups (F = 11, K = 12, KF = 10, C = 15 were used for cellular staining with Fos immunohistochemistry or FluoroJade-B (FJB, followed by cell counting in eleven cortical and three hippocampal areas. Long-term cognitive testing using a delayed non-match to sample (DNMS paradigm in the 8-arm radial maze was performed in adult rats receiving the same treatments (F = 20, K = 24, KF = 21, C = 27 in the neonatal period. Results Greater cell death occurred in F vs. C, K, KF in parietal and retrosplenial areas, vs. K, KF in piriform, temporal, and occipital areas, vs. C, K in frontal and hindlimb areas. In retrosplenial cortex, less Fos expression occurred in F vs. C, KF. Cell death correlated inversely with Fos expression in piriform, retrosplenial, and occipital areas, but only in F. Cortical expression of glial fibrillary acidic protein (GFAP was elevated in F, K and KF vs. C. No significant differences occurred in Caspase-3, Bax, and Bcl-2 expression between groups, but cellular changes in cortical areas were significantly correlated with protein expression patterns. Cluster analysis of the frequencies and durations of behaviors grouped them as exploratory, learning, preparatory, consumptive, and foraging behaviors. Neonatal inflammatory pain exposure reduced exploratory behaviors in adult

  10. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  11. Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.

    Science.gov (United States)

    Tu, Min-Yu; Chen, Hsiao-Ling; Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

    2015-01-01

    Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. ClinicalTrials.gov NCT02361372.

  12. Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.

    Directory of Open Access Journals (Sweden)

    Min-Yu Tu

    Full Text Available Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg supplemented with calcium bicarbonate (CaCO3, 1,500 mg and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients.ClinicalTrials.gov NCT02361372.

  13. Predicting short-term mortality in advanced decompensated heart failure - role of the updated acute decompensated heart failure/N-terminal pro-B-type natriuretic Peptide risk score.

    Science.gov (United States)

    Scrutinio, Domenico; Ammirati, Enrico; Passantino, Andrea; Guida, Pietro; D'Angelo, Luciana; Oliva, Fabrizio; Ciccone, Marco Matteo; Iacoviello, Massimo; Dentamaro, Ilaria; Santoro, Daniela; Lagioia, Rocco; Sarzi Braga, Simona; Guzzetti, Daniela; Frigerio, Maria

    2015-01-01

    The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF). We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow χ(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models. Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.

  14. Fall Preventive Exercise With or Without Behavior Change Support for Community-Dwelling Older Adults: A Randomized Controlled Trial With Short-Term Follow-up.

    Science.gov (United States)

    Arkkukangas, Marina; Söderlund, Anne; Eriksson, Staffan; Johansson, Ann-Christin

    2017-02-27

    In Western countries, falls and fall-related injuries are a well-known threat to health in the aging population. Studies indicate that regular exercise improves strength and balance and can therefore decrease the incidence of falls and fall-related injuries. The challenge, however, is to provide exercise programs that are safe, effective, and attractive to the older population. The aim of this study was to investigate the short-term effect of a home-based exercise program with or without motivational interviewing (MI) compared with standard care on physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency. A total of 175 older adults participated in this randomized controlled study. They were randomly allocated for the Otago Exercise Program (OEP) (n = 61), OEP combined with MI (n = 58), or a control group (n = 56). The participants' mean age was 83 years. The recruitment period was from October 2012 to May 2015. Measurements of physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency were done before and 12 weeks after randomization. A total of 161 participants were followed up, and there were no significant differences between groups after a period of 12 weeks of regular exercise. Within the OEP + MI group, physical performance, fall self-efficacy, physical activity level, and handgrip strength improved significantly; likewise, improved physical performance and fall self-efficacy were found in the control group. A corresponding difference did not occur in the OEP group. Adherence to the exercise was generally high in both exercise groups. In the short-term perspective, there were no benefits of an exercise program with or without MI regarding physical performance, fall self-efficacy, activity level, handgrip strength, adherence to the exercise, and fall frequency in comparison to a control group. However, some small

  15. Efficacy of short-term high-dose statin in preventing contrast-induced nephropathy: a meta-analysis of seven randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Yongchuan Li

    Full Text Available A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathy have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of short-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of the potential benefits of statin therapy.We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statin treatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2-5 days after contrast administration and need for dialysis.Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall results based on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significant reduction in risk of CIN (RR =0.51, 95% CI 0.34-0.76, p =0.001; I(2 = 0%. The incidence of acute renal failure requiring dialysis was not significant different after the use of statin (RR = 0.33, 95% CI 0.05-2.10, p = 0.24; I(2 = 0%. The use of statin was not associated with a significant decrease in the plasma C-reactive protein level (SMD -0.64, 95% CI: -1.57 to 0.29, P = 0.18, I(2 = 97%.Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered in the context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statin based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for statin in CIN prevention.

  16. Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins.

    Science.gov (United States)

    Nahuis, M J; Kose, N; Bayram, N; van Dessel, H J H M; Braat, D D M; Hamilton, C J C M; Hompes, P G A; Bossuyt, P M; Mol, B W J; van der Veen, F; van Wely, M

    2011-07-01

    Long-term effects of laparoscopic electrocautery of the ovaries are unknown. To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins, we followed women with clomiphene-resistant polycystic ovary syndrome (PCOS) randomly allocated to one of these treatments until 8-12 years after their initial treatment. Between February 1998 and October 2001 168 women with clomiphene citrate-resistant PCOS were included in a randomized controlled trial comparing an electrocautery strategy to a strategy starting with rFSH. In 2009 these women were contacted about their reproductive outcome and menstrual cycle regularity. Analysis was by intention-to-treat. We compared time to conception resulting in live birth, subsequent pregnancies, ectopic and multiple pregnancies, menopause, as well as minimal and maximal menstrual cycle length. After 8-12 years, the cumulative proportion of women with a first child was 86% in women who had been allocated to electrocautery versus 81% in women who had been allocated to immediate rFSH [relative ratio (RR): 1.1; 95% confidence interval (CI): 0.92-1.2]. Treatment with electrocautery resulted in a significantly lower need for stimulated cycles to reach a live birth; 53% after electrocautery versus 76% after rFSH (RR: 0.69; 95% CI: 0.55-0.88).The cumulative proportion of women with a second child was 61% after electrocautery versus 46% after immediate rFSH (RR: 1.4; 95% CI: 1.00-1.9). Overall, there were 7 twins out of 134 deliveries (5%) after electrocautery versus 10 twins out of 124 deliveries (8%) in the rFSH group (RR: 0.65; 95% CI: 0.25-1.6). Fifty-four per cent of the women allocated to electrocautery had a regular menstrual cycle 8-12 years after randomization versus 36% in those allocated to rFSH (RR: 1.5; 95% CI: 0.87-2.6). In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries is as effective as ovulation induction with FSH treatment in terms of live births, but reduces

  17. A family of cell-adhering peptides homologous to fibrinogen C-termini

    International Nuclear Information System (INIS)

    Levy-Beladev, Liron; Levdansky, Lilia; Gaberman, Elena; Friedler, Assaf; Gorodetsky, Raphael

    2010-01-01

    Research highlights: → Cell-adhesive sequences homologous to fibrinogen C-termini exist in other proteins. → The extended homologous cell-adhesive C-termini peptides family is termed Haptides. → In membrane-like environment random coiled Haptides adopt a helical conformation. → Replacing positively charged residues with alanine reduces Haptides activity. -- Abstract: A family of cell-adhesive peptides homologous to sequences on different chains of fibrinogen was investigated. These homologous peptides, termed Haptides, include the peptides Cβ, preCγ, and CαE, corresponding to sequences on the C-termini of fibrinogen chains β, γ, and αE, respectively. Haptides do not affect cell survival and rate of proliferation of the normal cell types tested. The use of new sensitive assays of cell adhesion clearly demonstrated the ability of Haptides, bound to inert matrices, to mediate attachment of different matrix-dependent cell types including normal fibroblasts, endothelial, and smooth muscle cells. Here we present new active Haptides bearing homologous sequences derived from the C-termini of other proteins, such as angiopoietin 1 and 2, tenascins C and X, and microfibril-associated glycoprotein-4. The cell adhesion properties of all the Haptides were found to be associated mainly with their 11 N-terminal residues. Mutated preCγ peptides revealed that positively charged residues account for their attachment effect. These results suggest a mechanism of direct electrostatic interaction of Haptides with the cell membrane. The extended Haptides family may be applied in modulating adhesion of cells to scaffolds for tissue regeneration and for enhancement of nanoparticulate transfection into cells.

  18. Peptide Vaccines for Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Rory C. F. De Brito

    2018-05-01

    Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  19. Peptide Vaccines for Leishmaniasis.

    Science.gov (United States)

    De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

    2018-01-01

    Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  20. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  1. Traditional Chinese Herbal Patch for Short-Term Management of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Xuezong Wang

    2012-01-01

    Full Text Available Objective. To assess the short-term efficacy and safety of two kinds of Traditional Chinese herbal patches, Fufang Nanxing Zhitong Gao (FNZG and Shangshi Jietong Gao (SJG, for painful knee osteoarthritis (OA. Methods. Patients were randomly enrolled in a double-blind, placebo-controlled study to receive FNZG (n=60, SJG (n=60, or placebo patch (n=30 for 7 days. Outcome measures included visual analogue scale (VAS, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, and Traditional Chinese Medicine Syndrome Questionnaire (TCMSQ subscale. Results. Although there was no significant difference among, three groups in short-term pain management, patients receiving FNZG got significant improvement in symptom of fear of coldness as compared with placebo patch (P=0.029. The most common local adverse events of rash, itching, erythema, and slightly damaged skin were observed in 7% of participants. Conclusions. FNZG may be a useful treatment for symptom of knee OA and merits long-term study in broader populations.

  2. Long-term follow-up of a randomized trial of family foundations: effects on children's emotional, behavioral, and school adjustment.

    Science.gov (United States)

    Feinberg, Mark E; Jones, Damon E; Roettger, Michael E; Solmeyer, Anna; Hostetler, Michelle L

    2014-12-01

    This study examines long-term effects of a transition to parenthood program, Family Foundations, designed to enhance child outcomes through a strategic focus on supporting the coparenting relationship. Roughly 5 to 7 years after baseline (pregnancy), parent and teacher reports of internalizing and externalizing problems and school adjustment were collected by mail for 98 children born to couples enrolled in the randomized trial. Teachers reported significantly lower levels of internalizing problems among children in the intervention group compared with children in the control group and, consistent with prior findings at age 3, lower levels of externalizing problems for boys in the intervention group. Baseline level of observed couple negative communication moderated intervention effects for parent and teacher report of child adjustment and teacher report of school adjustment and adaptation. Effect sizes ranged from 0.40 to 0.98. Results indicate that relatively brief preventive programs for couples at the transition to parenthood have the capacity to promote long-term positive benefits for children's adjustment. Although we attended to missing data issues in several ways, high levels of attrition in this long-term follow-up study is a cause for caution.

  3. Effect of Long-Term Consumption of Lactobacillus paracasei SD1 on Reducing Mutans streptococci and Caries Risk: A Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Rawee Teanpaisan

    2015-04-01

    Full Text Available Background: A previous study revealed Lactobacillus paracasei SD1, a probiotic strain, could reduce mutans streptococci (MS. The aim of this study was to evaluate the long-term effects of L. paracasei SD1 on the colonization of MS, and whether caries lesions developed. Methods: After informed consent, 122 children were recruited and randomly assigned to the probiotic or control groups. The probiotic group received milk-powder containing L. paracasei SD1 and the control group received standard milk-powder once daily for six months. Salivary MS and lactobacilli were enumerated using differential culture at baseline and at three-month intervals for 12 months. The persistence of L. paracasei SD1 was investigated using AP-PCR for DNA-fingerprinting. Oral health was examined at baseline and at the end of the study according to WHO criteria. Results: The long-term consumption could prolong colonization of L. paracasei SD1. Significantly reduced MS counts and increased lactobacilli levels were found among children in the probiotic group. There were less caries lesions in the probiotic group at the end of the study. A significant reduction of the development of new caries lesions (4.5 times was observed in the high caries risk group but not in the low caries risk group. Conclusions: Results demonstrate that the long-term daily ingestion of the human-derived probiotic L. paracasei SD1 significantly reduces the number of MS and caries risk in the high caries group.

  4. Immediate and Short-Term Effects of Upper Thoracic Manipulation on Myoelectric Activity of Sternocleidomastoid Muscles in Young Women With Chronic Neck Pain: A Randomized Blind Clinical Trial.

    Science.gov (United States)

    Pires, Paulo Fernandes; Packer, Amanda Carine; Dibai-Filho, Almir Vieira; Rodrigues-Bigaton, Delaine

    2015-10-01

    The aim of this study was to assess the immediate and short-term effects of upper thoracic spine manipulation on pain intensity and myoelectric activity of the sternocleidomastoid muscles in young women with chronic neck pain. A randomized clinical trial was carried out involving 32 women with chronic neck pain (mean age, 24.8 ± 5.4 years) allocated to an experimental group and a placebo group. Three evaluations were carried out: baseline, immediate postintervention, and short-term postintervention (48-72 hours after intervention). Myoelectric activity of the right and left sternocleidomastoid muscles was assessed at rest and during isometric contractions for cervical flexion and elevation of the shoulder girdle. Neck pain intensity was assessed at rest using a visual analog scale. Comparisons of the data were performed using 2-way repeated-measures analysis of variance with the Bonferroni correction. The level of significance was set at P 0.40). No statistically significant differences were found for any of the variables analyzed in the intergroup comparisons at the different evaluation times (P > .05). No statistically significant differences were found in the intragroup or intergroup analyses of the experimental and placebo groups regarding myoelectric activity of the cervical muscles or the intensity of neck pain at rest in the immediate or short-term postintervention evaluations. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  5. Laparoscopic Complete Mesocolic Excision versus Open Complete Mesocolic Excision for Transverse Colon Cancer: Long-Term Survival Results of a Prospective Single Centre Non-Randomized Study.

    Science.gov (United States)

    Storli, Kristian Eeg; Eide, Geir Egil

    2016-01-01

    Laparoscopic complete mesocolic excision (CME) used in the treatment of transverse colon cancer has been questioned on the basis of the technical challenges. The aim of this study was to evaluate the medium- and long-term clinical and survival outcomes after laparoscopic and open CME for transverse colon cancer and to compare the 2 approaches. This study was a retrospective non-randomized study of patients with prospectively registered data on open and laparoscopic CME for transverse colon cancer tumour-node-metastasis stages I-III operated on between 2007 and 2014. This was a single-centre study in a community teaching hospital. A total of 56 patients with transverse colon cancer were included, excluding those with tumours in the colonic flexures. The outcome aims were 4-year time to recurrence (TTR) and cancer-specific survival (CSS). Morbidity was also measured. The 4-year TTR was 93.9% in the laparoscopic group and 91.3% in the open group (p = 0.71). The 4-year CSS was 97.0% in the laparoscopic group and 91.3% in the open group (p = 0.42). This was a prospective single-institution study with a small sample size. Results of the study suggest that the laparoscopic CME approach might be the preferred approach for transverse colon cancer, especially regarding its benefits in terms of short-term morbidity, length of stay and oncological outcome. © 2016 S. Karger AG, Basel.

  6. Evaluation of CART peptide level in rat plasma and CSF: Possible role as a biomarker in opioid addiction.

    Science.gov (United States)

    Bakhtazad, Atefeh; Vousooghi, Nasim; Garmabi, Behzad; Zarrindast, Mohammad Reza

    2016-10-01

    It has been shown previously that cocaine- and amphetamine-regulated transcript (CART) peptide has a modulatory role and homeostatic regulatory effect in motivation to and reward of the drugs of abuse specially psychostimulants. Recent data also showed that in addition to psychostimulants, CART is critically involved in the different stages of opioid addiction. Here we have evaluated the fluctuations in the level of CART peptide in plasma and CSF in different phases of opioid addiction to find out whether CART can serve as a suitable marker in opioid addiction studies. Male rats were randomly distributed in groups of control, acute low-dose (10mg/kg) morphine, acute high-dose morphine (80mg/kg), chronic escalating doses of morphine, withdrawal syndrome precipitated by administration of naloxone (1mg/kg), and abstinent after long-term drug-free maintenance of addicted animals. The level of CART peptide in CSF and plasma samples was measured by enzyme immunoassay. CART peptide concentration in the CSF and plasma was significantly elevated in acute high-dose morphine and withdrawal state animals and down-regulated in addicted rats. In abstinent group, CART peptide level was up-regulated in plasma but not in CSF samples. As the observed results are in agreement with data regarding the CART mRNA and protein expression in the brain reward pathway in opioid addiction phases, it may be suggested that evaluation of CART peptide level in CSF or plasma could be a suitable marker which reflects the rises and falls of the peptide concentration in brain in the development of opioid addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Short-term effects of instruction in home heating on indoor temperature and blood pressure in elderly people: a randomized controlled trial.

    Science.gov (United States)

    Saeki, Keigo; Obayashi, Kenji; Kurumatani, Norio

    2015-11-01

    Increased mortality from cardiovascular disease in winter is partly explained by increased blood pressure (BP) caused by cold exposure. For physicians, instruction in home heating is feasible option to reduce cold exposure, but the effectiveness remains unknown. To determine whether instruction in home heating increases indoor temperatures and decreases ambulatory BP among elderly people, we conducted an open-label, simply randomized, controlled trial in the winters. As an intervention, the participants were asked to set the heating device in the living room to start 1 h before estimated rising time with target temperature at 24°C, and to stay in the living room until 2 h after rising as long as possible. Repeatedly measured ambulatory BP, physical activity, and indoor temperatures until 4 h after rising were assessed using multilevel linear regression model with random intercept among individual. A total of 359 eligible participants (mean age ± standard deviation: 71.6 ± 6.6) were randomly allocated to the control group (n = 173) and intervention group (n = 186). Intervention significantly increased living room temperature by 2.09°C (95% confidence interval 1.28-2.90), and significantly decreased SBP and DBP by 4.43/2.33 mmHg (95% confidence interval 0.97-7.88/0.08-4.58 mmHg) after adjusting for confounders including age, sex, antihypertensive medication, household income, and physical activity. Short-term effect of instruction in home heating showed larger increase of indoor temperature than that of insulation intervention. Significant reduction of BPsuggests the effectiveness on preventing cardiovascular incidence in winter. To summarize, instruction in heating significantly decreased BP.

  8. The Aged Residential Care Healthcare Utilization Study (ARCHUS): a multidisciplinary, cluster randomized controlled trial designed to reduce acute avoidable hospitalizations from long-term care facilities.

    Science.gov (United States)

    Connolly, Martin J; Boyd, Michal; Broad, Joanna B; Kerse, Ngaire; Lumley, Thomas; Whitehead, Noeline; Foster, Susan

    2015-01-01

    To assess effect of a complex, multidisciplinary intervention aimed at reducing avoidable acute hospitalization of residents of residential aged care (RAC) facilities. Cluster randomized controlled trial. RAC facilities with higher than expected hospitalizations in Auckland, New Zealand, were recruited and randomized to intervention or control. A total of 1998 residents of 18 intervention facilities and 18 control facilities. A facility-based complex intervention of 9 months' duration. The intervention comprised gerontology nurse specialist (GNS)-led staff education, facility bench-marking, GNS resident review, and multidisciplinary (geriatrician, primary-care physician, pharmacist, GNS, and facility nurse) discussion of residents selected using standard criteria. Primary end point was avoidable hospitalizations. Secondary end points were all acute admissions, mortality, and acute bed-days. Follow-up was for a total of 14 months. The intervention did not affect main study end points: number of acute avoidable hospital admissions (RR 1.07; 95% CI 0.85-1.36; P = .59) or mortality (RR 1.11; 95% CI 0.76-1.61; P = .62). This multidisciplinary intervention, packaging selected case review, and staff education had no overall impact on acute hospital admissions or mortality. This may have considerable implications for resourcing in the acute and RAC sectors in the face of population aging. Australian and New Zealand Clinical Trials Registry (ACTRN12611000187943). Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  9. Long Term Follow-Up after a Randomized Integrated Educational and Psychosocial Intervention in Patient-Partner Dyads Affected by Heart Failure.

    Directory of Open Access Journals (Sweden)

    Maria Liljeroos

    Full Text Available To date, contemporary heart failure care remains patient-focused, but awareness of the partners' and families' situation is increasing. Randomized studies have mainly evaluated the short-term effects of dyadic interventions. Therefore, the aim of this study was to determine the 24-month effects of an intervention with psych-educational support in dyads of heart failure patients and their partners.This study used a randomized study design and 155 patient-partner dyads were enrolled. The intervention included a nurse-led program of three sessions addressing psychoeducational support.The intervention did not have any effect on health, depressive symptoms or perceived control among the patient-partner dyads after 24 months. Furthermore, time to first event did not differ significantly between the intervention group and the control patients.This study may be regarded as a first step in trying to understand dyads' need for supportive care. Individualized and more targeted interventions seem necessary to achieve a higher impact on dyad outcomes.ClinicalTrials.gov NCT02398799.

  10. Long-term impact of pre-operative physical rehabilitation protocol on the 6-min walk test of patients with adolescent idiopathic scoliosis: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    V.L. dos Santos Alves

    2015-05-01

    Full Text Available Background: Monitored physical activities in patients with adolescent idiopathic scoliosis (AIS have been shown to improve physical performance, endurance and cardiopulmonary function and may be assessed by the 6-min walk test (6MWT. We aimed to evaluate the long-term results of the 6MWT after a rehabilitation protocol employed before surgical correction for AIS. Methods: This prospective randomized clinical trial studied the impact of a 4-month pre-operative physical rehabilitation protocol on post-operative cardiopulmonary function and physical endurance, by using the 6MWT, in patients with AIS submitted to surgical correction, comparing them to matched controls without physical rehabilitation. Studied variables were heart and respiratory rate, systolic and diastolic blood pressure, peripheral blood oxygen saturation, Borg score, and distance walked. Patients were assessed at baseline, after 4 months of rehabilitation, and 3, 6 and 12 months post-operatively. Results: A total of 50 patients with AIS were included in the study and allocated blindly, by simple randomization, into either one of the two groups, with 25 patients each: study group (pre-operative physical rehabilitation and control group. The physical rehabilitation protocol promoted significant progressive improvement in heart and respiratory rate, peripheral blood oxygen saturation, distance walked, and level of effort assessed by the Borg scale after surgery. Conclusions: Post-surgical recovery, evaluated by 6MWT, was significantly better in patients who underwent a 4-month pre-operative physical rehabilitation protocol. Keywords: Scoliosis, Exercise, Exercise movement techniques, Exercise therapy, Exercise test

  11. Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Jill M Hamilton-Reeves

    Full Text Available We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA, hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer.We conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n=42 or placebo (n=44 for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant.These data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA.ClinicalTrials.gov NCT00255125.

  12. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

    Science.gov (United States)

    Gratwohl, A; Pfirrmann, M; Zander, A; Kröger, N; Beelen, D; Novotny, J; Nerl, C; Scheid, C; Spiekermann, K; Mayer, J; Sayer, H G; Falge, C; Bunjes, D; Döhner, H; Ganser, A; Schmidt-Wolf, I; Schwerdtfeger, R; Baurmann, H; Kuse, R; Schmitz, N; Wehmeier, A; Fischer, J Th; Ho, A D; Wilhelm, M; Goebeler, M-E; Lindemann, H W; Bormann, M; Hertenstein, B; Schlimok, G; Baerlocher, G M; Aul, C; Pfreundschuh, M; Fabian, M; Staib, P; Edinger, M; Schatz, M; Fauser, A; Arnold, R; Kindler, T; Wulf, G; Rosselet, A; Hellmann, A; Schäfer, E; Prümmer, O; Schenk, M; Hasford, J; Heimpel, H; Hossfeld, D K; Kolb, H-J; Büsche, G; Haferlach, C; Schnittger, S; Müller, M C; Reiter, A; Berger, U; Saußele, S; Hochhaus, A; Hehlmann, R

    2016-03-01

    Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (Ptreatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.

  13. Long-term effectiveness of mailed nicotine replacement therapy: study protocol of a randomized controlled trial 5-year follow-up.

    Science.gov (United States)

    Kushnir, Vladyslav; Selby, Peter; Zawertailo, Laurie; Tyndale, Rachel F; Leatherdale, Scott T; Cunningham, John A

    2017-07-18

    Our group recently completed a randomized controlled trial, evaluating the efficacy of providing 5 weeks of free nicotine replacement therapy (NRT; in the form of the nicotine patch) by expedited postal mail without behavioral assistance to regular adult smokers interested in receiving it. The findings revealed that mailed provision of nicotine patches resulted in more than a doubling of quit rates at a six-month follow-up compared to a no intervention control group. While this trial provided evidence for the effectiveness of mailed nicotine patches in promoting cessation, the findings speak only to the short term effectiveness of this approach. As relapse to smoking is known to occur beyond the 6 month period, it is important to evaluate whether the net benefit of NRT in naturalistic settings can be maintained long-term. The present study aims to perform a 5-year follow-up survey of participants in the original trial to evaluate the long-term effectiveness of mailed NRT. Trained interviewers will contact participants in the randomized controlled trial 5 years post-enrollment. A total of 924 participants will be eligible to be contacted. Interviewers will first assess participants' smoking status and their level of nicotine dependence. Participants reporting not currently smoking will be asked whether they have smoked tobacco, even a puff, in the last 30 days (primary outcome measure: 30-day point prevalence abstinence), past 6 months (secondary outcome measure: prolonged 6-month abstinence), and since the 8-week follow-up survey (secondary outcome measure: > 4 year continuous abstinence). Interviewers will be blind to experimental condition at the time the primary outcome measure will be assessed. It is hypothesized that participants who received nicotine patches at baseline will display significantly higher quit rates at the 5-year follow-up as compared to participants who did not receive nicotine patches at baseline. If the study finds that the mailed

  14. Comparative short-term effects of two thoracic spinal manipulation techniques in subjects with chronic mechanical neck pain: a randomized controlled trial.

    Science.gov (United States)

    Casanova-Méndez, Amaloha; Oliva-Pascual-Vaca, Angel; Rodriguez-Blanco, Cleofás; Heredia-Rizo, Alberto Marcos; Gogorza-Arroitaonandia, Kristobal; Almazán-Campos, Ginés

    2014-08-01

    Spinal Manipulation (SM) has been purported to decrease pain and improve function in subjects with non-specific neck pain. Previous research has investigated which individuals with non-specific neck pain will be more likely to benefit from SM. It has not yet been proven whether or not the effectiveness of thoracic SM depends on the specific technique being used. This double-blind randomized trial has compared the short-term effects of two thoracic SM maneuvers in subjects with chronic non-specific neck pain. Sixty participants were distributed randomly into two groups. One group received the Dog technique (n = 30), with the subject in supine position, and the other group underwent the Toggle-Recoil technique (n = 30), with the participant lying prone, T4 being the targeted area in both cases. Evaluations were made of self-reported neck pain (Visual Analogue Scale); neck mobility (Cervical Range of Motion); and pressure pain threshold at the cervical and thoracic levels (C4 and T4 spinous process) and over the site described for location of tense bands of the upper trapezius muscle. Measurements were taken before intervention, immediately afterward, and 20 min later. Both maneuvers improved neck mobility and mechanosensitivity and reduced pain in the short term. No major or clinical differences were found between the groups. In the between-groups comparison slightly better results were observed in the Toggle-Recoil group only for cervical extension (p = 0.009), right lateral flexion (p = 0.004) and left rotation (p < 0.05). Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study.

    Science.gov (United States)

    Lundholm, Kent; Gunnebo, Lena; Körner, Ulla; Iresjö, Britt-Marie; Engström, Cecilia; Hyltander, Anders; Smedh, Ulrika; Bosaeus, Ingvar

    2010-04-15

    The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 microg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 microg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism. (c) 2010 American Cancer Society.

  16. Long-term symptom control of gastro-oesophageal reflux disease 12 years after laparoscopic Nissen or 180° anterior partial fundoplication in a randomized clinical trial.

    Science.gov (United States)

    Roks, D J; Broeders, J A; Baigrie, R J

    2017-06-01

    Laparoscopic 180° anterior fundoplication has been shown to achieve similar reflux control to Nissen fundoplication, with fewer side-effects, up to 5 years. However, there is a paucity of long-term follow-up data on this technique and antireflux surgery in general. This study reports 12-year outcomes of a double-blind RCT comparing laparoscopic Nissen versus 180° laparoscopic anterior fundoplication for gastro-oesophageal reflux disease (GORD). Patients with proven GORD were randomized to laparoscopic Nissen or 180° anterior fundoplication. The 12-year outcome measures included reflux control, dysphagia, gas-related symptoms and patient satisfaction. Measures included scores on a visual analogue scale, a validated Dakkak score for dysphagia and Visick scores. Of the initial 163 patients randomized (Nissen 84, anterior 79), 90 (55·2 per cent) completed 12-year follow-up (Nissen 52, anterior 38). There were no differences in heartburn, dysphagia, gas-related symptoms, patient satisfaction or surgical reintervention rate. Use of acid-suppressing drugs was less common after Nissen than after 180° anterior fundoplication: four of 52 (8 per cent) and 11 of 38 (29 per cent) respectively (P = 0·008). The proportion of patients with absent or only mild symptoms was slightly higher after Nissen fundoplication: 45 of 50 (90 per cent) versus 28 of 38 (74 per cent) (P = 0·044). The two surgical procedures provided similar control of heartburn and post-fundoplication symptoms, with similar patient satisfaction and reoperation rates on long-term follow-up. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  17. Long-term remineralizing effect of MI Paste Plus on regression of early caries after orthodontic fixed appliance treatment: a 12-month follow-up randomized controlled trial.

    Science.gov (United States)

    Beerens, Moniek W; Ten Cate, Jacob M; Buijs, Mark J; van der Veen, Monique H

    2017-11-17

    Casein-phosphopeptide-amorphous-calcium-fluoride-phosphate (CPP-ACFP) can remineralize subsurface lesions. It is the active ingredient of MI-Paste-Plus® (MPP). The long-term remineralization efficacy is unknown. To evaluate the long-term effect of MPP versus a placebo paste on remineralization of enamel after fixed orthodontic treatment over a 12-month period. This trial was designed as a prospective, double-blinded, placebo-controlled RCT. Patients with subsurface lesions scheduled for removal of the appliance were included. They applied either MPP or control paste once a day at bedtime for 12 months, complementary to normal oral hygiene. Changes in enamel lesions (primary outcome) were fluorescence loss and lesion area determined by quantitative light-induced fluorescence (QLF). Secondary outcomes were Microbial composition, by conventional plating, and acidogenicity of plaque, by capillary ion analysis (CIA), and lesion changes scored visually on clinical photographs. Participants [age = 15.5 years (SD = 1.6)] were randomly assigned to either the MPP or the control group, as determined by a computer-randomization scheme, created and locked before the start of the study. Participants received neutral-coloured concealed toothpaste tubes marked A or B. The patients and the observers were blinded with respect to the content of tube A or B. A total of 51 patients were analysed; MPP (n = 25) versus control group (n = 26); data loss (n = 14). There was no significant difference between the groups over time for all the used outcome measures. There was a significant improvement in enamel lesions (fluorescence loss) over time in both groups (P orthodontic fixed appliance treatment did not improve these lesions during the 1 year following debonding. This trial is registered at the medical ethical committee of the VU Medical Centre in Amsterdam (NL.199226.029.07). © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society

  18. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: long-term symptomatic follow-up of a prospective randomized controlled trial.

    Science.gov (United States)

    Kummerow Broman, Kristy; Phillips, Sharon E; Faqih, Adil; Kaiser, Joan; Pierce, Richard A; Poulose, Benjamin K; Richards, William O; Sharp, Kenneth W; Holzman, Michael D

    2018-04-01

    Our prior randomized controlled trial of Heller myotomy alone versus Heller plus Dor fundoplication for achalasia from 2000 to 2004 demonstrated comparable postoperative resolution of dysphagia but less gastroesophageal reflux after Heller plus Dor. Patient-reported outcomes are needed to determine whether the findings are sustained long-term. We actively engaged participants from the prior randomized cohort, making up to six contact attempts per person using telephone, mail, and electronic messaging. We collected patient-reported measures of dysphagia and gastroesophageal reflux using the Dysphagia Score and the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) instrument. Patient-reported re-interventions for dysphagia were verified by obtaining longitudinal medical records. Among living participants, 27/41 (66%) were contacted and all completed the follow-up study at a mean of 11.8 years postoperatively. Median Dysphagia Scores and GERD-HRQL scores were slightly worse for Heller than Heller plus Dor but were not statistically different (6 vs 3, p = 0.08 for dysphagia, 15 vs 13, p = 0.25 for reflux). Five patients in the Heller group and 6 in Heller plus Dor underwent re-intervention for dysphagia with most occurring more than five years postoperatively. One patient in each group underwent redo Heller myotomy and subsequent esophagectomy. Nearly all patients (96%) would undergo operation again. Long-term patient-reported outcomes after Heller alone and Heller plus Dor for achalasia are comparable, providing support for either procedure.

  19. Short and long term effects of left and bilateral repetitive transcranial magnetic stimulation in schizophrenia patients with auditory verbal hallucinations: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Leonie Bais

    Full Text Available BACKGROUND: Repetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation. METHODS: In this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS, the Auditory Hallucinations Rating Scale (AHRS, and the Positive and Negative Affect Scale (PANAS. We included follow-up measures with the AHRS and PANAS at four weeks and three months. RESULTS: The interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups. CONCLUSION: We did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider

  20. Efficacy and short-term safety of topical Dwarf Elder (Sambucus ebulus L.) versus diclofenac for knee osteoarthritis: A randomized, double-blind, active-controlled trial.

    Science.gov (United States)

    Jabbari, Marzie; Hashempur, Mohammad Hashem; Razavi, Seyede Zahra Emami; Shahraki, Hadi Raeisi; Kamalinejad, Mohammad; Emtiazy, Majid

    2016-07-21

    Sambucus ebulus L. (S. ebulus) has had long-standing application in Traditional Persian Medicine for joint pain and for a variety of bone and joint disorders. According to traditional use of S. ebulus and its relevant pharmacologic properties, this study was designed to evaluate the efficacy and short-term safety of topical use of S. ebulus in patients with knee osteoarthritis (OA). Seventy nine patients with knee OA were randomly enrolled in 2 parallel arms of a pilot randomized, double-blind, active-controlled clinical trial. The patients were treated by topical S. ebulus gel or 1% diclofenac gel, three times a day, as much as a fingertip unit for 4 weeks. Patients were assessed prior to enrollment and, then, 2 and 4 weeks subsequent to the intervention, in terms of scores of visual analogue scale (VAS) for self-grading of their knee joint pain, and according to 3 different domains of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Any observed adverse effects were also scrutinized. The mean values of WOMAC pain score, total WOMAC score and VAS score for pain of the S. ebulus group were significantly lower compared with the diclofenac group (P=0.004, P=0.04, and P<0.001, respectively). In addition, no serious adverse effect was reported. This pilot study showed that topical treatment with S. ebulus gel can be recommended for alleviating symptoms of patients with knee OA. However, longer trials involving larger samples size, are needed for achieving a comprehensive understanding about the efficacy and safety of S. ebulus in knee OA. Copyright © 2016. Published by Elsevier Ireland Ltd.

  1. Effects of Long-Term Acupuncture Treatment on Resting-State Brain Activity in Migraine Patients: A Randomized Controlled Trial on Active Acupoints and Inactive Acupoints

    Science.gov (United States)

    Zhao, Ling; Liu, Jixin; Zhang, Fuwen; Dong, Xilin; Peng, Yulin; Qin, Wei; Wu, Fumei; Li, Ying; Yuan, Kai; von Deneen, Karen M.; Gong, Qiyong; Tang, Zili; Liang, Fanrong

    2014-01-01

    Background Acupuncture has been commonly used for preventing migraine attacks and relieving pain during a migraine, although there is limited knowledge on the physiological mechanism behind this method. The objectives of this study were to compare the differences in brain activities evoked by active acupoints and inactive acupoints and to investigate the possible correlation between clinical variables and brain responses. Methods and Results A randomized controlled trial and resting-state functional magnetic resonance imaging (fMRI) were conducted. A total of eighty migraineurs without aura were enrolled to receive either active acupoint acupuncture or inactive acupoint acupuncture treatment for 8 weeks, and twenty patients in each group were randomly selected for the fMRI scan at the end of baseline and at the end of treatment. The neuroimaging data indicated that long-term active acupoint therapy elicited a more extensive and remarkable cerebral response compared with acupuncture at inactive acupoints. Most of the regions were involved in the pain matrix, lateral pain system, medial pain system, default mode network, and cognitive components of pain processing. Correlation analysis showed that the decrease in the visual analogue scale (VAS) was significantly related to the increased average Regional homogeneity (ReHo) values in the anterior cingulate cortex in the two groups. Moreover, the decrease in the VAS was associated with increased average ReHo values in the insula which could be detected in the active acupoint group. Conclusions Long-term active acupoint therapy and inactive acupoint therapy have different brain activities. We postulate that acupuncture at the active acupoint might have the potential effect of regulating some disease-affected key regions and the pain circuitry for migraine, and promote establishing psychophysical pain homeostasis. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-13003635 PMID:24915066

  2. Short-term effects of a rights-based sexuality education curriculum for high-school students: a cluster-randomized trial.

    Science.gov (United States)

    Constantine, Norman A; Jerman, Petra; Berglas, Nancy F; Angulo-Olaiz, Francisca; Chou, Chih-Ping; Rohrbach, Louise A

    2015-03-26

    An emerging model for sexuality education is the rights-based approach, which unifies discussions of sexuality, gender norms, and sexual rights to promote the healthy sexual development of adolescents. A rigorous evaluation of a rights-based intervention for a broad population of adolescents in the U.S. has not previously been published. This paper evaluates the immediate effects of the Sexuality Education Initiative (SEI) on hypothesized psychosocial determinants of sexual behavior. A cluster-randomized trial was conducted with ninth-grade students at 10 high schools in Los Angeles. Classrooms at each school were randomized to receive either a rights-based curriculum or basic sex education (control) curriculum. Surveys were completed by 1,750 students (N = 934 intervention, N = 816 control) at pretest and immediate posttest. Multilevel regression models examined the short-term effects of the intervention on nine psychosocial outcomes, which were hypothesized to be mediators of students' sexual behaviors. Compared with students who received the control curriculum, students receiving the rights-based curriculum demonstrated significantly greater knowledge about sexual health and sexual health services, more positive attitudes about sexual relationship rights, greater communication about sex and relationships with parents, and greater self-efficacy to manage risky situations at immediate posttest. There were no significant differences between the two groups for two outcomes, communication with sexual partners and intentions to use condoms. Participation in the rights-based classroom curriculum resulted in positive, statistically significant effects on seven of nine psychosocial outcomes, relative to a basic sex education curriculum. Longer-term effects on students' sexual behaviors will be tested in subsequent analyses. ClinicalTrials.gov NCT02009046.

  3. Short-term combined effects of thoracic spine thrust manipulation and cervical spine nonthrust manipulation in individuals with mechanical neck pain: a randomized clinical trial.

    Science.gov (United States)

    Masaracchio, Michael; Cleland, Joshua A; Hellman, Madeleine; Hagins, Marshall

    2013-03-01

    Randomized clinical trial. To investigate the short-term effects of thoracic spine thrust manipulation combined with cervical spine nonthrust manipulation (experimental group) versus cervical spine nonthrust manipulation alone (comparison group) in individuals with mechanical neck pain. Research has demonstrated improved outcomes with both nonthrust manipulation directed at the cervical spine and thrust manipulation directed at the thoracic spine in patients with neck pain. Previous studies have not determined if thoracic spine thrust manipulation may increase benefits beyond those provided by cervical nonthrust manipulation alone. Sixty-four participants with mechanical neck pain were randomized into 1 of 2 groups, an experimental or comparison group. Both groups received 2 treatment sessions of cervical spine nonthrust manipulation and a home exercise program consisting of active range-of-motion exercises, and the experimental group received additional thoracic spine thrust manipulations. Outcome measures were collected at baseline and at a 1-week follow-up, and included the numeric pain rating scale, the Neck Disability Index, and the global rating of change. Participants in the experimental group demonstrated significantly greater improvements (Ppain rating scale and Neck Disability Index at the 1-week follow-up compared to those in the comparison group. In addition, 31 of 33 (94%) participants in the experimental group, compared to 11 of 31 participants (35%) in the comparison group, indicated a global rating of change score of +4 or higher at the 1-week follow-up, with an associated number needed to treat of 2. Individuals with neck pain who received a combination of thoracic spine thrust manipulation and cervical spine nonthrust manipulation plus exercise demonstrated better overall short-term outcomes on the numeric pain rating scale, the Neck Disability Index, and the global rating of change.

  4. Peptides as Therapeutic Agents for Dengue Virus.

    Science.gov (United States)

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

  5. Pain relief effect of breast feeding and music therapy during heel lance for healthy-term neonates in China: a randomized controlled trial.

    Science.gov (United States)

    Zhu, Jiemin; Hong-Gu, He; Zhou, Xiuzhu; Wei, Haixia; Gao, Yaru; Ye, Benlan; Liu, Zuguo; Chan, Sally Wai-Chi

    2015-03-01

    to test the effectiveness of breast feeding (BF), music therapy (MT), and combined breast feeding and music therapy (BF+MT) on pain relief in healthy-term neonates during heel lance. randomised controlled trial. in the postpartum unit of one university-affiliated hospital in China from August 2013 to February 2014. among 288 healthy-term neonates recruited, 250 completed the trial. All neonates were undergoing heel lancing for metabolic screening, were breast fed, and had not been fed for the previous 30 minutes. all participants were randomly assigned into four groups - BF, MT, BF+MT, and no intervention - with 72 neonates in each group. Neonates in the control group received routine care. Neonates in the other three intervention groups received corresponding interventions five minutes before the heel lancing and throughout the whole procedure. Neonatal Infant Pain Scale (NIPS), latency to first cry, and duration of first crying. mean changes in NIPS scores from baseline over time was dependent on the interventions given. Neonates in the BF and combined BF+MT groups had significantly longer latency to first cry, shorter duration of first crying, and lower pain mean score during and one minute after heel lance, compared to the other two groups. No significant difference in pain response was found between BF groups with or without music therapy. The MT group did not achieve a significantly reduced pain response in all outcome measures. BF could significantly reduce pain response in healthy-term neonates during heel lance. MT did not enhance the effect of pain relief of BF. healthy-term neonates should be breast fed to alleviate pain during heel lance. There is no need for the additional input of classical music on breast feeding in clinic to relieve procedural pain. Nurses should encourage breast feeding to relieve pain during heel lance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Peptide stabilized amphotericin B nanodisks

    Science.gov (United States)

    Tufteland, Megan; Pesavento, Joseph B.; Bermingham, Rachelle L.; Hoeprich, Paul D.; Ryan, Robert O.

    2007-01-01

    Nanometer scale apolipoprotein A-I stabilized phospholipid disk complexes (nanodisks; ND) have been formulated with the polyene antibiotic amphotericin B (AMB). The present studies were designed to evaluate if a peptide can substitute for the function of the apolipoprotein component of ND with respect to particle formation and stability. An 18-residue synthetic amphipathic α-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2), solubilized vesicles comprised of egg phosphatidylcholine (egg PC), dipentadecanoyl PC or dimyristoylphosphatidylcholine (DMPC) at rates greater than or equal to solubilization rates observed with human apolipoprotein A-I (apoA-I; 243 amino acids). Characterization studies revealed that interaction with DMPC induced a near doubling of 4F tryptophan fluorescence emission quantum yield (excitation 280 nm) and a ~7 nm blue shift in emission wavelength maximum. Inclusion of AMB in the vesicle substrate resulted in formation of 4F AMB-ND. Spectra of AMB containing particles revealed the antibiotic is a highly effective quencher of 4F tryptophan fluorescence emission, giving rise to a Ksv = 7.7 × 104. Negative stain electron microscopy revealed that AMB-ND prepared with 4F possessed a disk shaped morphology similar to ND prepared without AMB or prepared with apoA-I. In yeast and pathogenic fungi growth inhibition assays, 4F AMB-ND was as effective as apoA-I AMB-ND. The data indicate that AMB-ND generated using an amphipathic peptide in lieu of apoA-I form a discrete population of particles that possess potent biological activity. Given their intrinsic versatility, peptides may be preferred for scale up and clinical application of AMB-ND. PMID:17293004

  7. Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency

    Directory of Open Access Journals (Sweden)

    Brissette Suzanne

    2011-07-01

    Full Text Available Abstract Background Substitution with opioid-agonists (e.g., methadone has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST. In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes. Methods Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI, conducted in Vancouver and Montreal (Canada between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8 was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group. Results A total of 232 (92% and 237 (94% participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by

  8. Long-term Results of the UCSF-LBNL Randomized Trial: Charged Particle With Helium Ion Versus Iodine-125 Plaque Therapy for Choroidal and Ciliary Body Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Kavita K., E-mail: Kavita.mishra@ucsf.edu [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Quivey, Jeanne M.; Daftari, Inder K. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Weinberg, Vivian [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Cole, Tia B. [The Tumori Foundation, San Francisco, California (United States); Patel, Kishan [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Castro, Joseph R.; Phillips, Theodore L. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Char, Devron H. [The Tumori Foundation, San Francisco, California (United States); Department of Ophthalmology, University of California-San Francisco, San Francisco, California (United States); Department of Ophthalmology, Stanford University, Palo Alto, California (United States)

    2015-06-01

    Purpose: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. Methods and Materials: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. Results: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). Conclusions: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.

  9. Referral from primary care to a physical activity programme: establishing long-term adherence? A randomized controlled trial. Rationale and study design

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    Puig-Ribera Anna

    2009-01-01

    Full Text Available Abstract Background Declining physical activity is associated with a rising burden of global disease. There is little evidence about effective ways to increase adherence to physical activity. Therefore, interventions are needed that produce sustained increases in adherence to physical activity and are cost-effective. The purpose is to assess the effectiveness of a primary care physical activity intervention in increasing adherence to physical activity in the general population seen in primary care. Method and design Randomized controlled trial with systematic random sampling. A total of 424 subjects of both sexes will participate; all will be over the age of 18 with a low level of physical activity (according to the International Physical Activity Questionnaire, IPAQ, self-employed and from 9 Primary Healthcare Centres (PHC. They will volunteer to participate in a physical activity programme during 3 months (24 sessions; 2 sessions a week, 60 minutes per session. Participants from each PHC will be randomly allocated to an intervention (IG and control group (CG. The following parameters will be assessed pre and post intervention in both groups: (1 health-related quality of life (SF-12, (2 physical activity stage of change (Prochaska's stages of change, (3 level of physical activity (IPAQ-short version, (4 change in perception of health (vignettes from the Cooperative World Organization of National Colleges, Academies, and Academic Associations of Family Physicians, COOP/WONCA, (5 level of social support for the physical activity practice (Social Support for Physical Activity Scale, SSPAS, and (6 control based on analysis (HDL, LDL and glycated haemoglobin. Participants' frequency of visits to the PHC will be registered over the six months before and after the programme. There will be a follow up in a face to face interview three, six and twelve months after the programme, with the reduced version of IPAQ, SF-12, SSPAS, and Prochaska's stages

  10. Effects of neurofeedback on the short-term memory and continuous attention of patients with moderate traumatic brain injury: A preliminary randomized controlled clinical trial

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    Reza Rostami

    2017-10-01

    Full Text Available Purpose: There are some studies which showed neurofeedback therapy (NFT can be effective in clients with traumatic brain injury (TBI history. However, randomized controlled clinical trials are still needed for evaluation of this treatment as a standard option. This preliminary study was aimed to evaluate the effect of NFT on continuous attention (CA and short-term memory (STM of clients with moderate TBI using a randomized controlled clinical trial (RCT. Methods: In this preliminary RCT, seventeen eligible patients with moderate TBI were randomly allocated in two intervention and control groups. All the patients were evaluated for CA and STM using the visual continuous attention test and Wechsler memory scale-4th edition (WMS-IV test, respectively, both at the time of inclusion to the project and four weeks later. The intervention group participated in 20 sessions of NFT through the first four weeks. Conversely, the control group participated in the same NF sessions from the fifth week to eighth week of the project. Results: Eight subjects in the intervention group and five subjects in the control group completed the study. The mean and standard deviation of participants' age were (26.75 ± 15.16 years and (27.60 ± 8.17 years in experiment and control groups, respectively. All of the subjects were male. No significant improvement was observed in any variables of the visual continuous attention test and WMS-IV test between two groups (p ≥ 0.05. Conclusion: Based on our literature review, it seems that our study is the only study performed on the effect of NFT on TBI patients with control group. NFT has no effect on CA and STM in patients with moderate TBI. More RCTs with large sample sizes, more sessions of treatment, longer time of follow-up and different protocols are recommended. Keywords: Neurofeedback, Brain injuries, Attention, Short-term memory

  11. Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study

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    Nannini C

    2013-01-01

    Full Text Available Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital, Prato, ItalyBackground: The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly.Methods: In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up.Results: During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1% patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1 and 21 received etanercept 50 mg weekly (group 2. At the end of follow-up, 19 of 22 (86.3% subjects in group 1 and 19 of 21 (90.4% in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group

  12. Dinosaur peptides suggest mechanisms of protein survival.

    Science.gov (United States)

    San Antonio, James D; Schweitzer, Mary H; Jensen, Shane T; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P R O

    2011-01-01

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  13. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    Energy Technology Data Exchange (ETDEWEB)

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O. (Harvard-Med); (IIT); (NCSU); (UPENN); (Manchester); (Orthovita)

    2011-09-16

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  14. Evaluation of dermal wound healing activity of synthetic peptide SVVYGLR.

    Science.gov (United States)

    Uchinaka, Ayako; Kawaguchi, Naomasa; Ban, Tsuyoshi; Hamada, Yoshinosuke; Mori, Seiji; Maeno, Yoshitaka; Sawa, Yoshiki; Nagata, Kohzo; Yamamoto, Hirofumi

    2017-09-23

    SVVYGLR peptide (SV peptide) is a 7-amino-acid sequence with angiogenic properties that is derived from osteopontin in the extracellular matrix and promotes differentiation of fibroblasts to myofibroblast-like cells and the production of collagen type Ⅲ by cardiac fibroblasts. However, the effects of SV peptide on dermal cells and tissue are unknown. In this study, we evaluated the effects of this peptide in a rat model of dermal wound healing. The synthetic SV peptide was added to dermal fibroblasts or keratinocytes, and their cellular motility was evaluated. In an in vivo wound healing exeriment, male rats aged 8 weeks were randomly assigned to the SV peptide treatment, non-treated control, or phosphate-buffered saline (PBS) groups. Wound healing was assessed by its repair rate and histological features. Scratch assay and cell migration assays using the Chemotaxicell method showed that SV peptide significantly promoted the cell migration in both fibroblasts and keratinocytes. In contrast the proliferation potency of these cells was not affected by SV peptide. In the rat model, wound healing progressed faster in the SV peptide-treated group than in the control and PBS groups. The histopathological analyses showed that the SV peptide treatment stimulated the migration of fibroblasts to the wound area and increased the number of myofibroblasts. Immunohistochemical staining showed a marked increase of von Willebland factor-positive neomicrovessels in the SV peptide-treated group. In conclusion, SV peptide has a beneficial function to promote wound healing by stimulating granulation via stimulating angiogenesis, cell migration, and the myofibroblastic differentiation of fibroblasts. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Long-term maintenance therapy for vulvar lichen sclerosus: the results of a randomized study comparing topical vitamin E with an emollient.

    Science.gov (United States)

    Virgili, Annarosa; Minghetti, Sara; Borghi, Alessandro; Corazza, Monica

    2013-04-01

    The chronic and relapsing nature of vulvar lichen sclerosus (VLS) represents a challenge for its long-term management after an effective treatment with topical corticosteroids. To compare the effect of topical vitamin E with that of an emollient in reducing the risk of VLS relapse over a 52-week maintenance treatment. 156 patients with VLS were enrolled in a 12-week active treatment phase on topical 0.1% mometasone furoate ointment once daily. Those who achieved disease remission entered a 52-week maintenance phase in which patients were randomized to apply either an emollient or topical vitamin E once daily. 80 patients entered the maintenance phase. At 52 weeks, for the vitamin E maintenance group, the cumulative crude relapse rate was 27.8% and the cumulative modified crude relapse rate was 55.6%. For the emollient maintenance group, the cumulative crude relapse rate was 22.7% and the cumulative modified crude relapse rate was 50.0%. The median time to relapse was 20 weeks for the vitamin E group and 18.7 weeks for the emollient group. Once VLS has been stabilized with topical corticosteroids, long-term treatment with both vitamin E and emollients may be considered in maintain LS remission.

  16. Long-Term Use of Probiotics Lactobacillus and Bifidobacterium Has a Prophylactic Effect on the Occurrence and Severity of Pouchitis: A Randomized Prospective Study

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    Banasiewicz Tomasz

    2014-01-01

    Full Text Available Aim. The aim of the study was to assess the impact of the long-term use of the composite probiotics in patients after restorative proctocolectomy. Method. Forty-three patients (20 females and 23 males, aged 21 to 68 years after restorative proctocolectomy were included in the study. After randomization patients were divided into placebo group and treatment group with oral intake of probiotic containing Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidus. Patients were investigated during initial visit and during final visit after 9 months. All patients were subjected to standard clinical and endoscopic examination with microscopic study of the specimens. Concentrations of calprotectin and pyruvate kinase isoenzyme M2-PK were determined in all cases. Results. The average severity of pouchitis and the number of patients with pouchitis significantly decrease after 9 months of the probiotic taking. The concentrations of calprotectin and pyruvate kinase isoenzyme M2-PK significantly decreased after the therapy. Conclusions. Nine months of the probiotic treatment (Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidus reduced the number of patients with pouchitis, decreased the PDAI score, and also decreased the fecal pyruvate kinase and calprotectin. The long-term probiotics use is safe and well accepted and can be an effective method of the pouchitis prevention.

  17. Comparison between the effects of trigger point mesotherapy versus acupuncture points mesotherapy in the treatment of chronic low back pain: a short term randomized controlled trial.

    Science.gov (United States)

    Di Cesare, Annalisa; Giombini, Arrigo; Di Cesare, Mariachiara; Ripani, Maurizio; Vulpiani, Maria Chiara; Saraceni, Vincenzo Maria

    2011-02-01

    The goal of this study was to compare the effects of trigger point (TRP) mesotherapy and acupuncture (ACP) mesotherapy in the treatment of patients with chronic low back pain. Short term randomized controlled trial. 62 subjects with chronic low back pain were recruited at outpatients Physical Medicine and Rehabilitation Clinic at the University of Rome "La Sapienza" in the period between July 2006 and May 2008. Study subjects were assigned to receive 4 weeks treatments with either trigger point mesotherapy (TRP mesotherapy, n=29) or acupoints mesotherapy (ACP mesotherapy, n=33). Pain intensity with a pain visual analogic scale (VAS) and verbal rating scale (VRS) and pain disability with McGill Pain Questionnaire Short Form (SFMPQ), Roland Morris Disability Questionnaire (RMQ) and Oswestry Low Back Pain Disability Questionaire (ODQ). ACP mesotherapy shows a more effective results in VRS and VAS measures in the follow-up (p(VRS)=mesotherapy group. Our results suggest that the response to ACP mesotherapy may be greater than the response to TRP mesotherapy in the short term follow-up. This technique could be nevertheless a viable option as an adjunct treatment in an overall treatment planning of CLBP. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Effect of inpatient rehabilitation on quality of life and exercise capacity in long-term lung transplant survivors: a prospective, randomized study.

    Science.gov (United States)

    Ihle, Franziska; Neurohr, Claus; Huppmann, Patrick; Zimmermann, Gregor; Leuchte, Hanno; Baumgartner, Rainer; Kenn, Klaus; Sczepanski, Bernd; Hatz, Rudolf; Czerner, Stephan; Frey, Lorenz; Ueberfuhr, Peter; Bittmann, Iris; Behr, Jürgen

    2011-08-01

    The purpose of this study was to examine the effect of an inpatient rehabilitation program on health-related quality of life (HRQOL) and exercise capacity (EC) in long-term (>1 year after lung transplantation) survivors (LTSs) in comparison to a control group (CG). Sixty LTSs, 4.5 ± 3.2 years after lung transplantation (LTx), were randomly assigned to two equally sized groups that were stratified for gender and underlying disease. Thirty LTSs (age 49 ± 13 years, 13 male and 17 females, 19 double LTxs, 7 BOS Stage ≥ 1) attended an inpatient rehabilitation program (intervention group, IG) for 23 ± 5 days. The CG (age 50 ± 12 years, 13 males and 17 females, 20 double LTxs, 2 BOS Stage ≥ 1) received medical standard therapy (physiotherapy). Patients were evaluated by cardiopulmonary exercise testing, 6-minute walk test (6MWT), SF-36, SGRQ and the Quality of Life Profile for Chronic Diseases questionnaire before and after (18 ± 3 days) the program. The groups were statistically indistinguishable in terms of clinical data. Each treatment group significantly improved their sub-maximal EC (6MWT: IG, 493 ± 90 m vs 538 ± 90 m, p exercise tolerance in LTS. Our study results did not demonstrate a significant benefit of an inpatient over an outpatient exercise program. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. COMPLIANCE TO LONG-TERM TREATMENT OF CARDIOLOGIC PATIENTS WITH MILD TO MODERATE DEPRESSION: INEFFECTIVENESS OF ANTIDEPRESSIVE THERAPY WITH PIRLINDOL IN RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    E. V. Strokova

    2015-12-01

    Full Text Available Aim. To evaluate the influence of antidepressant therapy with pirlindol on compliance to the long-term treatment and quality of life in patients with cardiovascular diseases and mild to moderate depression. Material and methods. 61 patients with cardiovascular diseases and mild to moderate depression (according to Beck depression scale were randomized into two groups. Patients of intervention group received pirlindol, while patients of control group did not receive this drug. Compliance to cardiovascular and antidepressant treatment were estimated in 3 and 6 months. Adverse reactions and patients self-assessment of their well-being and global satisfaction in treatmen were also registered.  Results. 24 (75%, 2 (6% and 0 patients of intervention group continue pirlindol treatment in 1, 3 and 6 months, respectively. In 3 months of observation patients of intervention group took drugs for cardiovascular diseases more often than these in control group (81% vs 72%, respectively , р<0.05, they also less frequently showed adverse reactions (56% vs 72%, respectively ,p=0.01 and more often — improvement of their well-being (65% vs 50%, respectively , р=0.03. Compliance to cardiovascular therapy did not differ significantly in patients of both groups by the end the study.  Conclusion. Antidepressant therapy with pirlindol did not influence compliance to long-term cardiovascular treatment in patients with cardiovascular diseases and mild to moderate depression, apparently because of low compliance to pirlindol therapy.

  20. Predicting Long-Term Cognitive Outcome Following Breast Cancer with Pre-Treatment Resting State fMRI and Random Forest Machine Learning.

    Science.gov (United States)

    Kesler, Shelli R; Rao, Arvind; Blayney, Douglas W; Oakley-Girvan, Ingrid A; Karuturi, Meghan; Palesh, Oxana

    2017-01-01

    We aimed to determine if resting state functional magnetic resonance imaging (fMRI) acquired at pre-treatment baseline could accurately predict breast cancer-related cognitive impairment at long-term follow-up. We evaluated 31 patients with breast cancer (age 34-65) prior to any treatment, post-chemotherapy and 1 year later. Cognitive testing scores were normalized based on data obtained from 43 healthy female controls and then used to categorize patients as impaired or not based on longitudinal changes. We measured clustering coefficient, a measure of local connectivity, by applying graph theory to baseline resting state fMRI and entered these metrics along with relevant patient-related and medical variables into random forest classification. Incidence of cognitive impairment at 1 year follow-up was 55% and was predicted by classification algorithms with up to 100% accuracy ( p breast cancer. This information could inform treatment decision making by identifying patients at highest risk for long-term cognitive impairment.

  1. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Gao X

    2015-11-01

    Full Text Available Xiang Gao,1,2,* Xiaohong Zhang,3,* Jinlin Song,1,2 Xiao Xu,4 Anxiu Xu,1 Mengke Wang,4 Bingwu Xie,1 Enyi Huang,2 Feng Deng,1,2 Shicheng Wei2–41College of Stomatology, 2Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, 3Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, 4Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China*These authors contributed equally to this workAbstract: The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than

  2. Focused Screening of ECM-Selective Adhesion Peptides on Cellulose-Bound Peptide Microarrays.

    Science.gov (United States)

    Kanie, Kei; Kondo, Yuto; Owaki, Junki; Ikeda, Yurika; Narita, Yuji; Kato, Ryuji; Honda, Hiroyuki

    2016-11-19

    The coating of surfaces with bio-functional proteins is a promising strategy for the creation of highly biocompatible medical implants. Bio-functional proteins from the extracellular matrix (ECM) provide effective surface functions for controlling cellular behavior. We have previously screened bio-functional tripeptides for feasibility of mass production with the aim of identifying those that are medically useful, such as cell-selective peptides. In this work, we focused on the screening of tripeptides that selectively accumulate collagen type IV (Col IV), an ECM protein that accelerates the re-endothelialization of medical implants. A SPOT peptide microarray was selected for screening owing to its unique cellulose membrane platform, which can mimic fibrous scaffolds used in regenerative medicine. However, since the library size on the SPOT microarray was limited, physicochemical clustering was used to provide broader variation than that of random peptide selection. Using the custom focused microarray of 500 selected peptides, we assayed the relative binding rates of tripeptides to Col IV, collagen type I (Col I), and albumin. We discovered a cluster of Col IV-selective adhesion peptides that exhibit bio-safety with endothelial cells. The results from this study can be used to improve the screening of regeneration-enhancing peptides.

  3. Focused Screening of ECM-Selective Adhesion Peptides on Cellulose-Bound Peptide Microarrays

    Directory of Open Access Journals (Sweden)

    Kei Kanie

    2016-11-01

    Full Text Available The coating of surfaces with bio-functional proteins is a promising strategy for the creation of highly biocompatible medical implants. Bio-functional proteins from the extracellular matrix (ECM provide effective surface functions for controlling cellular behavior. We have previously screened bio-functional tripeptides for feasibility of mass production with the aim of identifying those that are medically useful, such as cell-selective peptides. In this work, we focused on the screening of tripeptides that selectively accumulate collagen type IV (Col IV, an ECM protein that accelerates the re-endothelialization of medical implants. A SPOT peptide microarray was selected for screening owing to its unique cellulose membrane platform, which can mimic fibrous scaffolds used in regenerative medicine. However, since the library size on the SPOT microarray was limited, physicochemical clustering was used to provide broader variation than that of random peptide selection. Using the custom focused microarray of 500 selected peptides, we assayed the relative binding rates of tripeptides to Col IV, collagen type I (Col I, and albumin. We discovered a cluster of Col IV-selective adhesion peptides that exhibit bio-safety with endothelial cells. The results from this study can be used to improve the screening of regeneration-enhancing peptides.

  4. Screening and Identification of Peptides Specifically Targeted to Gastric Cancer Cells from a Phage Display Peptide Library

    Science.gov (United States)

    Sahin, Deniz; Taflan, Sevket Onur; Yartas, Gizem; Ashktorab, Hassan; Smoot, Duane T

    2018-04-25

    Background: Gastric cancer is the second most common cancer among the malign cancer types. Inefficiency of traditional techniques both in diagnosis and therapy of the disease makes the development of alternative and novel techniques indispensable. As an alternative to traditional methods, tumor specific targeting small peptides can be used to increase the efficiency of the treatment and reduce the side effects related to traditional techniques. The aim of this study is screening and identification of individual peptides specifically targeted to human gastric cancer cells using a phage-displayed peptide library and designing specific peptide sequences by using experimentally-eluted peptide sequences. Methods: Here, MKN-45 human gastric cancer cells and HFE-145 human normal gastric epithelial cells were used as the target and control cells, respectively. 5 rounds of biopannning with a phage display 12-peptide library were applied following subtraction biopanning with HFE-145 control cells. The selected phage clones were established by enzyme-linked immunosorbent assay and immunofluorescence detection. We first obtain random phage clones after five biopanning rounds, determine the binding levels of each individual clone. Then, we analyze the frequencies of each amino acid in best binding clones to determine positively overexpressed amino acids for designing novel peptide sequences. Results: DE532 (VETSQYFRGTLS) phage clone was screened positive, showing specific binding on MKN-45 gastric cancer cells. DE-Obs (HNDLFPSWYHNY) peptide, which was designed by using amino acid frequencies of experimentally selected peptides in the 5th round of biopanning, showed specific binding in MKN-45 cells. Conclusion: Selection and characterization of individual clones may give us specifically binding peptides, but more importantly, data extracted from eluted phage clones may be used to design theoretical peptides with better binding properties than even experimentally selected ones

  5. Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

    Science.gov (United States)

    Lambertini, Matteo; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Scotto, Tiziana; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Levaggi, Alessia; Poggio, Francesca; Giraudi, Sara; Bighin, Claudia; Vecchio, Carlo; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia

    Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0

  6. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...

  7. Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up of a randomized clinical trial.

    Science.gov (United States)

    Rutqvist, L E; Pettersson, D; Johansson, H

    1993-02-01

    This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference-corresponding to a 16% reduction of deaths-in favor of the irradiated patients which, however, was not statistically significant (p = 0.09). Among those 169 patients who developed locoregional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p < 0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients.

  8. Effect of Lifestyle Modification Using a Smartphone Application on Obesity With Obstructive Sleep Apnea: A Short-term, Randomized Controlled Study.

    Science.gov (United States)

    Cho, Sung-Woo; Wee, Jee Hye; Yoo, Sooyoung; Heo, Eunyoung; Ryu, Borim; Kim, Yoojung; Lee, Joong Seek; Kim, Jeong-Whun

    2018-01-30

    To investigate the short-term effects of a lifestyle modification intervention based on a mobile application (app) linked to a hospital electronic medical record (EMR) system on weight reduction and obstructive sleep apnea (OSA). We prospectively enrolled adults (aged >20 years) with witnessed snoring or sleep apnea from a sleep clinic. The patients were randomized into the app user (n=24) and control (n=23) groups. The mobile app was designed to collect daily lifestyle data by wearing a wrist activity tracker and reporting dietary intake. A summary of the lifestyle data was displayed on the hospital EMR and was reviewed. In the control group, the lifestyle modification was performed as per usual practice. All participants underwent peripheral arterial tonometry (WatchPAT) and body mass index (BMI) measurements at baseline and after 4 weeks of follow-up. Age and BMI did not differ significantly between the two groups. While we observed a significant decrease in the BMI of both groups, the decrease was greater in the app user group (P sleep spent snoring at >45 dB was significantly improved in the app user group alone (P =0.014). In either group, among the participants with successful weight reduction, the apnea-hypopnea index was significantly reduced after 4 weeks (P =0.015). Multiple regression analyses showed that a reduction in the apnea-hypopnea index was significantly associated with BMI. Although a short-term lifestyle modification approach using a mobile app was more effective in achieving weight reduction, improvement in OSA was not so significant. Long-term efficacy of this mobile app should be evaluated in the future studies.

  9. Effectiveness of Cranberry Capsules to Prevent Urinary Tract Infections in Vulnerable Older Persons: A Double-Blind Randomized Placebo-Controlled Trial in Long-Term Care Facilities

    Science.gov (United States)

    Caljouw, Monique A A; van den Hout, Wilbert B; Putter, Hein; Achterberg, Wilco P; Cools, Herman J M; Gussekloo, Jacobijn

    2014-01-01

    Objectives To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. Design Double-blind randomized placebo-controlled multicenter trial. Setting Long-term care facilities (LTCFs). Participants LTCF residents (N = 928; 703 women, median age 84). Measurements Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. Results In participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57–0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68–1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412). Conclusion In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk. PMID:25180378

  10. Association of N-terminal pro-B-type natriuretic peptide with contrast-induced nephropathy and long-term outcomes in patients with chronic kidney disease and relative preserved left ventricular function.

    Science.gov (United States)

    Liu, Yuan-hui; Liu, Yong; Zhou, Ying-ling; Yu, Dan-qing; He, Peng-cheng; Xie, Nian-jin; Li, Hua-long; Wei-Guo; Chen, Ji-yan; Tan, Ning

    2015-04-01

    The aim of the present article was to evaluate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with contrast-induced nephropathy (CIN) and long-term outcomes in patients with chronic kidney disease (CKD) and relative preserved left ventricular function (LVF) undergoing percutaneous coronary intervention (PCI). We prospectively enrolled 1203 consecutive patients with CKD and preserved LVF undergoing elective PCI. The primary end point was the development of CIN, defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dL, from baseline within 48 to 72 hours after contrast medium exposure. CIN incidence varied from 2.2% to 5.2%. Univariate logistic analysis showed that lg-NT-pro-BNP was significantly associated with CIN (odds ratio [OR] = 3.93, 95% confidence interval [CI], 2.22-6.97, P pro-BNP remained a significant predictor of CIN (OR = 3.30, 95% CI, 1.57-6.93, P = 0.002), even after adjusting for potential confounding risk factors. These results were confirmed by using other CIN criteria, which were defined as elevations of the SCr by 25% or 0.5 and 0.3 mg/dL from the baseline. The best cutoff value of lg-NT-pro-BNP for detecting CIN was 2.73 pg/mL (537 pg/mL) with 73.1% sensitivity and 70.0% specificity according to the receiver operating characteristic (ROC) analysis (C statistic = 0.754, 95% CI, 0.67-0.84, P pro-BNP ≥537 pg/mL (2.73 pg/mL, lg-NT-pro-BNP) was associated with an increased risk of all-cause mortality and composite end points during 2.5 years of follow-up. NT-pro-BNP ≥537 pg/mL is independently associated with an increased risk of CIN with different definitions and poor clinical outcomes in patients with CKD and relative preserved LVF undergoing PCI.

  11. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  12. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  13. Inhibition of Plant-Pathogenic Bacteria by Short Synthetic Cecropin A-Melittin Hybrid Peptides

    OpenAIRE

    Ferre, Rafael; Badosa, Esther; Feliu, Lidia; Planas, Marta; Montesinos, Emili; Bardají, Eduard

    2006-01-01

    Short peptides of 11 residues were synthesized and tested against the economically important plant pathogenic bacteria Erwinia amylovora, Pseudomonas syringae, and Xanthomonas vesicatoria and compared to the previously described peptide Pep3 (WKLFKKILKVL-NH2). The antimicrobial activity of Pep3 and 22 analogues was evaluated in terms of the MIC and the 50% effective dose (ED50) for growth. Peptide cytotoxicity against human red blood cells and peptide stability toward protease degradation wer...

  14. Ultra-Short-Term Wind-Power Forecasting Based on the Weighted Random Forest Optimized by the Niche Immune Lion Algorithm

    Directory of Open Access Journals (Sweden)

    Dongxiao Niu

    2018-04-01

    Full Text Available The continuous increase in energy consumption has made the potential of wind-power generation tremendous. However, the obvious intermittency and randomness of wind speed results in the fluctuation of the output power in a wind farm, seriously affecting the power quality. Therefore, the accurate prediction of wind power in advance can improve the ability of wind-power integration and enhance the reliability of the power system. In this paper, a model of wavelet decomposition (WD and weighted random forest (WRF optimized by the niche immune lion algorithm (NILA-WRF is presented for ultra-short-term wind power prediction. Firstly, the original serials of wind speed and power are decomposed into several sub-serials by WD because the original serials have no obvious day characteristics. Then, the model parameters are set and the model trained with the sub-serials of wind speed and wind power decomposed. Finally, the WD-NILA-WRF model is used to predict the wind power of the relative sub-serials and the result is reconstructed to obtain the final prediction result. The WD-NILA-WRF model combines the advantage of each single model, which uses WD for signal de-noising, and uses the niche immune lion algorithm (NILA to improve the model’s optimization efficiency. In this paper, two empirical analyses are carried out to prove the accuracy of the model, and the experimental results verify the proposed model’s validity and superiority compared with the back propagation neural network (BP neural network, support vector machine (SVM, RF and NILA-RF, indicating that the proposed method is superior in cases influenced by noise and unstable factors, and possesses an excellent generalization ability and robustness.

  15. Long-term use of minimal footwear on pain, self-reported function, analgesic intake, and joint loading in elderly women with knee osteoarthritis: A randomized controlled trial.

    Science.gov (United States)

    Trombini-Souza, Francis; Matias, Alessandra B; Yokota, Mariane; Butugan, Marco K; Goldenstein-Schainberg, Claudia; Fuller, Ricardo; Sacco, Isabel C N

    2015-12-01

    Efforts have been made to retard the progressive debilitating pain and joint dysfunction in patients with knee osteoarthritis. We aimed to evaluate the therapeutic effect of a low-cost minimalist footwear on pain, function, clinical and gait-biomechanical aspects of elderly women with knee osteoarthritis. Throughout a randomized, parallel and controlled clinical trial, fifty-six patients with medial knee osteoarthritis were randomly allocated to an intervention (n=28) or control group (n=28), and assessed at baseline and after three and six months. The intervention involved wearing Moleca(®) footwear for at least 6h/day, 7 days/week, over 6 months. The pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index was the primary outcome. The secondary outcomes were the other subscales, Lequesne score, distance walked in 6 min, knee oedema and effusion, knee adduction moment and paracetamol intake. Intention-to-treat analysis was performed using two-way casewise ANOVA (coefficient. Intervention group showed improvement in pain (effect size: 1.41, p<.001), function (effect size: 1.22, p=.001), stiffness (effect size: 0.76, p=.001), Lequesne score (effect size: 1.07, p<.001), and reduction by 21.8% in the knee adduction moment impulse (p=.017) during gait wearing Moleca(®). The analgesic intake was lower in the intervention group. The long-term use of Moleca(®) footwear relieves pain, improves self-reported function, reduces the knee loading while wearing Moleca(®), refrains the increase of analgesic intake in elderly women with knee osteoarthritis and can be considered as a conservative mechanical treatment option. ClinicalTrials.gov (NCT01342458). Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A self-administered method of acute pressure block of sciatic nerves for short-term relief of dental pain: a randomized study.

    Science.gov (United States)

    Wang, Xiaolin; Zhao, Wanghong; Wang, Ye; Hu, Jiao; Chen, Qiu; Yu, Juncai; Wu, Bin; Huang, Rong; Gao, Jie; He, Jiman

    2014-08-01

    While stimulation of the peripheral nerves increases the pain threshold, chronic pressure stimulation of the sciatic nerve is associated with sciatica. We recently found that acute pressure block of the sciatic nerve inhibits pain. Therefore, we propose that, the pain pathology-causing pressure is chronic, not acute. Here, we report a novel self-administered method: acute pressure block of the sciatic nerves is applied by the patients themselves for short-term relief of pain from dental diseases. This was a randomized, single-blind study. Hospital patients. Patients aged 16-60 years with acute pulpitis, acute apical periodontitis, or pericoronitis of the third molar of the mandible experiencing pain ≥3 on the 11-point numerical pain rating scale. Three-minute pressure to sciatic nerves was applied by using the hands (hand pressure method) or by having the patients squat to force the thigh and shin as tightly as possible on the sandwiched sciatic nerve bundles (self-administered method). The primary efficacy variable was the mean difference in pain scores from the baseline. One hundred seventy-two dental patients were randomized. The self-administered method produced significant relief from pain associated with dental diseases (P ≤ 0.001). The analgesic effect of the self-administered method was similar to that of the hand pressure method. The self-administered method is easy to learn and can be applied at any time for pain relief. We believe that patients will benefit from this method. © 2014 The Authors. Pain Medicine published by Wiley Periodicals, Inc. on behalf of American Academy of Pain Medicine.

  17. Long-term outcomes of patent foramen ovale closure or medical therapy after cryptogenic stroke: A meta-analysis of randomized trials.

    Science.gov (United States)

    Abdelaziz, Hesham K; Saad, Marwan; Abuomara, Hossamaldin Z; Nairooz, Ramez; Pothineni, Naga Venkata K; Madmani, Mohamed E; Roberts, David H; Mahmud, Ehtisham

    2018-05-04

    To examine long-term clinical outcomes with transcatheter patent foramen ovale (PFO) closure versus medical therapy alone in patients with cryptogenic stroke. A long-standing debate regarding the optimal approach for the management of patients with PFO after a cryptogenic stroke exists. An electronic search was performed for randomized clinical trials (RCTs) reporting clinical outcomes with PFO closure vs. medical therapy alone after stroke. Random effects DerSimonian-Laird risk ratios (RR) were calculated. The main outcome was recurrence of stroke. Other outcomes included transient ischemic attack (TIA), new-onset atrial fibrillation/flutter (AF/AFL), major bleeding, serious adverse events, and device-related complications. All-cause mortality was also examined. Five RCTs with a total of 3,440 patients were included. At a mean follow-up of 4.02 ± 1.57 years, PFO closure was associated with less recurrence of stroke (RR = 0.43; 95% CI 0.19-0.91; P = .027) compared with medical therapy alone. No difference was observed between both strategies for TIA (P = .21), major bleeding (P = .69), serious adverse events (P = .35), and all-cause death (P = .48). However, PFO closure, was associated with increased new-onset AF/AFL (P < .001), risk of pulmonary embolism (P = .04), and device-related complications (P < .001). On a subgroup analysis, stroke recurrence rate remained lower in PFO closure arm regardless of the type of closure device used (P interaction  = .50), or the presence of substantial shunt in the majority of study population (P interaction  = .13). Transcatheter PFO closure reduces the recurrence of stroke compared with medical therapy alone, with no significant safety concerns. Close follow-up of patients after PFO closure is recommended to detect new-onset atrial arrhythmias. © 2018 Wiley Periodicals, Inc.

  18. Hyperbaric Oxygen Treatment of Chronic Refractory Radiation Proctitis: A Randomized and Controlled Double-Blind Crossover Trial With Long-Term Follow-Up

    International Nuclear Information System (INIS)

    Clarke, Richard E.; Tenorio, L. M. Catalina; Hussey, James R.; Toklu, Akin S.; Cone, D. Lindsie; Hinojosa, Jose G.; Desai, Samir P.; Dominguez Parra, Luis; Rodrigues, Sylvia D.; Long, Robert J.; Walker, Margaret B.

    2008-01-01

    Purpose: Cancer patients who undergo radiotherapy remain at life-long risk of radiation-induced injury to normal tissues. We conducted a randomized, controlled, double-blind crossover trial with long-term follow-up to evaluate the effectiveness of hyperbaric oxygen for refractory radiation proctitis. Methods and Materials: Patients with refractory radiation proctitis were randomized to hyperbaric oxygen at 2.0 atmospheres absolute (Group 1) or air at 1.1 atmospheres absolute (Group 2). The sham patients were subsequently crossed to Group 1. All patients were re-evaluated by an investigator who was unaware of the treatment allocation at 3 and 6 months and Years 1-5. The primary outcome measures were the late effects normal tissue-subjective, objective, management, analytic (SOMA-LENT) score and standardized clinical assessment. The secondary outcome was the change in quality of life. Results: Of 226 patients assessed, 150 were entered in the study and 120 were evaluable. After the initial allocation, the mean SOMA-LENT score improved in both groups. For Group 1, the mean was lower (p 0.0150) and the amount of improvement nearly twice as great (5.00 vs. 2.61, p = 0.0019). Similarly, Group 1 had a greater portion of responders per clinical assessment than did Group 2 (88.9% vs. 62.5%, respectively; p 0.0009). Significance improved when the data were analyzed from an intention to treat perspective (p = 0.0006). Group 1 had a better result in the quality of life bowel bother subscale. These differences were abolished after the crossover. Conclusion: Hyperbaric oxygen therapy significantly improved the healing responses in patients with refractory radiation proctitis, generating an absolute risk reduction of 32% (number needed to treat of 3) between the groups after the initial allocation. Other medical management requirements were discontinued, and advanced interventions were largely avoided. Enhanced bowel-specific quality of life resulted

  19. The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study

    International Nuclear Information System (INIS)

    Groot, Stefanie de; Vreeswijk, Maaike PG; Welters, Marij JP; Gravesteijn, Gido; Boei, Jan JWA; Jochems, Anouk; Houtsma, Daniel; Putter, Hein; Hoeven, Jacobus JM van der; Nortier, Johan WR; Pijl, Hanno; Kroep, Judith R

    2015-01-01

    Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC). Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level of γ-H2AX analyzed by flow cytometry. Thirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels of γ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients. STF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy. ClinicalTrials.gov: NCT01304251, March 2011

  20. The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study.

    Science.gov (United States)

    de Groot, Stefanie; Vreeswijk, Maaike P G; Welters, Marij J P; Gravesteijn, Gido; Boei, Jan J W A; Jochems, Anouk; Houtsma, Daniel; Putter, Hein; van der Hoeven, Jacobus J M; Nortier, Johan W R; Pijl, Hanno; Kroep, Judith R

    2015-10-05

    Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC). Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level of γ-H2AX analyzed by flow cytometry. Thirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels of γ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients. STF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy. ClinicalTrials.gov: NCT01304251 , March 2011.

  1. The Association of Fasting Glucose, Insulin, and C-Peptide, with 19-Year Incidence of Coronary Heart Disease in Older Japanese-American Men; the Honolulu Heart Program

    Directory of Open Access Journals (Sweden)

    Nazneem Wahab

    2018-04-01

    Full Text Available The role of fasting glucose, insulin levels, and C-peptide in coronary heart disease (CHD in non-diabetic individuals remains uncertain. We examined the association between fasting glucose, insulin and C-peptide with the long-term incidence of CHD in Japanese-American men. In 1980–1982, from a random sample of the Honolulu Heart Program men (n = 1378, aged 61–81 years, data on several CHD and metabolic risk factors were obtained to examine the relation of fasting glucose, insulin and C-peptide to 19-year CHD incidence. Age-adjusted incidence of CHD increased with increasing quintiles of glucose, insulin and C-peptide. Age-adjusted CHD rates in the glucose quintiles were 11.9, 11.6, 14.4, 18.1 and 24.1 per 1000 person-years (trend p < 0.001. In individual Cox models (lowest quintiles of glucose, insulin and C-peptide as reference the relative risks (95% confidence interval of CHD incidence for the glucose quintiles adjusting for age, smoking, hypertension, cholesterol, physical activity, and body mass index, were 0.9 (0.6–1.4, 1.2 (0.8–1.8, 1.4 (0.9–2.2, and 1.7 (1.1–2.6, respectively (trend p = 0.004. Insulin and C-peptide were not significantly associated with CHD on multivariate analysis. Fasting glucose remained the only significant predictor of increased CHD risk (p = 0.003 in a model combining all 3 metabolic variables. In this cohort, only fasting glucose independently predicts long-term incidence of CHD. Age-adjusted insulin and C-peptide levels were associated with CHD incidence, but after adjustment for other risk factors, do not independently predict CHD.

  2. Peptide aldehyde inhibitors of bacterial peptide deformylases.

    Science.gov (United States)

    Durand, D J; Gordon Green, B; O'Connell, J F; Grant, S K

    1999-07-15

    Bacterial peptide deformylases (PDF, EC 3.5.1.27) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity. Copyright 1999 Academic Press.

  3. An interactive health communication application for supporting parents managing childhood long-term conditions: outcomes of a randomized controlled feasibility trial.

    Science.gov (United States)

    Swallow, Veronica M; Knafl, Kathleen; Santacroce, Sheila; Campbell, Malcolm; Hall, Andrew G; Smith, Trish; Carolan, Ian

    2014-12-03

    Families living with chronic or long-term conditions such as chronic kidney disease (CKD), stages 3-5, face multiple challenges and respond to these challenges in various ways. Some families adapt well while others struggle, and family response to a condition is closely related to outcome. With families and professionals, we developed a novel condition-specific interactive health communication app to improve parents' management ability-the online parent information and support (OPIS) program. OPIS consists of a comprehensive mix of clinical caregiving and psychosocial information and support. The purpose of this study was to (1) assess feasibility of a future full-scale randomized controlled trial (RCT) of OPIS in terms of recruitment and retention, data collection procedures, and psychometric performance of the study measures in the target population, and (2) investigate trends in change in outcome measures in a small-scale RCT in parents of children with CKD stages 3-5. Parents were recruited from a pediatric nephrology clinic and randomly assigned to one of two treatment groups: usual support for home-based clinical caregiving (control) or usual support plus password-protected access to OPIS for 20 weeks (intervention). Both groups completed study measures at study entry and exit. We assessed feasibility descriptively in terms of recruitment and retention rates overall; assessed recruitment, retention, and uptake of the intervention between groups; and compared family condition management, empowerment to deliver care, and fathers' involvement between groups. We recruited 55 parents of 39 children (42% of eligible families). Of those, about three-quarters of intervention group parents (19/26, 73%) and control group parents (22/29, 76%) were retained through completion of 20-week data collection. The overall retention rate was 41/55 (75%). The 41 parents completing the trial were asked to respond to the same 10 questionnaire scales at both baseline and 20 weeks

  4. Long-term scar quality after hydrosurgical versus conventional debridement of deep dermal burns (HyCon trial): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Legemate, Catherine M; Goei, Harold; Middelkoop, Esther; Oen, Irma M M H; Nijhuis, Tim H J; Kwa, Kelly A A; van Zuijlen, Paul P M; Beerthuizen, Gerard I J M; Nieuwenhuis, Marianne K; van Baar, Margriet E; van der Vlies, Cornelis H

    2018-04-19

    Deep dermal burns require tangential excision of non-viable tissue and skin grafting to improve wound healing and burn-scar quality. Tangential excision is conventionally performed with a knife, but during the last decade hydrosurgery has become popular as a new tool for tangential excision. Hydrosurgery is generally thought to be a more precise and controlled manner of burn debridement leading to preservation of viable tissue and, therefore, better scar quality. Although scar quality is considered to be one of the most important outcomes in burn surgery today, no randomized controlled study has compared the effect of these two common treatment modalities with scar quality as a primary outcome. The aim of this study is, therefore, to compare long-term scar quality after hydrosurgical versus conventional tangential excision in deep dermal burns. A multicenter, randomized, intra-patient, controlled trial will be conducted in the Dutch burn centers of Rotterdam, Beverwijk, and Groningen. All patients with deep dermal burns that require excision and grafting are eligible. Exclusion criteria are: a burn wound burned > 30%, full-thickness burns, chemical or electrical burns, infected wounds (clinical symptoms in combination with positive wound swabs), insufficient knowledge of the Dutch or English language, patients that are unlikely to comply with requirements of the study protocol and follow-up, and patients who are (temporarily) incompetent because of sedation and/or intubation. A total of 137 patients will be included. Comparable wound areas A and B will be appointed, randomized and either excised conventionally with a knife or with the hydrosurgery system. The primary outcome is scar quality measured by the observer score of the Patient and Observer Scar Assessment Scale (POSAS); a subjective scar-assessment instrument, consisting of two separate six-item scales (observer and patient) that are both scored on a 10-point rating scale. This study will contribute to

  5. Effects of neurofeedback on the short-term memory and continuous attention of patients with moderate traumatic brain injury: A preliminary randomized controlled clinical trial.

    Science.gov (United States)

    Rostami, Reza; Salamati, Payman; Yarandi, Kourosh Karimi; Khoshnevisan, Alireza; Saadat, Soheil; Kamali, Zeynab Sadat; Ghiasi, Somaie; Zaryabi, Atefeh; Ghazi Mir Saeid, Seyed Shahab; Arjipour, Mehdi; Rezaee-Zavareh, Mohammad Saeid; Rahimi-Movaghar, Vafa

    2017-10-01

    There are some studies which showed neurofeedback therapy (NFT) can be effective in clients with traumatic brain injury (TBI) history. However, randomized controlled clinical trials are still needed for evaluation of this treatment as a standard option. This preliminary study was aimed to evaluate the effect of NFT on continuous attention (CA) and short-term memory (STM) of clients with moderate TBI using a randomized controlled clinical trial (RCT). In this preliminary RCT, seventeen eligible patients with moderate TBI were randomly allocated in two intervention and control groups. All the patients were evaluated for CA and STM using the visual continuous attention test and Wechsler memory scale-4th edition (WMS-IV) test, respectively, both at the time of inclusion to the project and four weeks later. The intervention group participated in 20 sessions of NFT through the first four weeks. Conversely, the control group participated in the same NF sessions from the fifth week to eighth week of the project. Eight subjects in the intervention group and five subjects in the control group completed the study. The mean and standard deviation of participants' age were (26.75 ± 15.16) years and (27.60 ± 8.17) years in experiment and control groups, respectively. All of the subjects were male. No significant improvement was observed in any variables of the visual continuous attention test and WMS-IV test between two groups (p ≥ 0.05). Based on our literature review, it seems that our study is the only study performed on the effect of NFT on TBI patients with control group. NFT has no effect on CA and STM in patients with moderate TBI. More RCTs with large sample sizes, more sessions of treatment, longer time of follow-up and different protocols are recommended. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  6. Impact of Sequencing Radiation Therapy and Chemotherapy on Long-Term Local Toxicity for Early Breast Cancer: Results of a Randomized Study at 15-Year Follow-Up

    Energy Technology Data Exchange (ETDEWEB)

    Pinnarò, Paola; Giordano, Carolina; Farneti, Alessia [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Strigari, Lidia; Landoni, Valeria [Department of Physics, Regina Elena National Cancer Institute, Rome (Italy); Marucci, Laura; Petrongari, Maria Grazia [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Sanguineti, Giuseppe, E-mail: sanguineti@ifo.it [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy)

    2016-07-15

    Purpose: To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery. Methods and Materials: From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years). Results: Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (<8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic

  7. Does a more extensive mucosal excision prevent haemorrhoidal recurrence after stapled haemorrhoidopexy? Long-term outcome of a randomized controlled trial.

    Science.gov (United States)

    Altomare, D F; Pecorella, G; Tegon, G; Aquilino, F; Pennisi, D; De Fazio, M

    2017-06-01

    The study aimed in a multicentric randomized controlled trial to define the role of a more extensive mucosal resection on recurrence of mucosal prolapse in patients with Stage III haemorrhoids undergoing stapled haemorrhoidopexy. In all, 135 patients were randomized to treatment with a PPH-01/03 (Ethicon EndoSurgery) or an EEA (Covidien) stapler. They were reviewed after a minimum follow-up of 4 years to determine the rate of recurrent mucosal prolapse and general condition (wellness evaluation score). Postoperative bowel dysfunction was assessed using the Rome III criteria. Eighty-seven (65%) of the 135 patients (48 in the EEA stapler group and 37 in the PPH group) were available for long-term follow-up. The two groups were comparable for age, gender and duration of follow-up (mean 49.3 ± 5.4 months and 49.0 ± 5.3 months respectively). In the EEA group, 11 (23%) patients had some degree of recurrent prolapse compared with 12 (32%) in the PPH group (P = 0.409). Persistence of anal bleeding was significantly higher in the PPH group (P = 0.04) while the postoperative Haemorrhoid Symptom Score was significantly better in the EEA group (1.73 ± 1.65 vs 3.17 ± 1.94, P < 0.001). The wellness evaluation score was significantly better in the EEA group (1.2 ± 1.27 vs 0.6 ± 1.0, P = 0.028). Furthermore, 7 (15%) of the patients in the EEA group complained of some evacuation disturbance compared with 13 (36%) in the PPH group (P = 0.021). The study failed to demonstrate any significant difference in the long-term recurrence rate of Stage III haemorrhoids using EEA or PPH. Nevertheless, use of the larger volume EEA provides better symptom resolution compared with PPH. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  8. Impact of Sequencing Radiation Therapy and Chemotherapy on Long-Term Local Toxicity for Early Breast Cancer: Results of a Randomized Study at 15-Year Follow-Up

    International Nuclear Information System (INIS)

    Pinnarò, Paola; Giordano, Carolina; Farneti, Alessia; Strigari, Lidia; Landoni, Valeria; Marucci, Laura; Petrongari, Maria Grazia; Sanguineti, Giuseppe

    2016-01-01

    Purpose: To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery. Methods and Materials: From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years). Results: Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (<8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic

  9. Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register.

    Science.gov (United States)

    Chen, Lingjing; Eloranta, Sandra; Martling, Anna; Glimelius, Ingrid; Neovius, Martin; Glimelius, Bengt; Smedby, Karin E

    2018-03-01

    A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). We identified 14,901 rectal cancer patients diagnosed 1995-2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980-1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92-1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93-1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (IRR register  = 1.41, 95% CI 1.15-2.72; IRR trials  = 1.41, 95% CI 0.97-2.04), that remained during the first 6 months following surgery among patients treated 2006-2009, after the introduction of antithrombotic treatment (IRR 6 months  = 2.30, 95% CI 1.01-5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Preoperative radiotherapy did not affect rectal cancer patients' risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Friction massage versus kinesiotaping for short-term management of latent trigger points in the upper trapezius: a randomized controlled trial.

    Science.gov (United States)

    Mohamadi, Marzieh; Piroozi, Soraya; Rashidi, Iman; Hosseinifard, Saeed

    2017-01-01

    Latent trigger points in the upper trapezius muscle may disrupt muscle movement patterns and cause problems such as cramping and decreased muscle strength. Because latent trigger points may spontaneously become active trigger points, they should be addressed and treated to prevent further problems. In this study we compared the short-term effect of kinesiotaping versus friction massage on latent trigger points in the upper trapezius muscle. Fifty-eight male students enrolled with a stratified sampling method participated in this single-blind randomized clinical trial (Registration ID: IRCT2016080126674N3) in 2016. Pressure pain threshold was recorded with a pressure algometer and grip strength was recorded with a Collin dynamometer. The participants were randomly assigned to two different treatment groups: kinesiotape or friction massage. Friction massage was performed daily for 3 sessions and kinesiotape was used for 72 h. One hour after the last session of friction massage or removal of the kinesiotape, pressure pain threshold and grip strength were evaluated again. Pressure pain threshold decreased significantly after both friction massage (2.66 ± 0.89 to 2.25 ± 0.76; P  = 0.02) and kinesiotaping (2.00 ± 0.74 to 1.71 ± 0.65; P  = 0.01). Grip strength increased significantly after friction massage (40.78 ± 9.55 to 42.17 ± 10.68; P  = 0.03); however there was no significant change in the kinesiotape group (39.72 ± 6.42 to 40.65 ± 7.3; P  = 0.197). There were no significant differences in pressure pain threshold (2.10 ± 0.11 & 1.87 ± 0.11; P  = 0.66) or grip strength (42.17 ± 10.68 & 40.65 ± 7.3; P  = 0.53) between the two study groups. Friction massage and kinesiotaping had identical short-term effects on latent trigger points in the upper trapezius. Three sessions of either of these two interventions did not improve latent trigger points. Registration ID in IRCT: IRCT2016080126674N3.

  11. Predictors for contrast media-induced nephropathy and long-term survival: Prospectively assessed data from the randomized controlled Dialysis-Versus-Diuresis (DVD) trial

    Science.gov (United States)

    Hölscher, Birgit; Heitmeyer, Christine; Fobker, Manfred; Breithardt, Günter; Schaefer, Roland M; Reinecke, Holger

    2008-01-01

    BACKGROUND: Among the numerous studies concerning contrast media-induced nephropathy (CIN), there was no prospective trial that provided data on the long-term outcomes. OBJECTIVES: To prospectively assess predictors of CIN and long-term outcomes of affected patients. METHODS: Four hundred twelve consecutive patients with serum creatinine levels of 115 μmol/L to 309 μmol/L (1.3 mg/dL to 3.5 mg/dL) undergoing elective coronary angiography were included. Patients were randomly assigned to periprocedural hydration alone, hydration plus onetime hemodialysis or hydration plus N-acetylcysteine. RESULTS: Multivariate logistic regression identified the following as predictors of CIN within 72 h (equivalent to an increase in creatinine 44.2 μmol/L [0.5 mg/dL] or more) : prophylactic postprocedural hemodialysis (OR 2.86, 95% CI 1.07 to 7.69), use of angiotensin-converting enzyme inhibitors (OR 6.16, 95% CI 2.01 to 18.93), baseline glomerular filtration rate (OR 0.94, 95% CI 0.90 to 0.98) and the amount of contrast media given (OR 1.01, 95% CI 1.00 to 1.01). With regard to long-term outcome (mean follow-up 649 days), multivariate Cox regression models found elevated creatinine levels at 30 days (hazard rate ratio [HRR] 5.48, 95% CI 2.85 to 10.53), but not CIN within 72 h (HRR 1.12, 95% CI 0.63 to 2.02), to be associated with increased mortality. In addition, independent predictors for death during follow-up included left ventricular ejection fraction lower than 35% (HRR 4.01, 95% CI 2.22 to 7.26), serum phosphate (HRR 1.64, 95% CI 1.10 to 2.43) and hemoglobin (HRR 0.80, 95% CI 0.67 to 0.96). CONCLUSION: From the present prospective trial, performance of post-procedural hemodialysis, use of angiotensin-converting enzyme inhibitors, reduced baseline glomerular filtration rate and amount of contrast media were independent predictors of CIN within 72 h after catheterization. Assessing renal function after 30 days, rather than within 72 h, seemed to be more predictive for

  12. The long-term outcomes of interventions for the management of attention-deficit hyperactivity disorder in children and adolescents: a systematic review of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Parker J

    2013-09-01

    Full Text Available Jack Parker,1 Gill Wales,2 Nevyne Chalhoub,1 Val Harpin2 1Child and Adolescent Mental Health Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK; 2Paediatric Neurodisability, Ryegate Children’s Centre, Sheffield Children’s NHS Foundation Trust, Sheffield, UK Purpose: To systematically identify and review the currently available evidence on the long-term outcomes of recommended attention-deficit hyperactivity disorder (ADHD interventions following randomized controlled trials with children and young people. Method: A systematic search was conducted to identify trials >1 year in length using the following databases: CINAHL (January 1982– July 2012, MEDLINE (Ovid and Cambridge Scientific Abstracts [CSA], Psych info, Science Direct (Elsevier, and Cochrane Library. Hand searches of key journals in the subject, book chapters, and conference proceedings were also carried out. Relevant papers were critically appraised using the Cochrane risk of bias tool. Results: Eight controlled trials were identified as being relevant, of duration ranging from 1 year to 8 years (at follow up. The total number of participants in the studies was 1,057, of whom 579 (54.7% were from one cohort and included 26 different outcome measures. Results suggest there is moderate-to-high-level evidence that combined pharmacological and behavioral interventions, and pharmacological interventions alone can be effective in managing the core ADHD symptoms and academic performance at 14 months. However, the effect size may decrease beyond this period. Conclusion: This review has highlighted the paucity and limitations of the evidence investigating the long-term outcomes of recommended interventions for managing ADHD symptoms. There is little evidence to suggest that the effects observed over the relatively short term are maintained throughout longer periods of impairment. Furthermore, much of the existing evidence examining effectiveness beyond 12 months does not

  13.  Pleiotropic action of proinsulin C-peptid

    Directory of Open Access Journals (Sweden)

    Michał Usarek

    2012-03-01

    Full Text Available  Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic β cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. However, in the last two decades research has brought a substantial amount of data indicating a crucial role of C-peptide in regulating various processes in different types of cells and organs. C-peptide acts presumably via either G-protein-coupled receptor or directly inside the cell, after being internalized. However, a receptor binding this peptide has not been identified yet. This peptide ameliorates pathological changes induced by type 1 diabetes mellitus, including glomerular hyperfiltration, vessel endothelium inflammation and neuron demyelinization. In diabetic patients and diabetic animal models, C-peptide substitution in physiological doses improves the functional and structural properties of peripheral neurons and protects against hyperglycemia-induced apoptosis, promoting neuronal development, regeneration and cell survival. Moreover, it affects glycogen synthesis in skeletal muscles. In vitro C-peptide promotes disaggregation of insulin oligomers, thus enhancing its bioavailability and effects on metabolism. There are controversies concerning the biological action of C-peptide, particularly with respect to its effect on Na /K -ATPase activity. Surprisingly, the excess of circulating peptide associated with diabetes type 2 contributes to atherosclerosis development. In view of these observations, long-term, large-scale clinical investigations using C-peptide physiological doses need to be conducted in order to determine safety and health outcomes of long-term administration of C-peptide to diabetic patients.

  14. Metal Ion Controlled Polymorphism of a Peptide

    DEFF Research Database (Denmark)

    Hemmingsen, Lars Bo Stegeager; Jancso, Attila; Szunyogh, Daniel

    2011-01-01

    ions on fully or partially unstructured proteins, or the effect of metal ions on protein aggregation. Metal ions may be employed to fold (or misfold) individual peptides in a controlled manner depending on the potential metal ion coordinating amino acid side chains (Cys, His, Asp, Glu......In this work a metal ion binding model dodecapeptide was investigated in terms of its capacity to adopt different structures depending on the metal ion to peptide stoichiometry. The dodecapeptide is much simpler than real proteins, yet displays sufficient complexity to model the effect of metal......, …) in the peptide, and the ligand and structural preferences of the metal ion (in our studies Zn2+, Cd2+, Hg2+, Cu+/2+). Simultaneously, new species such as metal ion bridged ternary complexes or even oligomers may be formed. In recent previous studies we have observed similar polymorphism of zinc finger model...

  15. Individualized nutrition intervention is of major benefit to colorectal cancer patients: long-term follow-up of a randomized controlled trial of nutritional therapy.

    Science.gov (United States)

    Ravasco, Paula; Monteiro-Grillo, Isabel; Camilo, Maria

    2012-12-01

    In our published randomized trial in colorectal cancer, group 1 (n = 37) received individualized nutritional counseling and education about regular foods, group 2 (n = 37) received dietary supplements and consumed their usual diet of regular foods, and group 3 (n = 37) consumed their usual diet of regular foods. Neither group 2 nor group 3 received individualized counseling. Early nutritional counseling during radiotherapy was highly effective at reducing acute radiotherapy toxicity and improving nutritional intake/status and quality of life (QoL). Efficacy persisted for 3 mo after the intervention. The objective was to perform long-term follow-up in survivors of that clinical trial to specifically evaluate survival, late toxicity, QoL, and nutritional variables. Medical data were collected from patients' records, and prescheduled interviews were conducted by dietitians for individualized evaluations. Analyses and comparisons between groups (adjusted for stage) were performed after a median follow-up of 6.5 (range: 4.9-8.1) y. Patients complied with the Radiotherapy Department's follow-up protocol. Nutritional deterioration was higher (P nutritional status was maintained in 91% of group 1 patients but not in any of the group 3 patients (P group 2 > group 1 (P group 1 (P nutritional status and intake (P nutritional status, and QoL predicted shorter survival and late toxicity (HR: 8.25; 95% CI: 2.74, 1.47; P nutrition at improving long-term prognosis in colorectal cancer. Overall, the data indicate that early individualized nutritional counseling and education during radiotherapy is valuable for patients.

  16. Long-term mother and child mental health effects of a population-based infant sleep intervention: cluster-randomized, controlled trial.

    Science.gov (United States)

    Hiscock, Harriet; Bayer, Jordana K; Hampton, Anne; Ukoumunne, Obioha C; Wake, Melissa

    2008-09-01

    Maternal depression is an established risk for adverse child development. Two thirds of clinically significant depressive symptoms occur in mothers reporting an infant sleep problem. We aimed to determine the long-term effects of a behavioral intervention for infant sleep problems on maternal depression and parenting style, as well as on child mental health and sleep, when the children reached 2 years of age. We conducted a cluster-randomized trial in well-child centers across 6 government areas of Melbourne, Australia. Participants included 328 mothers reporting an infant sleep problem at 7 months, drawn from a population sample (N = 739) recruited at 4 months. We compared the usual well-child care (n = 154) versus a brief behavior-modification program designed to improve infant sleep (n = 174) delivered by well-child nurses at ages 8 to 10 months and measured maternal depression symptoms (Edinburgh Postnatal Depression Scale); parenting practices (Parent Behavior Checklist); child mental health (Child Behavior Checklist); and maternal report of a sleep problem (yes or no). At 2 years, mothers in the intervention group were less likely than control mothers to report clinical depression symptoms: 15.4% vs 26.4% (Edinburgh Postnatal Depression Scale community cut point) and 4.2% vs 13.2% (Edinburgh Postnatal Depression Scale clinical cut point). Neither parenting style nor child mental health differed markedly between the intervention and control groups. A total of 27.3% of children in the intervention group versus 32.6% of control children had a sleep problem. The sleep intervention in infancy resulted in sustained positive effects on maternal depression symptoms and found no evidence of longer-term adverse effects on either mothers' parenting practices or children's mental health. This intervention demonstrated the capacity of a functioning primary care system to deliver effective, universally offered secondary prevention.

  17. The Long-Term Impact of Neurofeedback on Symptom Burden and Interference in Patients With Chronic Chemotherapy-Induced Neuropathy: Analysis of a Randomized Controlled Trial.

    Science.gov (United States)

    Prinsloo, Sarah; Novy, Diane; Driver, Larry; Lyle, Randall; Ramondetta, Lois; Eng, Cathy; Lopez, Gabriel; Li, Yisheng; Cohen, Lorenzo

    2018-05-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment and may adversely affect quality of life (QOL) for years. We explored the long-term effects of electroencephalographic neurofeedback (NFB) as a treatment for CIPN and other aspects of QOL. Seventy-one cancer survivors (mean age 62.5; 87% females) with CIPN were randomized to NFB or to a waitlist control (WLC) group. The NFB group underwent 20 sessions of NFB where rewards were given for voluntary changes in electroencephalography. Measurements of pain, cancer-related symptoms, QOL, sleep, and fatigue were obtained at baseline, end of treatment, and one and four months later. Seventy one participants enrolled in the study. At the end of treatment, 30 in the NFB group and 32 in the WLC group completed assessments; at four months, 23 in the NFB group and 28 in the WLC completed assessments. Linear mixed model analysis revealed significant group × time interaction for pain severity. A general linear model determined that the NFB group had greater improvements in worst pain (primary outcome) and other symptoms such as numbness, cancer-related symptom severity, symptom interference, physical functioning, general health, and fatigue compared with the WLC group at the end of treatment and four months (all P < 0.05). Effect sizes were moderate or large for most measures. NFB appears to result in long-term reduction in multiple CIPN symptoms and improved postchemotherapy QOL and fatigue. Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  18. Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study

    Directory of Open Access Journals (Sweden)

    Kanaley Jill

    2011-10-01

    Full Text Available Abstract Background Evidence indicates that dietary fats and physical activity influence bone health. The purpose of this study was to examine the effects of long-term aerobic exercise and omega-3 (N-3 supplementation on serum inflammatory markers, bone mineral density (BMD, and bone biomarkers in post-menopausal women. Methods Seventy-nine healthy sedentary post-menopausal women aged 58-78 years participated in this study. Subjects were randomized to one of 4 groups: exercise + supplement (E+S, n = 21, exercise (E, n = 20, supplement (S, n = 20, and control (Con, n = 18 groups. The subjects in the E+S and E groups performed aerobic exercise training (walking and jogging up to 65% of HRmax, three times a week for 24 weeks. Subjects in the E+S and S groups consumed 1000 mg/d N-3 for 24 weeks. The lumbar spine (L2-L4 and femoral neck BMD, serum tumor necrosis factor (TNF α, interleukin (IL 6, prostaglandin (PG E2, estrogen, osteocalcin, 1, 25-dihydroxyvitamin D3 (1, 25 Vit D, C-telopeptide (CTX, parathyroid hormone (PTH and calcitonin (CT were measured at baseline, the end of week 12 and 24. Results Serum estrogen, osteocalcin, 1, 25 Vit D, CT, L2-L4 and femoral neck BMD measures increased (P 2 decreased (P 2-L4 and femoral neck BMD, estrogen, osteocalcin, and CT were negatively (P 2. PTH and CT were correlated positively and negatively with IL-6, respectively (P Conclusions The present study demonstrates that long-term aerobic exercise training plus N-3 supplementation have a synergistic effect in attenuating inflammation and augmenting BMD in post-menopausal osteoporosis.

  19. Do TETRA (Airwave) base station signals have a short-term impact on health and well-being? A randomized double-blind provocation study.

    Science.gov (United States)

    Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

    2010-06-01

    "Airwave" is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general. We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported "electrosensitivity" and of participants who served as controls. Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being. We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham. Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself.

  20. Comparative randomized open-label trial on efficacy and safety of Persen® and Persen® Night herbal extracts in patients with short-term insomnia

    Directory of Open Access Journals (Sweden)

    A. P. Rachin

    2016-01-01

    Full Text Available Herbal sedatives serve an alternative to antipsychotics and hypnotics aimed to alleviate symptoms of anxious disorders and insomnia. Valeriana officinalis L., Mentha piperita L. and Melissa officinalis are most widely used in neurology as sedatives of herbal origin. We present the results of a randomized open-label trial on efficiency and safety of Persen® and Persen® Night containing extracts of the above mentioned plants in patients with short-term insomnia. The study consisted of 60 subjects of 18–65 y.o. (mean 42.4 ± 6.9 y.o. with short-term insomnia due to adjustment disorder or mixed anxiety-depressive disorders: 30 of them got Persen® 2 tablets a day and 30 – Persen® Night, 1 capsule 30–60 min before sleep during 4 weeks. The majority (76.5 % of patients referred the onset of insomnia with psychosocial traumatic stressor. Persen® Night’s main action was found on superficial sleep, number of night awakenings, sleep onset rate. At the end of the therapy with this substance 39.7 % of patients fell asleep in 10–15 min, and 92.2 % – in 30 min, accordingly, while for Persen® at 17.4 and 80.3 % accordingly (р < 0.05. In the meantime Persen® decreased the bad sleep perception at awakening and day somnolence, mostly attributed to the mood improvement and decrease of anxiety. Levels of efficacy and safety for both substances were significant, allowing to regard them as potential phytotherapeutic agent in the treatment of insomnia and mixed anxiety-depressive disorders.

  1. Long-term effects of high-intensity interval training in heart transplant recipients: A 5-year follow-up study of a randomized controlled trial.

    Science.gov (United States)

    Yardley, Marianne; Gullestad, Lars; Bendz, Bjørn; Bjørkelund, Elisabeth; Rolid, Katrine; Arora, Satish; Nytrøen, Kari

    2017-01-01

    Previous studies have demonstrated that high-intensity interval training (HIT) is superior to moderate-continuous exercise in general and in cardiovascular diseases. Recently, we also found HIT safe and efficient after heart transplantation (HTx). This study reports the 5-year long-term effects. Forty-one HTx patients who had completed the previous 12-month randomized controlled trial, comparing HIT intervention with usual care, were eligible. In particular, we measured VO 2peak , muscular capacity, intravascular ultrasound, and questionnaires measuring physical and mental health. The baseline mean±SD values were as follows: age; 49.1±16.5 years, men; 68%, time since HTx: 4.1±2.2 years. Within the HIT group, initial VO 2peak increased significantly from 27.7±5.7 to 31.2±5.3 mL/kg/min. However, during the next 4 years, VO 2peak decreased to 26.0±6.2 mL/kg/min. The control group showed slightly decreasing VO 2peak values during the entire 5-year period. The HIT group reported significantly less anxiety symptoms, but there were no long-term differences in VO 2peak , muscular capacity, or cardiac allograft vasculopathy between the groups. The similar VO 2peak values correspond to our findings of similar everyday activity. Our findings suggest that intermittent periods of HIT may be necessary to maintain the initial benefits gained from the intervention. However, HIT probably reduces the burden of anxiety, which is a frequent health issue following HTx. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Secondary Prevention of Chronic PTSD by Early and Short-Term Administration of Escitalopram: A Prospective Randomized, Placebo-Controlled, Double-Blind Trial.

    Science.gov (United States)

    Zohar, Joseph; Fostick, Leah; Juven-Wetzler, Alzabeta; Kaplan, Zeev; Shalev, Hadar; Schreiber, Gavriel; Miroshnik, Natalie; Shalev, Arieh Y; Stein, Dan J; Seedat, Soraya; Suliman, Sharain; Klein, Ehud

    Prospective studies have not identified a viable pharmacologic strategy for secondary prevention of posttraumatic stress disorder (PTSD). The authors examined whether preventive intervention via early and short-term administration of a selective serotonin reuptake inhibitor (SSRI), within 1 month of exposure to a traumatic event (before diagnosis of PTSD could be made), may reduce the severity of PTSD symptoms according to DSM-IV at 13 months' follow-up. Over 25,000 screening calls to patients referred to an emergency department for a traumatic event performed between June 2006 and December 2008 yielded 353 participants who were recruited within the month following a traumatic event . Participants were randomly assigned in a double-blind design to escitalopram (n = 176) or placebo (n = 177). The per-protocol analysis comprised 198 participants (escitalopram, n = 102; placebo, n = 96) who received treatment for 12 to 24 weeks and were available for follow-up at week 56. The primary outcome measure, the Clinician Administered PTSD Scale (CAPS), revealed no prevention effect. However, a secondary outcome, the Pittsburgh Sleep Quality Inventory (PSQI), showed better results for the SSRI group than for the placebo group. For a subset of participants who experienced intentional trauma (missile attacks, rape, or physical assault; n = 50), the prevention effect was found on both primary and secondary measures (CAPS, PSQI and measures of depression and global illness severity). Early and short-term administration of escitalopram was not shown to prevent PTSD, although it did improve sleep quality. In a subgroup of participants who experienced intentional trauma, however, this early-treatment approach may be effective as secondary prevention. This large study is the first to investigate the preventive effect of early administration of escitalopram on PTSD. It highlights the relevance of the type of trauma (intentional vs unintentional) to the outcome. Clinical

  3. Long-term psychological benefits of cognitive-behavioral stress management for women with breast cancer: 11-year follow-up of a randomized controlled trial.

    Science.gov (United States)

    Stagl, Jamie M; Bouchard, Laura C; Lechner, Suzanne C; Blomberg, Bonnie B; Gudenkauf, Lisa M; Jutagir, Devika R; Glück, Stefan; Derhagopian, Robert P; Carver, Charles S; Antoni, Michael H

    2015-06-01

    Breast cancer survivors experience long-term physical and psychological sequelae after their primary treatment that negatively influence their quality of life (QOL) and increase depressive symptoms. Group-based cognitive-behavioral stress management (CBSM) delivered after surgery for early-stage breast cancer was previously associated with better QOL over a 12-month follow-up and with fewer depressive symptoms up to 5 years after study enrollment. This 8- to 15-year follow-up (median, 11 years) of a previously conducted trial (NCT01422551) evaluated whether women in this cohort receiving CBSM had fewer depressive symptoms and better QOL than controls at an 8- to 15-year follow-up. Women with stage 0 to IIIb breast cancer were initially recruited 2 to 10 weeks after surgery and randomized to a 10-week CBSM intervention or a 1-day psychoeducational control group. One hundred women (51 CBSM patients and 49 controls) were recontacted 8 to 15 years after study enrollment to participate in a follow-up assessment. The Center for Epidemiologic Studies-Depression (CES-D) scale and the Functional Assessment of Cancer Therapy-Breast (FACT-B) were self-administered. Multiple regression was employed to evaluate group differences on the CES-D scale and FACT-B over and above effects of confounding variables. Participants assigned to CBSM reported significantly lower depressive symptoms (d, 0.63; 95% confidence interval [CI], 0.56-0.70) and better QOL (d, 0.58; 95% CI, 0.52-0.65) above the effects of the covariates. Women who received CBSM after surgery for early-stage breast cancer reported lower depressive symptoms and better QOL than the control group up to 15 years later. Early implementation of cognitive-behavioral interventions may influence long-term psychosocial functioning in breast cancer survivors. © 2015 American Cancer Society.

  4. Cognitively oriented behavioral rehabilitation in combination with Qigong for patients on long-term sick leave because of burnout: REST--a randomized clinical trial.

    Science.gov (United States)

    Stenlund, Therese; Ahlgren, Christina; Lindahl, Bernt; Burell, Gunilla; Steinholtz, Katarina; Edlund, Curt; Nilsson, Leif; Knutsson, Anders; Birgander, Lisbeth Slunga

    2009-01-01

    Despite an increase in the occurrence of burnout, there is no agreement on what kind of rehabilitation these patients should be offered. Primary aim of this study was to evaluate effects on psychological variables and sick leave rates by two different group rehabilitation programs for patients on long-term sick leave because of burnout. Rehabilitation program A (Cognitively oriented Behavioral Rehabilitation (CBR) and Qigong) was compared with rehabilitation program B (Qigong only). In a randomized clinical trial, 96 women and 40 men with a mean age of 41.6 +/- 7.4 years were allocated to one of the two rehabilitation programs. A per-protocol analysis showed no significant difference in treatment efficacy between the groups. Both groups improved significantly over time with reduced levels of burnout, self-rated stress behavior, fatigue, depression, anxiety, obsessive-compulsive symptoms, and sick leave rates. In an intention-to-treat analysis, patients in program A had fewer obsessive-compulsive symptoms and larger effect sizes in self-rated stress behavior and obsessive-compulsive symptoms compared to patients in program B. This study showed no differences in effect between CBR and Qigong compared with Qigong only in a per-protocol analysis. Both rehabilitation programs showed positive effect for patients with burnout.

  5. Long-term Impact of Weight Loss Intervention on Changes in Cognitive Function: Exploratory Analyses from the Action for Health in Diabetes Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Espeland, Mark A; Carmichael, Owen; Hayden, Kathleen; Neiberg, Rebecca H; Newman, Anne B; Keller, Jeffery N; Wadden, Thomas A; Rapp, Stephen R; Hill, James O; Horton, Edward S; Johnson, Karen C; Wagenknecht, Lynne; Wing, Rena R

    2018-03-14

    Diabetes adversely impacts cognition. Lifestyle change can improve diabetes control and potentially improve cognition. We examined whether weight loss through reduced caloric intake and increased physical activity was associated with slower cognitive aging in older adults with type 2 diabetes mellitus. The Look AHEAD randomized controlled clinical trial delivered 10 years of intensive lifestyle intervention (ILI) that yielded long-term weight losses. During 5 years spanning the end of intervention and postintervention follow-up, repeated cognitive assessments were obtained in 1,091 individuals who had been assigned to ILI or a control condition of diabetes support and education (DSE). We compared the means and slopes of scores on cognitive testing over these repeated assessments. Compared with DSE, assignment to ILI was associated with a -0.082 SD deficit in mean global cognitive function across repeated assessments (p = .010). However, overweight (body mass index [BMI] memory. The behavioral weight loss intervention was associated with small relative deficits in cognitive function among individuals who were obese and marginally greater cognitive decline overall compared to control. ClinicalTrials.gov Identifier: NCT00017953.

  6. Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Mehdi Hadadzadeh

    2013-10-01

    Full Text Available Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB. The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (<35%, candidate for elective OPCAB, were enrolled in this study. They were randomly assigned to two groups. One group received milrinone (50 μg/kg intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 μg/kg/min. Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05. The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031. There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

  7. Effects of a manualized short-term treatment of internet and computer game addiction (STICA: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jäger Susanne

    2012-04-01

    Full Text Available Abstract Background In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA and computer addiction (CA in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy. Methods/design This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA. The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment. Discussion A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed. Trial Registration ClinicalTrials (NCT01434589

  8. Effects of a manualized short-term treatment of internet and computer game addiction (STICA): study protocol for a randomized controlled trial

    Science.gov (United States)

    2012-01-01

    Background In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA) and computer addiction (CA) in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy. Methods/design This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA). The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression) will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment. Discussion A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed. Trial Registration ClinicalTrials (NCT01434589) PMID:22540330

  9. Short-Term Effects of Kinesio Taping in Women with Pregnancy-Related Low Back Pain: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Kaplan, Şeyhmus; Alpayci, Mahmut; Karaman, Erbil; Çetin, Orkun; Özkan, Yasemin; İlter, Server; Şah, Volkan; Şahin, Hanım Güler

    2016-04-18

    BACKGROUND Pregnancy-related low back pain is a common condition during pregnancy. Kinesio tape is a drug-free elastic therapeutic tape used for treating various musculoskeletal problems. The aim of this study was to investigate the short-term effects of lumbar Kinesio taping on pain intensity and disability in women with pregnancy-related low back pain. MATERIAL AND METHODS A total of 65 patients with pregnancy-related low back pain were randomly allocated into either Kinesio taping (n=33) or control (n=32) groups. The intervention group was treated with paracetamol plus Kinesio taping, while the control group received only paracetamol. Kinesio taping was applied in the lumbar flexion position, and four I-shaped bands were used. Two bands were attached horizontally, with space correction technique. The remaining 2 bands, 1 on each side of the lumbar spine, were placed vertically, with inhibition technique. Low back pain intensity was measured on a 10-cm visual analogue scale (VAS), and the Roland-Morris Disability Questionnaire (RMDQ) was used for evaluation of disability. RESULTS Pain intensity and RMDQ scores improved significantly in both groups at 5 days compared with baseline. Considering the degree of treatment effect (the change from baseline to day 5), the Kinesio taping group was significantly superior than the control group in all outcome measures (for all, Plow back pain.

  10. Long-term outcome of a randomized controlled universal prevention trial through a positive parenting program: is it worth the effort?

    Science.gov (United States)

    Hahlweg, Kurt; Heinrichs, Nina; Kuschel, Annett; Bertram, Heike; Naumann, Sebastian

    2010-05-16

    Approximately 20% of children experience internalizing or externalizing DSM-IV-TR disorders. This prevalence rate cannot be reduced through treatment only. Effective preventive interventions are therefore urgently needed. The aim of the current investigation is to evaluate the two-year efficacy of the group Triple P parenting program administered universally for the prevention of child behavior problems. Based on their respective preschool, N = 280 families were randomly assigned either to the parent training or to the control group. The efficacy was analyzed using multi-source assessments, including questionnaires by mother and father, behavioral observation of mother-child interaction, and teacher evaluations. At the 2-year follow-up, both parents in the Triple P intervention reported significant reductions in dysfunctional parenting behavior, and mothers also an increase in positive parenting behavior. In addition, mothers reported significant reductions in internalizing and externalizing child behavior. Single-parent mothers in the Triple P intervention did not report significant changes in parenting or child problem behavior which is primarily due to inexplicable high positive effects in single parent mothers of the control group. Neither mother-child interactions nor teacher ratings yielded significant results. The results support the long-term efficacy of the Triple P - group program as a universal prevention intervention for changing parenting behavior in two-parent households, but not necessarily in single-parent mothers.

  11. Effects of a manualized short-term treatment of internet and computer game addiction (STICA): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Jäger, Susanne; Müller, Kai W; Ruckes, Christian; Wittig, Tobias; Batra, Anil; Musalek, Michael; Mann, Karl; Wölfling, Klaus; Beutel, Manfred E

    2012-04-27

    In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA) and computer addiction (CA) in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy. This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA). The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression) will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment. A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed. ClinicalTrials (NCT01434589).

  12. Long-term outcome of a randomized controlled universal prevention trial through a positive parenting program: is it worth the effort?

    Directory of Open Access Journals (Sweden)

    Bertram Heike

    2010-05-01

    Full Text Available Abstract Background Approximately 20% of children experience internalizing or externalizing DSM-IV-TR disorders. This prevalence rate cannot be reduced through treatment only. Effective preventive interventions are therefore urgently needed. The aim of the current investigation is to evaluate the two-year efficacy of the group Triple P parenting program administered universally for the prevention of child behavior problems. Methods Based on their respective preschool, N = 280 families were randomly assigned either to the parent training or to the control group. The efficacy was analyzed using multi-source assessments, including questionnaires by mother and father, behavioral observation of mother-child interaction, and teacher evaluations. Results At the 2-year follow-up, both parents in the Triple P intervention reported significant reductions in dysfunctional parenting behavior, and mothers also an increase in positive parenting behavior. In addition, mothers reported significant reductions in internalizing and externalizing child behavior. Single-parent mothers in the Triple P intervention did not report significant changes in parenting or child problem behavior which is primarily due to inexplicable high positive effects in single parent mothers of the control group. Neither mother-child interactions nor teacher ratings yielded significant results. Conclusions The results support the long-term efficacy of the Triple P - group program as a universal prevention intervention for changing parenting behavior in two-parent households, but not necessarily in single-parent mothers.

  13. Low-Intensity Wheelchair Training in Inactive People with Long-Term Spinal Cord Injury: A Randomized Controlled Trial on Propulsion Technique.

    Science.gov (United States)

    van der Scheer, Jan W; de Groot, Sonja; Vegter, Riemer J K; Hartog, Johanneke; Tepper, Marga; Slootman, Hans; Veeger, DirkJan H E J; van der Woude, Lucas H V

    2015-11-01

    The objective of this study was to investigate the effects of a low-intensity wheelchair training on propulsion technique in inactive people with long-term spinal cord injury. Participants in this multicenter nonblinded randomized controlled trial were inactive manual wheelchair users with spinal cord injury for at least 10 yrs (N = 29), allocated to exercise (n = 14) or no exercise. The 16-wk training consisted of wheelchair treadmill propulsion at 30%-40% heart rate reserve or equivalent in rate of perceived exertion, twice a week, 30 mins per session. Propulsion technique was assessed at baseline as well as after 8, 16, and 42 wks during two submaximal treadmill-exercise blocks using a measurement wheel attached to a participant's own wheelchair. Changes over time between the groups were analyzed using Mann-Whitney U tests on difference scores (P propulsion technique were not found in this group. Perhaps, substantial effects require a higher intensity or frequency. Investigating whether more effective and feasible interventions exist might help reduce the population's risk of upper-body joint damage during daily wheelchair propulsion.

  14. Assessing and comparing the short-term effects of TPB only and TPB plus implementation intentions interventions on snacking behavior in Iranian adolescent girls: a cluster randomized trial.

    Science.gov (United States)

    Karimi-Shahanjarini, Akram; Rashidian, Arash; Omidvar, Nasrin; Majdzadeh, Reza

    2013-01-01

    The evidence for the effectiveness of theory of planned behavior (TPB)-based interventions is mixed. There is also mixed evidence on the effectiveness of adding implementation intentions to TPB-based interventions. In this study we assessed and compared the short-term effects of TPB-only intervention and TPB plus implementation intentions intervention on snacking behavior and intention to consume unhealthy snacks in Iranian adolescent girls. Three-arm cluster randomized controlled trial. Ten middle schools in Tehran (Iran). A total of 29 classes included 739 female adolescents (age range: 12-15 years). Intervention. Two brief interventions including TPB-only intervention and TPB plus implementation intentions intervention. Food frequency questionnaire and intentions at baseline, 10 days, and 3 months measuring snacking behavior and cognitions about unhealthy snack consumption, respectively. Hierarchical linear modeling to assess the interventions' effects. Both interventions successfully decreased intention to consume and consumption of unhealthy snacks at postintervention. Calculation of the effect sizes revealed that the TPB plus implementation intentions intervention was more effective than the TPB-only intervention. The effects remained significant at 3-month follow-up in the TPB plus implementation intentions intervention group only, although the effect size decreased. Overall, the study suggests that adding implementation intentions on top of TPB-based persuasive messages improves effectiveness and sustainability of desirable changes.

  15. Peptide Integrated Optics.

    Science.gov (United States)

    Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil

    2018-02-01

    Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Antimicrobial Peptides from Plants

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    James P. Tam

    2015-11-01

    Full Text Available Plant antimicrobial peptides (AMPs have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic, lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.

  17. The long-term effects of naprapathic manual therapy on back and neck pain - Results from a pragmatic randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bohman Tony

    2010-02-01

    Full Text Available Abstract Background Back and neck pain are very common, disabling and recurrent disorders in the general population and the knowledge of long-term effect of treatments are sparse. The aim of this study was to compare the long-term effects (up to one year of naprapathic manual therapy and evidence-based advice on staying active regarding non-specific back and/or neck pain. Naprapathy, a health profession mainly practiced in Sweden, Finland, Norway and in the USA, is characterized by a combination of manual musculoskeletal manipulations, aiming to decrease pain and disability in the neuromusculoskeletal system. Methods Subjects with non-specific pain/disability in the back and/or neck lasting for at least two weeks (n = 409, recruited at public companies in Sweden, were included in this pragmatic randomized controlled trial. The two interventions compared were naprapathic manual therapy such as spinal manipulation/mobilization, massage and stretching, (Index Group, and advice to stay active and on how to cope with pain, provided by a physician (Control Group. Pain intensity, disability and health status were measured by questionnaires. Results 89% completed the 26-week follow-up and 85% the 52-week follow-up. A higher proportion in the Index Group had a clinically important decrease in pain (risk difference (RD = 21%, 95% CI: 10-30 and disability (RD = 11%, 95% CI: 4-22 at 26-week, as well as at 52-week follow-ups (pain: RD = 17%, 95% CI: 7-27 and disability: RD = 17%, 95% CI: 5-28. The differences between the groups in pain and disability considered over one year were statistically significant favoring naprapathy (p ≤ 0.005. There were also significant differences in improvement in bodily pain and social function (subscales of SF-36 health status favoring the Index Group. Conclusions Combined manual therapy, like naprapathy, is effective in the short and in the long term, and might be considered for patients with non-specific back and/or neck

  18. Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study.

    Science.gov (United States)

    Zhou, Yongfang; Jin, Xiaodong; Kang, Yan; Liang, Guopeng; Liu, Tingting; Deng, Ni

    2014-06-16

    Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients. A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events. The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01). Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical

  19. Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study

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    Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France); Chabaud, Sylvie [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Lagrange, Jean-Leon [Department of Radiation Oncology, Centre Hospitalo-Universitaire H. Mondor, Créteil (France); Richaud, Pierre [Department of Radiation Oncology, Institut Bergognié, Bordeaux (France); Le Prise, Elisabeth [Department of Radiation Oncology, Centre Eugène Marquis, Rennes (France); Wagner, Jean-Philippe [Department of Radiation Oncology, Institut Andrée Dutreix, Dunkerque (France); Azria, David [Department of Radiation Oncology, Institut de Cancérologie de Montpellier, Montpellier (France); Beckendorf, Veronique [Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy (France); Suchaud, Jean-Philippe [Department of Radiation Oncology, Centre Hospitalier de Roanne, Roanne (France); Bernier, Valerie [Department of Radiation Oncology, Centre Oscar Lambret, Lille (France); Perol, David [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Carrie, Christian [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France)

    2016-11-15

    Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

  20. An interdisciplinary knowledge translation intervention in long-term care: Study protocol for the vitamin D and osteoporosis study (ViDOS pilot cluster randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kennedy Courtney C

    2012-05-01

    Full Text Available Abstract Background Knowledge translation (KT research in long-term care (LTC is still in its early stages. This protocol describes the evaluation of a multifaceted, interdisciplinary KT intervention aimed at integrating evidence-based osteoporosis and fracture prevention strategies into LTC care processes. Methods and design The Vitamin D and Osteoporosis Study (ViDOS is underway in 40 LTC homes (n = 19 intervention, n = 21 control across Ontario, Canada. The primary objectives of this study are to assess the feasibility of delivering the KT intervention, and clinically, to increase the percent of LTC residents prescribed ≥800 IU of vitamin D daily. Eligibility criteria are LTC homes that are serviced by our partner pharmacy provider and have more than one prescribing physician. The target audience within each LTC home is the Professional Advisory Committee (PAC, an interdisciplinary team who meets quarterly. The key elements of the intervention are three interactive educational sessions led by an expert opinion leader, action planning using a quality improvement cycle, audit and feedback reports, nominated internal champions, and reminders/point-of-care tools. Control homes do not receive any intervention, however both intervention and control homes received educational materials as part of the Ontario Osteoporosis Strategy. Primary outcomes are feasibility measures (recruitment, retention, attendance at educational sessions, action plan items identified and initiated, internal champions identified, performance reports provided and reviewed, and vitamin D (≥800 IU/daily prescribing at 6 and 12 months. Secondary outcomes include the proportion of residents prescribed calcium supplements and osteoporosis medications, and falls and fractures. Qualitative methods will examine the experience of the LTC team with the KT intervention. Homes are centrally randomized to intervention and control groups in blocks of variable size using

  1. Effectiveness of a long-term use of a minimalist footwear versus habitual shoe on pain, function and mechanical loads in knee osteoarthritis: a randomized controlled trial.

    Science.gov (United States)

    Trombini-Souza, Francis; Fuller, Ricardo; Matias, Alessandra; Yokota, Mariane; Butugan, Marco; Goldenstein-Schainberg, Claudia; Sacco, Isabel C N

    2012-07-12

    Recent studies have shown an important reduction of joint overload during locomotion in elderly women with knee osteoarthritis (OA) after short-term use of minimalist shoes. Our aim is to investigate the chronic effect of inexpensive and minimalist footwear on the clinical and functional aspects of OA and gait biomechanics of elderly women with knee OA. Fifty-six elderly women with knee OA grade 2 or 3 (Kellgren and Lawrence) are randomized into blocks and allocated to either the intervention group, which will use flexible, non-heeled shoes- Moleca®-for six months for at least six hours daily, or the control group, which could not use these shoes. Neither group is undergoing physical therapy treatment throughout the intervention period. Moleca® is a women's double canvas, flexible, flat walking shoe without heels, with a 5-mm anti-slip rubber sole and a 3-mm internal wedge of ethylene vinyl acetate. Both groups will be followed for six months and will be assessed at baseline condition, after three months, and after six months (end of intervention). All the assessments will be performed by a physiotherapist that is blind to the group allocation. The primary outcome is the pain Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score. The secondary outcomes are global WOMAC score; joint stiffness and disability WOMAC scores; knee pain with a visual analogue scale; walking distance in the six-minute walk test; Lequesne score; amount and frequency (number of days) of paracetamol (500 mg) intake over six months; knee adduction moment during gait; global medical assessment score; and global patient auto-assessment score. At baseline, all patients receive a diary to record the hours of daily use of the footwear intervention; every two weeks, the same physiotherapist makes phone calls to all patients in order to verify adherence to treatment. The statistical analysis will be based on intention-to-treat analysis, as well as general linear models of

  2. Effectiveness of a long-term use of a minimalist footwear versus habitual shoe on pain, function and mechanical loads in knee osteoarthritis: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Trombini-Souza Francis

    2012-07-01

    Full Text Available Abstract Background Recent studies have shown an important reduction of joint overload during locomotion in elderly women with knee osteoarthritis (OA after short-term use of minimalist shoes. Our aim is to investigate the chronic effect of inexpensive and minimalist footwear on the clinical and functional aspects of OA and gait biomechanics of elderly women with knee OA. Methods/Design Fifty-six elderly women with knee OA grade 2 or 3 (Kellgren and Lawrence are randomized into blocks and allocated to either the intervention group, which will use flexible, non-heeled shoes— Moleca®—for six months for at least six hours daily, or the control group, which could not use these shoes. Neither group is undergoing physical therapy treatment throughout the intervention period. Moleca® is a women’s double canvas, flexible, flat walking shoe without heels, with a 5-mm anti-slip rubber sole and a 3-mm internal wedge of ethylene vinyl acetate. Both groups will be followed for six months and will be assessed at baseline condition, after three months, and after six months (end of intervention. All the assessments will be performed by a physiotherapist that is blind to the group allocation. The primary outcome is the pain Western Ontario and McMaster Universities Osteoarthritis (WOMAC score. The secondary outcomes are global WOMAC score; joint stiffness and disability WOMAC scores; knee pain with a visual analogue scale; walking distance in the six-minute walk test; Lequesne score; amount and frequency (number of days of paracetamol (500 mg intake over six months; knee adduction moment during gait; global medical assessment score; and global patient auto-assessment score. At baseline, all patients receive a diary to record the hours of daily use of the footwear intervention; every two weeks, the same physiotherapist makes phone calls to all patients in order to verify adherence to treatment. The statistical analysis will be based on intention

  3. Efficacy and cost-effectiveness of an experimental short-term inpatient Dialectical Behavior Therapy (DBT) program: study protocol for a randomized controlled trial.

    Science.gov (United States)

    van den Bosch, Louisa M C; Sinnaeve, Roland; Hakkaart-van Roijen, Leona; van Furth, Eric F

    2014-05-01

    outpatient patients can pose a dilemma for mental health care professionals. Although hospitalization seems inevitable under some circumstances, it has proven to be harmful in its own right. This paper outlines the background and methods of a randomized trial evaluating the possible surplus value of a short-term inpatient DBT program.

  4. Long-term HPV type-specific risks for ASCUS and LSIL: a 14-year follow-up of a randomized primary HPV screening trial.

    Science.gov (United States)

    Elfström, K Miriam; Smelov, Vitaly; Johansson, Anna L V; Eklund, Carina; Naucler, Pontus; Arnheim-Dahlström, Lisen; Dillner, Joakim

    2015-01-15

    Human papillomavirus (HPV) infections result in a significant burden of low-grade cervical lesions. Between 1997 and 2000, our randomized trial of primary HPV screening enrolled 12,527 women participating in population-based screening. Women between 32 and 38 years of age (median: 34, interquartile range: 33-37) were randomized to HPV and cytology double testing (intervention arm, n = 6,257 enrolled, n = 5,888 followed-up) or to cytology, with samples frozen for future HPV testing (control arm, n = 6,270 enrolled, n = 5,795 followed-up). We estimated the HPV type-specific, long-term absolute risks (AR), and population attributable proportions (PAR) for cytological diagnoses of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) and for histopathologically diagnosed cervical intraepithelial neoplasia grade 1 (CIN1). The women were followed using comprehensive, nationwide register-based follow-up. During a mean follow-up time of 11.07 years, 886 ASCUS and LSIL lesions were detected, 448 in the intervention arm and 438 in the control arm. Poisson regression estimated the incidence rate ratios (IRRs) of low-grade lesions by HPV type. The IRRs were strongly dependent on follow-up time. The IRRs for ASCUS/LSIL associated with high-risk HPV positivity were 18.6 (95% CI: 14.9-23.4) during the first screening round, 4.1 (95% CI: 2.8-6.2) during the second, 2.6 (95% CI: 1.7-4.1) during the third, and 1.1 (95% CI: 0.7-1.8) for >9 years of follow-up, with similar declines seen for the individual types. Type 16 contributed consistently to the greatest proportion of ASCUS, LSIL, and CIN1 risk in the population (first screening round PAR: ASCUS: 15.5% (95% CI: 9.7-21.9), LSIL: 14.7% (95% CI: 8.0-20.9), and CIN1: 13.4% (95% CI: 3.2-22.5)), followed by type 31 [8.4% (95% CI: 4.2-12.5) for ASCUS to 17.3% (95% CI: 6.8-26.6) for CIN1]. In summary, most ASCUS/LSIL lesions associated with HPV infection are caused by new HPV

  5. Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers

    Science.gov (United States)

    Rexeisen, Emilie Lynn

    umbilical vein endothelial cells and alpha5beta1 integrins immobilized on an AFM tip preferred binding to a fibronectin mimetic peptide that contained both hydrophilic and hydrophobic residues in the linker and a medium length spacer. Most cells require a three-dimensional scaffold in order to thrive. To incorporate the fibronectin mimetic peptide into a three-dimensional structure, a single hydrocarbon tail was attached to form a peptideamphiphile. Single-tailed peptide-amphiphiles have been shown to form nanofibers in solution and gel after screening of the electrostatic charges in the headgroup. These gels show promise as scaffolds for tissue engineering. A fibronectin mimetic peptide-amphiphile containing a linker with alternating hydrophobic and hydrophilic residues was designed to form nanofibers in solution. The critical micelle concentration of the peptide-amphiphile was determined to be 38 muM, and all subsequent experiments were performed above this concentration. Circular dichroism (CD) spectroscopy indicated that the peptide headgroup of the peptide-amphiphile forms an alpha+beta secondary structure; whereas, the free peptide forms a random secondary structure. Cryogenic-transmission electron microscopy (cryo-TEM) and small angle neutron scattering showed that the peptide-amphiphile self-assembled into nanofibers. The cryo-TEM images showed single nanofibers with a diameter of 10 nm and lengths on the order of microns. Images of higher peptideamphiphile concentrations showed evidence of bundling between individual nanofibers, which could give rise to gelation behavior at higher concentrations. The peptide-amphiphile formed a gel at concentrations above 6 mM. A 10 mM sample was analyzed with oscillating plate rheometry and was found to have an elastic modulus within the range of living tissue, showing potential as a possible scaffold for tissue engineering.

  6. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    ) , which promotes intestinal growth and is used to treat bowel disorders such as inflammatory bowel diseases and short bowel syndrome, and the 32 amino acid salmon calcitonin (sCT), which lowers blood calcium and is employed in the treatment of post-menopausal osteoporosis and hypercalcemia. The two...... peptides are similar in size and structure, but oppositely charged at physiological pH. Both peptides were acylated with linear acyl chains of systematically increasing length, where sCT was furthermore acylated at two different positions on the peptide backbone. For GLP-2, we found that increasing acyl...... remained optimal overall. The results indicate that rational acylation of GLP-2 can increase its in vitro intestinal absorption, alone or in combination with permeation enhancers, and are consistent with the initial project hypothesis. For sCT, an unpredicted effect of acylation largely superseded...

  7. On Random Numbers and Design

    Science.gov (United States)

    Ben-Ari, Morechai

    2004-01-01

    The term "random" is frequently used in discussion of the theory of evolution, even though the mathematical concept of randomness is problematic and of little relevance in the theory. Therefore, since the core concept of the theory of evolution is the non-random process of natural selection, the term random should not be used in teaching the…

  8. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  9. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    of these are currently being used in quantitative structure--activity relationship (QSAR) studies for AMP optimization. Additionally, some key commercial computational tools are discussed, and both successful and less successful studies are referenced, illustrating some of the challenges facing AMP scientists. Through...... examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion. Expert opinion: Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge...

  10. Effects of hybrid cycling versus handcycling on wheelchair-specific fitness and physical activity in people with long-term spinal cord injury : a 16-week randomized controlled trial

    NARCIS (Netherlands)

    Bakkum, A. J. T.; de Groot, S.; Stolwijk-Swuste, J. M.; van Kuppevelt, D. J.; van der Woude, L. H. V.; Janssen, T. W. J.

    Study design: This is an open randomized controlled trial. Objective: The objective of this study was to investigate the effects of a 16-week hybrid cycle versus handcycle exercise program on fitness and physical activity in inactive people with long-term spinal cord injury (SCI). Setting: The study

  11. Effects of hybrid cycling versus handcycling on wheelchair-specific fitness and physical activity in people with long-term spinal cord injury: a 16-week randomized controlled trial

    NARCIS (Netherlands)

    Bakkum, A.J.T.; de Groot, S.; Stolwijk-Swuste, J.M.; van Kuppevelt, D.J.; van der Woude, L.H.V.; Janssen, T.W.J.

    2015-01-01

    Study design:This is an open randomized controlled trial.Objective:The objective of this study was to investigate the effects of a 16-week hybrid cycle versus handcycle exercise program on fitness and physical activity in inactive people with long-term spinal cord injury (SCI).Setting:The study was

  12. Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: RENEW: a randomized controlled trial.

    Science.gov (United States)

    Morey, Miriam C; Snyder, Denise C; Sloane, Richard; Cohen, Harvey Jay; Peterson, Bercedis; Hartman, Terryl J; Miller, Paige; Mitchell, Diane C; Demark-Wahnefried, Wendy

    2009-05-13

    Five-year survival rates for early stage colorectal, breast, and prostate cancer currently exceed 90% and are increasing. Cancer survivors are at greater risk for second malignancies, other comorbidities, and accelerated functional decline. Lifestyle interventions may provide benefit, but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status. To determine whether a telephone counseling and mailed print material-based diet and exercise intervention is effective in reorienting functional decline in older, overweight cancer survivors. Randomized controlled trial of 641 overweight (body mass index > or = 25 and or = 5 years) survivors (aged 65-91 years) of colorectal, breast, and prostate cancer, who were randomly assigned to an intervention group (n = 319) or delayed intervention (control) group (n = 322) in Canada, the United Kingdom, and 21 US states. Individuals were recruited for the Reach out to Enhance Wellness (RENEW) trial from July 1, 2005, through May 17, 2007. A 12-month, home-based tailored program of telephone counseling and mailed materials promoting exercise, improved diet quality, and modest weight loss. The control group was wait-listed for 12 months. Change in self-reported physical function on the Short-Form 36 physical function subscale (score range, 0-100; a high score indicates better functioning) from baseline to 12 months was the primary end point. Secondary outcomes included changes in function on the basic and advanced lower extremity function subscales of the Late Life Function and Disability Index (score range, 0-100), physical activity, body mass index, and overall health-related quality of life. The mean baseline Short-Form 36 physical function score was 75.7. At the 12-month follow-up, the mean function scores declined less rapidly in the intervention group (-2.15; 95% confidence interval [CI], -0.36 to -3.93) compared with the control group (-4.84; 95% CI, -3

  13. Short- and Long-Term Effects of Wholegrain Oat Intake on Weight Management and Glucolipid Metabolism in Overweight Type-2 Diabetics: A Randomized Control Trial

    Directory of Open Access Journals (Sweden)

    Xue Li

    2016-09-01

    Full Text Available Glycemic control and weight reduction are primary goals for the management of overweight and obese type 2 diabetes mellitus (T2DM. Effective management cannot be achieved without an appropriate diet. Our study aimed to evaluate the short- and long-term effects of oat intake and develop a reasonable dietary plan for overweight T2DM patients. A randomized control trial, registered under ClinicalTrials.gov (Identification code: NCT01495052, was carried out among adult T2DM patients. A subgroup of 298 overweight subjects was selected and received a 30-day centralized intervention and 1-year free-living follow-up. Participants were randomly allocated to one of the following four groups. The usual care group (n = 60 received no intervention; the healthy diet group (n = 79 received a low-fat and high-fiber diet (“healthy diet”; the 50 g-oats group (n = 80 and 100 g-oats group (n = 79 received the “healthy diet” with the same amount of cereals replaced by 50 g and 100 g oats respectively. Anthropometric, blood glycemic and lipid variables were measured. For the 30-day intervention, significant differences in the changes of FPG (fasting plasma glucose, PPG (postprandial plasma glucose, HbA1c (glycosylated hemoglobin, HOMA-IR (homeostasis model assessment of insulin resistance, TC (total cholesterol, TG (total triglycerides, and LDL-c (low-density lipoprotein cholesterol were observed among the four groups. Compared to the healthy diet group, the 50 g-oats group had a bigger reduction in PPG (mean difference (MD: −1.04 mmol/L; 95% CI: −2.03, −0.05 and TC (MD: −0.24 mmol/L; 95% CI: −0.47, −0.01; the 100 g-oats group had a bigger reduction in PPG (MD: −1.48 mmol/L; 95% CI: −2.57, −0.39, HOMA-IR (MD: −1.77 mU·mol/L2; 95% CI: −3.49, −0.05, TC (MD: −0.33 mmol/L; 95% CI: −0.56, −0.10 and LDL-c (MD: −0.22 mmol/L; 95% CI: −0.41, −0.03. In the 1-year follow-up, greater effects in reducing weight (MD: −0.89 kg; 95% CI

  14. Short- and medium-term efficacy of a Web-based computer-tailored nutrition education intervention for adults including cognitive and environmental feedback: randomized controlled trial.

    Science.gov (United States)

    Springvloet, Linda; Lechner, Lilian; de Vries, Hein; Candel, Math J J M; Oenema, Anke

    2015-01-19

    Web-based, computer-tailored nutrition education interventions can be effective in modifying self-reported dietary behaviors. Traditional computer-tailored programs primarily targeted individual cognitions (knowledge, awareness, attitude, self-efficacy). Tailoring on additional variables such as self-regulation processes and environmental-level factors (the home food environment arrangement and perception of availability and prices of healthy food products in supermarkets) may improve efficacy and effect sizes (ES) of Web-based computer-tailored nutrition education interventions. This study evaluated the short- and medium-term efficacy and educational differences in efficacy of a cognitive and environmental feedback version of a Web-based computer-tailored nutrition education intervention on self-reported fruit, vegetable, high-energy snack, and saturated fat intake compared to generic nutrition information in the total sample and among participants who did not comply with dietary guidelines (the risk groups). A randomized controlled trial was conducted with a basic (tailored intervention targeting individual cognition and self-regulation processes; n=456), plus (basic intervention additionally targeting environmental-level factors; n=459), and control (generic nutrition information; n=434) group. Participants were recruited from the general population and randomly assigned to a study group. Self-reported fruit, vegetable, high-energy snack, and saturated fat intake were assessed at baseline and at 1- (T1) and 4-months (T2) postintervention using online questionnaires. Linear mixed model analyses examined group differences in change over time. Educational differences were examined with group×time×education interaction terms. In the total sample, the basic (T1: ES=-0.30; T2: ES=-0.18) and plus intervention groups (T1: ES=-0.29; T2: ES=-0.27) had larger decreases in high-energy snack intake than the control group. The basic version resulted in a larger decrease in

  15. Peptide Based Radiopharmaceuticals: Specific Construct Approach

    Energy Technology Data Exchange (ETDEWEB)

    Som, P; Rhodes, B A; Sharma, S S

    1997-10-21

    The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures). In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays

  16. Effects of prenatal music stimulation on state/trait anxiety in full-term pregnancy and its influence on childbirth: a randomized controlled trial.

    Science.gov (United States)

    García González, J; Ventura Miranda, M I; Requena Mullor, M; Parron Carreño, T; Alarcón Rodriguez, R

    2018-04-01

    Many researchers have pointed out the strong relationship between maternal psychological well-being and fetal welfare during pregnancy. The impact of music interventions during pregnancy should be examined in depth, as they could have an impact on stress reduction, not only during pregnancy but also during the course of delivery, and furthermore induce fetal awareness. This study aimed to investigate the effect of music on maternal anxiety, before and after a non-stress test (NST), and the effect of music on the birthing process. The four hundred and nine pregnant women coming for routine prenatal care were randomized in the third trimester to receive either music (n = 204) or no music (n = 205) stimulation during an NST. The primary outcome was considered as the maternal state anxiety score before and after the NST, and the secondary outcome was the birthing process. Before their NST, full-term pregnant women who had received music intervention were found to have a similar state-trait anxiety score to those from the control group, with 38.10 ± 8.8 and 38.08 ± 8.2, respectively (p = .97). After the NST, the mean state-trait anxiety score of each group was recorded, with results of 30.58 ± 13.2 for those with music intervention, and 43.11 ± 15.0 for those without music intervention (p < .001). In the control group, the NST was followed by a statistically significant increase in the state-trait anxiety score (38.08 ± 8.2 versus 43.11 ± 15.0, p < .001). However, listening to music during the NST resulted in a statistically significant decrease in the state-trait anxiety score of the study group (38.10 ± 8.8 versus 30.58 ± 13.2, OR = 0.87, p < .001). Furthermore, the first stage of labor was shorter in women who received music stimulation (OR = 0.92, p < .004). They also presented a more natural delivery beginning (spontaneous) and less medication (stimulated and induced) than those who were

  17. Effects of long-term balance training with vibrotactile sensory augmentation among community-dwelling healthy older adults: a randomized preliminary study.

    Science.gov (United States)

    Bao, Tian; Carender, Wendy J; Kinnaird, Catherine; Barone, Vincent J; Peethambaran, Geeta; Whitney, Susan L; Kabeto, Mohammed; Seidler, Rachael D; Sienko, Kathleen H

    2018-01-18

    Sensory augmentation has been shown to improve postural stability during real-time balance applications. Limited long-term controlled studies have examined retention of balance improvements in healthy older adults after training with sensory augmentation has ceased. This pilot study aimed to assess the efficacy of long-term balance training with and without sensory augmentation among community-dwelling healthy older adults. Twelve participants (four males, eight females; 75.6 ± 4.9 yrs) were randomly assigned to the experimental group (n = 6) or control group (n = 6). Participants trained in their homes for eight weeks, completing three 45-min exercise sessions per week using smart phone balance trainers that provided written, graphic, and video guidance, and monitored trunk sway. During each session, participants performed six repetitions of six exercises selected from five categories (static standing, compliant surface standing, weight shifting, modified center of gravity, and gait). The experimental group received vibrotactile sensory augmentation for four of the six repetitions per exercise via the smart phone balance trainers, while the control group performed exercises without sensory augmentation. The smart phone balance trainers sent exercise performance data to a physical therapist, who recommended exercises on a weekly basis. Balance performance was assessed using a battery of clinical balance tests (Activity Balance Confidence Scale, Sensory Organization Test, Mini Balance Evaluation Systems Test, Five Times Sit to Stand Test, Four Square Step Test, Functional Reach Test, Gait Speed Test, Timed Up and Go, and Timed Up and Go with Cognitive Task) before training, after four weeks of training, and after eight weeks of training. Participants in the experimental group were able to use vibrotactile sensory augmentation independently in their homes. After training, the experimental group had significantly greater improvements in Sensory

  18. Long term effects of self-determination theory and motivational interviewing in a web-based physical activity intervention: randomized controlled trial.

    Science.gov (United States)

    Friederichs, Stijn A H; Oenema, Anke; Bolman, Catherine; Lechner, Lilian

    2015-08-18

    Our main objective in the current study was to evaluate the long-term effectiveness (12 months from baseline) of I Move (a web-based computer tailored physical activity intervention, based on self-determination theory and motivational interviewing). To this end, we compared I Move to a web-based computer tailored physical activity intervention based on traditional health behavior theories (Active Plus), and to a no-intervention control group. As a secondary objective, the present study aimed to identify participant characteristics that moderate the long term effects of I Move and Active Plus. A randomized controlled trial was conducted, comparing three research conditions: 1) the I Move condition, participants in this condition received I Move; 2) the Active Plus condition, participants in this condition received Active Plus; 3) the control condition; participants in this condition received no intervention and were placed on a waiting list. Main outcome measures were weekly minutes of moderate to vigorous physical activity and weekly days with minimal 30 min of physical activity. All measurements were taken by web-based questionnaires via the study website. Intervention effects were analyzed using multilevel linear regression analyses. At 12 months from baseline, I Move was found to be effective in increasing weekly minutes of moderate to vigorous physical activity (ES = .13), while Active Plus was not. In contrast, Active Plus was found to be effective in increasing weekly days with ≥ 30 min PA at 12 months (ES = .11), while I Move was not. No moderators of the effects of I Move were found. The results suggest that web-based computer tailored physical activity interventions might best include elements based on both self-determination theory/motivational interviewing and traditional health behavioral theories. To be more precise, it is arguable that the focus of the theoretical foundations, used in new web-based PA interventions should depend on the

  19. Short-term effects of the "Together at School" intervention program on children's socio-emotional skills: a cluster randomized controlled trial.

    Science.gov (United States)

    Kiviruusu, Olli; Björklund, Katja; Koskinen, Hanna-Leena; Liski, Antti; Lindblom, Jallu; Kuoppamäki, Heini; Alasuvanto, Paula; Ojala, Tiina; Samposalo, Hanna; Harmes, Nina; Hemminki, Elina; Punamäki, Raija-Leena; Sund, Reijo; Santalahti, Päivi

    2016-05-26

    Together at School is a universal intervention program designed to promote socio-emotional skills among primary-school children. It is based on a whole school approach, and implemented in school classes by teachers. The aim of the present study is to examine the short-term effects of the intervention program in improving socio-emotional skills and reducing psychological problems among boys and girls. We also examine whether these effects depend on grade level (Grades 1 to 3) and intervention dosage. This cluster randomized controlled trial design included 79 Finnish primary schools (40 intervention and 39 control) with 3 704 children. The outcome measures were the Strengths and Difficulties Questionnaire (SDQ) and the Multisource Assessment of Social Competence Scale (MASCS) with teachers as raters. The intervention dosage was indicated by the frequencies six central tools were used by the teachers. The data was collected at baseline and 6 months later. Intervention effects were analyzed using multilevel modeling. When analyzed across all grades no intervention effect was observed in improving children's socio-emotional skills or in reducing their psychological problems at 6-month follow-up. Among third (compared to first) graders the intervention decreased psychological problems. Stratified analyses by gender showed that this effect was significant only among boys and that among them the intervention also improved third graders' cooperation skills. Among girls the intervention effects were not moderated by grade. Implementing the intervention with intended intensity (i.e. a high enough dosage) had a significant positive effect on cooperation skills. When analyzed separately among genders, this effect was significant only in girls. These first, short-term results of the Together at School intervention program did not show any main effects on children's socio-emotional skills or psychological problems. This lack of effects may be due to the relatively short follow

  20. What is Result: Short-term Medium Chain Triglyceride Diet Effective on
Postoperative Outcome in Lung Cancer Surgery? A Prospective Randomized Study

    Directory of Open Access Journals (Sweden)

    Na DU

    2016-12-01

    Full Text Available Background and objective It has been proven that medium chain triglyceride (MCT diet was contribute to fast track recovery after surgery in patients with operation. In this study, the benefit of postoperative short term MCT diet support was investigated for non-small cell lung cancer patients who underwent anatomic resection. Methods A prospective study was planned with the approval of our institutional review board. 117 lung cancer patients who underwent anatomic resection in a single medical group between December 2015 and March 2016 were randomized. 62 patients were applied a MCT diet. and 55 patients in the control group who were fed with only normal diet, and the serum albumin levels, anus exhaust time, chest drainage, chest drainage time, the hospitalization time of post operation, average hospital cost were analysed. Results The mean anus exhaust time in MCT group [(27.87±14.38 h] was significantly shorter than that in RDG group [(45.18±8.62 h] (P<0.001; The mean chest tube drainage time in MCT group [(75.40±48.41 h] were less than that in RDG group [(110.64±94.19 h] (P=0.025. The mean chest tube drainage volume in MCT group [395 mL] were less than that in RDG group [590 mL] (P=0.027. The hospitalization time of post operation was (5.26±2.96 d in MCT group against (6.73±3.99 d in RGD group (P=0.030. The serum albumin levels of postoperative in MCT group [(37.26±2.70 g/L] was significantly higher than that in RDG group [(35.92±3.12 g/L] (P=0.023. Conclusion The results of this study demonstrated that postoperative short term MCT diet is beneficial in postoperative gastrointestinal function fast recovered and shorten the hospitalization time in non-small cell lung cancer patients after surgery.

  1. Early prevention of antisocial personality: long-term follow-up of two randomized controlled trials comparing indicated and selective approaches.

    Science.gov (United States)

    Scott, Stephen; Briskman, Jackie; O'Connor, Thomas G

    2014-06-01

    Antisocial personality is a common adult problem that imposes a major public health burden, but for which there is no effective treatment. Affected individuals exhibit persistent antisocial behavior and pervasive antisocial character traits, such as irritability, manipulativeness, and lack of remorse. Prevention of antisocial personality in childhood has been advocated, but evidence for effective interventions is lacking. The authors conducted two follow-up studies of randomized trials of group parent training. One involved 120 clinic-referred 3- to 7-year-olds with severe antisocial behavior for whom treatment was indicated, 93 of whom were reassessed between ages 10 and 17. The other involved 109 high-risk 4- to 6-year-olds with elevated antisocial behavior who were selectively screened from the community, 90 of whom were reassessed between ages 9 and 13. The primary psychiatric outcome measures were the two elements of antisocial personality, namely, antisocial behavior (assessed by a diagnostic interview) and antisocial character traits (assessed by a questionnaire). Also assessed were reading achievement (an important domain of youth functioning at work) and parent-adolescent relationship quality. In the indicated sample, both elements of antisocial personality were improved in the early intervention group at long-term follow-up compared with the control group (antisocial behavior: odds ratio of oppositional defiant disorder=0.20, 95% CI=0.06, 0.69; antisocial character traits: B=-4.41, 95% CI=-1.12, -8.64). Additionally, reading ability improved (B=9.18, 95% CI=0.58, 18.0). Parental expressed emotion was warmer (B=0.86, 95% CI=0.20, 1.41) and supervision was closer (B=-0.43, 95% CI=-0.11, -0.75), but direct observation of parenting showed no differences. Teacher-rated and self-rated antisocial behavior were unchanged. In contrast, in the selective high-risk sample, early intervention was not associated with improved long-term outcomes. Early intervention with

  2. Long-term follow-up of a randomized controlled trial on additional core stability exercises training for improving dynamic sitting balance and trunk control in stroke patients.

    Science.gov (United States)

    Cabanas-Valdés, Rosa; Bagur-Calafat, Caritat; Girabent-Farrés, Montserrat; Caballero-Gómez, Fernanda Mª; du Port de Pontcharra-Serra, Helena; German-Romero, Ana; Urrútia, Gerard

    2017-11-01

    Analyse the effect of core stability exercises in addition to conventional physiotherapy training three months after the intervention ended. A randomized controlled trial. Outpatient services. Seventy-nine stroke survivors. In the intervention period, both groups underwent conventional physiotherapy performed five days/week for five weeks, and in addition the experimental group performed core stability exercises for 15 minutes/day. Afterwards, during a three-month follow-up period, both groups underwent usual care that could eventually include conventional physiotherapy or physical exercise but not in a controlled condition. Primary outcome was trunk control and dynamic sitting balance assessed by the Spanish-Version of Trunk Impairment Scale 2.0 and Function in Sitting Test. Secondary outcomes were standing balance and gait evaluated by the Berg Balance Scale, Tinetti Test, Brunel Balance Assessment, Spanish-Version of Postural Assessment Scale for Stroke and activities of daily living using the Barthel Index. A total of 68 subjects out of 79 completed the three-month follow-up period. The mean difference (SD) between groups was 0.78 (1.51) points ( p = 0.003) for total score on the Spanish-Version of Trunk Impairment Scale 2.0, 2.52 (6.46) points ( p = 0.009) for Function in Sitting Test, dynamic standing balance was 3.30 (9.21) points ( p= 0.009) on the Berg Balance Scale, gait was 0.82 (1.88) points ( p = 0.002) by Brunel Balance Assessment (stepping), and 1.11 (2.94) points ( p = 0.044) by Tinetti Test (gait), all in favour of core stability exercises. Core stability exercises plus conventional physiotherapy have a positive long-term effect on improving dynamic sitting and standing balance and gait in post-stroke patients.

  3. The Effects of Intravenous Hydration on Amniotic Fluid Volume and Pregnancy Outcomes in Women with Term Pregnancy and Oligohydramnios: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mahnaz Shahnazi

    2012-08-01

    Full Text Available Introduction: Amniotic fluid is an important factor in the prediction of fetal survival. The aim of this research was to evaluate the effects of intravenous hydration of mothers on amniotic fluid volume and in turn on pregnancy outcomes. Methods: The current single blind controlled clinical trial was conducted on 20 pregnant mothers with amniot-ic fluid index of lower or equal to 5 cm and gestational age of 37-41 weeks. The subjects were divided into two groups of case and control through simple random sampling. Am-niotic fluid index was measured in all participants. The case group received one liter of isotonic saline during 30 minutes by the bolus method. Reevaluations of amniotic fluid index in both groups were made 90 minutes after baseline measurement. Independent t-test and paired t-test were used to compare the two groups and mean amniotic fluid in-dex before and after treatment, respectively. Results: Hydration of mothers significantly increased the amniotic fluid index in the case group (mean change: 1.5 cm; 95%CI: 0.46 - 2.64; P = 0.01. The mean change of amniotic fluid index in the control group did not significantly increase (P = 0.06. The elevation of amniotic fluid index in the hydra-tion group (32% was significantly higher than the control group (1% (P = 0.03. Conclusion: In this study intravenous hydration increased amniotic fluid index of mothers with term pregnancy and oligohydramnios. Since it caused no complications for the moth-er and the fetus, it can be used as an effective method in management of oligohydramnios.

  4. Does long term sport rock climbing training affect on echocardiography and heart rate variability in sedentary adults? A randomized, and controlled study.

    Directory of Open Access Journals (Sweden)

    Aras Dicle

    2016-03-01

    Full Text Available ABSTRACT: Regular physical activity can cause some long term effects on human body. The purpose of this research was to examine the effect of sport rock climbing (SRC training at 70 % HRmax level on echocardiography (ECHO and heart rate variability (HRV for one hour a day and three days a week in an eight-week period. A total of 19 adults participated in this study voluntarily. The subjects were randomly divided into two groups as experimental (EG and control (CG. While the EG went and did climbing training by using the top-rope method for 60 minutes a day, three days a week for 8 weeks and didn’t join any other physical activity programs, CG didn’t train and take part in any physical activity during the course of the study. Same measurements were repeated at the end of eight weeks. According to the findings, no significant change was observed in any of the ECHO and HRV parameters. However, an improvement was seen in some HRV parameters [average heart rate (HRave, standard deviation of all NN intervals (SDNN, standard deviation of the averages of NN intervals in all five-minute segments of the entire recording (SDANN, percent of difference between adjacent NN intervals that are greater than 50 ms (PNN50, square root of the mean of the sum of the squares of differences between adjacent NN interval (RMSSD] in EG. An exercise program based on SRC should be made more than eight weeks in order to have statistically significant changes with the purpose of observing an improvement in heart structure and functions. Keywords: Echocardiography, heart rate variability, sport rock climbing

  5. SNAP-Ed (Supplemental Nutrition Assistance Program-Education) Increases Long-Term Food Security among Indiana Households with Children in a Randomized Controlled Study.

    Science.gov (United States)

    Rivera, Rebecca L; Maulding, Melissa K; Abbott, Angela R; Craig, Bruce A; Eicher-Miller, Heather A

    2016-11-01

    Food insecurity is negatively associated with US children's dietary intake and health. The Supplemental Nutrition Assistance Program-Education (SNAP-Ed) aims to alleviate food insecurity by offering nutrition, budgeting, and healthy lifestyle education to low-income individuals and families. The objective of this study was to evaluate the long-term impact of the Indiana SNAP-Ed on food security among households with children. A randomized, controlled, parallel study design with SNAP-Ed as an intervention was carried out during a 4- to 10-wk intervention period. Intervention group participants received the first 4 Indiana SNAP-Ed curriculum lessons. Study participants (n = 575) were adults aged ≥18 y from low-income Indiana households with ≥1 child living in the household. Both treatment groups completed an assessment before and after the intervention period and 1 y after recruitment. The 18-item US Household Food Security Survey Module was used to classify the primary outcomes of food security for the household and adults and children in the household. A linear mixed model was used to compare intervention with control group effects over time on food security. Mean ± SEM changes in household food security score and food security score among household adults from baseline to 1-y follow-up were 1.2 ± 0.4 and 0.9 ± 0.3 units lower, respectively, in the intervention group than in the control group (P security score from baseline to 1-y follow-up among household children was not significantly different in the intervention group compared with the control group. SNAP-Ed improved food security over a longitudinal time frame among low-income Indiana households with children in this study. SNAP-Ed may be a successful intervention to improve food security. © 2016 American Society for Nutrition.

  6. HIV gender-based vulnerabilities of women using drugs in long-term heterosexual relationships: baseline results from a randomized trial in Ukraine

    Directory of Open Access Journals (Sweden)

    Shulga, Liudmyla

    2012-07-01

    Full Text Available BACKGROUND: Sexual way of HIV transmission in Ukraine outweighs parenteral route since 2007. In response to situation change couple’s counseling for IDUs was introduced and is currently tested within randomized trial.METHODS: Baseline data were collected in June-September 2011: 548 IDU couples in 10 cities were surveyed and screened for HIV and Hepatitis C. Participants were recruited using respondent-driven sampling method. RESULTS: The average age of participants varied between 30 – 33 years old with women being 3 years younger. On many aspects drug using couples in long-term relationships share the same values as non-drug using couples. However, drug use resulted into specific HIV/STIs risks for the couple. Common reasons of being with the current partner included mutual understanding (98%; similar life styles (90%; understanding life with addiction (88%; and love (87%. At the same time, looking at the quality time partners spend together, it was found that mostly, they are connected by their drug use, fear of social exclusion and economical reasons. Although these factors are important for both men and women, they have a bigger impact on women and put them into more vulnerable position: 25% have children who in 59% of cases mostly live with mother and her partner; 40% live in a partner’s house; 30% are financially supported by partners; 77% women get drugs from partners and only 20% are first one to be injected. Trust also seems to be an issue. Thus, 83% of respondents believe that they know the HIV/STI status of their partner and 90% of those believe it to be negative, while 20% of those surveyed appeared to be HIV positive and about 30% Hepatitis C positive. CONCLUSIONS: Understanding characteristics of sexual partners is crucial for HIV prevention programme design and implementation.

  7. Is the adjuvant albendazole treatment really needed with PAIR in the management of liver hydatid cysts? A prospective, randomized trial with short-term follow-up results.

    Science.gov (United States)

    Akhan, Okan; Yildiz, Adalet Elcin; Akinci, Devrim; Yildiz, Baris Dogu; Ciftci, Turkmen

    2014-12-01

    The purpose of this study was to determine the safety and efficacy of adjuvant albendazole medication in percutaneous liver hydatid cyst treatment with puncture, aspiration, injection, and reaspiration (PAIR) method. Between November 2007 and May 2011, total of 39 patients with newly diagnosed liver hydatid cyst (total of 77 cysts) were prospectively randomized and enrolled in 3 groups. In the first group, cysts (n = 14) were treated with PAIR without albendazole. In the second (n = 16) and third groups (n = 47), cysts were treated with PAIR with albendazole 1 week before and 1 month after the procedure, with albendazole 1 week before and 3 months after the procedure respectively. Technical and clinical success rates were 100 and 96.1% respectively. In 3 of 77 cysts (3.9%), findings of recurrence were detected on US imaging. All recurrent cysts were in group 1 and recurrence rates in this group were statistically different from cysts of second and third groups (p = 0.005). Side effects of albendazole were detected in 7 of 29 patients (24.1%), and no statistically significant difference was observed between the second (15.3%) and third (38.4%) groups (p = 0.378). Use of albendazole medication as an adjuvant to percutaneous treatment of liver hydatid cyst decreases the recurrence rate. Although there is no statistically significant difference between groups 2 and 3 in terms of efficacy and recurrence rate, patients in group 3 had a higher rate of side effect. Therefore, we conclude that albendazole treatment 1 week before and 1 month after PAIR treatment is sufficient to reduce/prevent recurrences.

  8. Physiotherapy and physical functioning post-stroke: exercise habits and functioning 4 years later? Long-term follow-up after a 1-year long-term intervention period: a randomized controlled trial.

    Science.gov (United States)

    Langhammer, Birgitta; Lindmark, Birgitta; Stanghelle, Johan K

    2014-01-01

    Physical activity is mandatory if patients are to remain healthy and independent after stroke. Maintenance of motor function, tone, grip strength, balance, mobility, gait, independence in personal and instrumental activities of daily living, health-related quality-of-life and an active lifestyle 4 years post-stroke. A prospective randomized controlled trial. Four years post-stroke, 37 of the 75 participating persons were eligible for follow-up; 19 (54.3%) from the intensive exercise group and 18 (45%) from the regular exercise group. Both groups were performing equally well with no significant differences in total scores on the BI (p = 0.3), MAS (p = 0.4), BBS (p = 0.1), TUG (p = 0.08), 6MWT (p = 0.1), bilateral grip strength (affected hand, p = 0.8; non-affected hand, p = 0.9) nor in the items of NHP (p > 0.005). Independence in performing the IADL was 40%, while 60% had help from relatives or community-based services. This longitudinal study shows that persons with stroke in two groups with different exercise regimes during the first year after stroke did not differ in long-term outcomes. Both groups maintained function and had a relatively active life style 4 years after the acute incident. The results underline the importance of follow-up testing and encouragement to exercise, to motivate and sustain physical activity patterns, to maintain physical function, not only in the acute but also in the chronic phase of stroke.

  9. Improvement of autism spectrum disorder symptoms in three children by using gastrin‐releasing peptide

    Directory of Open Access Journals (Sweden)

    Michele Michelin Becker

    2016-05-01

    Conclusions: This study suggests that the gastrin‐releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials–randomized, double‐blinded, and with more children–are needed to better evaluate the possible therapeutic effects of gastrin‐releasing peptide in autism.

  10. [Distiller Yeasts Producing Antibacterial Peptides].

    Science.gov (United States)

    Klyachko, E V; Morozkina, E V; Zaitchik, B Ts; Benevolensky, S V

    2015-01-01

    A new method of controlling lactic acid bacteria contamination was developed with the use of recombinant Saccharomyces cerevisiae strains producing antibacterial peptides. Genes encoding the antibacterial peptides pediocin and plantaricin with codons preferable for S. cerevisiae were synthesized, and a system was constructed for their secretory expression. Recombinant S. cerevisiae strains producing antibacterial peptides effectively inhibit the growth of Lactobacillus sakei, Pediacoccus pentasaceus, Pediacoccus acidilactici, etc. The application of distiller yeasts producing antibacterial peptides enhances the ethanol yield in cases of bacterial contamination. Recombinant yeasts producing the antibacterial peptides pediocin and plantaricin can successfully substitute the available industrial yeast strains upon ethanol production.

  11. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... peptides has only been elucidated during the last decade. The cellular synthesis including amino acid modifications and proteolytic cleavages has proven considerably more complex than initially perceived. Consequently, the elimination phase of the peptide products in circulation is not yet well....... An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  12. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

  13. Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.

    Science.gov (United States)

    Jensterle, Mojca; Kravos, Nika Aleksandra; Goričar, Katja; Janez, Andrej

    2017-01-31

    Liraglutide 3 mg was recently approved as an anti-obesity drug. Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist. We compared weight-lowering potential of liraglutide 1.2 mg in combination with metformin to liraglutide 3 mg monotherapy in obese PCOS. Thirty obese women with PCOS (aged 33.1 ± 6.1 years, BMI 38.3 ± 5.4 kg/m 2 ) were randomized to combination (COMBO) of metformin (MET) 1000 mg BID and liraglutide 1.2 mg QD (N = 15) or liraglutide 3 mg (LIRA3) QD alone (N = 15) for 12 weeks. The primary outcome was change in anthropometric measures of obesity. Both treatments led to significant weight loss (-3.6 ± 2.5 kg, p = 0.002 in COMBO vs -6.3 ± 3.7 kg, p = 0.001 in LIRA3). BMI and waist circumference reduction in LIRA3 was greater than in COMBO (-2.2 ± 1.3 vs -1.3 ± 0.9 kg/m 2 , p = 0.05 and -4.2 ± 3.4 vs -2.2 ± 6.2 cm, p = 0.014, respectively). Both interventions resulted in a significant decrease of post-OGTT glucose levels. COMBO significantly reduced total testosterone and was associated with less nausea. Short-term interventions with COMBO and LIRA3 both led to significant improvement of measures of obesity in obese PCOS, LIRA3 being superior to COMBO. However, COMBO further improved androgen profile beyond weight reduction and was associated with better tolerability. The study was retrospectively registered with ClinicalTrials.gov ( NCT02909933 ) on 16 th of September 2016.

  14. The Short-term Effects of ASPIRA: A Web-based, Multimedia Smoking Prevention Program for Adolescents in Romania: A Cluster Randomized Trial.

    Science.gov (United States)

    Nădăşan, Valentin; Foley, Kristie L; Pénzes, Melinda; Paulik, Edit; Mihăicuţă, Ștefan; Ábrám, Zoltán; Bálint, Jozsef; Csibi, Monika; Urbán, Robert

    2017-08-01

    Although web-based, multimedia smoking prevention programs have been tested in several high-income countries, their efficacy in Central and Eastern Europe is unknown. The aim of this trial was to assess the short-term effects of ASPIRA, among Romanian and Hungarian speaking ninth graders in Tirgu Mures, Romania. ASPIRA is the Romanian acronym for the translated and adapted version of ASPIRE, "A Smoking Prevention Interactive Experience," an evidence-based smoking prevention program originally developed to prevent tobacco use among high school students in the United States. Sixteen high schools in Tirgu Mures, Romania were randomized to receive five weekly sessions of the ASPIRA web-based, multimedia program or to a control condition. Socio-demographic data, psychosocial characteristics, and smoking behavior were collected from students at baseline and at 6 months. A hierarchical logistic regression analysis was conducted to test the efficacy of the intervention on smoking initiation and current smoking among 1369 students. Never-smoker students in the intervention arm were 35% less likely to report smoking initiation 6 months after the baseline assessment (OR = 0.65, 95%CI: 0.44-0.97). Reduced smoking initiation was observed most notably among students who were exposed to at least 75% of the ASPIRA program. There was no statistically significant effect of the intervention on current tobacco use (OR = 0.80, 95%CI: 0.44-1.46). ASPIRA, an adapted version of the evidence-based, multimedia ASPIRE program that was originally developed and tested in the United States may decrease smoking initiation among multi-ethnic adolescents in Central and Eastern Europe. (1). Web-based, multimedia smoking prevention programs may be effective tools to prevent smoking initiation among multi-ethnic adolescent communities in Central and Eastern Europe. (2). The degree of exposure is critical, only high exposure to the multimedia smoking prevention program is associated with reduced

  15. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C.; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-01-01

    Background Optimal treatment and precise classification for anaplastic glioma are needed. Methods The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Results Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6–10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4–5.1] y vs 4.4 [3.3–5.3) y), PFS (2.5 [1.3–3.5] y vs 2.7 [1.9–3.2] y), and OS (8 [5.5–10.3] y vs 6.5 [5.4–8.3] y). Oligodendroglial versus astrocytic histology—but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status—revealed a strong prognostic value of CIMPpos with (CIMPcodel) versus without 1p/19 co-deletion (CIMPnon-codel) versus CIMPneg. but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMPcodel tumors (HR B1 vs B2 0.39 [0.17–0.92], P = .031). In CIMPneg. tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. Conclusions There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. Trial Registration: clinicaltrials.gov Identifier: NCT00717210. PMID:27370396

  16. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide.

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-11-01

    Optimal treatment and precise classification for anaplastic glioma are needed. The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6-10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4-5.1] y vs 4.4 [3.3-5.3) y), PFS (2.5 [1.3-3.5] y vs 2.7 [1.9-3.2] y), and OS (8 [5.5-10.3] y vs 6.5 [5.4-8.3] y). Oligodendroglial versus astrocytic histology-but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status-revealed a strong prognostic value of CIMP pos with (CIMP codel ) versus without 1p/19 co-deletion (CIMP non-codel ) versus CIMP neg . but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMP codel tumors (HR B1 vs B2 0.39 [0.17-0.92], P = .031). In CIMP neg . tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. clinicaltrials.gov Identifier: NCT00717210. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. INTERNALIZATION OF ANTIMICROBIAL PEPTIDE ACIPENSIN 1 INTO HUMAN TUMOR CELLS

    Directory of Open Access Journals (Sweden)

    E. S. Umnyakova

    2016-01-01

    Full Text Available Search for new compounds providing delivery of drugs into infected or neoplastic cells, is an important direction of biomedical research. Cell-penetrating peptides are among those compounds, due to their ability to translocate through membranes of eukaryotic cells, serving as potential carriers of various therapeutic agents to the target cells. The aim of present work was to investigate the ability of acipensin 1, an antimicrobial peptide of innate immune system, for in vitro penetration into human tumor cells. Acipensin 1 is a cationic peptide that we have previously isolated from leukocytes of the Russian sturgeon, Acipenser gueldenstaedtii. Capability of acipensin 1 to enter the human erytroleukemia K-562 cells has been investigated for the first time. A biotechnological procedure for producing a recombinant acipensin 1 peptide has been developed. The obtained peptide was conjugated with a fluorescent probe BODIPY FL. By means of confocal microscopy, we have shown that the tagged acipensin 1 rapidly enters into K-562 cells and can be detected in the intracellular space within 5 min after its addition to the cell culture. Using flow cytometry technique, penetration kinetics of the labeled peptide into K-562 cells (at nontoxic micromolar concentrations has been studied. We have observed a rapid internalization of the peptide to the target cells, thus confirming the results of microscopic analysis, i.e, the labeled acipensin was detectable in K-562 cells as soon as wihin 2-3 seconds after its addition to the incubation medium. The maximum of fluorescence was reached within a period of approx. 45 seconds, with further “plateau” at the terms of >100 seconds following cell stimulation with the test compound. These data support the concept, that the antimicrobial peptides of innate immunity system possess the features of cell-penetrating peptides, and allow us to consider the studied sturgeon peptide a promising template for development of new

  18. Impact of Short- and Long-term Tai Chi Mind-Body Exercise Training on Cognitive Function in Healthy Adults: Results From a Hybrid Observational Study and Randomized Trial.

    Science.gov (United States)

    Walsh, Jacquelyn N; Manor, Brad; Hausdorff, Jeffrey; Novak, Vera; Lipsitz, Lewis; Gow, Brian; Macklin, Eric A; Peng, Chung-Kang; Wayne, Peter M

    2015-07-01

    Cognitive decline amongst older adults is a significant public health concern. There is growing interest in behavioral interventions, including exercise, for improving cognition. Studies to date suggest tai chi (TC) may be a safe and potentially effective exercise for preserving cognitive function with aging; however, its short-term and potential long-term impact on physically active, healthy adults is unclear. To compare differences in cognitive function among long-term TC expert practitioners and age-matched and gender-matched TC-naïve adults and to determine the effects of short-term TC training on measures of cognitive function in healthy, nonsedentary adults. A hybrid design including an observational comparison and a 2-arm randomized clinical trial (RCT). Healthy, nonsedentary, TC-naive adults (50 y-79 y) and age-matched and gender-matched long-term TC experts. A cross-sectional comparison of cognitive function in healthy TC-naïve (n=60) and TC expert (24.5 y ÷ 12 y experience; n=27) adults: TC-naïve adults then completed a 6-month, 2-arm, wait-list randomized clinical trial of TC training. Six measures of cognitive function were assessed for both cross-sectional and longitudinal comparisons. TC experts exhibited trends towards better scores on all cognitive measures, significantly so for category fluency (P=.01), as well as a composite z score summarizing all 6 cognitive assessments (P=.03). In contrast, random assignment to 6 months of TC training in TC-naïve adults did not significantly improve any measures of cognitive function. In healthy nonsedentary adults, long-term TC training may help preserve cognitive function; however, the effect of short-term TC training in healthy adults remains unclear. ClinicalTrials.gov NCT01340365.

  19. Duloxetine in the long-term management of diabetic peripheral neuropathic pain: An open-label, 52-week extension of a randomized controlled clinical trial.

    Science.gov (United States)

    Wernicke, Joachim F; Raskin, Joel; Rosen, Amy; Pritchett, Yili L; D'Souza, Deborah N; Iyengar, Smriti; Knopp, Kelly; Le, Trong K

    2006-09-01

    Duloxetine hydrochloride, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, is relatively balanced in its affinity for both 5-HT and NE reuptake inhibition and is the first US Food and Drug Administration-approved prescription drug for the management of diabetic peripheral neuropathic pain (DPNP). The aim of this study was to determine whether management of DPNP with duloxetine interferes with the treatment of diabetes. It also examined the tolerability of long-term exposure to duloxetine with regard to the progression of diabetic complications, and assessed the impact of DPNP management with duloxetine versus routine care. This was a 52-week, multicenter, re-randomized, open-label extension of a parallel, double-blind, randomized, placebo-controlled, acute (12-week) study. Patients who completed the duloxetine or placebo acute treatment period were randomly reassigned in a 2:1 ratio to treatment with duloxetine 60 mg BID or routine care for an additional 52 weeks. The study included male and female outpatients aged ≥18 years with a diagnosis of DPNP caused by type 1 or type 2 diabetes. Over the course of the 52-week study, visits were scheduled on the following weeks (of the extension phase of the study): 1 (via phone only), 2, 4, 8, 12, 20, 28, 40, and 52. Tolerability was assessed by review and analyses of discontinuation rates, adverse events (AEs), laboratory data, vital signs, electrocardiographic results, concomitant medications, and diabetic complications. Treatment-emergent AEs (TEAEs) were defined as AEs that appeared during therapy (were not present at baseline) or were exacerbated during treatment. Data on AEs and concomitant medications were collected at every visit. Data on blood pressure, heart rate, and significant hypoglycemic events were collected at every visit starting from week 2. Fasting clinical chemistry and electrolyte group laboratory assessments were done at every visit, starting from week 4. Electrocardiographic

  20. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  1. NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?).

    Science.gov (United States)

    Stienen, Susan; Salah, Khibar; Moons, Arno H; Bakx, Adrianus L; van Pol, Petra; Kortz, R A Mikael; Ferreira, João Pedro; Marques, Irene; Schroeder-Tanka, Jutta M; Keijer, Jan T; Bayés-Genis, Antoni; Tijssen, Jan G P; Pinto, Yigal M; Kok, Wouter E

    2018-04-17

    The concept of natriuretic peptide guidance has been extensively studied in patients with chronic heart failure (HF), with only limited success. The effect of NT-proBNP (N-terminal probrain natriuretic peptide)-guided therapy in patients with acute decompensated HF using a relative NT-proBNP target has not been investigated. This study aimed to assess whether NT-proBNP-guided therapy of patients with acute decompensated HF using a relative NT-proBNP target would lead to improved outcomes compared with conventional therapy. We conducted a prospective randomized controlled trial to study the impact of in-hospital guidance for acute decompensated HF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. Patients with acute decompensated HF with NT-proBNP levels >1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point was dual: a composite of all-cause mortality and HF readmissions in 180 days and the number of days alive out of the hospital in 180 days. Secondary end points were